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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. Alvarsson, M
    et al.
    Sundkvist, G
    Lager, I
    Henricsson, M
    Berntorp, K
    Fernqvist-Forbes, E
    Steen, L
    Westermark, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Westermark, P
    Orn, T
    Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients2003In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, no 8, p. 2231-2237Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - To evaluate whether treatment with insulin in recently diagnosed type 2 diabetes is advantageous compared with glibenclamide treatment. RESEARCH DESIGN AND METHODS - ▀-Cell function, glycemic control, and quality of life were monitored over 2 years in 39 patients with islet cell antibody-negative type 2 diabetes diagnosed 0-2 years before inclusion in a Swedish multicenter randomized clinical trial. Patients were randomized to either two daily injections of premixed 30% soluble and 70% NPH insulin or glibenclamide (3.5-10.5 mg daily). C-peptide-glucagon tests were performed yearly in duplicate after 2-3 days of temporary withdrawal of treatment. RESULTS - After 1 year the glucagon-stimulated C-peptide response was increased in the insulin-treated group by 0.14 ▒ 0.08 nmol/l, whereas it was decreased by 0.12 ▒ 0.08 nmol/l in the glibenclamide group, P < 0.02 for difference between groups. After 2 years, fasting insulin levels were higher after treatment withdrawal in the insulin-treated versus the glibenclamide-treated group (P = 0.02). HbA1c levels decreased significantly during the first year in both groups, however, at the end of the second year, HbA1c had deteriorated in the glibenclamide group (P < 0.01), but not in the insulin-treated group. The difference in evolution of HbA1c during the second year was significant between groups, P < 0.02 A questionnaire indicated no difference in well-being related to treatment. CONCLUSIONS - Early insulin versus glibenclamide treatment in type 2 diabetes temporarily prolongs endogenous insulin secretion and promotes better metabolic control.

  • 5. Andersson, P O
    et al.
    Wikby, Anders
    Jönköping University, School of Health Science, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health Science, HHJ. Ageing - living conditions and health.
    Hörnquist, J O
    Influence of insulin pen injection frequency on quality of life1990In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 13, no 11, p. 1135-1136Article in journal (Refereed)
  • 6.
    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.

  • 7.
    Axelsson, Stina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Cheramy, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Åkerman, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Pihl, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Cellular and Humoral Immune responses in Type 1 Diabetic patients participating in a Phase III GAD-alum Intervention Trial2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 11, p. 3418-3424Article in journal (Refereed)
    Abstract [en]

    OBJECTIVEGAD formulated in aluminum hydroxide (GAD-alum) has previously been shown to induce preservation of residual insulin secretion in recent-onset type 1 diabetes, but recent phase II and III GAD-alum trials failed to reach primary outcomes. The European phase III study was therefore closed after 15 months, and only a minority of patients completed the 30 months of follow-up.RESEARCH DESIGN AND METHODSThis study aimed to characterize cellular and humoral responses in the Swedish patients (n = 148) participating in the phase III trial, receiving four (4D) or two (2D) GAD-alum doses or placebo. Serum GAD(65) antibody (GADA) levels, GADA IgG1-4 subclass distribution, cytokine secretion, and proliferative responses in peripheral blood mononuclear cells (PBMCs) were analyzed.RESULTSThe GAD(65)-induced cytokine profile tended to switch toward a predominant Th2-associated profile over time both in the 2D and 4D group. The groups also displayed increased GADA levels and PBMC proliferation compared with placebo, whereas GADA IgG subclass distribution changed in 4D patients.CONCLUSIONSBoth 2D and 4D patients displayed GAD(65)-specifc cellular and humoral effects after GAD-alum treatment, but at different time points and magnitudes. No specific immune markers could be associated with treatment efficacy.

  • 8.
    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.

  • 9.
    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.

