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  • 1. Agardh, Emilie E
    et al.
    Ahlbom, Anders
    Andersson, Tomas
    Efendic, Suad
    Grill, Valdemar
    Hallqvist, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet.
    Norman, Anders
    Ostenson, Claes-Göran
    Work stress and low sense of coherence is associated with type 2 diabetes in middle-aged Swedish women.2003Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, nr 3, s. 719-24Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The risk of type 2 diabetes is suggested to be increased for individuals exposed to stress. We analyzed the association of work stress by high demands, low decision latitude, and job strain (combination of high demands and low decision latitude) with type 2 diabetes. We also studied low sense of coherence (SOC) (a factor for successful coping with stressors) in association with type 2 diabetes. Finally, we investigated the combination of SOC and demands or SOC and decision latitude in association with the disease.

    RESEARCH DESIGN AND METHODS: This cross-sectional study recruited 4821 healthy Swedish women (aged 35-56 years) residing in five municipalities in the Stockholm area. An oral glucose tolerance test identified 52 women with type 2 diabetes. Relative risks (RRs) with 95% CIs were estimated in a logistic multiple regression analysis.

    RESULTS: No association was found between high demands and type 2 diabetes (RR 1.1 [CI 0.5-2.2]). Low decision latitude was associated with type 2 diabetes with a RR of 2.2 (1.0-4.8). The RR of type 2 diabetes with low SOC was 3.7 (1.2-11.2). The combination of low SOC and low decision latitude was associated with type 2 diabetes with a RR of 2.6 (1.2-5.7). Homeostasis model assessment revealed an association of 4.2 (1.2-15.0) between low SOC and insulin resistance.

    CONCLUSIONS: This study provided new evidence that stress factors such as low decision latitude at work and low SOC were associated with type 2 diabetes in middle-aged Swedish women.

  • 2. Agardh, Emilie E
    et al.
    Ahlbom, Anders
    Andersson, Tomas
    Efendic, Suad
    Grill, Valdemar
    Hallqvist, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet.
    Ostenson, Claes-Göran
    Explanations of socioeconomic differences in excess risk of type 2 diabetes in Swedish men and women.2004Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 27, nr 3, s. 716-21Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: We investigated to what extent socioeconomic differences in type 2 diabetes risk could be explained by established risk factors (obesity, physical inactivity, smoking, and heredity) and psychosocial factors (low decision latitude at work and low sense of coherence).

    RESEARCH DESIGN AND METHODS: This cross-sectional study comprised 3,128 healthy Swedish men and 4,821 women, aged 35-56 years, living in the Stockholm area. An oral glucose tolerance test identified 55 men and 52 women with type 2 diabetes. The relative contribution of established and psychosocial factors to socioeconomic differences in diabetes risk was assessed by comparing analyses with adjustment for different sets of these factors.

    RESULTS: The relative risks (RRs) for type 2 diabetes in middle and low socioeconomic groups in men were 2.4 (95% CI 1.0-5.3) and 2.9 (1.5-5.7), respectively, and in women 3.2 (1.5-6.6) and 2.7 (1.3-5.9), respectively. In men, the RRs decreased to 1.9 (0.8-4.4) and 2.1 (1.0-4.2) after adjustment for established risk factors; no further change was found when psychosocial factors were included. In women, the RRs changed to 2.4 (1.1-5.2) and 1.6 (0.7-3.8) by including established risk factors and to 2.3 (1.0-5.1) and 1.9 (0.8-4.3) by inclusion of psychosocial factors. After adjustment for both established and psychosocial factors, the RRs were 1.4 (0.6-3.6) and 1.0 (0.4-2.5), respectively.

    CONCLUSIONS: In men, the excess risk of type 2 diabetes was partly explained by established risk factors (36-42%), whereas psychosocial factors had no effect. In women, most of the socioeconomic differences in type 2 diabetes were explained by simultaneous adjustment for established risk factors and psychosocial factors (81-100%).

  • 3. Ahrén, Bo
    et al.
    Simonsson, Erik
    Larsson, Hillevi
    Landin-Olsson, Mona
    Torgeirsson, Hlin
    Jansson, Per-Anders
    Sandqvist, Madeléne
    Båvenholm, Peter
    Efendic, Suad
    Eriksson, Jan W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin diabetes och metabolism.
    Dickinson, Sheila
    Holmes, David
    Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes.2002Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 25, nr 5, s. 869-75Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Glucagon-like peptide-1 (GLP-1) has been proposed as a new treatment modality for type 2 diabetes. To circumvent the drawback of the short half-life of GLP-1, inhibitors of the GLP-1-degrading enzyme dipeptidyl peptidase IV (DPP IV) have been examined. Such inhibitors improve glucose tolerance in insulin-resistant rats and mice. In this study, we examined the 4-week effect of 1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP DPP728), a selective, orally active inhibitor of DPP IV, in subjects with diet-controlled type 2 diabetes in a placebo-controlled double-blind multicenter study.

    RESEARCH DESIGN AND METHODS: A total of 93 patients (61 men and 32 women), aged 64 +/- 9 years (means +/- SD) and with BMI 27.3 +/- 2.7 kg/m(2), entered the study. Fasting blood glucose was 8.5 +/- 1.5 mmol/l, and HbA(1c) was 7.4 +/- 0.7%. Before and after treatment with NVP DPP728 at 100 mg x 3 (n = 31) or 150 mg x 5 (n = 32) or placebo (n = 30), subjects underwent a 24-h study with standardized meals (total 2,000 kcal).

    RESULTS: Compared with placebo, NVP DPP728 at 100 mg t.i.d. reduced fasting glucose by 1.0 mmol/l (mean), prandial glucose excursions by 1.2 mmol/l, and mean 24-h glucose levels by 1.0 mmol/l (all P < 0.001). Similar reductions were seen in the 150-mg b.i.d. treatment group. Mean 24-h insulin was reduced by 26 pmol/l in both groups (P = 0.017 and P = 0.023). Although not an efficacy parameter foreseen in the study protocol, HbA(1c) was reduced to 6.9 +/- 0.7% in the combined active treatment groups (P < 0.001). Laboratory safety and tolerability was good in all groups.

    CONCLUSIONS: We conclude that inhibition of DPP IV is a feasible approach to the treatment of type 2 diabetes in the early stage of the disease.

  • 4.
    Arnlöv, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Impact of BMI and the metabolic syndrome on the risk of diabetes in middle-aged men2011Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, nr 1, s. 61-65Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE- The existence of an obese subgroup with a healthy metabolic profile and low diabetes risk has been proposed; yet long-term data are lacking. We aimed to investigate associations between combinations of BMI categories and metabolic syndrome and risk of type 2 diabetes in middle-aged men.

    RESEARCH DESIGN AND METHODS- At age 50, cardiovascular risk factors were assessed in 1,675 participants without diabetes in the community-based Uppsala Longitudinal Study of Adult Men (ULSAM) study. According to BMI/metabolic syndrome status, they were categorized as normal weight (BMI <25 kg/m(2)) without metabolic syndrome (National Cholesterol Education Program criteria, n = 853), normal weight with metabolic syndrome (n = 60), overweight (BMI 25-30 kg/m(2)) without metabolic syndrome (n = 557), overweight with metabolic syndrome (n = 117), obese (BMI >30 kg/m(2)) without metabolic syndrome (n = 28), and obese with metabolic syndrome (n = 60). We investigated the associations between BMI/metabolic syndrome categories at baseline and diabetes incidence.

    RESULTS- After 20 years, 160 participants had developed diabetes. In logistic regression models adjusting for age, smoking, and physical activity, increased risks for diabetes were observed in the normal weight with metabolic syndrome (odds ratio 3.28 [95% CI] 1.38-7.81; P = 0.007), overweight without metabolic syndrome (3.49[2.26-5.42]; P < 0.001), overweight with metabolic syndrome (7.77 [4.44-13.62]; P < 0.001), obese without metabolic syndrome (11.72 [4.88-28.16]; P < 0.001), and obese with metabolic syndrome (10.06 [5.19-19.51]; P < 0.001) categories compared with the normal weight without metabolic syndrome category.

    CONCLUSIONS- Overweight or obese men without metabolic syndrome were at increased risk for diabetes. Our data provide further evidence that overweight and obesity in the absence of the metabolic syndrome should not be considered a harmless condition.

  • 5.
    Basu, Samar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Vessby, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Vessby, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Type 1 diabetes is associated with increased cyclooxygenase- and cytokine-mediated inflammation2005Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 28, nr 6, s. 1371-1375Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The extent of involvement of cyclooxygenase (COX)-mediated inflammation in type 1 diabetes is unknown, and the association between the COX- and cytokine-mediated inflammatory responses in type 1 diabetes is not fully understood.

    RESEARCH DESIGN AND METHODS: Plasma high-sensitivity C-reactive protein (CRP), 24-h urinary and plasma 15-keto-dihydro-prostaglandin F(2alpha) (a metabolite of prostaglandin F(2alpha) [PGF(2alpha)] and an indicator of COX-mediated inflammation), serum amyloid protein A (SAA), and interleukin (IL)-6 (indicators of inflammation) were measured in 38 subjects with type 1 diabetes and 41 healthy age- and sex-matched control subjects.

    RESULTS: The inflammatory indicators (urinary 15-keto-dihydro-PGF(2alpha), P < 0.01; IL-6, P < 0.04) were increased in men with diabetes. CRP and SAA did not show any significant difference between the diabetic and the control subjects. Urinary levels of 15-keto-dihydro-PGF(2alpha) correlated with the degree of glycemic control, HbA(1c) (r = 0.42, P < 0.0005). No correlation was found between the duration of diabetes and the inflammatory biomarkers or metabolic measurements.

    CONCLUSIONS: These results suggest that an early low-grade inflammatory process reflected by elevated levels of PGF(2alpha) and IL-6 is involved in type 1 diabetes. Thus, both COX- and cytokine-mediated inflammatory pathways are significantly related to type 1 diabetes.

  • 6.
    Benedict, Christian
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Brooks, Samantha J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Burgos, Jonathan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Kempton, Matthew J
    Nordenskjöld, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Nylander, Ruta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Craft, Suzanne
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Schiöth, Helgi B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Impaired Insulin Sensitivity as Indexed by the HOMA Score Is Associated With Deficits in Verbal Fluency and Temporal Lobe Gray Matter Volume in the Elderly2012Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 35, nr 3, s. 488-494Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE

    Impaired insulin sensitivity is linked to cognitive deficits and reduced brain size. However, it is not yet known whether insulin sensitivity involves regional changes in gray matter volume. Against this background, we examined the association between insulin sensitivity, cognitive performance, and regional gray matter volume in 285 cognitively healthy elderly men and women aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.

    RESEARCH DESIGN AND METHODS

    Insulin sensitivity was calculated from fasting serum insulin and plasma glucose determinations using the homeostasis model assessment of insulin resistance (HOMA-IR) method. Cognitive performance was examined by a categorical verbal fluency. Participants also underwent a magnetic resonance imaging (MRI) brain scan. Multivariate analysis using linear regression was conducted, controlling for potential confounders (sex, education, serum LDL cholesterol, mean arterial blood pressure, and abdominal visceral fat volume).

    RESULTS

    The HOMA-IR was negatively correlated with verbal fluency performance, brain size (S1), and temporal lobe gray matter volume in regions known to be involved in speech production (Brodmann areas 21 and 22, respectively). No such effects were observed when examining diabetic (n = 55) and cognitively impaired (n = 27) elderly subjects as separate analyses.

    CONCLUSIONS

    These cross-sectional findings suggest that both pharmacologic and lifestyle interventions improving insulin signaling may promote brain health in late life but must be confirmed in patient studies.

  • 7.
    Berhan, Yonas
    et al.
    Umeå universitet, Pediatrik.
    Eliasson, Mats
    Umeå universitet, Medicin.
    Möllsten, Anna
    Umeå universitet, Pediatrik.
    Waernbaum, Ingeborg
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Statistiska institutionen. Umeå universitet, Statistik.
    Dahlquist, Gisela
    Umeå universitet, Pediatrik.
    Impact of Parental Socioeconomic Status on Excess Mortality in a Population-Based Cohort of Subjects With Childhood-Onset Type 1 Diabetes2015Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 38, nr 5, s. 827-832Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aim of this study was to analyze the possible impact of parental and individual socioeconomic status (SES) on all-cause mortality in a population-based cohort of patients with childhood-onset type 1 diabetes.

