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  • 1.
    Abalo, Xesus
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Boije: Zebrafish Neuronal Networks. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lagman, David
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Univ Bergen, Sars Int Ctr Marine Mol Biol, Bergen, Norway.
    Heras, Gabriel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    del Pozo, Ana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Boije: Zebrafish Neuronal Networks. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eggert, Joel
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Emory Univ, Dept Med, Atlanta, GA 30322 USA.
    Larhammar, Dan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Larhammar: Pharmacology.
    Circadian regulation of phosphodiesterase 6 genes in zebrafish differs between cones and rods: Implications for photopic and scotopic vision2020In: Vision Research, ISSN 0042-6989, E-ISSN 1878-5646, Vol. 166, p. 43-51Article in journal (Refereed)
    Abstract [en]

    A correlation is known to exist between visual sensitivity and oscillations in red opsin and rhodopsin gene expression in zebrafish, both regulated by the clock gene. This indicates that an endogenous circadian clock regulates behavioural visual sensitivity, apart from the regulation exerted by the pineal organ. However, the specific mechanisms for cones (photopic vision) and rods (scotopic vision) are poorly understood. In this work, we performed gene expression, cosinor and immunohistochemical analyses to investigate other key genes involved in light perception, encoding the different subunits of phosphodiesterase pde6 and transducin G alpha(T), in constant lighting conditions and compared to normal light-dark conditions. We found that cones display prominent circadian oscillations in mRNA levels for the inhibitory subunit gene pde6ha that could contribute to the regulation of photopic sensitivity by preventing overstimulation in photopic conditions. In rods, the mRNA levels of the inhibitory subunit gene pde6ga oscillate under normal conditions and dampen down in constant light but continue oscillating in constant darkness. There is an increase in total relative expression for pde6gb in constant conditions. These observations, together with previous data, suggest a complex regulation of the scotopic sensitivity involving endogenous and non-endogenous components, possibly present also in other teleost species. The G alpha(T) genes do not display mRNA oscillations and therefore may not be essential for the circadian regulation of photosensitivity. In summary, our results support different regulation for the zebrafish photopic and scotopic sensitivities and suggest circadian regulation of pde6ha as a key factor regulating photopic sensitivity, while the regulatory mechanisms in rods appear to be more complex.

  • 2.
    Abolhassani, Hassan
    et al.
    Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.;Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Pediat Ctr Excellence, Childrens Med Ctr, Tehran, Iran.
    Vosughimotlagh, Ahmad
    North Khorasan Univ Med Sci, Dept Pediat, Bojnurd, Iran.
    Asano, Takaki
    Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, 1230 York Ave, New York, NY 10021 USA.
    Landegren, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Karolinska Inst, Ctr Mol Med, Dept Med Solna, Stockholm, Sweden.
    Boisson, Bertrand
    Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, 1230 York Ave, New York, NY 10021 USA.;Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM U1163, Paris, France.;Univ Paris, Imagine Inst, Paris, France.
    Delavari, Samaneh
    Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Pediat Ctr Excellence, Childrens Med Ctr, Tehran, Iran.
    Bastard, Paul
    Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM U1163, Paris, France.;Univ Paris, Imagine Inst, Paris, France.
    Aranda-Guillen, Maribel
    Karolinska Inst, Ctr Mol Med, Dept Med Solna, Stockholm, Sweden.
    Wang, Yating
    Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.
    Zuo, Fanglei
    Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.
    Sardh, Fabian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Karolinska Inst, Ctr Mol Med, Dept Med Solna, Stockholm, Sweden..
    Marcotte, Harold
    Karolinska Inst, Dept Lab Med, Stockholm, Sweden.;Karolinska Univ, Hosp Huddinge, Stockholm, Sweden.
    Du, Likun
    Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.
    Zhang, Shen-Ying
    Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, 1230 York Ave, New York, NY 10021 USA.
    Zhang, Qian
    Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, 1230 York Ave, New York, NY 10021 USA.
    Rezaei, Nima
    Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Pediat Ctr Excellence, Childrens Med Ctr, Tehran, Iran.
    Kampe, Olle
    Karolinska Inst, Ctr Mol Med, Dept Med Solna, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, Stockholm, Sweden.
    Casanova, Jean-Laurent
    Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, 1230 York Ave, New York, NY 10021 USA.;Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM U1163, Paris, France.;Univ Paris, Imagine Inst, Paris, France.;Howard Hughes Med Inst, New York, NY USA.
    Hammarstrom, Lennart
    Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.
    Pan-Hammarstrom, Qiang
    Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.
    X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia2022In: Journal of Clinical Immunology, ISSN 0271-9142, E-ISSN 1573-2592, Vol. 42, no 1, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Background Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk.

    Objectives We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI).

    Methods Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry.

    Results We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient.

    Conclusions We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively.

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  • 3.
    Abrahamsson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Postprandial Normoglycemic Hypokalemia-an Overlooked Complication to Gastric Bypass Surgery?2021In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 31, no 7, p. 3369-3371Article in journal (Refereed)
    Abstract [en]

    Obesity is one of the major health problems of the world, and one of the most common surgical treatments is the Roux-en-Y gastric bypass surgery. This can however lead to problems with postprandial hypoglycemia, but sometimes, the meal test does not render any signs of hypoglycemia. Here, 3 cases are presented with postprandial normoglycemic hypokalemia.

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  • 4.
    Abrahamsson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Response to Postprandial Hyperinsulinemic Normoglycemic Hypokalemic Response After Roux-en-Y Gastric Bypass Surgery2022In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 32, no 7, p. 2468-2468Article in journal (Other academic)
  • 5.
    Abrahamsson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Engström, Britt Edén
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Karlsson, Anders F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery: a potential new indication?2013In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 169, no 6, p. 885-889Article in journal (Refereed)
    Abstract [en]

    Objective: The number of morbidly obese subjects submitted to bariatric surgery is rising worldwide. In a fraction of patients undergoing gastric bypass (GBP), episodes with late postprandial hypoglycemia (PPHG) develop 1-3 years after surgery. The pathogenesis of this phenomenon is not fully understood; meal-induced rapid and exaggerated increases of circulating incretins and insulin appear to be at least partially responsible. Current treatments include low-carbohydrate diets, inhibition of glucose intestinal uptake, reduction of insulin secretion with calcium channel blockers, somatostatin analogs, or diazoxide, a KATP channel opener. Even partial pancreatectomy has been advocated. In type 2 diabetes, GLP1 analogs have a well-documented effect of stabilizing glucose levels without causing hypoglycemia. Design: We explored GLP1 analogs as open treatment in five consecutive GBP cases seeking medical attention because of late postprandial hypoglycemic symptoms. Results: Glucose measured in connection with the episodes in four of the cases had been 2.7, 2.5, 1.8, and 1.6 mmol/l respectively. The patients consistently described that the analogs eliminated their symptoms, which relapsed in four of the five patients when treatment was reduced/discontinued. The drug effect was further documented in one case by repeated 24-h continuous glucose measurements. Conclusion: These open, uncontrolled observations suggest that GLP1 analogs might provide a new treatment option in patients with problems of late PPHG.

  • 6.
    Abrahamsson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Engström, Britt Edén
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Karlsson, Anders F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Hypoglycemia in everyday life after gastric bypass and duodenal switch2015In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 173, no 1, p. 91-100Article in journal (Refereed)
    Abstract [en]

    Design: Gastric bypass (GBP) and duodenal switch (DS) in morbid obesity are accompanied by marked metabolic improvements, particularly in glucose control. In recent years, episodes of severe late postprandial hypoglycemia have been increasingly described in GBP patients; data in DS patients are scarce. We recruited three groups of subjects; 15 GBP, 15 DS, and 15 non-operated overweight controls to examine to what extent hypoglycemia occurs in daily life. Methods: Continuous glucose monitoring (CGM) was used during 3 days of normal activity. The glycemic variability was measured by mean amplitude of glycemic excursion and continuous overall net glycemic action. Fasting blood samples were drawn, and the patients kept a food and symptom log throughout the study. Results: The GBP group displayed highly variable CGM curves, and 2.9% of their time was spent in hypoglycemia (< 3.3 mmol/l, or 60 mg/dl). The DS group had twice as much time in hypoglycemia (5.9%) and displayed CGM curves with little variation as well as lower HbA1c levels (29.3 vs 35.9 mmol/mol, P < 0.05). Out of a total of 72 hypoglycemic episodes registered over the 3-day period, 70 (97%) occurred in the postprandial state and only about one-fifth of the hypoglycemic episodes in the GBP and DS groups were accompanied by symptoms. No hypoglycemias were seen in controls during the 3-day period. Conclusion: Both types of bariatric surgery induce marked, but different, changes in glucose balance accompanied by frequent, but mainly unnoticed, hypoglycemic episodes. The impact and mechanism of hypoglycemic unawareness after weight-reduction surgery deserves to be clarified.

  • 7.
    Abrahamsson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lau Börjesson, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wiklund, Urban
    Umea Univ, Biomed Engn, Dept Radiat Sci, Umea, Sweden.
    Karlsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Gastric bypass reduces symptoms and hormonal responses to hypoglycemia2016In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 9, p. 2667-2675Article in journal (Refereed)
    Abstract [en]

    Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.

  • 8.
    Adolfsson, Peter
    et al.
    Department of Pediatrics, The Hospital of Halland, Kungsbacka, Sweden.; Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden..
    Hartvig, Niels Væver
    Data Science, Novo Nordisk A/S, Søborg, Denmark.
    Kaas, Anne
    Medical & Science, and Novo Nordisk A/S, Søborg, Denmark..
    Møller, Jonas Bech
    Digital Health, Novo Nordisk A/S, Søborg, Denmark.
    Hellman, Jarl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Increased Time in Range and Fewer Missed Bolus Injections After Introduction of a Smart Connected Insulin Pen2020In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 22, no 10, p. 709-718Article in journal (Refereed)
    Abstract [en]

    Background: This observational study investigated whether the connected NovoPen® 6 could influence insulin regimen management and glycemic control in people with type 1 diabetes (T1D) using a basal-bolus insulin regimen and continuous glucose monitoring in a real-world setting. Methods: Participants from 12 Swedish diabetes clinics downloaded pen data at each visit (final cohort: n = 94). Outcomes included time in range (TIR; sensor glucose 3.9-10.0 mmol/L), time in hyperglycemia (>10 mmol/L), and hypoglycemia (L1: 3.0- <3.9 mmol/L; L2: <3.0 mmol/L). Missed bolus dose (MBD) injections were meals without bolus injection within -15 and +60 min from the start of a meal. Outcomes were compared between the baseline and follow-up periods (≥5 health care professional visits). Data were analyzed from the first 14 days following each visit. For the TIR and total insulin dose analyses (n = 94), a linear mixed model was used, and for the MBD analysis (n = 81), a mixed Poisson model was used. Results: TIR significantly increased (+1.9 [0.8; 3.0]95% CI h/day; P < 0.001) from baseline to follow-up period, with a corresponding reduction in time in hyperglycemia (-1.8 [-3.0; -0.6]95% CI h/day; P = 0.003) and L2 hypoglycemia (-0.3 [-0.6; -0.1]95% CI h/day; P = 0.005), and no change in time in L1 hypoglycemia. MBD injections decreased by 43% over the study (P = 0.002). Change in MBD injections corresponded to a decrease from 25% to 14% based on the assumption that participants had three main meals per day. Conclusions: Our study highlights the potential benefit on glycemic control and dosing behavior when reliable insulin dose data from a connected pen contribute to insulin management in people with T1D.