  • 10.
    Berhan, Yonas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Waernbaum, Ingeborg
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Impact of Parental Socioeconomic Status on Excess Mortality in a Population-Based Cohort of Subjects With Childhood-Onset Type 1 Diabetes2015In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 38, no 5, p. 827-832Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 11.
    Besser, Rachel E J
    et al.
    University of Exeter, England .
    Shields, Beverley M
    University of Exeter, England .
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Hattersley, Andrew T.
    University of Exeter, England .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Lessons From the Mixed-Meal Tolerance Test Use of 90-minute and fasting C-peptide in pediatric diabetes2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 2, p. 195-201Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-Mixed-meal tolerance test (MMTT) area under the curve C-peptide (AUC CP) is the gold-standard measure of endogenous insulin secretion in type 1 diabetes but is intensive and invasive to perform. The 90-minMMTT-stimulated CP andgt;= 0.2 nmol/L (90CP) is related to improved clinical outcomes, and CP andgt;= 0.1 nmol/L is the equivalent fasting measure (FCP). We assessed whether 90CP or FCP are alternatives to a full MMTT. less thanbrgreater than less thanbrgreater thanRESEARCH DESIGN AND METHODS-CP was measured during 1,334 MMTTs in 421 type 1 diabetes patients aged, 18 years at 3, 9, 18, 48, and 72 months duration. We assessed: 1) correlation between mean AUC CP and 90CP or FCP; 2) sensitivity and specificity of 90CP andgt;= 0.2 nmol/L and FCP andgt;= 0.1 nmol/L to detect peak CP andgt;= 0.2 nmol/L and the equivalent AUC CP; and 3) how the time taken to reach the CP peak varied with age of diagnosis and diabetes duration. less thanbrgreater than less thanbrgreater thanRESULTS-AUC CP was highly correlated to 90CP (r(s) = 0.96; P andlt; 0.0001) and strongly correlated to FCP (r(s) = 0.84; P andlt; 0.0001). AUC CP andgt;= 23 nmol/L/150 min was the equivalent cutoff for peak CP andgt;= 0.2 nmol/L (98% sensitivity/97% specificity). A 90CP andgt;= 0.2 nmol/L correctly classified 96% patients using AUC or peak CP, whereas FCP andgt;= 0.1 nmol/L classified 83 and 85% patients, respectively. There was only a small difference seen between peak and 90CP (median 0.02 nmol/L). The CP peak occurred earlier in patients with longer diabetes duration (6.1 min each 1-year increase in duration) and younger age (2.5 min each 1-year increase). less thanbrgreater than less thanbrgreater thanCONCLUSIONS-90CP is a highly sensitive and specific measure of AUC and peak CP in children and adolescents with type 1 diabetes and offers a practical alternative to a full MMTT. Diabetes Care 36:195-201, 2013

  • 12.
    Birkebaek, Niels H.
    et al.
    Aarhus Univ Hosp, Denmark.
    Hermann, Julia M.
    Univ Ulm, Germany; German Ctr Diabet Res, Germany.
    Hanberger, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Charalampopoulos, Dimitrios
    UCL, England.
    Holl, Reinhard W.
    Univ Ulm, Germany; German Ctr Diabet Res, Germany.
    Skrivarhaug, Torild
    Oslo Univ Hosp, Norway.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Warner, Justin T.
    Childrens Hosp Wales, Wales.
    Drivvoll, Ann K.
    Oslo Univ Hosp, Norway.
    Svensson, Ann-Marie
    Reg Vastra Gotaland, Sweden.
    Stephenson, Terence
    UCL, England.
    Hofer, Sabine E.
    Med Univ Innsbruck, Austria.
    Fredheim, Siri
    Herlev Univ Hosp, Denmark.
    Kummernes, Siv J.
    Oslo Univ Hosp, Norway.
    Amin, Rakesh
    UCL, England.
    Rami-Merhar, Birgit
    Med Univ Vienna, Austria.
    Johansen, Anders
    Rigshosp, Denmark.
    Kapellen, Thomas M.
    Univ Childrens Hosp Leipzig, Germany.
    Hilgard, Doerte
    Pediat Diabetol Practice, Germany.
    Dahl-Jorgensen, Knut
    Univ Oslo, Norway; Univ Oslo, Norway.
    Froehlich-Reiterer, Elke
    Med Univ Graz, Austria.
    Fritsch, Maria
    Med Univ Vienna, Austria.
    Hanas, Ragnar
    NU Hosp Grp, Sweden; Univ Gothenburg, Sweden.
    Svensson, Jannet
    Herlev Univ Hosp, Denmark.
    Letter: Center Size and Glycemic Control: An International Study With 504 Centers From Seven Countries in DIABETES CARE, vol 42, issue 3, pp E37-E392019In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 42, no 3, p. E37-E39Article in journal (Other academic)
    Abstract [en]