    RESEARCH DESIGN AND METHODS: Subjects recorded in the Swedish Childhood Diabetes Registry (SCDR) from 1 January 1978 to 31 December 2008 were included (n =14,647). The SCDR was linked to the Swedish Cause of Death Registry (CDR) and the Longitudinal Integration Database for Health Insurance and Labour Market Studies (LISA).

    RESULTS: At a mean follow-up of 23.9 years (maximum 46.5 years), 238 deaths occurred in a total of 349,762 person-years at risk. In crude analyses, low maternal education predicted mortality for male patients only (P = 0.046), whereas parental income support predicted mortality in both sexes (P < 0.001 for both). In Cox models stratified by age-at-death group and adjusted for age at onset and sex, parental income support predicted mortality among young adults (≥18 years of age) but not for children. Including the adult patient’s own SES in a Cox model showed that individual income support to the patient predicted mortality occurring at ≥24 years of age when adjusting for age at onset, sex, and parental SES.

    CONCLUSIONS: Exposure to low SES, mirrored by the need for income support, increases mortality risk in patients with childhood-onset type 1 diabetes who died after the age of 18 years.

  • 8. Brinck, Jonas
    et al.
    Hagström, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Nåtman, Jonatan
    Franzén, Stefan
    Eeg-Olofsson, Katarina
    Nathanson, David
    Eliasson, Björn
    Cardiovascular Outcomes in Patients With Both Diabetes and Phenotypic Familial Hypercholesterolemia: A Nationwide Register-Based Cohort Study2022Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 45, nr 12, s. 3040-3049Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Patients with diabetes or familial hypercholesterolemia (FH) have an increased incidence of cardiovascular diseases compared with the population, but whether this risk is exacerbated in patients with combined traits is unknown.

    RESEARCH DESIGN AND METHODS: In this Swedish nationwide, register-based cohort study, patients with diabetes were included between 2002 and 2020. Adjusted Cox proportional hazards models were used to assess the risk of cardiovascular events in patients with or without phenotypic FH (≥6 points for phenotypic FH according to Dutch Lipid Clinic Network criteria) compared with general population control subjects without diabetes as reference.

    RESULTS: A total of 45,585 patients with type 1 diabetes (227,923 control subjects) and 655,250 patients with type 2 diabetes (655,250 control subjects) were followed for a median of 14.1 and 7.9 years, respectively. Of those, 153 and 7,197, respectively, had phenotypic FH. Compared with control subjects, patients with diabetes and phenotypic FH had higher risk of cardiovascular mortality (type 1: hazard ratio 21.3 [95% CI 14.6-31.0]; type 2: 2.40 [2.19-2.63]) and of a cardiovascular event (type 1: 15.1 [11.1-20.5]; type 2: 2.73 [2.58-2.89]). Further, patients with diabetes and phenotypic FH had higher LDL-cholesterol levels during observation (P < 0.05) and increased risk of all major cardiovascular outcomes (P < 0.0001) than patients with diabetes but without FH. The proportion receiving lipid-lowering treatment was higher in patients with phenotypic FH (P < 0.0001).

    CONCLUSIONS: Patients with both diabetes and phenotypic FH are more at risk for adverse cardiovascular outcomes and have higher LDL-cholesterol levels despite receiving intensified lipid-lowering therapy.

  • 9. Butwicka, Agnieszka
    et al.
    Frisen, Louise
    Almqvist, Catarina
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lichtenstein, Paul
    Risks of Psychiatric Disorders and Suicide Attempts in Children and Adolescents With Type 1 Diabetes: A Population-Based Cohort Study2015Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 38, nr 3, s. 453-459Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE To assess the risk of psychiatric disorders and suicide attempts in children with type 1 diabetes and their healthy siblings. RESEARCH DESIGN AND METHODS We performed a population-based case-cohort study of individuals born in Sweden between 1973 and 2009. Children with type 1 diabetes (n = 17,122) and their healthy siblings (n = 18,847) were identified and followed until their 18th birthday. Their risk of psychiatric disorders was compared with that of matched control subjects. RESULTS The risk of psychiatric morbidity in children with type 1 diabetes compared with the general population was tripled within 6 months after the onset of diabetes (hazard ratio [HR] 3.0 [95% CI 2.7-3.4]) and doubled within the total observation period (HR 2.1 [95% CI 2.0-2.2]). An increased risk was noted in suicide attempts (HR 1.7 [95% CI 1.4-2.0]) and in most categories of psychiatric disorders. The risk of psychiatric disorders in probands declined from HR 2.7 (95% CI 2.2-3.3) for those in the cohort born 1973-1986 to 1.9 (95% CI 1.8-2.0) in those born 1997-2009. The risk for any psychiatric disorders among siblings of patients with type 1 diabetes was estimated to be HR 1.1 (95% CI 1.0-1.1), and there was no increased risk in any of the specific category of disorders. CONCLUSIONS Children with type 1 diabetes are at high risk of psychiatric disorders, which seems to be a consequence of the disease rather than due to a common familial etiology. The results support recommendations on comprehensive mental health surveillance in children with type 1 diabetes, especially in recently diagnosed children.

  • 10.
    Cederholm, Jan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och klinisk epidemiologi.
    Eeg-Olofsson, Katarina
    Eliasson, Björn
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Nilsson, Peter M
    Gudbjörnsdottir, Soffia
    Risk prediction of cardiovascular disease in type 2 diabetes: A risk equation from the Swedish National Diabetes Register (NDR)2008Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, nr 10, s. 2038-2043Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE - Risk prediction models obtained in samples from the general population do mot perform well in type 2 diabetic patients. Recently, 5-year risk estimates were proposed as being more accurate than 10-year risk estimates. This study presents a diabetes-specific equation for estimation of the absolute 5-year risk of first incident fatal/nonfatal cardiovascular disease (CVD) in type 2 diabetic patients with the use of A1C and clinical characteristics.RESEARCH DESIGN AND METHODS - The study was based on 11,646 female and male patients, aged 18-70 years, from the Swedish National Diabetes Register with 1,482 first incident CVD events based on 58,342 person-years with mean follow-up) of 5.64 years.RESULTS - This risk equation incorporates A1C, as in the UK Prospective Diabetes Study risk engine, and several clinical characteristics: onset age of diabetes, diabetes duration, sex, BMI, smoking, systolic blood pressure, and antihypertensive and lipid-reducing drugs. All predictors included were associated with the Outcome (P < 0.0001, except for BMI P = 0.0016) with Cox regression analysis. Calibration was excellent when assessed by comparing observed and predicted risk. Discrimination was sufficient, with a receiver operator curve statistic of 0.70. Mean 5-year risk of CVD in all patients was 12.0 +/- 7.5%, whereas 54% of the patients had a 5-year risk >= 10%.CONCLUSIONS - This more simplified risk equation enables 5-year risk prediction of CVD based on easily available nonlaboratory predictors in clinical practice and A1C and was elaborated in a large observational study obtained from the normal patient population aged up to 70 years.

  • 11.
    Chen, Jie
    et al.
    Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Zhejiang, Peoples R China.;Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, Changsha, Peoples R China..
    Yuan, Shuai
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden..
    Fu, Tian
    Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, Changsha, Peoples R China..
    Ruan, Xixian
    Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, Changsha, Peoples R China..
    Qiao, Jie
    Zhejiang Univ, Dept Endocrinol & Metab, Affiliated Hosp 2, Hangzhou, Peoples R China..
    Wang, Xiaoyan
    Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, Changsha, Peoples R China..
    Li, Xue
    Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Zhejiang, Peoples R China.;Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Scotland..
    Gill, Dipender
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, London, England..
    Burgess, Stephen
    Univ Cambridge, MRC Biostat Unit, Cambridge, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Giovannucci, Edward L.
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA..
    Larsson, Susanna C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Medicinsk epidemiologi. Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden..
    Gastrointestinal Consequences of Type 2 Diabetes Mellitus and Impaired Glycemic Homeostasis: A Mendelian Randomization Study2023Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 46, nr 4, s. 828-835Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: We conducted a Mendelian randomization (MR) study to examine the associations of type 2 diabetes and glycemic traits with gastrointestinal diseases (GDs).

    RESEARCH DESIGN AND METHODS: Uncorrelated genetic variants associated with type 2 diabetes (n = 231), fasting insulin (n = 38), fasting glucose (n = 71), and hemoglobin A1c (n = 75) at the genome-wide significance were selected as instrument variables. Genetic associations with 23 common GDs were obtained from the FinnGen and UK Biobank studies and other large consortia.

    RESULTS: Genetic liability to type 2 diabetes was associated with the risk of 12 GDs. Per 1-unit increase in the log-transformed odds ratio (OR) of type 2 diabetes, the OR was 1.06 (95% CI, 1.03-1.09) for gastroesophageal reflux disease, 1.12 (95% CI, 1.07-1.17) for gastric ulcer, 1.11 (95% CI, 1.03-1.20) for acute gastritis, 1.07 (95% CI, 1.01-1.13) for chronic gastritis, 1.08 (95% CI, 1.03-1.12) for irritable bowel syndrome, 1.04 (95% CI, 1.01-1.07) for diverticular disease, 1.08 (95% CI, 1.02-1.14) for acute pancreatitis, 1.09 (95% CI, 1.05-1.12) for cholelithiasis, 1.09 (95% CI, 1.05-1.13) for cholelithiasis with cholecystitis, 1.29 (95% CI, 1.17-1.43) for nonalcoholic fatty liver disease, 1.12 (95% CI, 1.03-1.21) for liver cirrhosis, and 0.93 (95% CI, 0.89-0.97) for ulcerative colitis. Genetically predicted higher levels of fasting insulin and glucose were associated with six and one GDs, respectively.

    CONCLUSIONS: Associations were found between genetic liability to type 2 diabetes and an increased risk of a broad range of GDs, highlighting the importance of GD prevention in patients with type 2 diabetes.

  • 12. Eeg-Olofsson, Katarina
    et al.
    Cederholm, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och klinisk epidemiologi.
    Nilsson, Peter M
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Svensson, Ann-Marie
    Gudbjörnsdóttir, Soffia
    Eliasson, Björn
    Glycemic control and cardiovascular disease in 7,454 patients with type 1 diabetes: an observational study from the Swedish National Diabetes Register (NDR).2010Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 33, nr 7, s. 1640-1646Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE

    We assessed the association between A1C and cardiovascular diseases (CVDs) in an observational study of patients with type 1 diabetes followed for 5 years.

    RESEARCH DESIGN AND METHODS

    A total of 7,454 patients were studied from the Swedish National Diabetes Register (aged 20-65 years, diabetes duration 1-35 years, followed from 2002 to 2007).

    RESULTS

    Hazard ratios (HRs) for fatal/nonfatal coronary heart disease (CHD) per 1% unit increase in baseline or updated mean A1C at Cox regression analysis were 1.31 and 1.34 and 1.26 and 1.32, respectively, for fatal/nonfatal CVD (all P < 0.001 after adjustment for age, sex, diabetes duration, blood pressure, total and LDL cholesterol, triglycerides, BMI, smoking, and history of CVD). HRs were only slightly lower for CHD (P = 0.002) and CVD (P = 0.002-0.007) after also adjusting for albuminuria. Adjusted 5-year event rates of CHD and CVD increased progressively with higher A1C, ranging from 5 to 12%, as well as when subgrouped by shorter (1-20 years) or longer (21-35 years) duration of diabetes. A group of 4,186 patients with A1C 5-7.9% (mean 7.2) at baseline showed risk reductions of 41% (95% confidence intervals: 15-60) (P = 0.005) for fatal/nonfatal CHD and 37% (12-55) (P = 0.008) for CVD, compared with 3,268 patients with A1C 8-11.9% (mean 9.0), fully adjusted also for albuminuria.

    CONCLUSIONS

    This observational study of patients in modern everyday clinical practice demonstrates progressively increasing risks for CHD and CVD with higher A1C, independently of traditional risk factors, with no J-shaped risk curves. A baseline mean A1C of 7.2% showed considerably reduced risks of CHD and CVD compared with A1C 9.0%, emphasizing A1C as a strong independent risk factor in type 1 diabetes.