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  • 9.
    Ahmed, Fozia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Hetty, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Vranic, Milica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Fanni, Giovanni
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    ESR2 expression in subcutaneous adipose tissue is related to body fat distribution in women, and knockdown impairs preadipocyte differentiation2022In: Adipocyte, ISSN 2162-3945, E-ISSN 2162-397X, Vol. 11, no 1, p. 434-447Article in journal (Refereed)
    Abstract [en]

    Oestrogen receptor 2 (ESR2) expression has been shown to be higher in subcutaneous adipose tissue (SAT) from postmenopausal compared to premenopausal women. The functional significance of altered ESR2 expression is not fully known. This study investigates the role of ESR2 for adipose tissue lipid and glucose metabolism. SAT biopsies were obtained from 44 female subjects with or without T2D. Gene expression of ESR2 and markers of adipose function and metabolism was assessed. ESR2 knockdown was performed using CRISPR/Cas9 in preadipocytes isolated from SAT of females, and differentiation rate, lipid storage, and glucose uptake were measured. ESR2 expression was inversely correlated with measures of central obesity and expression of some fatty acid oxidation markers, and positively correlated with lipid storage and glucose transport markers. Differentiation was reduced in ESR2 knockdown preadipocytes. This corresponded to reduced expression of markers of differentiation and lipogenesis. Glucose uptake was reduced in knockdown adipocytes. Our results indicate that ESR2 deficiency in women is associated with visceral adiposity and impaired subcutaneous adipocyte differentiation as well as glucose and lipid utilization. High ESR2 expression, as seen after menopause, could be a contributing factor to SAT expansion. This may support a possible target to promote a healthy obesity phenotype.

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  • 10.
    Ahmed, Fozia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kamble, Prasad G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Hetty, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Fanni, Giovanni
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Vranic, Milica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sarsenbayeva, Assel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kristofi, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Almby, Kristina E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Svensson, Maria K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Role of Estrogen and Its Receptors in Adipose Tissue Glucose Metabolism in Pre- and Postmenopausal Women2022In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 107, no 5, p. E1879-E1889Article in journal (Refereed)
    Abstract [en]

    Context: Reduced estrogen levels in postmenopausal women predispose them to metabolic side effects, including insulin resistance and type 2 diabetes; however, the cellular mechanisms are not well understood.

    Objective: This work aimed to study the expression of estrogen receptors in adipose tissue from pre- and postmenopausal women and the effects of estradiol (E2) on glucose uptake of adipocytes.

    Methods: Subcutaneous (SAT) and visceral adipose tissue (VAT) obtained from pre- and postmenopausal women (19-51 and 46-75 years old, respectively) were used to measure gene expression of ESR1 and ESR2. SAT tissue was incubated with E2, and glucose uptake and estrogen receptor levels were measured. Polymorphisms in ESR1 and ESR2 were addressed in public databases to identify single nucleotide polymorphisms associated with metabolic traits.

    Results: ESR2 expression was lower in pre- vs postmenopausal women, corresponding to lower ESR1:ESR2 gene expression ratio in postmenopausal women. In premenopausal women, the expression of ESR1 was higher in VAT than in SAT. In both pre- and postmenopausal women, ESR2 expression was lower in VAT than in SAT. In late, but not pre- or early postmenopausal women, E2 reduced glucose uptake and GLUT4 protein and increased expression of ESR2. ESR1 polymorphisms were associated with weight, body fat distribution, and total cholesterol, and ESR2 polymorphisms were associated with total cholesterol and triglyceride levels and with body fat percentage.

    Conclusion: E2 inhibits glucose utilization in human adipocytes in late postmenopausal women. Changes in glucose utilization over time since menopause may be explained by a lower ESR1:ESR2 ratio. This can have clinical implications on the timing of estrogen treatment in postmenopausal women.

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  • 11.
    Ahmed, Fozia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Inst Savoir Montfort, 1E103,713 Montreal Rd, Ottawa, ON K1K 0T2, Canada.;Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON K1N 6N5, Canada..
    Pereira, Maria João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Aguer, Celine
    Inst Savoir Montfort, 1E103,713 Montreal Rd, Ottawa, ON K1K 0T2, Canada.;Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON K1N 6N5, Canada.;Univ Ottawa, Fac Hlth Sci, Sch Human Kinet, Ottawa, ON K1N 6N5, Canada.;Univ Ottawa, Fac Hlth Sci, Interdisciplinary Sch Hlth Sci, Ottawa, ON K1N 6N5, Canada..
    Bisphenols and the Development of Type 2 Diabetes: The Role of the Skeletal Muscle and Adipose Tissue2021In: Environments, E-ISSN 2076-3298, Vol. 8, no 4, article id 35Article, review/survey (Refereed)
    Abstract [en]

    Bisphenol A (BPA) and bisphenol S (BPS) are environmental contaminants that have been associated with the development of insulin resistance and type 2 diabetes (T2D). Two organs that are often implicated in the development of insulin resistance are the skeletal muscle and the adipose tissue, however, seldom studies have investigated the effects of bisphenols on their metabolism. In this review we discuss metabolic perturbations that occur in both the skeletal muscle and adipose tissue affected with insulin resistance, and how exposure to BPA or BPS has been linked to these changes. Furthermore, we highlight the possible effects of BPA on the cross-talk between the skeletal muscle and adipose tissue.

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  • 12.
    Ahmed, Fozia
    et al.
    Inst Savoir Montfort Rech, 1E103,713 Montreal Rd, Ottawa, ON K1K 0T2, Canada; Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada.
    Sarsenbayeva, Assel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Aguer, Céline
    Inst Savoir Montfort Rech, 1E103,713 Montreal Rd, Ottawa, ON K1K 0T2, Canada; Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada; Univ Ottawa, Fac Hlth Sci, Sch Human Kinet, Ottawa, ON, Canada; Univ Ottawa, Fac Hlth Sci, Interdisciplinary Sch Hlth Sci, Ottawa, ON, Canada.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    The effects of bisphenol A and bisphenol S on adipokine expression and glucose metabolism in human adipose tissue2020In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 445, article id 152600Article in journal (Refereed)
    Abstract [en]

    Purpose

    The environmental endocrine disruptors, bisphenol A (BPA) and bisphenol S (BPS) are associated with the development of type 2 diabetes. We aim to study the effects of BPA or BPS exposure on adipokine expression in human adipose tissue and on adipocyte glucose uptake.

    Methods

    Human subcutaneous adipose tissue was treated for 24 or 72 h with environmentally-relevant and supraphysiological concentrations of BPA or BPS (1–104 nM). Following exposure, gene expression of proinflammatory cytokines, adipokines, and estrogen receptors was measured in adipose tissue. Glucose uptake and the insulin signalling pathway were analyzed in isolated adipocytes following adipose tissue culture with BPA for 24 h.

    Results

    Adipose tissue treated with BPA for 24 h had reduced expression of the proinflammatory genes (IL6, IL1B, TNFA) and adipokines (ADIPOQ, FABP4). BPA and BPS had no effect on the expression of other proinflammatory genes (IL33), adipokines (LEP), or receptors (ESR1, ESR2) after 72-h exposure. Adipose tissue treated with environmentally-relevant concentrations of BPA for 24 h had reduced insulin-stimulated glucose uptake, without altered gene and protein levels of key insulin signalling pathway markers.

    Conclusions

    We found that human adipose tissue treated with environmentally-relevant concentrations of BPA for 24 h, but not BPS, reduced expression of proinflammatory genes and adipokines. Furthermore, BPA reduced glucose uptake in adipocytes independently of insulin signalling. Such mechanisms can contribute to the development of insulin resistance associated with BPA exposure.

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  • 13.
    Ahmed, Fozia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Vranic, Milica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Hetty, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Mathioudaki, Argyri
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Patsoukaki, Vagia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Fanni, Giovanni
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Increased OCT3 Expression in Adipose Tissue With Aging: Implications for Catecholamine and Lipid Turnover and Insulin Resistance in Women2023In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 165, no 1, article id bqad172Article in journal (Refereed)
    Abstract [en]

    Background Catecholamine-stimulated lipolysis is reduced with aging, which may promote adiposity and insulin resistance. Organic cation transporter 3 (OCT3), which is inhibited by estradiol (E2), mediates catecholamine transport into adipocytes for degradation, thus decreasing lipolysis. In this study, we investigated the association of OCT3 mRNA levels in subcutaneous adipose tissue (SAT) with aging and markers of insulin resistance in women.Methods SAT biopsies were obtained from 66 women with (19) or without (47) type 2 diabetes (age 22-76 years, 20.0-40.1 kg/m2). OCT3 mRNA and protein levels were measured for group comparisons and correlation analysis. SAT was incubated with E2 and OCT3 mRNA levels were measured. Associations between OCT3 single nucleotide polymorphisms (SNPs) and diabetes-associated traits were assessed.Results OCT3 mRNA and protein levels in SAT increased with aging. SAT from postmenopausal women had higher levels of OCT3 than premenopausal women, and there was a dose-dependent reduction in OCT3 mRNA levels in SAT treated with E2. OCT3 mRNA levels were negatively associated with markers of insulin resistance, and ex vivo lipolysis. OCT3 SNPs were associated with BMI, waist to hip ratio, and circulating lipids (eg, triglycerides).Conclusion OCT3 mRNA and protein levels in SAT increased with aging, and mRNA levels were negatively associated with markers of insulin resistance. E2 incubation downregulated OCT3 mRNA levels, which may explain lower OCT3 mRNA in premenopausal vs postmenopausal women. High OCT3 protein levels in adipose tissue may result in increased catecholamine degradation, and this can contribute to the reduction in lipolysis observed in women with aging.

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  • 14.
    Al-Amin, Rasel A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Johansson, Lars
    Department of Medical Biochemistry and Biophysics, Chemical Biology Consortium Sweden (CBCS), Science for Life Laboratory, Karolinska Institutet.
    Abdurakhmanov, Eldar
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Landegren, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Center for Molecular Medicine, Department of Medicine (Solna), Science for Life Laboratory, Karolinska Institutet.
    Löf, Liza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Arngården, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Blokzijl, Andries
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Svensson, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hammond, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lönn, Peter
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Haybaeck, Johannes
    Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck; Diagnostic and Research Institute of Pathology, Medical University of Graz.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jenmalm Jensen, Annika
    Department of Medical Biochemistry and Biophysics, Chemical Biology Consortium Sweden (CBCS), Science for Life Laboratory, Karolinska Institutet.
    Danielson, U. Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lundbäck, Thomas
    Department of Medical Biochemistry and Biophysics, Chemical Biology Consortium Sweden (CBCS), Science for Life Laboratory, Karolinska Institutet.
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Monitoring drug–target interactions through target engagement-mediated amplification on arrays and in situ2022In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 50, no 22, p. e129-e129Article in journal (Refereed)
    Abstract [en]

    Drugs are designed to bind their target proteins in physiologically relevant tissues and organs to modulate biological functions and elicit desirable clinical outcomes. Information about target engagement at cellular and subcellular resolution is therefore critical for guiding compound optimization in drug discovery, and for probing resistance mechanisms to targeted therapies in clinical samples. We describe a target engagement-mediated amplification (TEMA) technology, where oligonucleotide-conjugated drugs are used to visualize and measure target engagement in situ, amplified via rolling-circle replication of circularized oligonucleotide probes. We illustrate the TEMA technique using dasatinib and gefitinib, two kinase inhibitors with distinct selectivity profiles. In vitro binding by the dasatinib probe to arrays of displayed proteins accurately reproduced known selectivity profiles, while their differential binding to fixed adherent cells agreed with expectations from expression profiles of the cells. We also introduce a proximity ligation variant of TEMA to selectively investigate binding to specific target proteins of interest. This form of the assay serves to improve resolution of binding to on- and off-target proteins. In conclusion, TEMA has the potential to aid in drug development and clinical routine by conferring valuable insights in drug–target interactions at spatial resolution in protein arrays, cells and in tissues.

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  • 15.
    Aldenbratt, Annika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lindberg, Christopher
    Johannesson, Elias
    Hammarsten, Ola
    Svensson, Maria K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Estimation of kidney function in patients with primary neuromuscular diseases: is serum cystatin C a better marker of kidney function than creatinine?2022In: JN. Journal of Nephrology, ISSN 1121-8428, E-ISSN 1724-6059, Vol. 35, no 2, p. 493-503Article in journal (Refereed)
    Abstract [en]

    Background: Using serum creatinine leads to an overestimation of kidney function in patients with primary neuromuscular disorders, and reduced kidney function may remain undetected. Cystatin C (CysC) could provide a better estimation.

    Aim: To evaluate the precision, accuracy, and bias of two creatinine-, one cystatin C-based and one combined equation to estimate glomerular filtration rate (eGFR) in patients with primary neuromuscular disease.

