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  • 1. Agardh, Emilie E
    et al.
    Ahlbom, Anders
    Andersson, Tomas
    Efendic, Suad
    Grill, Valdemar
    Hallqvist, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy.
    Norman, Anders
    Ostenson, Claes-Göran
    Work stress and low sense of coherence is associated with type 2 diabetes in middle-aged Swedish women.2003In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, no 3, p. 719-24Article in journal (Refereed)
    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 University, Disciplinary Domain of Medicine and Pharmacy.
    Ostenson, Claes-Göran
    Explanations of socioeconomic differences in excess risk of type 2 diabetes in Swedish men and women.2004In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 27, no 3, p. 716-21Article in journal (Refereed)
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Dickinson, Sheila
    Holmes, David
    Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes.2002In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 25, no 5, p. 869-75Article in journal (Refereed)
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Impact of BMI and the metabolic syndrome on the risk of diabetes in middle-aged men2011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, no 1, p. 61-65Article in journal (Refereed)
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Vessby, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Type 1 diabetes is associated with increased cyclooxygenase- and cytokine-mediated inflammation2005In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 28, no 6, p. 1371-1375Article in journal (Refereed)
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Burgos, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kempton, Matthew J
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Craft, Suzanne
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Impaired Insulin Sensitivity as Indexed by the HOMA Score Is Associated With Deficits in Verbal Fluency and Temporal Lobe Gray Matter Volume in the Elderly2012In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 35, no 3, p. 488-494Article in journal (Refereed)
    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. Butwicka, Agnieszka
    et al.
    Frisen, Louise
    Almqvist, Catarina
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lichtenstein, Paul
    Risks of Psychiatric Disorders and Suicide Attempts in Children and Adolescents With Type 1 Diabetes: A Population-Based Cohort Study2015In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 38, no 3, p. 453-459Article in journal (Refereed)
    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.

  • 8.
    Cederholm, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Eeg-Olofsson, Katarina
    Eliasson, Björn
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Nilsson, Peter M
    Gudbjörnsdottir, Soffia
    Risk prediction of cardiovascular disease in type 2 diabetes: A risk equation from the Swedish National Diabetes Register (NDR)2008In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, no 10, p. 2038-2043Article in journal (Refereed)
    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.

  • 9.
    Daivadanam, Meena
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics. Department of Public Health Sciences, Karolinska Institutet, Solna, Sweden.
    Gaps in Guidelines for the Management of Diabetes in Low- and Middle-Income Versus High-Income Countries: A Systematic Review2018In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 41, no 5, p. 1097-1105Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE The extent to which diabetes (DM) practice guidelines, often based on evidence from high-income countries (HIC), can be implemented to improve outcomes in low-and middle-income countries (LMIC) is a critical challenge. We carried out a systematic review to compare type 2 DM guidelines in individual LMIC versus HIC over the past decade to identify aspects that could be improved to facilitate implementation. RESEARCH DESIGN AND METHODS Eligible guidelines were sought from online databases and websites of diabetes associations and ministries of health. Type 2 DM guidelines published between 2006 and 2016 with accessible full publications were included. Each of the 54 eligible guidelines was assessed for compliance with the Institute of Medicine (IOM) standards, coverage of the cardiovascular quadrangle (epidemiologic surveillance, prevention, acute care, and rehabilitation), translatability, and its target audiences. RESULTS Most LMIC guidelines were inadequate in terms of applicability, clarity, and dissemination plan as well as socioeconomic and ethical-legal contextualization. LMIC guidelines targeted mainly health care providers, with only a few including patients (7%), payers (11%), and policy makers (18%) as their target audiences. Compared with HIC guidelines, the spectrum of DM clinical care addressed by LMIC guidelines was narrow. Most guidelines from the LMIC complied with less than half of the IOM standards, with 12% of the LMIC guidelines satisfying at least four IOM criteria as opposed to 60% of the HIC guidelines (P < 0.001). CONCLUSIONS A new approach to the contextualization, content development, and delivery of LMIC guidelines is needed to improve outcomes.