  • 13.
    Eeg-Olofsson, Katarina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Cederholm, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och klinisk epidemiologi.
    Nilsson, P.M.
    Gudbjörnsdottir, S.
    Eliasson, B.
    Glycemic and risk factor control in type 1 diabetes: results from 13,612 patients in a national diabetes register2007Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 30, nr 3, s. 496-502Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE - This study was designed to investigate the clinical characteristics of a large type 1 diabetic population and to evaluate the degree of fulfillment of recently updated treatment goals. RESEARCH DESIGN AND METHODS - The Swedish National Diabetes Register was initiated in 1996 as a tool for quality assurance in diabetes care. AlC levels, treatment, and risk factors were analyzed in two cross-sectional samples of 9,424 patients in 1997 and 13,612 patients in 2004 and in a smaller longitudinal sample from 1997 to 2004. RESULTS - Mean AlC decreased from 8.2 ± 1.3% in 1997 to 8.0 ± 1.2% in 2004 (P < 0.001). The proportion of patients reachingAlC <7.0% increased from 17.4 to 21.2% in 2004. A slow but significant improvement in blood pressure levels was seen, but only 61.3% reached the blood pressure goal of <130/80 mmHg in 2004. Lipid control improved, and the use of lipid-lowering drugs increased. Among patients treated with lipid-lowering agents, 38% reached the goal of total cholesterol <4.5 mmol/l, and 48% reached the goal of LDL cholesterol <2.5 mmol/l. Successful long-term glycemic and blood pressure control were both independently predicted by low BMI and the absence of microalbuminuria in 1997. CONCLUSIONS - In this large cohort of type 1 diabetic patients, there was a slow improvement in glycemic and risk factor control from 1997 to 2004, although the gap between the clinical results and current Swedish and American treatment goals is still unsatisfactory. It is crucial that additional measures be taken to improve risk factor control in type 1 diabetic patients.

  • 14. Ekberg, Karin
    et al.
    Brismar, Tom
    Johansson, Bo-Lennart
    Lindström, Per
    Juntti-Berggren, Lisa
    Norrby, Anders
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Arnqvist, Hans J.
    Bolinder, Jan
    Wahren, John
    C-Peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy2007Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 30, nr 1, s. 71-76Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE - C-peptide replacement in animals results in amelioration of diabetes-induced functional and structural abnormalities in peripheral nerves. The present study was undertaken to examine whether C-peptide administration to patients with type 1 diabetes and peripheral neuropathy improves sensory nerve function. RESEARCH DESIGN AND METHODS - This was an exploratory, double-blinded, randomized, and placebo-controlled study with three study groups that was carried out at five centers in Sweden. C-peptide was given as a replacement dose (1.5 mg/day, divided into four subcutaneous doses) or a dose three times higher (4.5 mg/day) during 6 months. Neurological examination and neurophysiological measurements were performed before and after 6 months of treatment with C-peptide or placebo. RESULTS - The age of the 139 patients who completed the protocol was 44.2 ± 0.6 (mean ± SE) years and their duration of diabetes was 30.6 ± 0.8 years. Clinical neurological impairment (NIA) (score >7 points) of the lower extremities was present in 86% of the patients at baseline. Sensory nerve conduction velocity (SCV) was 2.6 ± 0.08 SD below body height-corrected normal values at baseline and improved similarly within the two C-peptide groups (P < 0.007). The number of patients responding with a SCV peak potential improvement >1.0 m/s was greater in C-peptide-treated patients than in those receiving placebo (P < 0.03). In the least severely affected patients (SCV < 2.5 SD below normal at baseline, n = 70) SCV improved by 1.0 m/s (P < 0.014 vs. placebo). NIA score and vibration perception both improved within the C-peptide-treated groups (P < 0.011 and P < 0.002). A1C levels (7.6 ± 0.1% at baseline) decreased slightly but similarly in C-peptide- and placebo-treated patients during the study. CONCLUSIONS - C-peptide treatment for 6 months improves sensory nerve function in early-stage type 1 diabetic neuropathy.

  • 15. Eliasson, Björn
    et al.
    Cederholm, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Eeg-Olofsson, Katarina
    Svensson, Anne-Marie
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Gudbjörnsdottir, Soffia
    Clinical Usefulness of Different Lipid Measures for Prediction of Coronary Heart Disease in Type 2 Diabetes: A report from the Swedish National Diabetes Register2011Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, nr 9, s. 2095-2100Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: We assessed the association between different blood lipid measures and risk of fatal/nonfatal coronary heart disease (CHD).

    RESEARCH DESIGN AND METHODS: We conducted an observational study of patients with type 2 diabetes from the Swedish National Diabetes Register. Baseline LDL cholesterol, non-HDL cholesterol, ratio of non-HDL to HDL cholesterol (non-HDL:HDL), and ratio of triacylglycerol to HDL cholesterol (TG:HDL) was measured in 18,673 patients aged 30-70 years, followed for a mean of 4.8 years from 2003 to 2007.

    RESULTS: Hazard ratios (HRs) for CHD per 1-SD increment in lipid measures were 1.23 with non-HDL:HDL, 1.20 with non-HDL cholesterol, 1.17 with LDL cholesterol, and 1.15 with TG: HDL (all P < 0.001 when adjusted for clinical characteristics and nonlipid risk factors). The best global model fit was found with non-HDL:HDL. When patients within the lowest tertile of a lipid measure were compared with those with all lipid measures within the highest tertile, the adjusted HR for CHD was 0.62 with non-HDL:HDL <3.5 mmol/L, 0.65 with non-HDL cholesterol <3.3 mmol/L, and 0.70 with LDL cholesterol <2.5 mmol/L (all P < 0.001). The lowest tertile of LDL and non-HDL cholesterol corresponded with treatment targets according to U.S. and European guidelines. HRs for CHD were 0.52, 0.62, and 0.66 with the lowest deciles of non-HDL:HDL, non-HDL cholesterol, and LDL cholesterol mmol/L (all P < 0.001). Mean TG:HDL was considerably lower in patients within the lowest tertile of non-HDL:HDL, 0.82 +/- 0.47, than in those within the lowest tertile of LDL cholesterol (<2.5 mmol/L), 1.49 +/- 1.03.

    CONCLUSIONS: Non-HDL:HDL had a stronger effect on CHD risk than LDL cholesterol, and low TG:HDL values were more often seen within the lowest non-HDL:HDL tertile than within the lowest LDL cholesterol tertile. LDL cholesterol was not the best predictor of CHD risk in type 2 diabetes.

  • 16.
    Eriksson, Jan W
    Department of Medicine, Norrland University Hospital, Umeå, Sweden.
    Is hyperinsulinemia the cause of acanthosis nigricans in the type B syndrome of insulin resistance?1997Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 20, nr 6, s. 1045-1045Artikel i tidskrift (Refereegranskat)
  • 17.
    Eriksson, Jan W
    et al.
    Department of Medicine, Umeå University Hospital, Umeå, Sweden.
    Bremell, T
    Eliasson, B
    Fowelin, J
    Fredriksson, L
    Yu, Z W
    Successful treatment with plasmapheresis, cyclophosphamide, and cyclosporin A in type B syndrome of insulin resistance: a case report1998Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 21, nr 8, s. 1217-1220Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CASE HISTORY:

    A woman born in 1949 was diagnosed in 1990 with systemic lupus erythematosus. She was treated with prednisolone, and < 1 year later she presented with marked hyperglycemia. Large doses of insulin were given four times per day. Even though the patient was thin (BMI 17.4 kg/m2), very little improvement was seen.

    INVESTIGATIONS AND TREATMENT:

    Serum insulin levels were high, and a euglycemic clamp investigation confirmed severe insulin resistance. The patient's serum contained insulin receptor antibodies inhibiting insulin binding, and thus the patient had a type B syndrome of insulin resistance. After diet and exercise, glycemic control stabilized and insulin treatment was withdrawn. However, in late 1993 she was in a catabolic and hyperglycemic state even though prednisolone doses were increased and azathioprin was added. In early 1994 she was treated with plasmapheresis and cyclophosphamide i.v. Subsequently, cyclosporin A was started as a maintenance therapy in addition to azathioprin. There was a rapid and sustained clinical improvement. Since late 1994 and onward, there is no sign of diabetes or glucose intolerance and there are no demonstrable insulin receptor antibodies in the patient's serum.

    DISCUSSION:

    Severe type B insulin resistance may respond favorably to treatment with plasmapheresis and cyclophosphamide followed by cyclosporin A in combination with azathioprin.

  • 18.
    Espes, Daniel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Transplantation och regenerativ medicin.
    Singh, Kailash
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Sandler, Stellan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Carlsson, Per-Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Transplantation och regenerativ medicin.
    Increased Interleukin-35 Levels in Patients With Type 1 Diabetes With Remaining C-Peptide2017Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 40, nr 8, s. 1090-1095Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE Many patients with long-standing type 1 diabetes have remaining functional β-cells. This study investigated immunological differences between patients with or without measurable remaining endogenous insulin production after ≥10 years duration of disease.

    RESEARCH DESIGN AND METHODS Patients (n = 113; ≥18 years of age) with type 1 diabetes and with disease duration of ≥10 years were recruited at Uppsala University Hospital. Residual β-cell function was determined with an ultrasensitive C-peptide ELISA. Circulating cytokines, including interleukin-35 (IL-35), were determined in plasma. Additional blood samples were collected from 14 of the identified C-peptide–positive patients and 12 of the C-peptide–negative patients, as well as from 15 healthy control subjects, and were used for immediate investigation of peripheral blood mononuclear cells.

    RESULTS The blood concentration of the cytokine IL-35 was markedly lower in C-peptide–negative patients, and this was associated with a simultaneous decrease in the proportion of IL-35+ regulatory T cells (Tregs), IL-35+ regulatory B cells, and IL-35–producing CD8+Foxp3+ cells. IL-35 has previously been shown to maintain the phenotype of Tregs, block the differentiation of T-helper 17 cells, and thereby dampen immune assaults to β-cells. We found that the proportions of IL-17a+ cells among the Tregs, CD4+ T cells, and CD8+ T cells were lower in the C-peptide–positive patients.

    CONCLUSIONS Patients with remaining endogenous β-cell function after >10 years duration of type 1 diabetes differ immunologically from other patients with long-standing type 1 diabetes. In particular, they have a much higher IL-35 production.

  • 19. Ferrannini, Giulia
    et al.
    De Bacquer, Dirk
    De Backer, Guy
    Kotseva, Kornelia
    Mellbin, Linda
    Wood, David
    Rydén, Lars
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Screening for Glucose Perturbations and Risk Factor Management in Dysglycemic Patients With Coronary Artery Disease-A Persistent Challenge in Need of Substantial Improvement: A Report From ESC EORP EUROASPIRE V.2020Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 43, nr 4, s. 726-733Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Dysglycemia, in this survey defined as impaired glucose tolerance (IGT) or type 2 diabetes, is common in patients with coronary artery disease (CAD) and associated with an unfavorable prognosis. This European survey investigated dysglycemia screening and risk factor management of patients with CAD in relation to standards of European guidelines for cardiovascular subjects.

    RESEARCH DESIGN AND METHODS: The European Society of Cardiology's European Observational Research Programme (ESC EORP) European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) V (2016-2017) included 8,261 CAD patients, aged 18-80 years, from 27 countries. If the glycemic state was unknown, patients underwent an oral glucose tolerance test (OGTT) and measurement of glycated hemoglobin A1c. Lifestyle, risk factors, and pharmacological management were investigated.

    RESULTS: A total of 2,452 patients (29.7%) had known diabetes. OGTT was performed in 4,440 patients with unknown glycemic state, of whom 41.1% were dysglycemic. Without the OGTT, 30% of patients with type 2 diabetes and 70% of those with IGT would not have been detected. The presence of dysglycemia almost doubled from that self-reported to the true proportion after screening. Only approximately one-third of all coronary patients had completely normal glucose metabolism. Of patients with known diabetes, 31% had been advised to attend a diabetes clinic, and only 24% attended. Only 58% of dysglycemic patients were prescribed all cardioprotective drugs, and use of sodium-glucose cotransporter 2 inhibitors (3%) or glucagon-like peptide 1 receptor agonists (1%) was small.

    CONCLUSIONS: Urgent action is required for both screening and management of patients with CAD and dysglycemia, in the expectation of a substantial reduction in risk of further cardiovascular events and in complications of diabetes, as well as longer life expectancy.

  • 20.
    Florvall, Gösta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Helmersson, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hemocue urine albumin point-of-care test shows strong agreement with the results obtained with a large nephelometer2006Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 29, nr 2, s. 422-423Artikel i tidskrift (Refereegranskat)
  • 21. Gudbjörnsdottir, S
    et al.
    Cederholm, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och klinisk epidemiologi.
    Nilsson, P M
    Eliasson, B
    The National Diabetes Register in Sweden: an implementation of the St. Vincent Declaration for Quality Improvement in Diabetes Care2003Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, nr 4, s. 1270-1276Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:To monitor glycemic control, treatable risk factors, and treatment profile for quality assessment of diabetes care on a national scale.