    Patients and methods: Of the 418 patients initially identified at the out-patient clinic, data on kidney function was obtained for 145 adult patients (age 46 ± 14 years, BMI 26 ± 6 kg/m2) with primary neuromuscular disease. Kidney function was measured by iohexol clearance, and blood samples for serum creatinine and CysC were drawn simultaneously. Bias was defined as the mean difference between eGFR and measured iohexol clearance, and accuracy as the proportion of eGFRs within ± 10% (P10) of measured clearance.

    Results: Kidney function (iohexol clearance) was 81 ± 19 (38–134) ml/min/1.73m2. All equations overestimated kidney function by 22–60 ml/min/1.73m2. eGFR CysC had the lowest bias overall 22 (95% CI 20–26) ml/min/1.73m2 also at all levels of kidney function we evaluated (at 30–59 ml/min/1.73m2 bias was 27 (95% CI 21–35), at 60–89 it was 25 (95% CI 20–28) and at ≥ 90 it was 12 (95% CI 7–22)). eGFR CysC also had the best accuracy in patients with reduced kidney function (P10 was 5.9% at 30–59 ml/min/1.73m2).

    Conclusions: Cystatin C-based estimations of kidney function performed better than creatinine-based ones in patients with primary neuromuscular disease, but most importantly, all evaluated equations overestimated kidney function, especially in patients with reduced kidney function. Therefore, kidney function should be measured by gold-standard methods when precision and accuracy are needed.

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  • 16.
    Aldenbratt, Annika
    et al.
    Sahlgrens Univ Hosp, Dept Nephrol, Gothenburg, Sweden.
    Lindberg, Christopher
    Sahlgrens Univ Hosp, Dept Neurol, Neuromuscular Ctr, Gothenburg, Sweden.
    Svensson, Maria K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Reduced renal function in patients with Myotonic Dystrophy type 1 and the association to CTG expansion and other potential risk factors for chronic kidney disease2017In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 27, no 11, p. 1038-1042Article in journal (Refereed)
    Abstract [en]

    Myotonic dystrophy type 1 (DM1) affects several organs. Disease severity and age at onset are correlated to the CTG repeat expansion. The aim of this study was to assess renal function and the association to numbers of CTG repeat expansion in patients with DM1. Ninety-eight patients with DM1 were included. Glomerular filtration rate (measured GFR) was measured using iohexol clearance. Data on CTG repeats were available in 83/98 (85%) patients. The overall mGFR was 74 (16) ml/min/1.73 m(2) (range 38-134). Sixty-four patients (69%) had a mild and sixteen patients (17%) a moderate decrease in renal function (mGFR 60-89 and 30-59 ml/min/1.73 m(2), respectively). No correlations were found between CTG repeats and mGFR (r = 0.10, p = 0.4) or between CTG repeats and serum cystatin C (r = 0.12, p = 0.29). CTG repeats was positively correlated to creatinine-based estimates of GFR (eGFR) (modified diet in renal disease r = 0.49, p < 0.001, CKD-EPI creatinine equation; r = 0.50, p < 0.001), but analyses using Structural Equation Modeling showed no correlation. The correlation was explained by an indirect effect via serum creatinine and skeletal muscle mass index. In conclusion, patients with DM1 seem to have a slight decrease in renal function but there is no association between renal function and the number of CTG repeats, a marker of disease severity.

  • 17.
    Almby, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Brain-gut-adipose interplay in the antidiabetic effects of gastric bypass surgery2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Gastric bypass surgery (GBP) leads not only to considerable and consistent weight loss but to a number of beneficial metabolic effects, often including a swift remission of type 2 diabetes (T2DM). Increases in the gut hormone GLP-1 are considered central to this effect, although several other mechanism are likely involved. One complication to GBP is post-bariatric hypoglycaemia (PBH), where the individual suffers from episodes of low blood sugar after meals. The mechanism behind this is incompletely understood. 

    Previous research has reported an attenuation of the counterregulatory response to hypoglycaemia in patients after GBP. Many hypoglycaemic episodes also appear to be asymptomatic. Together, this has led to the hypothesis that GBP and PBH may involve an adaptation to lower blood glucose levels, a lowered glycaemic set point. As much of hypoglycaemia counterregulation involves the central nervous system (CNS), such an adaptation would presumably involve neuroendocrine mechanism. Experimental treatment with GLP-1 receptor agonists (GLP-1RA) has been reported as successful against PBH, which is paradoxical as GLP-1RA stimulate insulin release. 

    The aim of this thesis is to further explore the metabolic changes after GBP that may influence glycaemic control. In Paper I, euglycaemic-hypoglycaemic clamps were used to assess whether infusion with GLP-1RA affects the counterregulatory response to hypoglycaemia after GBP. In Paper II, normoglycaemic-hypoglycaemic clamps were performed before and after GBP during simultaneous brain imaging with fMRI and FDG-PET techniques, cognitive testing and assessment of counterregulatory hormones. Paper III details the time course of metabolic changes after GBP in patients with previous T2DM with focus on adipose tissue, including gene expression, and possible anti-inflammatory effects. Paper IV approaches the same question as Paper I, this time in the setting of a standardized meal test. All papers include assessment of heart rate variability (HRV) as a potential reflection of autonomic nervous system (ANS) activity. 

    In Paper I, we do not find indications that GLP-1RA affects counterregulatory hormones, but that it may affect ANS activation during hypoglycaemia. In contrast, Paper IV reports higher cortisol levels with GLP1-RA after a meal, and indications of ANS effects, but no effect on post-prandial glucose levels. Results from Paper II support the hypothesis that GBP attenuates hormonal counterregulatory responses and affects how the CNS responds to hypoglycaemia. In Paper III we report sustained improvements in glucose uptake in adipocytes, potentially indications of decreased low-grade inflammation and signs of transient increases in parasympathetic activity. 

    List of papers
    1. Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery
    Open this publication in new window or tab >>Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery
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    2019 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 181, no 2, p. 161-171Article in journal (Refereed) Published
    Abstract [en]

    Objectives: The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP).

    Design: Experimental hyperinsulinemic-hypoglycemic clamp study.

    Methods: Twelve post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/L) performed on separate days with concomitant infusions of the GLP-1 analog exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps.

    Results: No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines, cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed.

    Conclusions/interpretation: Short-term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.

    Place, publisher, year, edition, pages
    BIOSCIENTIFICA LTD, 2019
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-390513 (URN)10.1530/EJE-19-0171 (DOI)000472835100013 ()31176298 (PubMedID)
    Funder
    Swedish Diabetes AssociationErnfors FoundationEXODIAB - Excellence of Diabetes Research in Sweden
    Available from: 2019-08-12 Created: 2019-08-12 Last updated: 2023-12-14Bibliographically approved
    2. Effects of Gastric Bypass Surgery on the Brain: Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia
    Open this publication in new window or tab >>Effects of Gastric Bypass Surgery on the Brain: Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia
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    2021 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 70, no 6, p. 1265-1277Article in journal (Refereed) Published
    Abstract [en]

    While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by F-18-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.

    Place, publisher, year, edition, pages
    American Diabetes Association, 2021
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-452976 (URN)10.2337/db20-1172 (DOI)000671940300008 ()33674408 (PubMedID)
    Note

    K.E.A. and M.H.L. contributed equally.

    Available from: 2021-09-15 Created: 2021-09-15 Last updated: 2023-12-14Bibliographically approved
    3. Time Course of Metabolic, Neuroendocrine, and Adipose Effects During 2 Years of Follow-up After Gastric Bypass in Patients With Type 2 Diabetes
    Open this publication in new window or tab >>Time Course of Metabolic, Neuroendocrine, and Adipose Effects During 2 Years of Follow-up After Gastric Bypass in Patients With Type 2 Diabetes
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    2021 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 106, no 10Article in journal (Refereed) Published
    Abstract [en]

    Context: Roux-en-Y gastric bypass surgery (RYGB) markedly improves glycemia in patients with type 2 diabetes (T2D), but underlying mechanisms and changes over time are incompletely understood.

    Objective: Integrated assessment of neuroendocrine and metabolic changes over time in T2D patients undergoing RYGB.

    Design and Setting: Follow-up of single-center randomized study.

    Patients: Thirteen patients with obesity and T2D compared to 22 healthy subjects. Interventions: Blood chemistry, adipose biopsies, and heart rate variability were obtained before and 4, 24, and 104 weeks post-RYGB.

    Results: After RYGB, glucose-lowering drugs were discontinued and hemoglobin A1c fell from mean 55 to 41 mmol/mol by 104 weeks (P<0.001). At 4 weeks, morning cortisol (P<0.05) and adrenocorticotropin (P=0.09) were reduced by 20%. Parasympathetic nerve activity (heart rate variability derived) increased at 4 weeks (P<0.05) and peaked at 24 weeks (P<0.01). C-reactive protein (CRP) and white blood cells were rapidly reduced (P<0.01). At 104 weeks, basal and insulin-stimulated adipocyte glucose uptake increased by 3-fold vs baseline and expression of genes involved in glucose transport, fatty acid oxidation, and adipogenesis was upregulated (P<0.01). Adipocyte volume was reduced by 4 weeks and more markedly at 104 weeks, by about 40% vs baseline (P<0.01).

    Conclusions: We propose this order of events: (1) rapid glucose lowering (days); (2) attenuated cortisol axis activity and inflammation and increased parasympathetic tone (weeks); and (3) body fat and weight loss, increased adipose glucose uptake, and whole-body insulin sensitivity (months-years; similar to healthy controls). Thus, neuroendocrine pathways can partly mediate early glycemic improvement after RYGB, and adipose factors may promote long-term insulin sensitivity and normoglycemia.

    Place, publisher, year, edition, pages
    Endocrine SocietyThe Endocrine Society, 2021
    Keywords
    T2D, RYGB, neuroendocrine changes, adipose effects
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-457938 (URN)10.1210/clinem/dgab398 (DOI)000705200500042 ()34086911 (PubMedID)
    Funder
    Diabetesfonden, DIA2019-490Ernfors FoundationEXODIAB - Excellence of Diabetes Research in SwedenNovo Nordisk, NNF20OC0063864
    Available from: 2021-11-08 Created: 2021-11-08 Last updated: 2024-01-15Bibliographically approved
    4. Effects of acute GLP-1 receptor activation on the glycemic and neurohormonal responses to meal test after gastric bypass
    Open this publication in new window or tab >>Effects of acute GLP-1 receptor activation on the glycemic and neurohormonal responses to meal test after gastric bypass
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    (English)Manuscript (preprint) (Other academic)
    Keywords
    Roux-en Y gastric bypass, post-bariatric hypoglycaemia, GLP-1 analogue, hypoglycaemia counterregulation, cortisol
    National Category
    Endocrinology and Diabetes
    Research subject
    Medical Science
    Identifiers
    urn:nbn:se:uu:diva-517680 (URN)
    Available from: 2023-12-13 Created: 2023-12-13 Last updated: 2023-12-14
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  • 18.
    Almby, Kristina E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Abrahamsson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lundqvist, Martin H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Hammar, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Thombare, Ketan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Panagiotou, Amalia
    Uppsala Univ Hosp, Dept Internal Med, Uppsala, Sweden.
    Karlsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wiklund, Urban
    Umea Univ, Dept Radiat Sci, Biomed Engn, Umea, Sweden.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery2019In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 181, no 2, p. 161-171Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP).

    Design: Experimental hyperinsulinemic-hypoglycemic clamp study.

    Methods: Twelve post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/L) performed on separate days with concomitant infusions of the GLP-1 analog exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps.

    Results: No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines, cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed.

    Conclusions/interpretation: Short-term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.

  • 19.
    Almby, Kristina E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Akademiska Sjukhuset.
    Edholm, David
    Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Anastomotic Strictures After Roux-en-Y Gastric Bypass: a Cohort Study from the Scandinavian Obesity Surgery Registry2019In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 29, no 1, p. 172-177Article in journal (Refereed)
    Abstract [en]

    Background

    Roux-en-Y gastric bypass (RYGB) is the most common bariatric procedure worldwide. Anastomotic stricture is a known complication of RYGB. The aim was to explore the incidence and outcomes of strictures within the Scandinavian Obesity Surgery Registry (SOReg).