  • 10. Eeg-Olofsson, Katarina
    et al.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Nilsson, Peter M
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    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).2010In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 33, no 7, p. 1640-1646Article in journal (Refereed)
    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.

  • 11.
    Eeg-Olofsson, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    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 register2007In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 30, no 3, p. 496-502Article in journal (Refereed)
    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.

  • 12. Ekberg, Karin
    et al.
    Brismar, Tom
    Johansson, Bo-Lennart
    Lindström, Per
    Juntti-Berggren, Lisa
    Norrby, Anders
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Arnqvist, Hans J.
    Bolinder, Jan
    Wahren, John
    C-Peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy2007In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 30, no 1, p. 71-76Article in journal (Refereed)
    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.

  • 13. Eliasson, Björn
    et al.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Eeg-Olofsson, Katarina
    Svensson, Anne-Marie
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    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 Register2011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, no 9, p. 2095-2100Article in journal (Refereed)
    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.

  • 14.
    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?1997In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 20, no 6, p. 1045-1045Article in journal (Refereed)
  • 15.
    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 report1998In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 21, no 8, p. 1217-1220Article in journal (Refereed)
    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.

  • 16.
    Espes, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Singh, Kailash
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sandler, Stellan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Increased Interleukin-35 Levels in Patients With Type 1 Diabetes With Remaining C-Peptide2017In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 40, no 8, p. 1090-1095Article in journal (Refereed)
    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.

  • 17.
    Florvall, Gösta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hemocue urine albumin point-of-care test shows strong agreement with the results obtained with a large nephelometer2006In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 29, no 2, p. 422-423Article in journal (Refereed)
  • 18. Gudbjörnsdottir, S
    et al.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Nilsson, P M
    Eliasson, B
    The National Diabetes Register in Sweden: an implementation of the St. Vincent Declaration for Quality Improvement in Diabetes Care2003In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, no 4, p. 1270-1276Article in journal (Refereed)
    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.

  • 19. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and 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 Syndrome2010In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 33, no 4, p. 923-925Article in journal (Refereed)
    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.

  • 20. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and 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).2003In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, no 2, p. 349-54Article in journal (Refereed)
    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.

  • 21.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    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 Hypoglycemia2016In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 39, no 7, p. 1230-1240Article in journal (Refereed)
    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.

  • 22. 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 diabetes2012In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 35, no 3, p. 597-598Article in journal (Refereed)
    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.

  • 23.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    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 diabetes2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 10, p. 3187-3194Article in journal (Refereed)
    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.

  • 24. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Stegmayr, Birgitta
    Hyperglycemia and stroke mortality: comparison between fasting and 2-h glucose criteria2009In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 32, no 2, p. 348-354Article in journal (Refereed)
    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.

  • 25.
    Ingelsson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Circulating retinol-binding protein 4 and subclinical cardiovascular disease in the elderly2009In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 32, no 4, p. 733-735Article in journal (Refereed)
    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.

  • 26.
    Jansson, Stefan P. O.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Andersson, Dan K. G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Mortality Trends in Subjects With and Without Diabetes During 33 Years of Follow-up2010In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 33, no 3, p. 551-556Article in journal (Refereed)
    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.

  • 27.
    Jansson, Stefan P.O.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Andersson, Dan K.G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    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 diabetesIn: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548Article in journal (Refereed)
    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.

  • 28.
    Jobs, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jobs, Magnus
    University of Dalarna.
    Nerpin, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lars, Lind
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Serum cathepsin S is associated with decreased insulin sensitivity and the development of diabetes type 2 in a community-based cohort of elderly men2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 1, p. 163-165Article in journal (Refereed)
    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.

