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  • 1.
    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.

  • 2.
    Ek, Anna
    et al.
    Karolinska Inst, Inst Environm Med, Dept Clin Sci Intervent & Technol, Div Pediat, Solna, Sweden.
    Lewis Chamberlain, Kathryn
    Oregon Social Learning Ctr, Eugene, OR, USA.
    Sorjonen, Kimmo
    Karolinska Inst, Inst Environm Med, Div Psychol, Dept Clin Neurosci, Solna, Sweden.
    Hammar, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Karolinska Inst, Inst Environm Med, Dept Biostat, Solna, Sweden.
    Etminan Malek, Mahnoush
    Karolinska Inst, Inst Environm Med, Dept Publ Hlth Sci, Solna, Sweden; Karolinska Univ Hosp, Astrid Lindgren Childrenk Hosp, Stockholm, Sweden.
    Sandvik, Pernilla
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics. Karolinska Inst, Inst Environm Med, Dept Clin Sci Intervent & Technol, Div Pediat, Solna, Sweden.
    Somaraki, Maria
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics.
    Nyman, Jonna
    Karolinska Univ Hosp, Astrid Lindgren Childrenk Hosp, Stockholm, Sweden.
    Lindberg, Louise
    Karolinska Inst, Inst Environm Med, Dept Clin Sci Intervent & Technol, Div Pediat, Solna, Sweden.
    Nordin, Karin
    Karolinska Inst, Inst Environm Med, Dept Clin Sci Intervent & Technol, Div Pediat, Solna, Sweden.
    Ejderhamn, Jan
    Karolinska Univ Hosp, Astrid Lindgren Childrenk Hosp, Stockholm, Sweden.
    Fisher, Philip A
    Oregon Social Learning Ctr, Eugene, OR USA; Univ Oregon, Dept Psychol, Eugene, OR USA.
    Chamberlain, Patricia
    Oregon Social Learning Ctr, Eugene, OR USA.
    Marcus, Claude
    Karolinska Inst, Inst Environm Med, Dept Clin Sci Intervent & Technol, Div Pediat, Solna, Sweden.
    Nowicka, Paulina
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics. Karolinska Inst, Inst Environm Med, Dept Clin Sci Intervent & Technol, Div Pediat, Solna, Sweden.
    A Parent Treatment Program for Preschoolers With Obesity: A Randomized Controlled Trial2019In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 144, no 2, article id e20183457Article in journal (Refereed)
    Abstract [en]

    Background And Objectives: Early obesity treatment seems to be the most effective, but few treatments exist. In this study, we examine the effectiveness of a parent-only treatment program with and without booster sessions (Booster or No Booster) focusing on parenting practices and standard treatment (ST).

    Methods: Families of children 4 to 6 years of age with obesity were recruited from 68 child care centers in Stockholm County and randomly assigned to a parent-only program (10 weeks) with or without boosters (9 months) or to ST. Treatment effects on primary outcomes (BMI z score) and secondary outcomes (BMI and waist circumference) during a 12-month period were examined with linear mixed models. The influence of sociodemographic factors was examined by 3-way interactions. The clinically significant change in BMI z score (−0.5) was assessed with risk ratios.

    Results: A total of 174 children (mean age: 5.3 years [SD = 0.8]; BMI z score: 3.0 [SD = 0.6], 56% girls) and their parents (60% foreign background; 39% university degree) were included in the analysis (Booster, n = 44; No Booster, n = 43; ST, n = 87). After 12 months, children in the parent-only treatment had a greater reduction in their BMI z score (0.30; 95% confidence interval [CI]: −0.45 to −0.15) compared with ST (0.07; 95% CI: −0.19 to 0.05). Comparing all 3 groups, improvements in weight status were only seen for the Booster group (−0.54; 95% CI: −0.77 to −0.30). The Booster group was 4.8 times (95% CI: 2.4 to 9.6) more likely to reach a clinically significant reduction of ≥0.5 of the BMI z score compared with ST.

    Conclusion: A parent-only treatment with boosters outperformed standard care for obesity in preschoolers.

  • 3.
    Katsogiannos, Petros
    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.
    Wiklund, Urban
    Umea Univ, Radiat Sciences, BioMed Engn & Informat, Umea, Sweden.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    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, Clinical diabetology and metabolism.
    Hammar, Ulf
    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.
    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.
    Rapid changes in neuroendocrine regulation may contribute to reversal of type 2 diabetes after gastric bypass surgery2020In: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 67, no 2, p. 344-353Article in journal (Refereed)
    Abstract [en]

    Objective: To explore the role of hormones and the autonomic nervous system in the rapid remission of diabetes after Roux-en-Y Gastric Bypass (RYGB).

    Research design and methods: Nineteen obese patients with type 2 diabetes, 7 M/12 F, were randomized (2:1) to RYGB or standard-of-care medical treatment (control). At baseline and 4 and 24 weeks post surgery, fasting blood sampling, OGTT, intravenous arginine challenge, and heart-rate variability (HRV) assessments were performed.