    Method

    SOReg included prospective data from 36,362 patients undergoing bariatric surgery in the years 2007–2013. Outcomes were recorded at 30-day and at 1-year follow-up according to the standard SOReg routine. The medical charts of patients suffering from stricture after RYGB were requested and assessed.

    Setting

    National bariatric surgery registry

    Results

    Anastomotic stricture within 1 year of surgery was confirmed in 101 patients representing an incidence of 0.3%. Risk factors for stricture were patient age above 60 years (odds ratio (OR), 6.2 95% confidence interval (CI) 2.7–14.3), circular stapled gastrojejunostomy (OR 2.7, 95% CI 1.4–5.5), postoperative anastomotic leak (OR 8.9 95%, CI 4.7–17.0), and marginal ulcer (OR 30.0, 95% CI 19.2–47.0). Seventy-five percent of the strictures were diagnosed within 70 days of surgery. Two dilatations or less was sufficient to successfully treat 50% of patients. Ten pecent of patients developed perforation during dilatation, and the risk of perforating at each dilatation was 3.8%. Perforation required surgery in six cases but there was no mortality. Strictures in SOReg may be underreported, which could explain the low incidence in the study.

    Conclusion

    Most strictures present within 2 months and are successfully treated with two dilatations or less. Dilating a strictured gastrojejunostomy entails a risk of perforation (3.8%).

  • 20.
    Almby, Kristina E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Karlsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wiklund, Urban
    Umeå Univ, Dept Radiat Sci, Umeå, Sweden..
    Kamble, Prasad G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Time Course of Metabolic, Neuroendocrine, and Adipose Effects During 2 Years of Follow-up After Gastric Bypass in Patients With Type 2 Diabetes2021In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 106, no 10Article in journal (Refereed)
    Abstract [en]

    Context: Roux-en-Y gastric bypass surgery (RYGB) markedly improves glycemia in patients with type 2 diabetes (T2D), but underlying mechanisms and changes over time are incompletely understood.

    Objective: Integrated assessment of neuroendocrine and metabolic changes over time in T2D patients undergoing RYGB.

    Design and Setting: Follow-up of single-center randomized study.

    Patients: Thirteen patients with obesity and T2D compared to 22 healthy subjects. Interventions: Blood chemistry, adipose biopsies, and heart rate variability were obtained before and 4, 24, and 104 weeks post-RYGB.

    Results: After RYGB, glucose-lowering drugs were discontinued and hemoglobin A1c fell from mean 55 to 41 mmol/mol by 104 weeks (P<0.001). At 4 weeks, morning cortisol (P<0.05) and adrenocorticotropin (P=0.09) were reduced by 20%. Parasympathetic nerve activity (heart rate variability derived) increased at 4 weeks (P<0.05) and peaked at 24 weeks (P<0.01). C-reactive protein (CRP) and white blood cells were rapidly reduced (P<0.01). At 104 weeks, basal and insulin-stimulated adipocyte glucose uptake increased by 3-fold vs baseline and expression of genes involved in glucose transport, fatty acid oxidation, and adipogenesis was upregulated (P<0.01). Adipocyte volume was reduced by 4 weeks and more markedly at 104 weeks, by about 40% vs baseline (P<0.01).

    Conclusions: We propose this order of events: (1) rapid glucose lowering (days); (2) attenuated cortisol axis activity and inflammation and increased parasympathetic tone (weeks); and (3) body fat and weight loss, increased adipose glucose uptake, and whole-body insulin sensitivity (months-years; similar to healthy controls). Thus, neuroendocrine pathways can partly mediate early glycemic improvement after RYGB, and adipose factors may promote long-term insulin sensitivity and normoglycemia.

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  • 21.
    Almby, Kristina E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lundqvist, Martin H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Abrahamsson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kvernby, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Karlsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Fanni, Giovanni
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wiklund, Urban
    Umeå Univ, Dept Radiat Sci, Umeå, Sweden..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland..
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Effects of Gastric Bypass Surgery on the Brain: Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia2021In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 70, no 6, p. 1265-1277Article in journal (Refereed)
    Abstract [en]

    While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by F-18-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.

  • 22.
    Almby, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Wiklund, Urban
    Department of Radiation Sciences, Radiation Physics, Biomedical Engineering, Umeå University.
    Lundqvist, Martin H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Abrahamsson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Effects of acute GLP-1 receptor activation on the glycemic and neurohormonal responses to meal test after gastric bypassManuscript (preprint) (Other academic)
  • 23.
    Almdalal, Tarik
    et al.
    Department of Surgery and Urology, Eskilstuna Country Hospital, Eskilstuna, Sweden.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Regional Cancer Centre Stockholm-Gotland, Stockholm, Sweden;Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Solna, Sweden.
    Hellström, Mikael
    Department of Radiology, Sahlgrenska Academy/Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.
    Kjellman, Anders
    Department of Urology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Lindblad, Per
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lundstam, Sven
    Departments of Urology and Oncology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sundqvist, Pernilla
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Ljungberg, Börje
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Predictive characteristics for disease recurrence and overall survival in non-metastatic clinical T1 renal cell carcinoma: results from the National Swedish Kidney Cancer Register2023In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 57, no 1-6, p. 67-74Article in journal (Refereed)
    Abstract [en]

    Objective

    Patients with clinical T1 renal cell carcinoma (cT1RCC) have risks for recurrence and reduced overall survival despite being in the best prognostic group. This study aimed to evaluate the association of different treatments on disease recurrence and overall survival using clinical and pathological characteristics in a nation-wide cT1RCC cohort.

    Materials and methods

    A total of 4,965 patients, registered in the National Swedish Kidney Cancer Register (NSKCR) between 2005 and 2014, with ≥ 5-years follow-up were identified: 3,040 males and 1,925 females, mean age 65 years. Times to recurrence and overall survival were analyzed with Kaplan-Meier curves, log-rank test, and Cox regression models.

    Results

    Age, TNM-stage, tumor size, RCC-type, and performed treatment were all associated with disease recurrence. Patients selected for ablative treatments had increased risk for recurrent disease: hazard ratio (HR) = 3.79 [95% confidence interval (CI) = 2.69–5.32]. In multivariate analyses, age, gender, tumor size, RCC-type, N-stage, recurrence and performed treatment were all independently associated with overall survival. Patients with chRCC had a 41% better overall survival (HR = 0.59, 95% CI = 0.44–0.78; p < 0.001) than ccRCC. Patients treated with partial nephrectomy (PN) had an 18% better overall survival (HR = 0.83, 95% CI = 0.71–0.95, p < 0.001) than patients treated with radical nephrectomy.

    Conclusions

    Age, gender, T-stage, tumor size, RCC type and treatment modality are all associated with risk of recurrence. Furthermore, age, male gender, tumor size, N-stage and recurrence are associated with reduced overall survival. Patients with chRCC, compared with ccRCC and pRCC patients, and PN compared with RN treated patients, had an advantageous overall survival, indicating a possible survival advantage of nephron sparing treatment.

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  • 24.
    Barbosa, Pedro
    et al.
    Univ Coimbra, Inst Interdisciplinary Res, Doctoral Programme Expt Biol & Biomed PDBEB, Coimbra, Portugal.;Univ Coimbra, Ctr Neurosci & Cell Biol CNC, P-3004504 Coimbra, Portugal.;Univ Coimbra, Inst Interdisciplinary Res IIIUC, P-3030789 Coimbra, Portugal.;Univ Coimbra, Ctr Innovat Biomed & Biotechnol CIBB, P-3000504 Coimbra, Portugal..
    Pinho, Aryane
    Univ Coimbra, Inst Interdisciplinary Res, Doctoral Programme Expt Biol & Biomed PDBEB, Coimbra, Portugal.;Univ Coimbra, Ctr Neurosci & Cell Biol CNC, P-3004504 Coimbra, Portugal.;Univ Coimbra, Inst Interdisciplinary Res IIIUC, P-3030789 Coimbra, Portugal.;Univ Coimbra, Ctr Innovat Biomed & Biotechnol CIBB, P-3000504 Coimbra, Portugal.;Univ Coimbra, Dept Life Sci, P-3000456 Coimbra, Portugal..
    Lazaro, Andre
    Ctr Hosp & Univ Coimbra, Gen Surg Unit, P-3000075 Coimbra, Portugal.;Univ Coimbra, Coimbra Inst Clin & Biomed Res iCBR, Fac Med FMUC, Grp Environm Genet Oncobiol CIMAGO, P-3000548 Coimbra, Portugal..
    Rosendo-Silva, Daniela
    Univ Coimbra, Inst Interdisciplinary Res IIIUC, P-3030789 Coimbra, Portugal.;Univ Coimbra, Ctr Innovat Biomed & Biotechnol CIBB, P-3000504 Coimbra, Portugal.;Univ Coimbra, Coimbra Inst Clin & Biomed Res iCBR, Fac Med FMUC, Grp Environm Genet Oncobiol CIMAGO, P-3000548 Coimbra, Portugal.;Univ Coimbra, Coimbra Inst Clin & Biomed Res iCBR, Fac Med, P-3000548 Coimbra, Portugal..
    Paula, Diogo
    Univ Coimbra, Dept Life Sci, P-3000456 Coimbra, Portugal.;Ctr Hosp & Univ Coimbra, Gen Surg Unit, P-3000075 Coimbra, Portugal.;Clin Acad Ctr Coimbra CACC, P-3000061 Coimbra, Portugal..
    Campos, Jose
    Ctr Hosp & Univ Coimbra, Gen Surg Unit, P-3000075 Coimbra, Portugal.;Clin Acad Ctr Coimbra CACC, P-3000061 Coimbra, Portugal..
    Tralhao, Jose G.
    Ctr Hosp & Univ Coimbra, Gen Surg Unit, P-3000075 Coimbra, Portugal.;Clin Acad Ctr Coimbra CACC, P-3000061 Coimbra, Portugal.;Univ Coimbra, Coimbra Inst Clin & Biomed Res iCBR, Fac Med FMUC, Grp Environm Genet Oncobiol CIMAGO, P-3000548 Coimbra, Portugal.;Univ Coimbra, Inst Biophys, Fac Med, P-3000548 Coimbra, Portugal..
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Paiva, Artur
    Univ Coimbra, Inst Interdisciplinary Res IIIUC, P-3030789 Coimbra, Portugal.;Univ Coimbra, Ctr Innovat Biomed & Biotechnol CIBB, P-3000504 Coimbra, Portugal.;Ctr Hosp & Univ Coimbra, Gen Surg Unit, P-3000075 Coimbra, Portugal.;Clin Acad Ctr Coimbra CACC, P-3000061 Coimbra, Portugal.;Univ Coimbra, Coimbra Inst Clin & Biomed Res iCBR, Fac Med FMUC, Grp Environm Genet Oncobiol CIMAGO, P-3000548 Coimbra, Portugal.;Ctr Hosp & Univ Coimbra, Dept Clin Pathol, Flow Cytometry Unit, P-3000076 Coimbra, Portugal.;ESTESC Coimbra Hlth Sch, Inst Politecn Coimbra, Ciencias Biomed Lab, P-3046854 Coimbra, Portugal..
    Laranjeira, Paula
    Univ Coimbra, Ctr Neurosci & Cell Biol CNC, P-3004504 Coimbra, Portugal.;Univ Coimbra, Ctr Innovat Biomed & Biotechnol CIBB, P-3000504 Coimbra, Portugal.;Clin Acad Ctr Coimbra CACC, P-3000061 Coimbra, Portugal.;Univ Coimbra, Coimbra Inst Clin & Biomed Res iCBR, Fac Med FMUC, Grp Environm Genet Oncobiol CIMAGO, P-3000548 Coimbra, Portugal.;Ctr Hosp & Univ Coimbra, Dept Clin Pathol, Flow Cytometry Unit, P-3000076 Coimbra, Portugal.;Ctr Hosp & Univ Coimbra, Unidade Func Citometria Fluxo, Ave Bissaya Barreto,Bloco Hosp Celas 205, P-3000076 Coimbra, Portugal..
    Carvalho, Eugenia
    Univ Coimbra, Ctr Neurosci & Cell Biol CNC, P-3004504 Coimbra, Portugal.;Univ Coimbra, Inst Interdisciplinary Res IIIUC, P-3030789 Coimbra, Portugal.;Univ Coimbra, Ctr Innovat Biomed & Biotechnol CIBB, P-3000504 Coimbra, Portugal.;Univ Coimbra, Ctr Neurosci & Cell Biol, P-3004504 Coimbra, Portugal..
    CD8+Treg cells play a role in the obesity-associated insulin resistance2024In: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 336, article id 122306Article in journal (Refereed)
    Abstract [en]