  • 29. Kalani, Majid
    et al.
    Apelqvist, Jan
    Blombäck, Margareta
    Brismar, Kerstin
    Eliasson, Björn
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and 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.2003In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, no 9, p. 2575-80Article in journal (Refereed)
    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.

  • 30. Katoulis, E. C.
    et al.
    Ebdon-Parry, M.
    Lanshammar, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Vileikyte, L.
    Kulkarni, J.
    Boulton, A. J.
    Gait abnormalities in diabetic neuropathy1997In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 20, no 12, p. 1904-1907Article in journal (Refereed)
  • 31. Lee, Duk-Hee
    et al.
    Lind, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Jacobs, David R
    Salihovic, Samira
    van Bavel, Bert
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    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) study2011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, no 8, p. 1778-1784Article in journal (Refereed)
    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.

  • 32.
    Lind, P. Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Circulating Levels of Phthalate Metabolites Are Associated With Prevalent Diabetes in the Elderly2012In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 35, no 7, p. 1519-1524Article in journal (Refereed)
    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.

  • 33. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and 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.1999In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 22, no 3, p. 409-12Article in journal (Refereed)
    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.

  • 34. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and 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 diabetes1999In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 22, no 3, p. 409-412Article in journal (Refereed)
    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.

  • 35. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Scherstén, B
    Wibell, L
    Family characteristics and life events before the onset of autoimmune type 1 diabetes in young adults: a nationwide study.2001In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 24, no 6, p. 1033-7Article in journal (Refereed)
    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.

  • 36.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    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 Collaboration2015In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 38, no 10, p. 1921-1929Article in journal (Refereed)
    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.

  • 37. Nerpin, Elisabet
    et al.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jobs, Magnus
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Insulin sensitivity measured with euglycemic clamp is independently associated with glomerular filtration rate in a community-based cohort2008In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, no 8, p. 1550-1555Article in journal (Refereed)
    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.

  • 38. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Rolandsson, Olov
    Rotter, Jerome I
    Saylor, Georgia
    Sijbrands, Eric J G
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    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 studies2010In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 33, no 12, p. 2684-2691Article in journal (Refereed)
    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.

  • 39. Nilsson, Peter M.
    et al.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Diabetes, Hypertension, and Outcome Studies: Overview 20102011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, p. S109-S113Article in journal (Refereed)
  • 40. 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 Adolescents2011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, no 6, p. 1306-1311Article in journal (Refereed)
    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.

  • 41. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    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 Women2014In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 37, no 8, p. 2268-2275Article in journal (Refereed)
    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.

  • 42.
    Olsson, Gunilla M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Hulting, Anna-Lena
    Montgomery, Scott M
    Cognitive function in children and subsequent type 2 diabetes2008In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, no 3, p. 514-516Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess whether a diagnosis of type 2 diabetes by age 42 years is associated with prior cognitive deficits in childhood. RESEARCH DESIGN AND METHODS: Logistic regression estimated type 2 diabetes risk among 9,113 members of the 1958 British birth cohort of the National Child Development Study (NCDS). Associations with type 2 diabetes were estimated for general ability and reading comprehension assessments at age 11 years, modeled using SD units. Adjustment was for markers of early-life exposures, social and material family characteristics, sex, and disability, with further adjustment for BMI at age 7 years. RESULTS: Adjusted odds ratios (95% CIs) for type 2 diabetes (n = 69) are 0.67 (0.51-0.87) for general ability and 0.58 (0.44-0.77) for reading comprehension. Neither additional adjustment for BMI, nor limiting the definition of type 2 diabetes to onset after age 33 years altered the associations substantially. CONCLUSIONS: Impaired cognitive function may precede clinical onset of type 2 diabetes.