    RESEARCH DESIGN AND METHODS:Four samples of 23,546, 32,903, 30,311, and 29,769 patients with diabetes (1996-1999) were studied based on a repeated national screening and quality assessment of diabetes care by the National Diabetes Register, Sweden, with participation of both hospitals and primary health care. Clinical characteristics included were age, sex, diabetes duration and treatment, glycemic control (HbA(1c)), office blood pressure (BP), BMI, smoking habits, and use of lipid-lowering drugs in patients with type 1 or type 2 diabetes.

    RESULTS:Favorable decreases of mean HbA(1c) and BP values were registered during the 4-year study period for both type 1 (HbA(1c) 7.5-7.3% and BP 130/75-130/74 mmHg) and type 2 diabetic patients (HbA(1c) 7.0-6.7% and BP 151/82-147/80 mmHg). Treatment aims of HbA(1c) and BP levels were also achieved in increasing proportions for type 1 (HbA(1c) <7.5%: 50-58% and BP </=140/85 mmHg: 77-79%), and type 2 diabetic patients (HbA(1c) <7.5%: 66-73% and BP </=140/85 mmHg: 32-42%). The use of lipid-lowering drugs increased for type 1 (4-11%) and type 2 diabetic patients (10-22%). In type 2 diabetic patients, treatment with oral agents alone decreased, but combination therapy (insulin and oral agents) increased during the study period. Mean BMI increased during 1996-1999 in type 2 diabetic patients. High HbA(1c) and BP values in 1999 were predicted by high BMI values 1996 and by high increase of BMI during the period, independent of diabetes duration, age, and sex.

    CONCLUSIONS:Decreasing mean HbA(1c) and BP levels and the wider use of lipid-lowering drugs during the late 1990s in patients with diabetes in a national sample from Sweden should translate into clinical benefits regarding micro- and macrovascular complications as well as diabetes-related mortality.

  • 22. Gulseth, Hanne L.
    et al.
    Gjelstad, Ingrid M. F.
    Tierney, Audrey C.
    Lovegrove, Julie A.
    Defoort, Catherine
    Blaak, Ellen E.
    Lopez-Miranda, Jose
    Kiec-Wilk, Beata
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Roche, Helen M.
    Drevon, Christian A.
    Birkeland, Kare I.
    Serum Vitamin D Concentration Does Not Predict Insulin Action or Secretion in European Subjects With the Metabolic Syndrome2010Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 33, nr 4, s. 923-925Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE To investigate the relation between serum concentration of 25-hydroxyvitamin D [25(OH)D] and insulin action and secretion. RESEARCH DESIGN AND METHODS In a cross-sectional study of 446 Pan-European subjects with the metabolic syndrome, insulin action and secretion were assessed by homeostasis model assessment (HOMA) indexes and intravenous glucose tolerance test to calculate acute insulin response, insulin sensitivity, and disposition index. Serum 25(OH)D was measured by high-performance liquid chromatography/mass spectrometry. RESULTS - The 25(OH)D-3 concentration was 57.1 +/- 26.0 nmol/l (mean +/- SD), and only 20% of the subjects had 25(OH)D-3 levels >= 75 nmol/l. In multiple linear analyses, 25(OH)D-3 concentrations were not associated with parameters of insulin action or secretion after adjustment for BMI and other covariates. CONCLUSIONS In a large sample of subjects with the metabolic syndrome, serum concentrations of 25(OH)D-3 did not predict insulin action or secretion. Clear evidence that D vitamin status directly influences insulin secretion or action is still lacking.

  • 23. Henricsson, Marianne
    et al.
    Nyström, Lennarth
    Blohmé, Göran
    Ostman, Jan
    Kullberg, Carin
    Svensson, Maria
    Schölin, Anna
    Arnqvist, Hans J
    Björk, Elisabeth
    Bolinder, Jan
    Eriksson, Jan W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin diabetes och metabolism.
    Sundkvist, Göran
    The incidence of retinopathy 10 years after diagnosis in young adult people with diabetes: results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS).2003Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, nr 2, s. 349-54Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To estimate the prevalence and severity of diabetic retinopathy (DR) 10 years after diagnosis in a nationwide population-based cohort study of young adult diabetic patients in Sweden.

    RESEARCH DESIGN AND METHODS: The Diabetes Incidence Study in Sweden (DISS) aims to register all incident cases of diabetes aged 15-34 years in Sweden. In 1987-1988, 806 cases were reported, and 627 (78%) of them were followed up with regard to retinopathy 8-10 years later. The assessment was based on retinal photographs in most cases (86%).

    RESULTS: Ten years after diagnosis, retinopathy was found in 247 patients (39%). The retinopathy was mild in 206 (33%), whereas 30 (4.8%) patients had moderate nonproliferative DR (NPDR) and 11 (1.8%) had proliferative DR (PDR). Patients with retinopathy had worse glycemic control during the years than patients without (HbA(1c) 8.1 +/- 1.5% and 6.8 +/- 1.2%, respectively; P < 0.001). In a Cox regression analysis, time to retinopathy was related to high HbA(1c) (P < 0.001) and high BMI (P = 0.001). Patients with type 2 diabetes had an increased prevalence of severe retinopathy (NPDR or PDR) compared with those with type 1 diabetes (14 of 93 [15%] versus no or mild 24 of 471 [5%], respectively; P < 0.001).

    CONCLUSIONS: Despite modern diabetes management, 39% of young adult diabetic patients developed retinopathy within the first 10 years of the disease. Nevertheless, compared with the prevalence of retinopathy (63%), after a similar duration of diabetes before the Diabetes Control and Complications Trial, this prevalence was clearly lower. Current treatment aimed to achieve strict glycemic control has reduced the risk for developing retinopathy.

  • 24.
    Hering, Bernhard J.
    et al.
    Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN 55455 USA.;Univ Minnesota, Dept Surg, Box 242 UMHC, Minneapolis, MN 55455 USA..
    Clarke, William R.
    Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA..
    Bridges, Nancy D.
    NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA..
    Eggerman, Thomas L.
    NIDDK, NIH, Bethesda, MD 20892 USA..
    Alejandro, Rodolfo
    Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA..
    Bellin, Melena D.
    Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN 55455 USA.;Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA..
    Chaloner, Kathryn
    Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA..
    Czarniecki, Christine W.
    NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA..
    Goldstein, Julia S.
    NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA..
    Hunsicker, Lawrence G.
    Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA..
    Kaufman, Dixon B.
    Univ Wisconsin, Dept Surg, Div Transplantat, Madison, WI USA..
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Larsen, Christian P.
    Emory Univ, Emory Transplant Ctr, Atlanta, GA 30322 USA..
    Luo, Xunrong
    Northwestern Univ, Feinberg Sch Med, Comprehens Transplant Ctr, Chicago, IL 60611 USA..
    Markmann, James F.
    Harvard Med Sch, Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA USA..
    Naji, Ali
    Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA..
    Oberholzer, Jose
    Univ Illinois Hosp & Hlth Sci Syst, Div Transplantat, Chicago, IL USA..
    Posselt, Andrew M.
    Univ Calif San Francisco, Dept Surg, San Francisco, CA USA..
    Rickels, Michael R.
    Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA..
    Ricordi, Camillo
    Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA..
    Robien, Mark A.
    NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA..
    Senior, Peter A.
    Univ Alberta, Clin Islet Transplant Program, Edmonton, AB, Canada.;Univ Alberta, Fac Med & Dent, Edmonton, AB, Canada..
    Shapiro, A. M. James
    Univ Alberta, Clin Islet Transplant Program, Edmonton, AB, Canada.;Univ Alberta, Fac Med & Dent, Edmonton, AB, Canada..
    Stock, Peter G.
    Univ Calif San Francisco, Dept Surg, San Francisco, CA USA..
    Turgeon, Nicole A.
    Emory Univ, Emory Transplant Ctr, Atlanta, GA 30322 USA..
    Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia2016Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 39, nr 7, s. 1230-1240Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50-80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment. RESEARCH DESIGN AND METHODS This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA(1c) <7.0% (53 mmol/mol) at day 365 and freedom from SHEs from day 28 to day 365 after the first transplant. RESULTS The primary end point was successfully met by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA(1c) level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients. CONCLUSIONS Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.

  • 25. Hjern, Anders
    et al.
    Söderström, Ulf
    Department of Pediatrics, Mälarsjukhuset, Eskilstuna, Sweden .
    Åman, Jan
    East Africans in Sweden have a high risk for type 1 diabetes2012Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 35, nr 3, s. 597-598Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    To investigate the prevalence of type 1 diabetes in children with an origin in Sub-Saharan Africa in Sweden.

    RESEARCH DESIGN AND METHODS:

    Nationwide register study based on retrieved prescriptions of insulin during 2009 in children aged 0-18 years. The study population consisted of 35,756 children in families with an origin in Sub-Saharan Africa and 1,666,051 children with native Swedish parents.

    RESULTS:

    The odds ratio (OR) for insulin medication in Swedish-born children in families originating in East Africa was 1.29 (95% CI 1.02-1.63) compared with offspring of native Swedish parents, after adjustment for age and sex, and less common in children who themselves were born in East Africa: 0.50 (0.34-0.73). Offspring of parents from other parts of Sub-Saharan Africa had a comparatively low risk for insulin medication.

    CONCLUSIONS:

    This study indicates that Swedish-born children with an origin in East Africa have a high risk of type 1 diabetes.

  • 26.
    Hyllienmark, Lars
    et al.
    Section of Neurology, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
    Alstrand, Nils
    Department of Medical and Health Sciences, Linköping University and Östergötland County Council, Linköping, Sweden.
    Jonsson, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Ludvigsson, Johnny
    Division of Paediatrics, Department of Clinical and Experimental Medicine, Linköping University and Östergötland County Council, Linköping, Sweden.
    Cooray, Gerald
    Section of Clinical Neurophysiology, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
    Wahlberg-Topp, Jeanette
    Department of Medical and Health Sciences, Linköping University and Östergötland County Council, Linköping, Sweden.
    Early Electrophysiological Abnormalities and Clinical Neuropathy: A prospective study in patients with type 1 diabetes2013Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, nr 10, s. 3187-3194Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVEThe aim of this study was to elucidate whether subclinical nerve dysfunction as reflected by neurophysiological testing predicts the development of clinical neuropathy in patients with type 1 diabetes.RESEARCH DESIGN AND METHODSFifty-nine patients were studied twice with neurophysiological measurements at baseline and at follow-up. At baseline, patients were 15.5 3.22 years (range 7-22 years) of age, and duration of diabetes was 6.8 3.3 years. At follow-up, patients were 20-35 years of age, and disease duration was 20 +/- 5.3 years (range 10-31 years).RESULTSAt baseline, patients showed modestly reduced nerve conduction velocities and amplitudes compared with healthy subjects, but all were free of clinical neuropathy. At follow-up, clinical neuropathy was present in nine (15%) patients. These patients had a more pronounced reduction in peroneal motor nerve conduction velocity (MCV), median MCV, and sural sensory nerve action potential at baseline (P < 0.010-0.003). In simple logistic regression analyses, the predictor with the strongest association with clinical neuropathy was baseline HbA(1c) (R-2 = 48%, odds ratio 7.9, P < 0.002) followed by peroneal MCV at baseline (R-2 = 38%, odds ratio 0.6, P < 0.006). With the use of a stepwise forward analysis that included all predictors, first baseline HbA(1c) and then only peroneal MCV at baseline entered significantly (R-2 = 61%). Neuropathy impairment assessment showed a stronger correlation with baseline HbA(1c) ( = 0.40, P < 0.002) than with follow-up HbA(1c) ( = 0.034, P < 0.007).CONCLUSIONSEarly defects in nerve conduction velocity predict the development of diabetic neuropathy. However, the strongest predictor was HbA(1c) during the first years of the disease.