    Obesity-related chronic low-grade inflammation may trigger insulin resistance and type 2 diabetes (T2D) development. Cells with regulatory phenotype have been shown to be reduced during obesity, especially CD4+ Treg cells. However, little is known about the CD8+ Treg cells. Therefore, we aim to characterize the CD8+ Treg cells in human peripheral blood and adipose tissue, specifically, to address the effect of obesity and insulin resistance in this regulatory immune cell population. A group of 42 participants with obesity (OB group) were recruited. Fourteen of them were evaluated pre-and post-bariatric surgery. A group of age-and sex-matched healthy volunteers (n = 12) was also recruited (nOB group). CD8+ Treg cell quantification and phenotype were evaluated by flow cytometry, in peripheral blood (PB), subcutaneous (SAT), and visceral adipose tissues (VAT). The OB group displayed a higher percentage of CD8+ Treg cells in PB, compared to the nOB. In addition, they were preferentially polarized into Tc1-and Tc1/17-like CD8+ Treg cells, compared to nOB. Moreover, SAT displayed the highest content of CD8+ Tregs infiltrated, compared to PB or VAT, while CD8+ Tregs infiltrating VAT displayed a higher percentage of cells with Tc1-like phenotype. Participants with pre-diabetes displayed a reduced percentage of TIM-3+CD8+ Tregs in circulation, and PD-1+CD8+ Tregs infiltrated in the VAT. An in-crease in the percentage of circulating Tc1-like CD8+ Treg cells expressing PD-1 was observed post-surgery. In conclusion, obesity induces significant alterations in CD8+ Treg cells, affecting their percentage and phenotype, as well as the expression of important immune regulatory molecules.

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  • 25.
    Benedet, Patricia O.
    et al.
    Univ British Columbia, Life Sci Inst, Ctr Blood Res, Fac Med, Vancouver, BC, Canada.;Univ British Columbia, Life Sci Inst, Fac Med, Dept Med, Vancouver, BC, Canada.;Univ British Columbia, Life Sci Inst, Fac Med, Dept Pathol & Lab Med, Vancouver, BC, Canada..
    Safikhan, Nooshin S.
    Univ British Columbia, Life Sci Inst, Ctr Blood Res, Fac Med, Vancouver, BC, Canada.;Univ British Columbia, Life Sci Inst, Fac Med, Dept Med, Vancouver, BC, Canada.;Univ British Columbia, Life Sci Inst, Fac Med, Dept Pathol & Lab Med, Vancouver, BC, Canada..
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lum, Bryan M.
    Univ Alberta, Alberta Diabet Inst, Dept Physiol, Edmonton, AB, Canada.;Univ Alberta, Grp Mol & Cell Biol Lipids, Edmonton, AB, Canada..
    Botezelli, José Diego
    Univ British Columbia, Life Sci Inst, Ctr Blood Res, Fac Med, Vancouver, BC, Canada.;Univ British Columbia, Life Sci Inst, Fac Med, Dept Med, Vancouver, BC, Canada.;Univ British Columbia, Life Sci Inst, Fac Med, Dept Pathol & Lab Med, Vancouver, BC, Canada..
    Kuo, Cheng-Hsiang
    Natl Cheng Kung Univ, Int Ctr Wound Repair & Regenerat, Tainan, Taiwan..
    Wu, Hua-Lin
    Natl Cheng Kung Univ, Coll Med, Dept Biochem & Mol Biol, Tainan, Taiwan..
    Craddock, Barbara P.
    SUNY Stony Brook, Dept Physiol & Biophys, Stony Brook, NY USA..
    Miller, W. Todd
    SUNY Stony Brook, Dept Physiol & Biophys, Stony Brook, NY USA.;Vet Affairs Med Ctr, Northport, NY USA..
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Yue, Jessica T. Y.
    Univ Alberta, Alberta Diabet Inst, Dept Physiol, Edmonton, AB, Canada.;Univ Alberta, Grp Mol & Cell Biol Lipids, Edmonton, AB, Canada..
    Conway, Edward M.
    Univ British Columbia, Life Sci Inst, Ctr Blood Res, Fac Med, Vancouver, BC, Canada.;Univ British Columbia, Life Sci Inst, Fac Med, Dept Med, Vancouver, BC, Canada.;Univ British Columbia, Life Sci Inst, Fac Med, Dept Pathol & Lab Med, Vancouver, BC, Canada.;Univ British Columbia, Life Sci Inst, Ctr Blood Res, 4306-2350 Hlth Sci Mall, Vancouver, BC V6T 1Z3, Canada..
    CD248 promotes insulin resistance by binding to the insulin receptor and dampening its insulin-induced autophosphorylation2024In: EBioMedicine, E-ISSN 2352-3964, Vol. 99, article id 104906Article in journal (Refereed)
    Abstract [en]

    Background

    In spite of new treatments, the incidence of type 2 diabetes (T2D) and its morbidities continue to rise. The key feature of T2D is resistance of adipose tissue and other organs to insulin. Approaches to overcome insulin resistance are limited due to a poor understanding of the mechanisms and inaccessibility of drugs to relevant intracellular targets. We previously showed in mice and humans that CD248, a pre/adipocyte cell surface glycoprotein, acts as an adipose tissue sensor that mediates the transition from healthy to unhealthy adipose, thus promoting insulin resistance.

    Methods

    Molecular mechanisms by which CD248 regulates insulin signaling were explored using in vivo insulin clamp studies and biochemical analyses of cells/tissues from CD248 knockout (KO) and wild-type (WT) mice with diet-induced insulin resistance. Findings were validated with human adipose tissue specimens.

    Findings

    Genetic deletion of CD248 in mice, overcame diet-induced insulin resistance with improvements in glucose uptake and lipolysis in white adipose tissue depots, effects paralleled by increased adipose/adipocyte GLUT4, phosphorylated AKT and GSK3β, and reduced ATGL. The insulin resistance of the WT mice could be attributed to direct interaction of the extracellular domains of CD248 and the insulin receptor (IR), with CD248 acting to block insulin binding to the IR. This resulted in dampened insulin-mediated autophosphorylation of the IR, with reduced downstream signaling/activation of intracellular events necessary for glucose and lipid homeostasis.

    Interpretation

    Our discovery of a cell-surface CD248-IR complex that is accessible to pharmacologic intervention, opens research avenues toward development of new agents to prevent/reverse insulin resistance.

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  • 26.
    Biglarnia, Ali-Reza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nilsson, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    von Zur-Mühlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wagner, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation2011In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 24, no 8, p. e61-e66Article in journal (Refereed)
    Abstract [en]

    We describe the presumably first intentional ABO-incompatible deceased-donor kidney and pancreas transplantation with a severe antibody-mediated rejection during a rebound of isoagglutinins. Rejection was successfully treated with eculizumab, which inhibits the terminal pathway of complement. Complement analysis (C3, C3d,g, and a modified assay of classical complement-related hemolytic function) documented complement activation and confirmed that eculizumab completely blocked complement function. At 6 months, the patient had normal kidney and pancreas function, and histological evaluations revealed no evidence of sustained graft damage. This successful transplantation suggests that ABO barriers can safely be overcome without extensive preconditioning, when the complement inhibitor eculizumab is included.

  • 27.
    Billing, Ewa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    McKenna, S. P.
    Staun, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Lindqvist, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Adaptation of the Psoriatic Arthritis Quality of Life (PsAQoL) instrument for Sweden2010In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 39, no 3, p. 223-228Article in journal (Refereed)
    Abstract [en]

    Objective: The Psoriatic Arthritis Quality of Life (PsAQoL) questionnaire is the first disease-specific patient-derived instrument for assessing QoL in patients with PsA and has been extensively validated in this population. The aim of the adaptation process reported here was to develop a Swedish version of the PsAQoL that was equivalent to, and met the same psychometric and acceptability standards as, the original instrument, which was developed in the UK. Method:Translation of the original questionnaire into Swedish was performed by a professional and a lay panel. Field testing for face and content validity was performed by interviewing 13 patients. Finally, 123 patients with PsA were included in a test-retest postal survey designed to test reproducibility and construct validity. The PsAQoL was administered on two occasions approximately 2 weeks apart. The Nottingham Health Profile (NHP) was used as a comparator instrument. Results: The Swedish version of the PsAQoL questionnaire showed good reliability at both time points and, as expected, correlated with the NHP. The scale was able to distinguish between groups based on self-reported general health and flare-up. Patients with active symptoms of both arthritis and psoriasis had worse QoL. The results also indicated that duration of disease has a progressive impact on PsAQoL scores. Conclusions: This study provides evidence that the adapted PsAQoL can be used for clinical studies in Swedish patients. The instrument provides valuable information on the long-term effects of PsA on QoL.

  • 28.
    Birkeland, Kare I.
    et al.
    Oslo Univ Hosp, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Bodegard, Johan
    AstraZeneca, Fredrik Selmersvei 6, N-0601 Oslo, Norway..
    Banerjee, Amitava
    UCL, Inst Hlth Informat, London, England.;Univ Coll London Hosp, Dept Cardiol, London, England..
    Kim, Dae Jung
    Ajou Univ, Sch Med, Dept Endocrinol & Metab, Suwon, South Korea..
    Norhammar, Anna
    Karolinska Inst, Dept Med, Cardiol Unit, Solna, Sweden.;Capio St Gorans Hosp, Stockholm, Sweden..
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Thuresson, Marcus
    Statisticon AB, Uppsala, Sweden..
    Okami, Suguru
    AstraZeneca, Osaka, Japan..
    Ha, Kyoung Hwa
    Ajou Univ, Sch Med, Dept Endocrinol & Metab, Suwon, South Korea..
    Kossack, Nils
    Wissensch Inst Gesundheitsokon & Gesundheitssyste, Leipzig, Germany..
    Mamza, Jil Billy
    AstraZeneca, Luton, Beds, England..
    Zhang, Ruiqi
    AstraZeneca, Luton, Beds, England..
    Yajima, Toshitaka
    AstraZeneca, Osaka, Japan..
    Komuro, Issei
    Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Tokyo, Japan..
    Kadowaki, Takashi
    Tranomon Hosp, Tokyo, Japan..
    Lower cardiorenal risk withsodium-glucosecotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes without cardiovascular and renal diseases: A large multinational observational study2021In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 23, no 1, p. 75-85Article in journal (Refereed)
    Abstract [en]

    Aims We compared the new use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) versus dipeptidyl peptidase-4 inhibitor (DPP4i) and the risk of cardiorenal disease, heart failure (HF) or chronic kidney disease (CKD), in patients with type 2 diabetes without a history of prevalent cardiovascular and renal disease, defined as cardiovascular and renal disease (CVRD) free, managed in routine clinical practice. Materials and methods In this observational cohort study, patients were identified from electronic health records from England, Germany, Japan, Norway, South Korea and Sweden, during 2012-2018. In total, 1 006 577 CVRD-free new users of SGLT2i or DPP4i were propensity score matched 1:1. Unadjusted Cox regression was used to estimate hazard ratios (HRs) for outcomes: cardiorenal disease, HF, CKD, stroke, myocardial infarction (MI), cardiovascular and all-cause mortality. Results Baseline characteristics were well balanced between the treatment groups (n = 105 130 in each group) with total follow-up of 187 955 patient years. Patients had a mean age of 56 years, 43% were women and they were indexed between 2013 and 2018. The most commonly used agents were dapagliflozin (91.7% of exposure time) and sitagliptin/linagliptin (55.0%), in the SGLT2i and DPP4i, groups, respectively. SGLT2i was associated with lower risk of cardiorenal disease, HF, CKD, all-cause and cardiovascular mortality; HR (95% confidence interval), 0.56 (0.42-0.74), 0.71 (0.59-0.86), 0.44 (0.28-0.69), 0.67 (0.59-0.77), and 0.61 (0.44-0.85), respectively. No differences were observed for stroke [0.87 (0.69-1.09)] and MI [0.94 (0.80-1.11)]. Conclusion In this multinational observational study, SGLT2i was associated with a lower risk of HF and CKD versus DPP4i in patients with type 2 diabetes otherwise free from both cardiovascular and renal disease.