  • 43. Ong, Ken K.
    et al.
    Diderholm, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Salzano, Giuseppina
    Wingate, Dianne
    Hughes, Ieuan A.
    MacDougall, Jane
    Acerini, Carlo L.
    Dunger, David B.
    Pregnancy Insulin, Glucose, and BMI Contribute to Birth Outcomes in Nondiabetic Mothers2008In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, no 11, p. 2193-2197Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - We investigated the effects of normal variations in maternal glycemia on birth size and other birth outcomes.

    RESEARCH DESIGN AND METHODS - Women in two unselected birth cohorts, one retrospective (n = 3,158) and one prospective (n = 668), underwent an oral glucose challenge at 28 weeks of gestation. In the retrospective study, glycemia was linked to routine birth records. In the prospective study, offspring adiposity was assessed by skinfold thickness from birth to age 24 months.

    RESULTS - In the retrospective study, within the nondiabetic range (2.1-7.8 mmol/l), each 1 mmol/l rise in the mother's 60-min glucose level was associated with a (mean +/- SEM) 2.1 +/- 0.8% (P = 0.006) rise in absolute risk of assisted vaginal delivery, a 3.4 +/- 0.8% (P < 0.0001) rise in emergency cesarean delivery, a 3.1 +/- 0.7% (P < 0.0001) rise in elective cesarean delivery, and a 46 +/- 8 g (P < 0.0001) increase in offspring birth weight. in the prospective study, fetal macrosomia (birth weight >90th centile) was independently related to the mother's fasting glucose (odds ratio 2.61 per + 1 mmol/l [95% CI 1.15-5.93]) and prepregnancy BMI (1.10 per +1 kg/m(2) [1.04-1.18]). The mother's higher fasting glycemia (P = 0.004), lower insulin sensitivity (P = 0.01), and lower insulin secretion (P = 0.02) were independently related to greater offspring adiposity at birth. During postnatal follow-up, the correlation between the mother's glycemia and offspring adiposity disappeared by 3 months, whereas prepregnancy BMI was associated with offspring adiposity that was only apparent at 12 and 24 months (both P < 0.05).

    CONCLUSIONS - Prepregnancy BMI, pregnancy glycemia, insulin sensitivity, and insulin secretion all contribute to offspring adiposity and macrosomia and may be separate targets for intervention to optimize birth outcomes and later offspring health.

  • 44. Persson, Martina
    et al.
    Fadl, Helena
    Hanson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Pasupathy, Dharmintra
    Disproportionate Body Composition and Neonatal Outcome in Offspring of Mothers With and Without Gestational Diabetes Mellitus2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 11, p. 3543-3548Article in journal (Refereed)
    Abstract [en]

    OBJECTIVEHigh birth weight is a risk factor for neonatal complications. It is not known if the risk differs with body proportionality. The primary aim of this study was to determine the risk of adverse pregnancy outcome in relation to body proportionality in large-for-gestational-age (LGA) infants stratified by maternal gestational diabetes mellitus (GDM).RESEARCH DESIGN AND METHODSPopulation-based study of all LGA (birth weight [BW] >90th percentile) infants born to women with GDM (n = 1,547) in 1998-2007. The reference group comprised LGA infants (n = 83,493) born to mothers without diabetes. Data were obtained from the Swedish Birth Registry. Infants were categorized as proportionate (P-LGA) if ponderal index (PI) (BW in grams/length in cm(3)) was 90th percentile and as disproportionate (D-LGA) if PI >90th percentile. The primary outcome was a composite morbidity: Apgar score 0-3 at 5 min, birth trauma, respiratory disorders, hypoglycemia, or hyperbilirubinemia. Logistic regression analysis was used to obtain odds ratios (ORs) for adverse outcomes.RESULTSThe risk of composite neonatal morbidity was increased in GDM pregnancies versus control subjects but comparable between P- and D-LGA in both groups. D-LGA infants born to mothers without diabetes had significantly increased risk of birth trauma (OR 1.19 [95% CI 1.09-1.30]) and hypoglycemia (1.23 [1.11-1.37]). D-LGA infants in both groups had significantly increased odds of Cesarean section.CONCLUSIONSThe risk of composite neonatal morbidity is significantly increased in GDM offspring. In pregnancies both with and without GDM, the risk of composite neonatal morbidity is comparable between P- and D-LGA.