  • 27. Hyvärinen, Marjukka
    et al.
    Qiao, Qing
    Tuomilehto, Jaakko
    Laatikainen, Tiina
    Heine, Robert J
    Stehouwer, Coen D A
    Alberti, K George M M
    Pyörälä, Kalevi
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Stegmayr, Birgitta
    Hyperglycemia and stroke mortality: comparison between fasting and 2-h glucose criteria2009Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 32, nr 2, s. 348-354Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: We investigated stroke mortality in individuals in different categories of glycemia and compared hazard ratios (HRs) corresponding to a 1-SD increase in 2-h plasma glucose and fasting plasma glucose (FPG) criteria. RESEARCH DESIGN AND METHODS: We examined data from 2-h 75-g oral glucose tolerance tests taken from 13 European cohorts comprising 11,844 (55%) men and 9,862 (45%) women who were followed up for a median of 10.5 years. A multivariate adjusted Cox proportional hazards model was used to estimate HRs for stroke mortality. RESULTS: In men and women without a prior history of diabetes, multivariate adjusted HRs for stroke mortality corresponding to a 1-SD increase in FPG were 1.02 (95% CI 0.83-1.25) and 1.52 (1.22-1.88) and those in 2-h plasma glucose 1.21 (1.06-1.38) and 1.31 (1.06-1.61), respectively. Addition of 2-h plasma glucose to the model with FPG significantly improved prediction of stroke mortality in men (chi2 = 10.12; P = 0.001) but not in women (chi2 = 0.01; P = 0.94), whereas addition of FPG to 2-h plasma glucose improved stroke mortality in women (chi2 = 4.08; P = 0.04) but not in men (chi2 = 3.29; P = 0.07). CONCLUSIONS: Diabetes defined by either FPG or 2-h plasma glucose increases the risk of stroke mortality. In individuals without a history of diabetes, elevated 2-h postchallenge glucose is a better predictor than elevated fasting glucose in men, whereas the latter is better than the former in women.

  • 28.
    Ingelsson, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Circulating retinol-binding protein 4 and subclinical cardiovascular disease in the elderly2009Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 32, nr 4, s. 733-735Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: We evaluated associations of serum retinol-binding protein 4 (RBP4) with subclinical cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: Subclinical CVD was measured with echocardiography, carotid artery ultrasound, brachial artery ultrasound, and invasive forearm endothelial vasoreactivity in 1,008 70-year-old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. RESULTS: In analyses adjusted for multiple CVD risk factors, we observed inverse associations of RBP4 with carotid artery intima-media (beta -0.39, 95% CI -0.55 to -0.22) and plaque (beta -0.33, 95% CI -0.60 to -0.05) echogenicity (gray scale median). CONCLUSIONS: Circulating RBP4 concentrations were inversely associated with intima-media and plaque echogenicity in carotid arteries. These findings imply that RBP4 could be involved in the development of atherosclerosis.

  • 29.
    Jansson, Stefan P. O.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och klinisk epidemiologi.
    Andersson, Dan K. G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och klinisk epidemiologi.
    Svärdsudd, Kurt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och klinisk epidemiologi.
    Mortality Trends in Subjects With and Without Diabetes During 33 Years of Follow-up2010Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 33, nr 3, s. 551-556Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE - Mortality rates have declined substantially over the Past decades in the general population, but the situation among diabetic subjects is less clear. The aim of this study was to analyze mortality trends in diabetic and nondiabetic subjects during 1972-2004. RESEARCH DESIGN AND METHODS - Since 1972, all patients With diabetes are entered in a diabetes register at Laxa Primary Health Care Center; 776 incident cases were recorded Up to 2001. The register has been supplemented with a nondiabetic population of 3,880 subjects and with data from the National Cause of Death Register during 1972 to 2004. RESULTS - During the 33-year follow-up period, 233 (62.0%) diabetic women and 240 (60.0%) diabetic men and 995 (52.9%) nondiabetic women and 1,082 (54.1%) nondiabetic men died. The age-adjusted hazard ratio (HR) for all-cause mortality among diabetic and nondiabetic subjects was 1.17 (P < 0.0021) for all, 1.22 (P < 0.007) for women, and 1.13 (P = 0.095) for men. The corresponding cardiovascular disease (CVD) mortality HRs were 1.33 (P < 0.0001), 1.41 (P < 0.0003), and 1.27 (P < 0.0093), respectively. The CVD Mortality reduction across time was significant in nondiabetic subjects (P < 0.0001) and in men with diabetes (P = 0.014) but not in diabetic women (P = 0.69). The results regarding coronary heart disease (CHD) were similar (P < 0,0001, P < 0.006, and P = 0.17, respectively). The CVD and CHD mortality rate change across time was fairly linear in all groups. CONCLUSIONS - Diabetic subjects had less mortality rate reduction during follow-up than nondiabetic subjects. However the excess mortality risk for diabetic subjects was smaller than that found in Other Studies.

  • 30.
    Jansson, Stefan P.O.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Andersson, Dan K.G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Svärdsudd, Kurt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Mortality and cardiovascular outcomes in patients detected by screening or clinically diagnosed type 2 diabetes.: A 30-year follow-up study of 740 incident patients with type 2 diabetesIngår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    Screening for type 2 diabetes among high-risk subjects is recommended by many organizations. The aim of this study was to analyse all-cause mortality and cardiovascular disease (CVD) outcomes in type 2 diabetes subjects detected by screening and those clinically diagnosed during 30 years of follow-up.

    Research design and methods

    A diabetes register was established at the primary healthcare centre (PHCC) in Laxå, beginning in 1972 and based on data from clinical records with information on medical treatment and laboratory data as well as information on all-cause mortality, CVD, myocardial infarction (MI), and stroke events from National Registers. A total of 740 incident patients with type 2 diabetes were registered between 1972- 2001. In addition, case-finding procedures involving 85% of residents aged 35 to 79 were performed from 1983 onwards.

    Results

    Baseline characteristics showed a significantly higher CVD risk, mainly depending on more prevalent CVD events in the screened as compared with the clinically detected group (propensity score 0.59 vs. 0.46, p<0.0001). After a mean follow-up of 10 and 11.5 years for screening detected and clinically detected subjects respectively, HRs incidences were for all-cause mortality 1.01 (p=0.97), CVD 1.00 (p=0.99), and MI 1.03 (p=0.87). For stroke a 24% non-significant lower risk for screening detected as compared with clinically detected subjects were found, HR 0.76 (p=0.15).

    Conclusions

    No reduction in total mortality and CVD outcomes was found in type 2 diabetes subjects detected by screening as compared with those clinically diagnosed, even though stroke incidence tended to be lower.

  • 31.
    Jobs, Elisabeth
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Jobs, Magnus
    University of Dalarna.
    Nerpin, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Iggman, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Oxidativ stress och inflammation.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lars, Lind
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Serum cathepsin S is associated with decreased insulin sensitivity and the development of diabetes type 2 in a community-based cohort of elderly men2013Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, nr 1, s. 163-165Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes.

    RESEARCH DESIGN AND METHODS:

    Serum cathepsin S, insulin sensitivity (euglycemic-hyperinsulinemic clamp), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up.

    RESULTS:

    After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase -0.09 [95% CI -0.14 to -0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08-2.01], P = 0.01).

    CONCLUSIONS:

    Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.

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  • 32. Kalani, Majid
    et al.
    Apelqvist, Jan
    Blombäck, Margareta
    Brismar, Kerstin
    Eliasson, Björn
    Eriksson, Jan W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin diabetes och metabolism.
    Fagrell, Bengt
    Hamsten, Anders
    Torffvit, Ole
    Jörneskog, Gun
    Effect of dalteparin on healing of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease: a prospective, randomized, double-blind, placebo-controlled study.2003Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, nr 9, s. 2575-80Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Chronic foot ulcers are a common, severe, and expensive complication threatening life and limb in patients with diabetes. The aim of the present study was to investigate the effect of dalteparin on ulcer outcome in patients with diabetes, peripheral arterial occlusive disease, and chronic foot ulcers.

    RESEARCH DESIGN AND METHODS: A total of 87 patients were investigated in a prospective, randomized, double-blind, placebo-controlled trial. Participants were randomized to treatment with subcutaneous injection of 5000 units dalteparin (Fragmin, Pharmacia Corporation; n = 44) or an equivalent volume of physiological saline (n = 43) once daily until ulcer healing or for a maximum of 6 months. Ulcer outcome was investigated by evaluating the number of patients 1). who healed with intact skin; 2). in whom the study ulcer was improved, unchanged, or impaired; or 3). who were amputated above or below the ankle level, as compared with control subjects.

    RESULTS: Two patients, one on dalteparin and one on placebo, dropped out of the study. Ulcer outcome was significantly better (P = 0.042, two-sided chi(2) test for trend) in the dalteparin group (n = 43) compared with the placebo group (n = 42). A total of 29 patients healed with intact skin (n = 14) or decreased the ulcer area >or=50% (n = 15) in the dalteparin group compared with 20 (n = 9 and 11, respectively) in the placebo group. Five patients in each group showed impaired ulcer healing, i.e., the ulcer area increased >or=50%. Two patients in the dalteparin group were amputated compared with eight in the placebo group. Time to healing with intact skin was 17 +/- 8 weeks in the dalteparin group compared with 16 +/- 7 weeks in placebo group (NS).

    CONCLUSIONS: The results of the present study indicate that dalteparin improves the outcome of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease.

  • 33. Katoulis, E. C.
    et al.
    Ebdon-Parry, M.
    Lanshammar, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Reglerteknik.
    Vileikyte, L.
    Kulkarni, J.
    Boulton, A. J.
    Gait abnormalities in diabetic neuropathy1997Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 20, nr 12, s. 1904-1907Artikel i tidskrift (Refereegranskat)
  • 34.
    Kristofi, Robin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Bodegard, Johan
    AstraZeneca, Oslo, Norway..
    Norhammar, Anna
    Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden.;Capio St Goran Hosp, Stockholm, Sweden..
    Thuresson, Marcus
    Statisticon AB, Uppsala, Sweden..
    Nathanson, David
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Nystrom, Thomas
    Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden..
    Birkeland, Kare, I
    Univ Oslo, Oslo, Norway.;Oslo Univ Hosp, Oslo, Norway..
    Eriksson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Cardiovascular and Renal Disease Burden in Type 1 Compared With Type 2 Diabetes: A Two-Country Nationwide Observational Study2021Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 44, nr 5, s. 1211-1218Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE Type 1 diabetes (T1D) and type 2 diabetes (T2D) increase risks of cardiovascular (CV) and renal disease (CVRD) compared with diabetes-free populations. Direct comparisons between T1D and T2D are scarce. We examined this by pooling full-population cohorts in Sweden and Norway.

    RESEARCH DESIGN AND METHODS A total of 59,331 patients with T1D and 484,241 patients with T2D, aged 18-84 years, were followed over a mean period of 2.6 years from 31 December 2013. Patients were identified in nationwide prescribed drug and hospital registries in Norway and Sweden. Prevalence and event rates of myocardial infarction (MI), heart failure (HF), stroke, chronic kidney disease (CKD), all-cause death, and CV death were assessed following age stratification in 5-year intervals. Cox regression analyses were used to estimate risk.

    RESULTS The prevalence of CV disease was similar in T1D and T2D across age strata, whereas CKD was more common in T1D. Age-adjusted event rates comparing T1D versus T2D showed that HF risk was increased between ages 65 and 79 years, MI between 55 and 79 years, and stroke between 40 and 54 years (1.3-1.4-fold, 1.3-1.8-fold, and 1.4-1.7-fold, respectively). CKD risk was 1.4-3.0-fold higher in T1D at all ages. The all-cause death risk was 1.2-1.5-fold higher in T1D at age >50 years, with a similar trend for CV death.

    CONCLUSIONS Adult patients with T1D compared with those with T2D had an overall greater risk of cardiorenal disease (HF and CKD) across ages, MI and all-cause death at middle-older ages, and stroke at younger ages. The total age-adjusted CVRD burden and risks were greater among patients with T1D compared with those with T2D, highlighting their need for improved prevention strategies.