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  • 29.
    Birkeland, Kåre I.
    et al.
    Oslo Univ Hosp, Oslo, Norway.;Univ Oslo, Oslo, Norway.
    Bodegard, Johan
    AstraZeneca, Oslo, Norway.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Norhammar, Anna
    Dept Med, Cardiol Unit, Solna, Sweden.;Karolinska Inst, Stockholm, Sweden.;St Gorans Univ Hosp, Stockholm, Sweden.
    Haller, Hermann
    Hannover Med Sch, Div Nephrol, Hannover, Germany.
    Linssen, Gerard C. M.
    Hosp Grp Twente, Dept Cardiol, Hengelo, Netherlands.
    Banerjee, Amitava
    UCL, Inst Hlth Informat, London, England.;Univ Coll London Hosp, Dept Cardiol, London, England.
    Thuresson, Marcus
    Statisticon AB, Uppsala, Sweden.
    Okami, Suguru
    AstraZeneca, Osaka, Japan.
    Garal-Pantaler, Elena
    Team Gesundheit GmbH, Essen, Germany.
    Overbeek, Jetty
    PHARMO Inst Drug Outcomes Res CRS, Utrecht, Netherlands.
    Mamza, Jil Billy
    AstraZeneca, Luton, Beds, England.
    Zhang, Ruiqi
    AstraZeneca, Luton, Beds, England.
    Yajima, Toshitaka
    AstraZeneca, Osaka, Japan.
    Komuro, Issei
    Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Tokyo, Japan.
    Kadowaki, Takashi
    Univ Tokyo, Grad Sch Med, Dept Prevent Diabet & Lifestyle Related Dis, Tokyo, Japan.;Teikyo Univ, Mizonokuchi Hosp, Dept Metab & Nutr, Kawasaki, Kanagawa, Japan.
    Heart failure and chronic kidney disease manifestation and mortality risk associations in type 2 diabetes: A large multinational cohort study2020In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 22, no 9, p. 1607-1618Article in journal (Refereed)
    Abstract [en]

    Aims To examine the manifestation of cardiovascular or renal disease (CVRD) in patients with type 2 diabetes (T2D) initially free from CVRD as well as the mortality risks associated with these diseases.

    Methods Patients free from CVRD were identified from healthcare records in England, Germany, Japan, the Netherlands, Norway and Sweden at a fixed date. CVRD manifestation was defined by first diagnosis of cardiorenal disease, or a stroke, myocardial infarction (MI) or peripheral artery disease (PAD) event. The mortality risk associated with single CVRD history of heart failure (HF), chronic kidney disease (CKD), MI, stroke or PAD was compared with that associated with CVRD-free status.

    Results Of 1 177 896 patients with T2D, 772 336 (66%) were CVRD-free and followed for a mean of 4.5 years. A total of 137 081 patients (18%) developed a first CVRD manifestation, represented by CKD (36%), HF (24%), stroke (16%), MI (14%) and PAD (10%). HF or CKD was associated with increased cardiovascular and all-cause mortality risk: hazard ratio (HR) 2.02 (95% confidence interval [CI] 1.75-2.33) and HR 2.05 (95% CI 1.82-2.32), respectively. HF and CKD were separately associated with significantly increased mortality risks, and the combination was associated with the highest cardiovascular and all-cause mortality risk: HRs 3.91 (95% CI 3.02-5.07) and 3.14 (95% CI 2.90-3.40), respectively.

    Conclusion In a large multinational study of >750 000 CVRD-free patients with T2D, HF and CKD were consistently the most frequent first cardiovascular disease manifestations and were also associated with increased mortality risks. These novel findings show these cardiorenal diseases to be important and serious complications requiring improved preventive strategies.

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  • 30.
    Blixt, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research Sörmland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Rosenblad, Andreas Karlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research Sörmland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Reproductive Health Research.
    Funkquist, Eva-Lotta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Breastfeeding training improved healthcare professional's self-efficacy to provide evidence-based breastfeeding support: A pre-post intervention study2023In: Midwifery, ISSN 0266-6138, E-ISSN 1532-3099, Vol. 125, article id 103794Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To describe healthcare professional's (HCP's) perceived self-efficacy in their ability to provide breastfeeding support before and after a breastfeeding training program.

    DESIGN: Pre-post intervention study.

    SETTING: Antenatal care and child healthcare (CHC) centres in Sweden during 2020.

    PARTICIPANTS: An intervention group consisting of 39 HCPs (midwives 51.3%, child healthcare nurses 46.2%) completing a questionnaire at baseline and after intervention, and a control group of 34 HCPs (midwives 61.8%, child healthcare nurses 38.2%) completing a questionnaire at baseline.

    INTERVENTION: A breastfeeding training program in line with the Ten Steps to Successful Breastfeeding and WHO recommendations about breastfeeding.

    MEASUREMENTS AND FINDINGS: The 11-item Breastfeeding Support Confidence Scale (BSCS) measures HCP's self-efficacy regarding providing breastfeeding support in line with Ten Steps to Successful Breastfeeding and WHO recommendations. The intervention group experienced a significantly increased self-efficacy from pre-intervention to post-intervention for 8 of the 11 BSCS items, with the overall BSCS index score increasing from 36.87 to 39.56 points (p = 0.001). The index score in the intervention group at follow-up was significantly higher than the corresponding score in the control group at baseline (p = 0.025). The intervention group had significantly higher scores at follow-up than the control group at baseline on the questions: "I'm sure that I can help mothers continue to breastfeed even if the infant doesn't follow the growth curve" (p = 0.026) and "I'm sure that I can help mothers continue to breastfeed when the breastfeeding is painful" (p = 0.048).

    KEY CONCLUSIONS: The breastfeeding training program improved HCP' self-efficacy to provide evidence-based support to breastfeeding mothers.

    IMPLICATIONS FOR PRACTICE: This training program is well suited to implement in clinical practice and follows the Ten Steps to Successful Breastfeeding.

    TRIAL REGISTRATION: ACTRN12623000648628.

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  • 31.
    Bodegard, J.
    et al.
    AstraZeneca, Sodertalje, Sweden..
    Nathanson, D.
    Karolinska Inst, Dept Clin Sci & Educa, Stockholm, Sweden..
    Nystrom, T.
    Karolinska Inst, Stockholm, Sweden..
    Thuresson, M.
    Statisticon AB, Uppsala, Sweden..
    Norhammar, A.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Second-line treatment with sulfonylurea compared to DPP4 inhibitors demonstrated associations with earlier treatment intensification with insulin2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no Suppl. 1, p. S189-S189Article in journal (Other academic)
  • 32.
    Boersma, Greta J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Heurling, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pereira, Maria J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Johansson, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lau Börjesson, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skrtic, S.
    AstraZeneca, R&D, Gothenburg, Sweden.;AstraZeneca, Dept Med, Gothenburg, Sweden..
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Glucose uptake in skeletal muscle, brain and visceral adipose tissue assessed with PET/MR strongly predicts whole body glucose uptake during hyperinsulinaemia2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S80-S80Article in journal (Other academic)
  • 33.
    Boersma, Greta J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Johansson, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pereira, Maria J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Heurling, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Wallenberg Centre for Molecular and Translational Medicine and the Department of Psychiatry and Neurochemistry, University of Gothenburg, Sweden.
    Skrtic, Stanko
    Lau, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Panagiotou, Grigorios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, Mölndal, Sweden.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, Mölndal, Sweden.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study2018In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 50, no 8, p. 627-639Article in journal (Refereed)
    Abstract [en]

    We assessed glucose uptake in different tissues in type 2 diabetes (T2D), prediabetes, and control subjects to elucidate its impact in the development of whole-body insulin resistance and T2D. Thirteen T2D, 12 prediabetes, and 10 control subjects, matched for age and BMI, underwent OGTT and abdominal subcutaneous adipose tissue (SAT) biopsies. Integrated whole-body 18F-FDG PET and MRI were performed during a hyperinsulinemic euglycemic clamp to asses glucose uptake rate (MRglu) in several tissues. MRglu in skeletal muscle, SAT, visceral adipose tissue (VAT), and liver was significantly reduced in T2D subjects and correlated positively with M-values (r=0.884, r=0.574, r=0.707 and r=0.403, respectively). Brain MRglu was significantly higher in T2D and prediabetes subjects and had a significant inverse correlation with M-values (r=-0.616). Myocardial MRglu did not differ between groups and did not correlate with the M-values. A multivariate model including skeletal muscle, brain and VAT MRglu best predicted the M-values (adjusted r2=0.85). In addition, SAT MRglu correlated with SAT glucose uptake ex vivo (r=0.491). In different stages of the development of T2D, glucose uptake during hyperinsulinemia is elevated in the brain in parallel with an impairment in peripheral organs. Impaired glucose uptake in skeletal muscle and VAT together with elevated glucose uptake in brain were independently associated with whole-body insulin resistance, and these tissue-specific alterations may contribute to T2D development.

  • 34.
    Boersma, Greta J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Johansson, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skrtic, S.
    AstraZeneca, R&D, Gothenburg, Sweden.;Univ Gothenburg, Dept Med, Gothenburg, Sweden..
    Lau Börjesson, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Panagiotou, G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skeletal muscle and liver, but not brain, account for impaired glucose utilisation in type 2 diabetes: whole-body PET/MR during hyperinsulinaemic euglycaemic clamp2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, p. S33-S33Article in journal (Refereed)
  • 35.
    Boersma, Greta J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Johns Hopkins University, School of Medicine, Department of Psychiatry and Behavioral Sciences.
    Smeltzer, Michael D.
    University of Cincinnati Medical Center, Department of Psychiatry and Behavioral Neuroscience.
    Scott, Karen A.
    University of Cincinnati Medical Center, Department of Psychiatry and Behavioral Neuroscience; University College Cork, Department of Anatomy and Neuroscience.
    Scheurink, Anton J.
    University of Groningen, Department of Neuroendocrinology, GELIFES, Neurobiology.
    Tamashiro, Kellie L.
    Johns Hopkins University, School of Medicine, Department of Psychiatry and Behavioral Sciences.
    Sakai, Randall R.
    University of Cincinnati Medical Center, Department of Psychiatry and Behavioral Neuroscience.
    Stress coping style does not determine social status, but influences the consequences of social subordination stress2017In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 178, p. 126-133Article in journal (Refereed)
    Abstract [en]

    Chronic stress exposure may have negative consequences for health. One of the most common sources of chronic stress is stress associated with social interaction. In rodents, the effects of social stress can be studied in a naturalistic way using the visual burrow system (VBS). The way an individual copes with stress, their "stress coping style", may influence the consequences of social stress. In the current study we tested the hypothesis that stress coping style may modulate social status and influence the consequences of having a lower social status. We formed 7 VBS colonies, with 1 proactive coping male, 1 passive coping male, and 4 female rats per colony to assess whether a rat's coping style prior to colony formation could predict whether that individual is more likely to become socially dominant. The rats remained in their respective colonies for 14 days and the physiological and behavioral consequences of social stress were assessed. Our study shows that stress coping style does not predict social status. However, stress coping style may influence the consequences of having a lower social status. Subordinate passive and proactive rats had distinctly different wound patterns; proactive rats had more wounds on the front of their bodies. Behavioral analysis confirmed that proactive subordinate rats engaged in more offensive interactions. Furthermore, subordinate rats with a proactive stress coping style had larger adrenals, and increased stress responsivity to a novel acute stressor (restraint stress) compared to passive subordinate rats or dominant rats, suggesting that the allostatic load may have been larger in this group. (c) 2017 Elsevier Inc. All rights reserved.