  • 45.
    Persson, Martina
    et al.
    Dept of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.
    Norman, Mikael
    Hanson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Obstetric and perinatal outcomes in type 1 diabetic pregnancies: A large, population-based study2009In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 32, no 11, p. 2005-2009Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To perform comparative analyses of obstetric and perinatal outcomes between type 1 diabetic pregnancies and the general obstetric population in Sweden between 1991 and 2003. RESEARCH DESIGN AND METHODS: This was a population-based study. Data were obtained from the Medical Birth Registry, covering >98% of all pregnancies in Sweden. A total of 5,089 type 1 diabetic pregnancies and 1,260,207 control pregnancies were included. Odds ratios (ORs) were adjusted for group differences in maternal age, parity, BMI, chronic hypertensive disease, smoking habits, and ethnicity. RESULTS: In type 1 diabetes, preeclampsia was significantly more frequent (OR 4.47 [3.77-5.31]) as was delivery by cesarean section (5.31 [4.97-5.69]) compared with results for the general population. Stillbirth (3.34 [2.46-4.55]), perinatal mortality (3.29 [2.50-4.33]), and major malformations (2.50 [2.13-2.94]) were more common in type 1 diabetic than in control pregnancies. The risk of very preterm birth (<32 gestational weeks) was also higher among type 1 diabetic women (3.08 [2.45-3.87]). The incidence of fetal macrosomia (birth weight >or=2 SD above the mean) was increased in the diabetic group (11.45 [10.61-12.36]). CONCLUSIONS: Type 1 diabetes in pregnancy is still associated with considerably increased rates of adverse obstetric and perinatal outcomes. The eightfold increased risk for fetal macrosomia in type 1 diabetic pregnancies is unexpected and warrants further investigation.

  • 46. Persson, Martina
    et al.
    Pasupathy, Dharmintra
    Hanson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Norman, Mikael
    Birth Size Distribution in 3,705 Infants Born to Mothers With Type 1 Diabetes A population-based study2011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, no 5, p. 1145-1149Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-To characterize birth size distribution in infants born to mothers with type 1 diabetes. In particular, the relationship between birth weight (BW) and length (BL) was studied because it may provide information on different causal pathways of fetal macrosomia commonly seen in diabetic pregnancies. RESEARCH DESIGN AND METHODS-This was a population-based cohort study of 3,705 infants of type 1 diabetic mothers (1,876 boys), with a gestational age of 28-43 weeks, born in Sweden between 1998 and 2007. BW and BL were retrieved from the Medical Birth Registry and expressed as SD scores (SDS). Ponderal index (PI) was calculated as BW in g/length in cm(3). A BW > 90th and a PI 90th percentile, the infant was categorized as disproportionately large. Values are mean (SD). RESULTS-The BW distribution for offspring of type 1 diabetic mothers was bell-shaped, significantly broader, and markedly shifted to the right (BWSDS: 1.27 [1.48]) of the reference. Of the infants born to diabetic mothers, 47% were LGA, and among them, 46% were disproportionately large compared with 35% in nondiabetic LGA infants (P < 0.001). Female offspring of type 1 diabetic mothers had significantly higher BWSDS than males (1.34 vs. 1.20, P < 0.01), and preterm infants had higher BWSDS than term infants (1.41 vs. 1.23, P < 0.01) CONCLUSIONS-Fetal macrosomia in type 1 diabetic pregnancies is due to a right-shift and broadening of the entire BW distribution. The large number of disproportionate LGA infants born to type 1 diabetic mothers suggests an underlying metabolic problem. Fetal macrosomia was more pronounced in preterm and female offspring of type 1 diabetic mothers.