  • 35.
    Lai, Heidi T. M.
    et al.
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02155 USA.;Imperial Coll London, Dept Primary Care & Publ Hlth, London, England..
    Imamura, Fumiaki
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
    Korat, Andres V. Ardisson
    Harvard TH Chan Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA..
    Murphy, Rachel A.
    Univ British Columbia, Fac Med, Sch Populat & Publ Hlth, Vancouver, BC, Canada..
    Tintle, Nathan
    Dordt Univ, Dept Math & Stat, Sioux Ctr, IA USA.;Fatty Acid Res Inst, Sioux Falls, SD USA..
    Bassett, Julie K.
    Canc Council Victoria, Canc Epidemiol Div, Melbourne, Vic, Australia..
    Chen, Jiaying
    Brigham & Womens Hosp, Div Aging, Boston, MA USA..
    Kröger, Janine
    German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, Nuthetal, Germany..
    Chien, Kuo-Liong
    Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei, Taiwan..
    Senn, Mackenzie
    ARS, USDA, Childrens Nutr Res Ctr, Dept Pediat,Baylor Coll Med, Houston, TX USA..
    Wood, Alexis C.
    ARS, USDA, Childrens Nutr Res Ctr, Dept Pediat,Baylor Coll Med, Houston, TX USA..
    Forouhi, Nita G.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
    Schulze, Matthias B.
    German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, Nuthetal, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Univ Potsdam, Inst Nutr Sci, Nuthetal, Germany..
    Harris, William S.
    Fatty Acid Res Inst, Sioux Falls, SD USA.;Univ South Dakota, Sanford Sch Med, Dept Internal Med, Sioux Falls, SD USA..
    Vasan, Ramachandran S.
    Boston Univ, Sch Med, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Hu, Frank
    Harvard TH Chan Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA..
    Giles, Graham G.
    Canc Council Victoria, Canc Epidemiol Div, Melbourne, Vic, Australia.;Univ Melbourne, Ctr Epidemiol & Biostat, Parkville, Vic, Australia.;Monash Univ, Sch Clin Sci Monash Hlth, Precis Med, Clayton, Vic, Australia..
    Hodge, Allison
    Canc Council Victoria, Canc Epidemiol Div, Melbourne, Vic, Australia..
    Djousse, Luc
    Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA USA..
    Brouwer, Ingeborg A.
    Vrije Univ Amsterdam, Fac Sci, Amsterdam Publ Hlth Res Inst, Dept Hlth Sci, Amsterdam, Netherlands..
    Qian, Frank
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA..
    Sun, Qi
    Harvard TH Chan Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA..
    Wu, Jason H. Y.
    Univ New South Wales, Fac Med, George Inst Global Hlth, Sydney, NSW, Australia..
    Marklund, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02155 USA; Univ New South Wales, Fac Med, George Inst Global Hlth, Sydney, NSW, Australia.
    Lemaitre, Rozenn N.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA..
    Siscovick, David S.
    New York Acad Med, New York, NY USA..
    Fretts, Amanda M.
    Univ Washington, Dept Epidemiol, Sch Publ Hlth, Cardiovasc Hlth Res Unit, Seattle, WA USA..
    Shadyab, Aladdin H.
    Univ Calif San Diego, Sch Med, Family Med & Publ Hlth, La Jolla, CA 92093 USA..
    Manson, JoAnn E.
    Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA.;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Howard, Barbara, V
    Georgetown Univ, Med Ctr, Hyattsville, MD USA..
    Robinson, Jennifer G.
    Univ Iowa, Iowa City, IA USA..
    Wallace, Robert B.
    Univ Iowa, Iowa City, IA USA..
    Wareham, Nick J.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
    Chen, Yii-Der Ida
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, Lundquist Inst Biomed Innovat, Torrance, CA USA..
    Rotter, Jerome, I
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, Lundquist Inst Biomed Innovat, Torrance, CA USA..
    Tsai, Michael Y.
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA..
    Micha, Renata
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02155 USA..
    Mozaffarian, Dariush
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02155 USA..
    Trans Fatty Acid Biomarkers and Incident Type 2 Diabetes: Pooled Analysis of 12 Prospective Cohort Studies in the Fatty Acids and Outcomes Research Consortium (FORCE)2022Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 45, nr 4, s. 854-863Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis.

    RESEARCH DESIGN AND METHODS: We included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged >= 18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics.

    RESULTS: During a mean follow-up of 13.5 years, 2,843 cases of incident T2D were identified. In multivariable-adjusted pooled analyses, no significant associations with T2D were identified for trans/trans-18:2, relative risk (RR) 1.09 (95% CI 0.94-1.25); cis/trans-18:2, 0.89 (0.73-1.07); and trans/cis-18:2, 0.87 (0.73-1.03). Trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated with T2D (RR 0.81 [95% CI 0.67-0.99], 0.86 [0.75-0.99], and 0.84 [0.74-0.96], respectively). Findings were not significantly different according to prespecified sources of potential heterogeneity (each P >= 0.1).

    CONCLUSIONS: Circulating individual trans-18:2 TFA biomarkers were not associated with risk of T2D, while trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated. Findings may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), a general decline in TFA exposure due to policy changes during this period, or the relatively limited range of TFA levels.

  • 36. Larsson, S C
    et al.
    Giovannucci, E
    Wolk, A
    Diabetes and colorectal cancer incidence in the cohort of Swedish men2005Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 28, nr 7, s. 1805-1807Artikel i tidskrift (Refereegranskat)
  • 37. Latva-Rasku, Aino
    et al.
    Honka, Miikka-Juhani
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Mononen, Nina
    Lehtimäki, Terho
    Saltevo, Juha
    Kirjavainen, Anna K
    Saunavaara, Virva
    Iozzo, Patricia
    Johansson, Lars
    Oscarsson, Jan
    Hannukainen, Jarna C
    Nuutila, Pirjo
    The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity: A Randomized, Double-Blind, Placebo-Controlled Study With 8-Week Treatment in Type 2 Diabetes Patients.2019Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 42, nr 5, s. 931-937Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aim of this study was to investigate tissue-specific effects of dapagliflozin on insulin sensitivity and liver and body fat in patients with type 2 diabetes.

    RESEARCH DESIGN AND METHODS: This randomized, double-blind, parallel group, placebo-controlled study recruited 32 patients with type 2 diabetes. Enrolled patients were to have HbA1c 6.5-10.5% (48-91 mmol/mol) and ≥3 months of stable treatment with metformin, dipeptidyl peptidase 4 inhibitor, or their combination. Patients were randomized 1:1 to receive 10 mg dapagliflozin or placebo daily for 8 weeks. Before and after the intervention, tissue insulin sensitivity was measured using [18F]-fluorodeoxyglucose and positron emission tomography during hyperinsulinemic-euglycemic clamp. Liver proton density fat fraction (PDFF) and adipose tissue volumes were assessed using MRI, and blood biomarkers were analyzed.

    RESULTS: After 8 weeks, glycemic control was improved by dapagliflozin (placebo-corrected change in HbA1c -0.39%, P < 0.01), but whole-body glucose uptake was not increased (P = 0.90). Tissue-specific insulin-stimulated glucose uptake did not change in skeletal muscle, liver, myocardium, or white and brown adipose tissue, and endogenous glucose production remained unaffected. However, there were significant placebo-corrected decreases in liver PDFF (-3.74%, P < 0.01), liver volume (-0.10 L, P < 0.05), visceral adipose tissue volume (-0.35 L, P < 0.01), interleukin-6 (-1.87 pg/mL, P < 0.05), and N-terminal prohormone of brain natriuretic peptide (-96 ng/L, P = 0.03).

    CONCLUSIONS: In this study, 8 weeks of treatment with dapagliflozin reduced liver PDFF and the volume of visceral adipose tissue in obese patients with type 2 diabetes. Although glycemic control was improved, no effect on tissue-level insulin sensitivity was observed.

  • 38. Lee, Duk-Hee
    et al.
    Lind, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Jacobs, David R
    Salihovic, Samira
    van Bavel, Bert
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Polychlorinated biphenyls and organochlorine pesticides in plasma predict development of type 2 diabetes in the elderly: the prospective investigation of the vasculature in Uppsala Seniors (PIVUS) study2011Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, nr 8, s. 1778-1784Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Persistent organic pollutants (POPs), lipophilic chemicals that accumulate mainly in adipose tissue, have recently been linked to type 2 diabetes. However, evidence from prospective studies is sparse. This study was performed to evaluate prospective associations of type 2 diabetes with selected POPs among the elderly.

    RESEARCH DESIGN AND METHODS: Nineteen POPs (14 polychlorinated biphenyl [PCB] congeners, 3 organochlorine pesticides, 1 brominated diphenyl ether, and 1 dioxin) were measured in plasma collected at baseline in 725 participants, aged 70 years, of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS).

    RESULTS: After adjusting for known type 2 diabetes risk factors, including obesity, odds ratios (ORs) (95% CIs) for type 2 diabetes at age 75 years (n = 36) according to the quintiles of a summary measure of concentrations of PCBs (vs. the lowest quintile) were 4.5, 5.1, 8.8 (1.8-42.7), and 7.5 (1.4-38.8) (P(trend) <0.01). Among organochlorine pesticides, adjusted ORs across concentrations of trans-nonachlor showed that P(trend) = 0.03. Adjusted ORs (95% CIs) across quintiles of the sum of three organochlorine pesticides were 1.1, 1.6, 1.5, and 3.4 (1.0-11.7) (P(trend) = 0.03). Neither brominated diphenyl ether 47 nor dioxin was significantly associated with incident diabetes. The sum of PCBs improved reclassification significantly when added to traditional risk factors for diabetes.

    CONCLUSIONS: Despite the small number of incident cases, this study found that environmental exposure to some POPs substantially increased risk of future type 2 diabetes in an elderly population.

  • 39.
    Lind, Marcus
    et al.
    Univ Gothenburg, Dept Mol & Clin Med, Gothenburg, Sweden.;NU Hosp Grp, Dept Med, Uddevalla, Sweden..
    Olafsdottir, Arndis F.
    Univ Gothenburg, Dept Mol & Clin Med, Gothenburg, Sweden.;NU Hosp Grp, Dept Med, Uddevalla, Sweden..
    Hirsch, Irl B.
    Univ Washington, Sch Med, Seattle, WA USA..
    Bolinder, Jan
    Karolinska Univ, Karolinska Inst, Dept Med, Hosp Huddinge, Stockholm, Sweden..
    Dahlqvist, Sofia
    Univ Gothenburg, Dept Mol & Clin Med, Gothenburg, Sweden..
    Pivodic, Aldina
    Stat Konsultgrp, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci, Gothenburg, Sweden..
    Hellman, Jarl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Wijkman, Magnus
    Linköping Univ, Dept Internal Med, Norrköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Norrköping, Sweden..
    Schwarcz, Erik
    Örebro Univ, Fac Med & Hlth, Dept Internal Med, Örebro, Sweden..
    Albrektsson, Henrik
    Stat Konsultgrp, Gothenburg, Sweden..
    Heise, Tim
    Profil, Neuss, Germany..
    Polonsky, William
    Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.;Behav Diabet Inst, San Diego, CA USA..
    Sustained Intensive Treatment and Long-term Effects on HbA(1c) Reduction (SILVER Study) by CGM in People With Type 1 Diabetes Treated With MDI2021Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 44, nr 1, s. 141-149Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Continuous glucose monitoring (CGM) reduces HbA(1c) and time spent in hypoglycemia in people with type 1 diabetes (T1D) treated with multiple daily insulin injections (MDI) when evaluated over shorter time periods. It is unclear to what extent CGM improves and helps to maintain glucose control, treatment satisfaction, diabetes distress, hypoglycemic concerns, and overall well-being over longer periods of time.

    RESEARCH DESIGN AND METHODS: The GOLD trial was a randomized crossover trial performed over 16 months of CGM treatment in people with T1D treated with MDI. People completing the trial (n = 141) were invited to participate in the current SILVER extension study in which 107 patients continued CGM treatment over 1 year along with the support of a diabetes nurse every 3 months.

    RESULTS: The primary end point of the change in HbA(1c) over 1.0-1.5 years of CGM use compared with previous self-monitoring of blood glucose during GOLD showed a decrease in HbA(1c) of 0.35% (95% CI 0.19-0.50, P < 0.001). Time spent in hypoglycemia <3.0 mmol/L (54 mg/dL) and <4.0 mmol/L (72 mg/dL) decreased from 2.1% to 0.6% (P < 0.001) and from 5.4% to 2.9% (P < 0.001), respectively. Overall well-being (World Health Organization 5-item well-being index, P = 0.009), treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire, P < 0.001), and hypoglycemic confidence (P < 0.001) increased, while hypoglycemic fear (Hypoglycemia Fear Survey-Worry, P = 0.016) decreased and diabetes distress tended to decrease (Problem Areas in Diabetes Scale, P = 0.06). From randomization and screening in GOLD, HbA(1c) was lowered by 0.45% (P < 0.001) and 0.68% (P < 0.001) after 2.3 and 2.5 years, respectively.

    CONCLUSIONS: The SILVER study supports beneficial long-term effects from CGM on HbA(1c), hypoglycemia, treatment satisfaction, well-being, and hypoglycemic confidence in people with T1D managed with MDI.