  • 36.
    Brandao, Luiz Eduardo M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Westholm, Jakub Orzechowski
    Martikainen, Teemu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Westerlund, Nestori
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lampola, Lauri
    Popa, Alexandru
    Vogel, Heike
    Schürmann, Annette
    Dickson, Suzanne L
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Acute sleep loss alters circulating fibroblast growth factor 21 levels in humans: A randomised crossover trial.2022In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 31, no 2, article id e13472Article in journal (Refereed)
    Abstract [en]

    The hormone fibroblast growth factor 21 (FGF21) modulates tissue metabolism and circulates at higher levels in metabolic conditions associated with chronic sleep-wake disruption, such as type 2 diabetes and obesity. In the present study, we investigated whether acute sleep loss impacts circulating levels of FGF21 and tissue-specific production, and response pathways linked to FGF21. A total of 15 healthy normal-weight young men participated in a randomised crossover study with two conditions, sleep loss versus an 8.5-hr sleep window. The evening before each intervention, fasting blood was collected. Fasting, post-intervention morning skeletal muscle and adipose tissue samples underwent quantitative polymerase chain reaction and DNA methylation analyses, and serum FGF21 levels were measured before and after an oral glucose tolerance test. Serum levels of FGF21 were higher after sleep loss compared with sleep, both under fasting conditions and following glucose intake (~27%-30%, p = 0.023). Fasting circulating levels of fibroblast activation protein, a protein which can degrade circulating FGF21, were not altered by sleep loss, whereas DNA methylation in the FGF21 promoter region increased only in adipose tissue. However, even though specifically the muscle exhibited transcriptional changes indicating adverse alterations to redox and metabolic homeostasis, no tissue-based changes were observed in expression of FGF21, its receptors, or selected signalling targets, in response to sleep loss. In summary, we found that acute sleep loss resulted in increased circulating levels of FGF21 in healthy young men, which may occur independent of a tissue-based stress response in metabolic peripheral tissues. Further studies may decipher whether changes in FGF21 signalling after sleep loss modulate metabolic outcomes associated with sleep or circadian disruption.

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  • 37.
    Brorsson, A. L.
    et al.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Olinder, A. Lindholm
    Karolinska Inst, Dept Clin Sci & Educ, Soder Sjukhuset, Stockholm, Sweden..
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Viklund, G.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    An intervention with a person-centered program, guided self-determination-young, in groups of adolescents starting on insulin pump: a randomized controlled trial2016In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 18, no Suppl. 1, p. A104-A104Article in journal (Other academic)
  • 38.
    Brorsson, Anna Lena
    et al.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden;Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden.
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden.
    Franko, Mikael Andersson
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    Olinder, Anna Lindholm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    A person-centered education for adolescents with type 1 diabetes: A randomized controlled trial2019In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 20, no 7, p. 986-996Article in journal (Refereed)
    Abstract [en]

    Introduction: Young people with type 1 diabetes and their parents need to receive person-centered education to be able to manage their diabetes. Guided Self-Determination-Young (GSD-Y) is a person-centered communication and reflection education model that can be used in educational program for young people with type 1 diabetes.

    Objective: To evaluate whether GSD-Y leads to improved glycaemic control, increased self-perceived health and health-related quality of life, fewer diabetes-related family conflicts, and improved self-efficacy in a group-based intervention for adolescents starting continuous subcutaneous insulin infusion (CSII) and their parents.

    Methods: This randomized controlled trial included 71 adolescents starting CSII. Participants were followed for 12 months. The intervention group (n = 37) attended seven group training sessions over a period of 5 months, using the GSD-Y model, the control group received standard care. Variables evaluated were HbA1c, self-perceived health, health-related quality of life, family conflicts, self-efficacy, and usage of continuous glucose monitoring.

    Results: When adjusted for sex and family conflicts, there was a difference in glycaemic control between the groups at 12 months, favoring the intervention group (62 vs 70 mmol/mol, P = .009). When analyses were performed on boys and girls separately and adjusted for family conflicts, the only difference detected was for boys after 12 months (P = .019). The intervention showed no effect on self-perceived health, health-related related quality of life, family conflicts, or self-efficacy.

    Conclusions: An intervention with GSD-Y may have an effect on glycaemic control. The content of the GSD-Y groups may serve as a model for person-centered care in adolescents with type 1 diabetes.

  • 39. Brorsson, Anna Lena
    et al.
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Viklund, Gunnel
    Olinder, Anna Lindholm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    A multicentre randomized controlled trial of an empowerment-inspired intervention for adolescents starting continuous subcutaneous insulin infusion: a study protocol2013In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 13, p. 212-Article in journal (Refereed)
    Abstract [en]

    Background:

    Continuous subcutaneous insulin infusion (CSII) treatment among children with type 1 diabetes is increasing in Sweden. However, studies evaluating glycaemic control in children using CSII show inconsistent results. The distribution of responsibility for diabetes self-management between children and parents is often unclear and needs clarification. There is much published support for continued parental involvement and shared diabetes management during adolescence. Guided Self-Determination (GSD) is an empowerment-based, person-centred, reflection and problem solving method intended to guide the patient to become self-sufficient and develop life skills for managing difficulties in diabetes self-management. This method has been adapted for adolescents and parents as Guided Self-Determination-Young (GSD-Y). This study aims to evaluate the effect of an intervention with GSD-Y in groups of adolescents starting on insulin pumps and their parents on diabetes-related family conflicts, perceived health and quality of life (QoL), and metabolic control. Here, we describe the protocol and plans for study enrolment.

    Methods/design:

    This study is designed as a randomized, controlled, prospective, multicentre study. Eighty patients between 12-18 years of age who are planning to start CSII will be included. All adolescents and their parents will receive standard insulin pump training. The education intervention will be conducted when CSII is to be started and at four appointments in the first 4 months after starting CSII. The primary outcome is haemoglobin A1c levels. Secondary outcomes are perceived health and QoL, frequency of blood glucose self-monitoring and bolus doses, and usage of carbohydrate counting. The following instruments will be used: Disabkids, 'Check your health', the Diabetes Family Conflict Scale and the Swedish Diabetes Empowerment Scale. Outcomes will be evaluated within and between groups by comparing data at baseline, and at 6 and 12 months after starting treatment.

    Discussion:

    In this study, we will assess the effect of starting an CSII together with the model of GSD to determine whether this approach leads to retention of improved glycaemic control, QoL, responsibility distribution and reduced diabetes-related conflicts in the family.

  • 40.
    Brorsson, Anna Lena
    et al.
    Karolinska Inst & Hosp, Dept Womens & Childrens Hlth, S-17177 Stockholm, Sweden.
    Olinder, Anna Lindholm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden.
    Wikblad, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Viklund, Gunnel
    Karolinska Inst & Hosp, Dept Womens & Childrens Hlth, S-17177 Stockholm, Sweden.
    Parent's perception of their children's health, quality of life and burden of diabetes: testing reliability and validity of 'Check your Health' by proxy.2017In: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 31, no 3, p. 497-504Article in journal (Refereed)
    Abstract [en]

    AIM: To test the validity and reliability of the 'Check your Health by proxy' instrument in parents to children with diabetes aged 8-17 years.

    METHODS: One hundred and ninety-one caregivers and their children, aged 8-17 years, were included. All completed the 'Check your Health' questionnaire measuring quality of life and burden of diabetes, DISABKIDS self- or proxy version, and 45 completed the same questionnaires 2 weeks later.

    RESULTS: Test-retest reliability on the 'Check your Health' questionnaire by proxy was moderate to strong (r = 0.48-0.74), p < 0.002). Convergent validity was weak to moderate (r = 0.15-0.49, p < 0.05). The instrument showed acceptable discriminant validity. Parents reported lower scores than the children on emotional health and social relations and higher scores on physical and emotional burden and higher burden on quality of life. Poorer social relationships and quality of life were associated with higher reported disease severity. The diabetes burden domain of the questionnaire correlated to perceived severity of diabetes and to perceived health. Discriminant validity showed that poorer social relationships and quality of life were associated with higher severity of the disease. The diabetes burden domain of 'Check your Health' by proxy showed discriminant validity on perceived severity of diabetes.

    CONCLUSIONS: The instrument 'Check your Health' by proxy showed acceptable psychometric characteristics in parents to young people (8-17 years of age) with diabetes. We also concluded that parents reported that their children had lower health and higher burden of diabetes than the children did, and it correlated to reported disease severity.

  • 41. Brorsson, Anna Lena
    et al.
    Viklund, Gunnel
    Lindholm Olinder, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Karolinska Institutet Institutionen för klinisk forskning och utbildning Södersjukhuset.
    Granström, Therese
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Adolescents' perceptions of participation in group education using the Guided Self-Determination-Young method: a qualitative study.2017In: BMJ Open Diabetes Research & Care, ISSN 2052-4897, Vol. 5, no 1, article id e000432Article in journal (Refereed)
    Abstract [en]

    Objective: Guided Self-Determination (GSD) is a person-centered communication and reflection method. Education in groups may have a greater impact than the content of the education, and constructive communication between parents and adolescents has been shown to be of importance. The purpose of this study was to describe adolescents' perceptions of participation in group education with the Guided Self-Determination-Young (GSD-Y) method, together with parents, in connection with the introduction of continuous subcutaneous insulin infusion.

    Research design and methods: In the present qualitative interview study, 13 adolescents with type 1 diabetes were included after completing a GSD-Y group education program in connection with the introduction of continuous subcutaneous insulin infusion at three hospitals located in central Sweden. The adolescents were interviewed individually, and qualitative content analysis was applied to the interview transcripts.

    Results: Two categories that emerged from the analysis were the importance of context and growing in power through the group process. An overarching theme that emerged from the interviews was the importance of expert and referent power in growing awareness of the importance of self-management as well as mitigating the loneliness of diabetes.

    Conclusions: GSD-Y has, in various ways, mitigated experiences of loneliness and contributed to conscious reflection about self-management in the group (referent power) together with the group leader (expert power). Overall, this highlights the benefits of group education, and the GSD method emphasizes the person-centered approach.

    Trial registration number: ISRCTN22444034; Results.

  • 42.
    Brorsson, Anna Lena
    et al.
    Karolinska Hosp & Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Viklund, Gunnel
    Karolinska Hosp & Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Örtqvist, Eva
    Karolinska Hosp & Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Lindholm Olinder, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden.
    Does treatment with an insulin pump improve glycaemic control in children and adolescents with type 1 diabetes?: A retrospective case-control study2015In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 16, no 7, p. 546-553Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate long-term effects on glycaemic control, ketoacidosis, serious hypoglycaemic events, insulin requirements, and body mass index standard deviation scores (BMI-SDS) in children and adolescents with type 1 diabetes starting on continuous subcutaneous insulin infusion (CSII) compared with children and adolescents treated with multiple daily injections (MDI).

    METHODS: This retrospective case-control study compares 216 patients starting CSII with a control group on MDI (n = 215), matched for glycated hemoglobin (HbA1c), sex, and age during a 2-yr period. Variables collected were gender, age, HbA1c, insulin requirement, BMI, BMI-SDS, ketoacidosis, and serious hypoglycaemic events.

    RESULTS: In the CSII group there was an improvement in HbA1c after 6 and 12 months compared with the MDI group. For boys and girls separately the same effect was detected after 6 months, but only for boys after 12 months. The incidence of ketoacidosis was higher in the CSII group compared with the MDI group (2.8 vs. 0.5/100 person-yr). The incidences of severe hypoglycaemic episodes per 100 person-yr were three in the CSII group and six in the MDI group (p < 0.05). After 6, 12, and 24 months, the insulin requirement was higher in the MDI group.

    CONCLUSIONS: This study shows that treatment with CSII resulted in an improvement in HbA1c levels up to 1 yr and decreased the number of severe hypoglycaemic events, but the frequency of ketoacidosis increased. The major challenge is to identify methods to maintain the HbA1c improvement, especially among older children and teenagers, and reduce the frequency of ketoacidosis.