  • 47.
    Rasouli, Bahareh
    et al.
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, S-10401 Stockholm, Sweden..
    Andersson, Tomas
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, S-10401 Stockholm, Sweden.;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden..
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Grill, Valdemar
    Norwegian Univ Sci & Technol, NTNU Inst Canc Res & Mol Med, N-7034 Trondheim, Norway.;Univ Trondheim Hosp, Dept Endocrinol, Trondheim, Norway..
    Groop, Leif
    Lund Univ, Dept Clin Sci Malmo, Clin Res Ctr, Malmo, Sweden..
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Storm, Petter
    Lund Univ, Dept Clin Sci Malmo, Clin Res Ctr, Malmo, Sweden..
    Tuomi, Tiinamaija
    Helsinki Univ Hosp, Div Endocrinol, Helsinki, Finland.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland.;Univ Helsinki, Res Program Diabet & Obes, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Carlsson, Sofia
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, S-10401 Stockholm, Sweden..
    Smoking and the Risk of LADA: Results From a Swedish Population-Based Case-Control Study2016In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 39, no 5, p. 794-800Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Smoking is an established risk factor for type 2 diabetes. In contrast, it has been proposed that smoking may reduce the risk of latent autoimmune diabetes in adults (LADA), but studies are scarce. We aimed to study the impact of smoking on LADA and type 2 diabetes risks. RESEARCH DESIGN AND METHODS We used data from a Swedish case-control study including incident case patients with LADA (GAD antibody [GADA] positive, n = 377) and type 2 diabetes (GADA negative, n = 1,188) and control subjects randomly selected from the population (n = 1,472). We calculated odds ratios (ORs) with 95% CIs by logistic regression, adjusted for age, sex, BMI, family history of diabetes, and alcohol consumption. RESULTS There was no indication of reduced risk of LADA in smokers; instead, heavy smoking was associated with an increased risk of LADA (OR 1.37, 95% CI 1.02-1.84). Heavy smokers had higher levels of HOMA of insulin resistance (9.89 vs. 4.38, P = 0.0479) and HOMA of beta-cell function (55.7 vs. 42.5, P = 0.0204), but lower levels of GADA (75 vs. 250, P = 0.0445), compared with never smokers. Smokers also displayed an increased risk of type 2 diabetes (OR in ever smokers 1.53, 95% CI 1.25-1.88). CONCLUSIONS In this large population of LADA patients, we did not observe a protective effect of smoking on autoimmunity and the risk of LADA. A protective effect could possibly be masked by a smoking-induced aggravation of insulin resistance, akin to the diabetogenic effect seen in individuals with type 2 diabetes.

  • 48.
    Razmara, Masoud
    et al.
    Karolinska institutet.
    Hjemdahl, Paul
    Yngen, Marianne
    Ostenson, Claes-Göran
    Wallén, N Håkan
    Li, Nailin
    Food intake enhances thromboxane receptor-mediated platelet activation in type 2 diabetic patients but not in healthy subjects.2007In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 30, no 1, p. 138-40Article in journal (Refereed)
  • 49.
    Risérus, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Long-term predictors of insulin resistance: role of lifestyle and metabolic factors in middle-aged men2007In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 30, no 11, p. 2928-2933Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Predictors of insulin resistance have hitherto only been examined in cross-sectional studies without information on lifestyle factors. Few researchers have measured insulin sensitivity directly and compared different metabolic and lifestyle predictors in a large population. RESEARCH DESIGN AND METHODS: Our aim was to investigate independent long-term predictors of insulin sensitivity in a large population-based sample (the Uppsala Longitudinal Study of Adult Men cohort) of 50-year-old men who underwent a euglycemic clamp 20 years later (n = 770). Subjects with diabetes and treatment of cardiovascular disease at baseline were excluded. In linear regression models, metabolic (BMI, triglycerides, HDL cholesterol, glucose, and blood pressure) and lifestyle factors (physical activity, smoking, saturated fat biomarkers, and socioeconomic status) were independent variables at baseline (age 50 years) and insulin sensitivity-dependent variables at follow-up (age 70 years). A subsample of only normal-weight men from the initial population was also examined (n = 440). RESULTS: BMI was the strongest predictor of insulin sensitivity even after addition of metabolic factors. One SD (+/-2.8) increase in BMI corresponded to a mean 19% decrease in insulin sensitivity. After addition of lifestyle factors, all factors except triglycerides and smoking were significant predictors. BMI remained the strongest predictor (beta = -0.67 [95% CI -0.83 to -0.51], P < 0.0001) followed by physical activity, HDL cholesterol, saturated fat, and socioeconomic status (all P < 0.05). BMI remained the strongest predictor in normal-weight subjects also (P < 0.001). In addition, after adjustment for baseline insulin concentrations, BMI remained the strongest predictor (P < 0.001). CONCLUSIONS: Multiple factors, including novel factors such as saturated fat and socioeconomic status, independently predict insulin sensitivity after 20 years. BMI is, however, the single strongest predictor, even in normal-weight subjects.