  • 40.
    Lind, P. Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Circulating Levels of Phthalate Metabolites Are Associated With Prevalent Diabetes in the Elderly2012Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 35, nr 7, s. 1519-1524Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE-Phthalates are ubiquitous industrial high-volume chemicals known as ligands to peroxisome proliferator activated receptors (PPARs). Because PPAR-gamma agonists modulate insulin sensitivity and are used to treat type 2 diabetes, we investigated whether circulating levels of phthalate metabolites are related to prevalent type 2 diabetes. RESEARCH DESIGN AND METHODS-A total of 1,016 subjects, aged 70 years, were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors Study. Four phthalate metabolites were detected in almost all participant sera by an API 4000 liquid chromatograph/tandem mass spectrometer. Type 2 diabetes was defined as the use of pharmacological hypoglycemic agents or a fasting plasma glucose >7.0 mmol/L. RESULTS-A total of 114 subjects were shown to have diabetes. Following adjustment for sex, BMI, serum cholesterol and triglycerides, educational level, and smoking and exercise habits, high levels of the phthalate metabolites monomethyl phthalate (MMP) (P < 0.01), monoisobutyl phthalate (MiBP) (P < 0.05), and monoethyl phthalate (MEP) (P < 0.05), but not mono(2-ethylhexyl) phthalate, were associated with an increased prevalence of diabetes. Using the fasting proinsulin to insulin ratio as a marker of insulin secretion and the homeostasis model assessment-insulin resistance index as a marker of insulin resistance, MiBP was mainly related to poor insulin secretion, whereas MEP and MMP mainly were related to insulin resistance. CONCLUSIONS-The findings in this cross-sectional study showed that several phthalate metabolites are related to diabetes prevalence, as well as to markers of insulin secretion and resistance. These findings support the view that these commonly used chemicals might influence major factors that are regulating glucose metabolism in humans at the level of exposure of phthalate metabolites seen in the general elderly population.

  • 41. Littorin, B
    et al.
    Sundkvist, G
    Hagopian, W
    Landin-Olsson, M
    Lernmark, A
    Ostman, J
    Arnqvist, H J
    Blohmé, G
    Bolinder, J
    Eriksson, Jan W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin diabetes och metabolism.
    Lithner, F
    Scherstén, B
    Wibell, L
    Islet cell and glutamic acid decarboxylase antibodies present at diagnosis of diabetes predict the need for insulin treatment. A cohort study in young adults whose disease was initially labeled as type 2 or unclassifiable diabetes.1999Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 22, nr 3, s. 409-12Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To clarify the predictive value of islet cell antibody (ICA) and GAD65 antibody (GADA) present at diagnosis with respect to the need for insulin treatment 6 years after diagnosis in young adults initially considered to have type 2 or unclassifiable diabetes.

    RESEARCH DESIGN AND METHODS: The patient material was representative of the entire Swedish population, consisting of patients who were 15-34 years old at diagnosis of diabetes in 1987-1988 but were not considered to have type 1 diabetes at onset. At follow-up, 6 years after the diagnosis, it was noted whether the patient was treated with insulin. The presence of ICA was determined by an immunofluorescence assay, and GADAs were measured by a radioligand assay.

    RESULTS: Six years after diagnosis, 70 of 97 patients were treated with insulin, and 27 of 97 patients were treated with oral drugs or diet alone. At diagnosis, ICAs and GADAs were present in 41 (59%) of 70 patients and 41 (60%) of 68 patients, respectively, of those now treated with insulin, compared with only 1 (4%) of 26 patients and 2 (7%) of 27 patients who were still not treated with insulin. For either ICA or GADA, the corresponding frequencies were 50 (74%) of 68 for patients who were later treated with insulin and 3 (12%) of 26 for those who were still not treated with insulin, respectively. The sensitivity for later insulin treatment was highest (74%) for the presence of ICA or GADA, and the specificity was highest (100%) for ICA and GADA. The positive predictive value was 100% for the combination of ICA and GADA, 98% for ICA alone, and approximately 95% for GADA alone.

    CONCLUSIONS: Determination of the presence of ICA and GADA at diagnosis of diabetes improves the classification of diabetes and predicts the future need of insulin in young adults.

  • 42. Littorin, B
    et al.
    Sundkvist, G
    Hagopian, W
    Landin-Olsson, M
    Lernmark, A
    Ostman, J
    Arnqvist, HJ
    Blohme, G
    Bolinder, J
    Eriksson, Jan W.
    Lithner, F
    Schersten, B
    Wibell, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Islet cell and glutamic acid decarboxylase antibodies present at diagnosis of diabetes predict the need for insulin treatment: A cohort study in young adults whose disease was initially labeled as type 2 or unclassifiable diabetes1999Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 22, nr 3, s. 409-412Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    To clarify the predictive value of islet cell antibody (ICA) and GAD65 antibody (GADA) present at diagnosis with respect to the need for insulin treatment 6 years after diagnosis in young adults initially considered to have type 2 or unclassifiable diabetes.

    RESEARCH DESIGN AND METHODS:

    The patient material was representative of the entire Swedish population, consisting of patients who were 15-34 years old at diagnosis of diabetes in 1987-1988 but were not considered to have type 1 diabetes at onset. At follow-up, 6 years after the diagnosis, it was noted whether the patient was treated with insulin. The presence of ICA was determined by an immunofluorescence assay, and GADAs were measured by a radioligand assay.

    RESULTS:

    Six years after diagnosis, 70 of 97 patients were treated with insulin, and 27 of 97 patients were treated with oral drugs or diet alone. At diagnosis, ICAs and GADAs were present in 41 (59%) of 70 patients and 41 (60%) of 68 patients, respectively, of those now treated with insulin, compared with only 1 (4%) of 26 patients and 2 (7%) of 27 patients who were still not treated with insulin. For either ICA or GADA, the corresponding frequencies were 50 (74%) of 68 for patients who were later treated with insulin and 3 (12%) of 26 for those who were still not treated with insulin, respectively. The sensitivity for later insulin treatment was highest (74%) for the presence of ICA or GADA, and the specificity was highest (100%) for ICA and GADA. The positive predictive value was 100% for the combination of ICA and GADA, 98% for ICA alone, and approximately 95% for GADA alone.

    CONCLUSIONS:

    Determination of the presence of ICA and GADA at diagnosis of diabetes improves the classification of diabetes and predicts the future need of insulin in young adults.

  • 43. Littorin, B
    et al.
    Sundkvist, G
    Nyström, L
    Carlson, A
    Landin-Olsson, M
    Ostman, J
    Arnqvist, H J
    Björk, E
    Blohmé, G
    Bolinder, J
    Eriksson, Jan W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin diabetes och metabolism.
    Scherstén, B
    Wibell, L
    Family characteristics and life events before the onset of autoimmune type 1 diabetes in young adults: a nationwide study.2001Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 24, nr 6, s. 1033-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To elucidate whether family characteristics and stressful life events were associated with onset of autoimmune type 1 diabetes in young adults.

    RESEARCH DESIGN AND METHODS: This investigation was based on a nationwide study (Diabetes Incidence Study in Sweden) of newly diagnosed patients aged 15-34 years. Patients clinically classified as type 1 diabetic with antibodies to islet cells and/or to GAD65 were compared with age- and sex-matched control subjects via questionnaire. The questionnaire covered diabetes heredity, social environment, educational level, and life events experienced during the 12 months before diagnosis.

    RESULTS: The rate of response was 82% for the diabetic patients and 65% for the control subjects. Questionnaires from 349 diabetic patients and 979 control subjects were considered. Diabetes in relatives was more frequent in the patients (odds ratio [OR]2.6) who were born in Sweden and whose mothers were of Swedish origin. No major stress factors were detected in the diabetic patients; however, in comparison with the control subjects, the diabetic patients had experienced fewer conflicts with their parents and had less often broken contacts with friends.

    CONCLUSIONS: Young adults with recent-onset type 1 diabetes were more exposed to heredity for diabetes, but no major prediabetic stress factors were detected. Our study does not directly support the concept that psychosocial stressful life events are involved in the development of autoimmune type 1 diabetes in young adults.

  • 44.
    Lorenz, Matthias W.
    et al.
    Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany..
    Price, Jackie F.
    Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland..
    Robertson, Christine
    Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland..
    Bots, Michiel L.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Polak, Joseph F.
    Tufts Univ, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA..
    Poppert, Holger
    Tech Univ Munich, Univ Hosp, Dept Neurol, D-80290 Munich, Germany..
    Kavousi, Maryam
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Doerr, Marcus
    Greifswald Univ Clin, Dept Internal Med Cardiol B, Greifswald, Germany..
    Stensland, Eva
    Univ Tromso, Dept Clin Med, Tromso, Norway..
    Ducimetiere, Pierre
    Univ Paris 11, Paris, France..
    Ronkainen, Kimmo
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Kiechl, Stefan
    Med Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria..
    Sitzer, Matthias
    Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany.;Klinikum Herford, Dept Neurol, Herford, Germany..
    Rundek, Tatjana
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Liu, Jing
    Inst Heart Lung & Blood Vessel Dis, Dept Epidemiol, Beijing, Peoples R China..
    Bergstrom, Goran
    Univ Gothenburg, Wallenberg Lab Cardiovasc Res, Gothenburg, Sweden..
    Grigore, Liliana
    Bassini Hosp, SISA Ctr Study Atherosclerosis, Cinisello Balsamo, Italy.;IRCCS MultiMed, Milan, Italy..
    Bokemark, Lena
    Univ Gothenburg, Wallenberg Lab Cardiovasc Res, Gothenburg, Sweden..
    Friera, Alfonsa
    Univ Autonoma Madrid, Hosp Univ la Princesa, Dept Radiol, Madrid, Spain..
    Yanez, David
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Bickel, Horst
    Tech Univ Munich, Univ Hosp, Dept Psychiat, D-80290 Munich, Germany..
    Ikram, M. Arfan
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Voelzke, Henry
    Ernst Moritz Arndt Univ Greifswald, SHIP Clin Epidemiol Res, Inst Community Med, Greifswald, Germany.;German Ctr Cardiovasc Res, Greifswald, Germany..
    Johnsen, Stein Harald
    Univ Tromso, Dept Clin Med, Tromso, Norway.;Univ Hosp Northern Norway, Dept Neurol & Neurophysiol, Tromso, Norway..
    Empana, Jean Philippe
    INSERM U970, Paris, France..
    Tuomainen, Tomi-Pekka
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Willeit, Peter
    Med Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England..
    Steinmetz, Helmuth
    Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany..
    Desvarieux, Moise
    Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.;Ecole Hautes Etud Sante Publ, Paris, France.;INSERM U738, Paris, France..
    Xie, Wuxiang
    Inst Heart Lung & Blood Vessel Dis, Dept Epidemiol, Beijing, Peoples R China..
    Schmidt, Caroline
    Univ Gothenburg, Wallenberg Lab Cardiovasc Res, Gothenburg, Sweden..
    Norata, Giuseppe D.
    Bassini Hosp, SISA Ctr Study Atherosclerosis, Cinisello Balsamo, Italy.;Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy..
    Suarez, Carmen
    Univ Autonoma Madrid, Hosp Univ la Princesa, Dept Internal Med, Madrid, Spain..
    Sander, Dirk
    Tech Univ Munich, Univ Hosp, Dept Neurol, D-80290 Munich, Germany.;Benedictus Hosp Tutzing & Feldafing, Dept Neurol, Feldafing, Germany..
    Hofman, Albert
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA..
    Schminke, Ulf
    Greifswald Univ Clin, Dept Neurol, Greifswald, Germany..
    Mathiesen, Ellisiv
    Univ Tromso, Dept Clin Med, Tromso, Norway.;Univ Hosp Northern Norway, Dept Neurol & Neurophysiol, Tromso, Norway..
    Plichart, Matthieu
    INSERM U970, Paris, France.;Broca Hosp, Gerontol Dept, Paris, France..
    Kauhanen, Jussi
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Willeit, Johann
    Med Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria..
    Sacco, Ralph L.
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA..
    McLachlan, Stela
    Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland..
    Zhao, Dong
    Inst Heart Lung & Blood Vessel Dis, Dept Epidemiol, Beijing, Peoples R China..
    Fagerberg, Bjorn
    Univ Gothenburg, Wallenberg Lab Cardiovasc Res, Gothenburg, Sweden..
    Catapano, Alberico L.
    IRCCS MultiMed, Milan, Italy.;Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy..
    Gabriel, Rafael
    Univ Autonoma Madrid, Hosp Univ La Paz, Inst Invest IdiPAZ, Madrid, Spain..
    Franco, Oscar H.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Buelbuel, Alpaslan
    Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany..
    Scheckenbach, Frank
    Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany..
    Pflug, Anja
    Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany..
    Gao, Lu
    Inst Publ Hlth, MRC, Biostat Unit, Cambridge, England..
    Thompson, Simon G.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England..
    Carotid Intima-Media Thickness Progression and Risk of Vascular Events in People With Diabetes: Results From the PROG-IMT Collaboration2015Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 38, nr 10, s. 1921-1929Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVECarotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes.RESEARCH DESIGN AND METHODSIn a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis.RESULTSAverage mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08).CONCLUSIONSDespite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.