  • 43. Bruserud, Øyvind
    et al.
    Oftedal, Bergithe E.
    Landegren, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Erichsen, Martina M.
    Bratland, Eirik
    Lima, Kari
    Jørgensen, Anders P.
    Myhre, Anne G.
    Svartberg, Johan
    Fougner, Kristian J.
    Bakke, Åsne
    Nedrebø, Bjørn G.
    Mella, Bjarne
    Breivik, Lars
    Viken, Marte K.
    Knappskog, Per M.
    Marthinussen, Mihaela C.
    Løvås, Kristian
    Kämpe, Olle
    Wolff, Anette B.
    Husebye, Eystein S.
    A Longitudinal Follow-up of Autoimmune Polyendocrine Syndrome Type 12016In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 101, no 8, p. 2975-2983Article in journal (Refereed)
  • 44.
    Burman, Pia
    et al.
    Lund Univ, Skane Univ Hosp Malmo, Dept Endocrinol, S-20502 Malmo, Sweden..
    Edén-Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Ekman, Bertil
    Linkoping Univ, Dept Endocrinol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Karlsson, Anders F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Schwarcz, Erik
    Univ Orebro, Fac Med & Hlth, Dept Internal Med, SE-70182 Orebro, Sweden..
    Wahlberg, Jeanette
    Linkoping Univ, Dept Endocrinol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Limited value of cabergoline in Cushing's disease: a prospective study of a 6-week treatment in 20 patients2016In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 174, no 1, p. 17-24Article in journal (Refereed)
    Abstract [en]

    Context and objective: The role of cabergoline in Cushing's disease (CD) remains controversial. The experience is limited to case reports and few open studies that report the effects determined after >= 1 month of treatment. In prolactinomas and dopamine-responsive GH-secreting tumours, effects of cabergoline are seen within days or weeks. Here, we searched for short-term effects of cabergoline in CD. Design: Twenty patients (19 naive and one recurrent) were included in a prospective study. Cabergoline was administered in increasing doses of 0.5-5 mg/week over 6 weeks. Methods: Urinary free cortisol (UFC) 24 h, morning cortisol and ACTH, and salivary cortisol at 0800, 1600 and 2300 h were determined once weekly throughout. Diurnal curves (six samples) of serum cortisol were measured at start and end. Results: At study end, the median cabergoline dose was 5 mg, range 2.5-5 mg/week. The prolactin levels, markers of compliance, were suppressed in all patients. During the treatment, hypercortisolism varied, gradual and dose-dependent reductions were not seen. Five patients had a >50% decrease of UFC, three had a >50% rise of UFC. Salivary cortisol at 2300 h showed a congruent >50% change with UFC in two of the five cases with decreased UFC, and in one of the three cases with increased UFC. One patient with decreases in both UFC and 2300 h salivary cortisol also had a reduction in diurnal serum cortisol during the course of the study. Conclusions: Cabergoline seems to be of little value in the management of CD. Only one patient had a response-like pattern. Given the known variability of disease activity in CD, this might represent a chance finding.

  • 45.
    Casey, Jackie
    et al.
    Department of Clinical Sciences, Orthopaedics, Lund University, Lund, Sweden;Rehabilitation Engineering Centre, Musgrave Park Hospital, Belfast Health & Social Care Trust, Belfast, Northern Ireland.
    Agustsson, Atli
    Research Centre of Movement Science, Department of Physiotherapy, University of Iceland, Reykjavik, Iceland.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Rodby-Bousquet, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research, County of Västmanland. Department of Clinical Sciences, Orthopaedics, Lund University, Lund, Sweden.
    Relationship between scoliosis, windswept hips and contractures with pain and asymmetries in sitting and supine in 2450 children with cerebral palsy2022In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 44, no 22, p. 6738-6743Article in journal (Refereed)
    Abstract [en]

    Purpose: This cross-sectional study of 2450 children with cerebral palsy aimed to analyse the prevalenceand association of scoliosis, windswept hips, hip and knee contractures.

    Methods: Logistic regression was used to estimate associations with pain, postural asymmetries, and abil-ity to change position for children at Gross Motor Function Classification System (GMFCS) levels I–V,aged 0–18 years.

    Results: Most children with a deformity or contracture had postural asymmetries in both sitting andsupine positions; 10.5% had scoliosis, 8.7% windswept hips, 6.6% hip flexion and 19.2% knee contractures.Severe postural asymmetries increased the likelihood for scoliosis 9 times, for windswept hips 6 to 9 times,and for hip and knee flexion contractures 7 and 12 times respectively, adjusted for age, sex and GMFCSlevel. Hip flexion contractures and windswept hips increased the likelihood for pain by 1.5–1.6 times.

    Conclusion: The likelihood of having scoliosis, windswept hips and flexion contractures in the hips andknees increased if the child had postural asymmetries, and for increased age and higher GMFCS levels.Efforts should focus on preventing postural asymmetries from occurring or progressing, and on increasingthe child’s ability to change position. Reducing postural asymmetries may also reduce the likelihoodof pain.

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  • 46.
    Casey, Jackie
    et al.
    Lund Univ, Dept Clin Sci, Orthoped, S-22185 Lund, Sweden.;Belfast Hlth & Social Care Trust, Musgrave Pk Hosp, Reg Rehabil Engn Ctr, Belfast, Antrim, North Ireland..
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Rodby-Bousquet, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research, County of Västmanland. Lund Univ, Dept Clin Sci, Orthoped, S-22185 Lund, Sweden.
    Postural asymmetries, pain, and ability to change position of children with cerebral palsy in sitting and supine: a cross-sectional study2022In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 44, no 11, p. 2363-2371Article in journal (Refereed)
    Abstract [en]

    Purpose

    To examine any associations between postural asymmetries, postural ability, and pain for children with cerebral palsy in sitting and supine positions.

    Methods

    A cross-sectional study of 2,735 children with cerebral palsy, 0-18 years old, reported into the Swedish CPUP registry. Postural asymmetries, postural ability, the gross motor function classification system levels I–V, sex, age and report of pain were used to determine any relationship between these variables.

    Results

    Over half the children had postural asymmetries in sitting (n = 1,646; 60.2%) or supine (n = 1,467; 53.6%). These increased with age and as motor function decreased. Children were twice as likely to have pain if they had an asymmetric posture (OR 2.1–2.7), regardless of age, sex and motor function. Children unable to maintain or change position independently were at higher risk for postural asymmetries in both supine (OR 2.6–7.8) and sitting positions (OR 1.5–4.2).

    Conclusions

    An association was found between having an asymmetric posture and ability to change position in sitting and/or lying; and with pain. The results indicate the need to assess posture and provide interventions to address asymmetric posture and pain.

    Implications for rehabilitation

    • Postural asymmetries are present in children with cerebral palsy at all levels of gross motor function.

    • Postural asymmetries increase with age and are associated with pain.

    • Assessment of posture should be included in surveillance programs to enable early detection and treatment.

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  • 47.
    Castillejo-Lopez, Casimiro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Abalo, Xesus M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sidibeh, Cherno O
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Pereira, Maria J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kamble, Prasad G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    FKBP51 ablation using CRISPR/Cas-9 impairs adipocyte differentiation2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, p. S11-S12Article in journal (Other academic)
  • 48.
    Castillejo-Lopez, Casimiro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pjanic, Milos
    Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.
    Pirona, Anna Chiara
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. German Canc Res Ctr, Heidelberg, Germany.
    Hetty, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wabitsch, Martin
    Univ Ulm, Dept Pediat & Adolescent Med, Div Pediat Endocrinol & Diabet, Ulm, Germany.
    Wadelius, Claes
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Quertermous, Thomas
    Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Arner, Erik
    RIKEN, Lab Appl Regulatory Genom Network Anal, Ctr Integrat Med Sci, Yokohama, Kanagawa 2300045, Japan.
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Detailed Functional Characterization of a Waist-Hip Ratio Locus in 7p15.2 Defines an Enhancer Controlling Adipocyte Differentiation2019In: iScience, E-ISSN 2589-0042 , Vol. 20, p. 42-59Article in journal (Refereed)
    Abstract [en]

    We combined CAGE sequencing in human adipocytes during differentiation with data from genome-wide association studies to identify an enhancer in the SNX10 locus on chromosome 7, presumably involved in body fat distribution. Using reporter assays and CRISPR-Cas9 gene editing in human cell lines, we characterized the role of the enhancer in adipogenesis. The enhancer was active during adipogenesis and responded strongly to insulin and isoprenaline. The allele associated with increased waist-hip ratio in human genetic studies was associated with higher enhancer activity. Mutations of the enhancer resulted in less adipocyte differentiation. RNA sequencing of cells with disrupted enhancer showed reduced expression of established adipocyte markers, such as ADIPOQ and LPL, and identified CHI3L1 on chromosome 1 as a potential gene involved in adipocyte differentiation. In conclusion, we identified and characterized an enhancer in the SNX10 locus and outlined its plausible mechanisms of action and downstream targets.

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  • 49.
    Cato, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Reproductive Health Research.
    Funkquist, Eva-Lotta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics. Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden.
    Instrument development and an intervention to increase parents' self-efficacy regarding their infant's sleep2024In: Sexual & Reproductive HealthCare, ISSN 1877-5756, E-ISSN 1877-5764, Vol. 39, article id 100944Article in journal (Refereed)
    Abstract [en]

    Objective

    Many Swedish parents experience that their infant has sleeping problems. Parents’ self-efficacy regarding their infants’ sleep may play an important role in how they perceive these problems. This pilot study aimed to develop an instrument measuring parents’ self-efficacy regarding their infant’s sleep and to examine if parents’ self-efficacy was affected by an intervention focusing on parental education.

    Method

    Mothers and fathers, at a maternity unit in Sweden, were drawn into either an intervention (n = 46) or a control (n = 42) group. The intervention group received a home visit from a nurse who provided information about infant sleep; the importance of attachment; and advice regarding sleep, breastfeeding and bed sharing, including guidelines for safe bed sharing. Three months later, the participants answered questions on background data, breastfeeding, sleep and self-efficacy.

    Results

    The 11-item two-factor Uppsala Parental Self-Efficacy about Infant Sleep Instrument (UPPSEISI) was constructed to measure parents’ perceived self-efficacy. In adjusted analyses, being in the intervention group was associated with a higher self-efficacy (P = 0.035), as were being a mother (P = 0.003) and being satisfied with one’s own sleep (P = 0.007), while parents’ own sleeping problems were associated with a lower self-efficacy (P = 0.015).

    Conclusion

    Importantly, parental education may increase parents’ self-efficacy regarding their infant’s sleep.

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  • 50. Cederblad, Lars
    et al.
    Eklund, Gustav
    Vedal, Amund
    Hill, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Inflammation, Metabolism and Child Health Research.
    Caballero-Corbalán, José
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Hellman, Jarl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Abrahamsson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Wahlström-Johnsson, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Inflammation, Metabolism and Child Health Research.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Classification of Hypoglycemic Events in Type 1 Diabetes Using Machine Learning Algorithms2023In: Diabetes Therapy, ISSN 1869-6953, E-ISSN 1869-6961, Vol. 14, no 6, p. 953-965Article in journal (Refereed)
    Abstract [en]

    Introduction

    To improve the utilization of continuous- and flash glucose monitoring (CGM/FGM) data we have tested the hypothesis that a machine learning (ML) model can be trained to identify the most likely root causes for hypoglycemic events.

    Methods

    CGM/FGM data were collected from 449 patients with type 1 diabetes. Of the 42,120 identified hypoglycemic events, 5041 were randomly selected for classification by two clinicians. Three causes of hypoglycemia were deemed possible to interpret and later validate by insulin and carbohydrate recordings: (1) overestimated bolus (27%), (2) overcorrection of hyperglycemia (29%) and (3) excessive basal insulin presure (44%). The dataset was split into a training (n = 4026 events, 304 patients) and an internal validation dataset (n = 1015 events, 145 patients). A number of ML model architectures were applied and evaluated. A separate dataset was generated from 22 patients (13 ‘known’ and 9 ‘unknown’) with insulin and carbohydrate recordings. Hypoglycemic events from this dataset were also interpreted by five clinicians independently.

    Results

    Of the evaluated ML models, a purpose-built convolutional neural network (HypoCNN) performed best. Masking the time series, adding time features and using class weights improved the performance of this model, resulting in an average area under the curve (AUC) of 0.921 in the original train/test split. In the dataset validated by insulin and carbohydrate recordings (n = 435 events), i.e. ‘ground truth,’ our HypoCNN model achieved an AUC of 0.917.

    Conclusions

    The findings support the notion that ML models can be trained to interpret CGM/FGM data. Our HypoCNN model provides a robust and accurate method to identify root causes of hypoglycemic events.

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