  • 50.
    Ritsinger, Viveca
    et al.
    Karolinska Inst, Dept Med Solna, Cardiol Unit, Stockholm, Sweden.;Dept Res & Dev, Region Kronoberg, Vaxjo, Sweden..
    Hero, Christel
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Med, Gothenburg, Sweden..
    Svensson, Ann-Marie
    Natl Diabet Register, Ctr Registers, Gothenburg, Sweden..
    Saleh, Nawzad
    Karolinska Inst, Dept Med Solna, Cardiol Unit, Stockholm, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Eeg-Olofsson, Katarina
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Med, Gothenburg, Sweden..
    Norhammar, Anna
    Karolinska Inst, Dept Med Solna, Cardiol Unit, Stockholm, Sweden.;Capio ST Gorans Hosp, Stockholm, Sweden..
    Characteristics and Prognosis in Women and Men With Type 1 Diabetes Undergoing Coronary Angiography: A Nationwide Registry Report2018In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 41, no 4, p. 876-883Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To describe sex aspects on extent of coronary artery disease (CAD) and prognosis in a contemporary population with type 1 diabetes.

    RESEARCH DESIGN AND METHODS: All patients undergoing coronary angiography, 2001-2013, included in the Swedish Coronary Angiography and Angioplasty Registry and the Swedish National Diabetes Register as type 1 diabetes were followed for mortality until 31 December 2013. The coronary angiogram was classified into normal, one-vessel disease, two-vessel disease, three-vessel disease, and left main stem disease.

    RESULTS: In all, 2,776 patients (42% women) with mean age 58 years (SD 11) were followed for 7.2 years (SD 2.2). Diabetes duration was longer in women (37 14 vs. 34 +/- 14 years in men; P < 0.001), who also had more retinopathy (68% vs. 65%; P = 0.050), whereas microalbuminuria was less common (41% vs. 51%; P < 0.001). Indications for coronary angiography did not substantially differ in women and men. The extent of CAD was somewhat less severe in women (normal angiogram 23.5% vs. 19.1%, three-vessel and left main stem disease 34.5% vs. 40.4%; P = 0.002), whereas mortality did not differ (adjusted hazard ratio 1.03 [95% CI 0.88-1.20]; P = 0.754). The standard mortality ratio for women the first year was 7.49 (5.73-9.62) and for men was 4.58 (3.60-5.74).

    CONCLUSIONS: In patients with type 1 diabetes admitted for coronary angiography, the extent of CAD was almost similar in women and men, and total long-term mortality did not differ. Type 1 diabetes was associated with higher mortality risk in women than in men when compared with the general population. These data support that type 1 diabetes attenuates the cardiovascular risk difference seen in men and women in the general population.

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