    Results: At both 4 and 24 weeks post-RYGB the following effects were found: arginine-stimulated insulin secretion was reduced. GLP-1, GIP, and glucagon rise during OGTT was enhanced. IGF-1 and GH levels increased. In addition, total HRV and spectral components P-LF (power of low frequency) and P-HF (power of high frequency) increased. At 4 weeks, morning cortisol was lower than baseline and 24 weeks. At 24 weeks, NEFA levels during OGTT, and the P-LF/P-HF ratio decreased. None of these changes were seen in the control group.

    Conclusions: There were rapid changes within 4 weeks after RYGB: signs of enhanced parasympathetic nerve activity, reduced morning cortisol, and enhanced incretin and glucagon responses to glucose. The findings suggest that neurohormonal mechanisms can contribute to the rapid improvement of insulin resistance and glycemia following RYGB in type 2 diabetes.

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  • 4.
    Kennedy, Beatrice
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Peura, Sari
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Swedish Univ Agr Sci, Sci Life Lab, Dept Forest Mycol & Plant Pathol, Uppsala, Sweden.
    Hammar, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Vicenzi, Silvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Sweden;Univ Tasmania, Sch Med, Hobart, Tas, Australia.
    Hedman, Anna
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Almqvist, Catarina
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Unit Pediat Allergy & Pulmonol, Stockholm, Sweden.
    Andolf, Ellika
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Pershagen, Göran
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden;Ctr Occupat & Environm Med, Stockholm, Region Stockhol, Sweden.
    Dicksved, Johan
    Swedish Univ Agr Sci, Dept Anim Nutr & Management, Uppsala, Sweden.
    Bertilsson, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Sweden;Swedish Univ Agr Sci, Dept Aquat Sci & Assessment, Uppsala, Sweden.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Oral Microbiota Development in Early Childhood2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 19025Article in journal (Refereed)
    Abstract [en]

    Early life determinants of the oral microbiota have not been thoroughly elucidated. We studied the association of birth and early childhood characteristics with oral microbiota composition using 16 S ribosomal RNA (rRNA) gene sequencing in a population-based Swedish cohort of 59 children sampled at 6, 12 and 24 months of age. Repeated-measurement regression models adjusted for potential confounders confirmed and expanded previous knowledge about the profound shift of oral microbiota composition in early life. These alterations included increased alpha diversity, decreased beta diversity and alteration of bacterial composition with changes in relative abundance of 14 of the 20 most common operational taxonomic units (OTUs). We also found that birth characteristics, breastfeeding and antibiotic use were associated with overall phyla distribution and/or with the relative abundance of specific OTUs. Further, we detected a novel link between morning salivary cortisol level, a physiological marker of neuroendocrine activity and stress, and overall phyla distribution as well as with decreased abundance of the most common OTU mapped to the Streptococcaceae family. In conclusion, a major part of the maturation of the oral microbiome occurs during the first two years of life, and this development may be influenced by early life circumstances.

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  • 5.
    Yi-Ting, Lin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Family Med, Kaohsiung 807, Taiwan.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hammar, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ingelsson, Erik
    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.
    Ärnlöv, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, S-14152 Huddinge, Sweden;Dalarna Univ, Sch Hlth & Social Studies, S-79131 Falun, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci, Cardiovasc Epidemiol, S-21428 Malmo, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Univ New South Wales, George Inst Global Hlth, Sydney, NSW 2042, Australia.
    Proteomic Analysis of Longitudinal Changes in Blood Pressure2019In: JOURNAL OF CLINICAL MEDICINE, ISSN 2077-0383, Vol. 8, no 10, article id 1585Article in journal (Refereed)
    Abstract [en]

    Hypertension is the leading risk factor for premature death worldwide. The identification of modifiable causes of hypertension remains an imperative task. We aimed to investigate associations between 79 proteins implicated in cardiovascular disease and longitudinal blood pressure (BP) changes in three Swedish prospective cohorts. In a discovery phase, we investigated associations between baseline circulating protein levels assessed with a proximity extension assay and BP stage progression at follow-up 5 years later among persons without BP-lowering drugs at baseline in two independent community-based cohorts from the Prospective Investigation of the Vasculature in Uppsala Seniors study (PIVUS) and the Uppsala Longitudinal Study of Adult Men (ULSAM). We used an independent cohort, the Malmo Diet and Cancer Study (MDC), for replication. The primary outcome of BP stage progression was defined as per the 2017 AHA/ACC (American Heart Association/American College of Cardiology) Guideline BP categories. We also investigated associations of protein levels with changes in BP on a continuous scale, and meta-analyzed all three cohorts. Levels of renin were associated with BP stage progression with a 5% false discovery rate (FDR) in the ULSAM (n = 238) and PIVUS (n = 566) cohorts, but we could not replicate this association in the MDC cohort (n = 2659). The association in the discovery cohorts was modest, with an odds ratio for BP stage progression over 5 years of 1.33 (95% confidence interval 1.14 to 1.56) per standard deviation of baseline renin. In conclusion, we could not find any novel robust associations with longitudinal BP increase in a proximity extension assay-based proteomics investigation in three cohorts.

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