  • 45.
    Maffi, Paola
    et al.
    IRCCS Osped San Raffaele, San Raffaele Diabet Res Inst, Milan, Italy.
    Lundgren, Torbjorn
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Karolinska, Sweden.
    Tufveson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Rafael, Ehab
    Skane Univ Hosp, Malmo, Sweden.
    Shaw, James A. M.
    Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England;Newcastle Upon Tyne Hosp NHS Fdn Trust, Freeman Hosp, Newcastle Upon Tyne, Tyne & Wear, England.
    Liew, Aaron
    Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England;Newcastle Upon Tyne Hosp NHS Fdn Trust, Freeman Hosp, Newcastle Upon Tyne, Tyne & Wear, England.
    Saudek, Frantisek
    Inst Clin & Expt Med, Prague, Czech Republic.
    Witkowski, Piotr
    Univ Chicago Med, Transplantat Inst, Chicago, IL USA.
    Golab, Karolina
    Univ Chicago Med, Transplantat Inst, Chicago, IL USA.
    Bertuzzi, Federico
    Osped Niguarda Ca Granda, Milan, Italy.
    Gustafsson, Bengt
    Univ Gothenburg, Gothenburg, Sweden.
    Daffonchio, Luisa
    Dompe Farmaceut SpA, Dept Res & Dev, Milan, Italy.
    Ruffini, Pier Adelchi
    Dompe Farmaceut SpA, Dept Res & Dev, Milan, Italy.
    Piemonti, Lorenzo
    IRCCS Osped San Raffaele, San Raffaele Diabet Res Inst, Milan, Italy.
    Nano, Rita
    IRCCS Osped San Raffaele, Milan, Italy.
    Mercalli, Alessia
    IRCCS Osped San Raffaele, Milan, Italy.
    Lampasona, Vito
    IRCCS Osped San Raffaele, Milan, Italy.
    Magistretti, Paola
    IRCCS Osped San Raffaele, Milan, Italy.
    Sordi, Valeria
    IRCCS Osped San Raffaele, Milan, Italy.
    Antonio, Secchi
    IRCCS Osped San Raffaele, Milan, Italy.
    Antonioli, Barbara
    Osped Niguarda Ca Granda, Milan, Italy.
    Galuzzi, Marta
    Osped Niguarda Ca Granda, Milan, Italy.
    Tosca, Marta Cecilia
    Osped Niguarda Ca Granda, Milan, Italy.
    De Carlis, Luciano
    Osped Niguarda Ca Granda, Milan, Italy.
    Colussi, Giacomo
    Osped Niguarda Ca Granda, Milan, Italy.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Pollard, Helena
    Skane Univ Hosp, Malmo, Sweden.
    Targeting CXCR1/2 Does Not Improve Insulin Secretion After Pancreatic Islet Transplantation: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial in Type 1 Diabetes2020Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 43, nr 4, s. 710-718Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients.

    RESEARCH DESIGN AND METHODS: A phase 3, multicenter, randomized, double-blind, parallel-assignment study () was conducted in recipients of islet allotransplants randomized (2:1) to reparixin or placebo in addition to immunosuppression. Primary outcome was the area under the curve (AUC) for C-peptide during the mixed-meal tolerance test at day 75 +/- 5 after the first and day 365 +/- 14 after the last transplant. Secondary end points included insulin independence and standard measures of glycemic control.

    RESULTS: The intention-to-treat analysis did not show a significant difference in C-peptide AUC at both day 75 (27 on reparixin vs. 18 on placebo, P = 0.99) and day 365 (24 on reparixin vs. 15 on placebo, P = 0.71). There was no statistically significant difference between treatment groups at any time point for any secondary variable. Analysis of patient subsets showed a trend for a higher percentage of subjects retaining insulin independence for 1 year after a single islet infusion in patients receiving reparixin as compared with patients receiving placebo (26.7% vs. 0%, P = 0.09) when antithymocyte globulin was used as induction immunosuppression.

    CONCLUSIONS: In this first double-blind randomized trial, islet transplantation data obtained with reparixin do not support a role of CXCR1/2 inhibition in preventing islet inflammation-mediated damage.

  • 46. Nerpin, Elisabet
    et al.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jobs, Magnus
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Arnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Insulin sensitivity measured with euglycemic clamp is independently associated with glomerular filtration rate in a community-based cohort2008Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, nr 8, s. 1550-1555Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR. RESEARCH DESIGN AND METHODS: We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic clamp) and cystatin C-based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1,070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years. RESULTS: Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19 [95% CI 0.69-1.68]; P < 0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, and 2-h glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, and smoking), and lifestyle factors (BMI, physical activity, and consumption of tea, coffee, and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR also remained statistically significant in participants with normal fasting plasma glucose, normal glucose tolerance, and normal GFR (n = 443; P < 0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR <50 ml/min per 1.73 m(2)) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58 [95% CI 0.40-0.84]; P < 0.004). CONCLUSIONS: Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, before the onset of diabetes or prediabetic glucose elevations. Further studies are needed in order to establish causality.

  • 47. Nettleton, Jennifer A
    et al.
    McKeown, Nicola M
    Kanoni, Stavroula
    Lemaitre, Rozenn N
    Hivert, Marie-France
    Ngwa, Julius
    van Rooij, Frank J A
    Sonestedt, Emily
    Wojczynski, Mary K
    Ye, Zheng
    Tanaka, Tosh
    Garcia, Melissa
    Anderson, Jennifer S
    Follis, Jack L
    Djousse, Luc
    Mukamal, Kenneth
    Papoutsakis, Constantina
    Mozaffarian, Dariush
    Zillikens, M Carola
    Bandinelli, Stefania
    Bennett, Amanda J
    Borecki, Ingrid B
    Feitosa, Mary F
    Ferrucci, Luigi
    Forouhi, Nita G
    Groves, Christopher J
    Hallmans, Goran
    Harris, Tamara
    Hofman, Albert
    Houston, Denise K
    Hu, Frank B
    Johansson, Ingegerd
    Kritchevsky, Stephen B
    Langenberg, Claudia
    Launer, Lenore
    Liu, Yongmei
    Loos, Ruth J
    Nalls, Michael
    Orho-Melander, Marju
    Renstrom, Frida
    Rice, Kenneth
    Riserus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Rolandsson, Olov
    Rotter, Jerome I
    Saylor, Georgia
    Sijbrands, Eric J G
    Sjögren, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Smith, Albert
    Steingrímsdóttir, Laufey
    Uitterlinden, André G
    Wareham, Nicholas J
    Prokopenko, Inga
    Pankow, James S
    van Duijn, Cornelia M
    Florez, Jose C
    Witteman, Jacqueline C M
    Dupuis, Josée
    Dedoussis, George V
    Ordovas, Jose M
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Cupples, L Adrienne
    Siscovick, David S
    Franks, Paul W
    Meigs, James B
    Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies2010Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 33, nr 12, s. 2684-2691Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin.

    RESEARCH DESIGN AND METHODS:

    Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically significant.

    RESULTS:

    Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P < 0.0001 and -0.011 pmol/l [ln] insulin [-0.015 to -0.007], P = 0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele.

    CONCLUSIONS:

    Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.

  • 48. Nilsson, Peter M.
    et al.
    Cederholm, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Diabetes, Hypertension, and Outcome Studies: Overview 20102011Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, s. S109-S113Artikel i tidskrift (Refereegranskat)
  • 49. Nowicka, Paulina
    et al.
    Santoro, Nicola
    Liu, Haibei
    Lartaud, Derek
    Shaw, Melissa
    Goldberg, Rachel
    Guandalini, Cindy
    Savoye, Mary
    Rose, Paulina
    Sonia, Caprio
    Utility of Hemoglobin A1c for Diagnosing Prediabetes and Diabetes in Obese Children and Adolescents2011Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, nr 6, s. 1306-1311Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE—Hemoglobin A1c (A1C) has emerged as a recommended diagnostic tool for identifying diabetes and subjects at risk for the disease. This recommendation is based on data in adults showing the relationship between A1C with future development of diabetes and microvascular complications. However, studies in the pediatric population are lacking.

    RESEARCH DESIGN AND METHODS—We studied a multiethnic cohort of 1,156 obese children and adolescents without a diagnosis of diabetes (male, 40%/female, 60%). All subjects underwent an oral glucose tolerance test (OGTT) and A1C measurement. These tests were repeated after a follow-up time of ;2 years in 218 subjects.

    RESULTS—At baseline, subjects were stratified according to A1C categories: 77% with normal glucose tolerance (A1C,5.7%), 21% at risk for diabetes (A1C 5.7–6.4%), and 1% with diabetes (A1C .6.5%). In the at risk for diabetes category, 47% were classified with prediabetes or diabetes, and in the diabetes category, 62% were classified with type 2 diabetes by the OGTT. The area under the curve receiver operating characteristic for A1C was 0.81 (95%CI 0.70–0.92). The threshold for identifying type 2 diabetes was 5.8%, with 78% specificity and 68% sensitivity. In the subgroup with repeated measures, a multivariate analysis showed that the strongest predictors of 2-h glucose at follow-up were baseline A1C and 2-h glucose, independently of age, ethnicity, sex, fasting glucose, and follow-up time.

    CONCLUSIONS—The American Diabetes Association suggested that an A1C of 6.5% underestimates the prevalence of prediabetes and diabetes in obese children and adolescents. Given the low sensitivity and specificity, the use of A1C by itself represents a poor diagnostic tool for prediabetes and type 2 diabetes in obese children and adolescents.

  • 50. Nyberg, Solja T.
    et al.
    Fransson, Eleonor I.
    Heikkila, Katriina
    Ahola, Kirsi
    Alfredsson, Lars
    Bjorner, Jakob B.
    Borritz, Marianne
    Burr, Hermann
    Dragano, Nico
    Goldberg, Marcel
    Hamer, Mark
    Jokela, Markus
    Knutsson, Anders
    Koskenvuo, Markku
    Koskinen, Aki
    Kouvonen, Anne
    Leineweber, Constanze
    Madsen, Ida E. H.
    Hanson, Linda L. Magnusson
    Marmot, Michael G.
    Nielsen, Martin L.
    Nordin, Maria
    Oksanen, Tuula
    Pejtersen, Jan H.
    Pentti, Jaana
    Rugulies, Reiner
    Salo, Paula
    Siegrist, Johannes
    Steptoe, Andrew
    Suominen, Sakari
    Theorell, Tores
    Vaananen, Ari
    Vahtera, Jussi
    Virtanen, Marianna
    Westerholm, Peter J. M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Westerlund, Hugo
    Zins, Marie
    Batty, G. David
    Brunner, Eric J.
    Ferrie, Jane E.
    Singh-Manoux, Archana
    Kivimaki, Mika
    Job Strain as a Risk Factor for Type 2 Diabetes: A Pooled Analysis of 124,808 Men and Women2014Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 37, nr 8, s. 2268-2275Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE The status of psychosocial stress at work as a risk factor for type 2 diabetes is unclear because existing evidence is based on small studies and is subject to confounding by lifestyle factors, such as obesity and physical inactivity. This collaborative study examined whether stress at work, defined as "job strain," is associated with incident type 2 diabetes independent of lifestyle factors. RESEARCH DESIGN AND METHODS We extracted individual-level data for 124,808 diabetes-free adults from 13 European cohort studies participating in the IPD-Work Consortium. We measured job strain with baseline questionnaires. Incident type 2 diabetes at follow-up was ascertained using national health registers, clinical screening, and self-reports. We analyzed data for each study using Cox regression and pooled the study-specific estimates in fixed-effect meta-analyses. RESULTS There were 3,703 cases of incident diabetes during a mean follow-up of 10.3 years. After adjustment for age, sex, and socioeconomic status (SES), the hazard ratio (HR) for job strain compared with no job strain was 1.15 (95% CI 1.06-1.25) with no difference between men and women (1.19 [1.06-1.34] and 1.13 [1.00-1.28], respectively). In stratified analyses, job strain was associated with an increased risk of diabetes among those with healthy and unhealthy lifestyle habits. In a multivariable model adjusted for age, sex, SES, and lifestyle habits, the HR was 1.11 (1.00-1.23). CONCLUSIONS Findings from a large pan-European dataset suggest that job strain is a risk factor for type 2 diabetes in men and women independent of lifestyle factors.

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