    n/a

  • 13. Birkeland, Kare I.
    et al.
    Home, Philip D.
    Wendisch, Ulrich
    Ratner, Robert E.
    Johansen, Thue
    Endahl, Lars A.
    Lyby, Karsten
    Jendle, Johan
    Örebro University, School of Health and Medical Sciences.
    Roberts, Anthony P.
    DeVries, J. Hans
    Meneghini, Luigi F.
    Insulin degludec in type 1 diabetes: a randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine2011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, no 3, p. 661-665Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Insulin degludec (IDeg) is a basal insulin that forms soluble multihexamers after subcutaneous injection, resulting in an ultra-long action profile. We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1 diabetes.

    RESEARCH DESIGN AND METHODS: In this 16-week, randomized, open-label trial, participants (mean: 45.8 years old, A1C 8.4%, fasting plasma glucose [FPG] 9.9 mmol/L, BMI 26.9 kg/m(2)) received subcutaneous injections of IDeg(A) (600 mu mol/L; n = 59), IDeg(B) (900 mu mol/L; n = 60), or insulin glargine (IGlar; n = 59), all given once daily in the evening. Insulin aspart was administered at mealtimes.

    RESULTS: At 16 weeks, mean A1C was comparable for IDeg(A) (7.8 +/- 0.8%), IDeg(B) (8.0 +/- 1.0%), and IGlar (7.6 +/- 0.8%), as was FPG (8.3 +/- 4.0, 8.3 +/- 2.8, and 8.9 +/- 3.5 mmol/L, respectively). Estimated mean rates of confirmed hypoglycemia were 28% lower for IDeg(A) compared with IGlar (rate ratio [RR]: 0.72 [95% CI 0.52-1.00]) and 10% lower for IDeg(B) compared with IGlar (RR: 0.90 [0.65-1.24]); rates of nocturnal hypoglycemia were 58% lower for IDeg(A) (RR: 0.42 [0.25-0.69]) and 29% lower for IDeg(B) (RR: 0.71 [0.44-1.16]). Mean total daily insulin dose was similar to baseline. The frequency and pattern of adverse events was similar between insulin treatments.

    CONCLUSIONS: In this clinical exploratory phase 2 trial in people with type 1 diabetes, IDeg is safe and well tolerated and provides comparable glycemic control to IGlar at similar doses, with reduced rates of hypoglycemia.

  • 14.
    Bojestig, M
    et al.
    Linkoping Univ Hosp, Dept Med & Care, SE-58185 Linkoping, Sweden.
    Karlberg, BE
    Lindström, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Reduction of ACE activity is insufficient to decrease microalbuminuria in normotensive patients with type 1 diabetes2001In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 24, no 5, p. 919-924Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - To study whether administration of 1.25 and 5.0 mg ramipril daily, compared with placebo treatment, reduces the urinary albumin excretion rate (UAER) in normotensive patients with type 1 diabetes. RESEARCH DESIGN AND METHODS - Ramipril was administered double blind at two different doses(1.25 [n = 19] and 5.0 mg [n = 18]), and compared with placebo [n = 18] after a single-blind placebo period of 1-4 weeks. The patients (total, n = 55, women, n = 14) were followed for 2 years. To document an effect on the renin-angiotensin system, ACE activity and plasma-renin activity (PRA) were measured. In addition, 24-h ambulatory blood pressure (BP) was recorded at baseline and repeated after 1 and 2 years using a Spacelab 90207 ambulatory BP recording device (Spacelab, Redmont, CA). RESULTS - Both doses of ramipril were sufficient to reduce ACE activity and to increase PRA significantly as compared with placebo (P < 0.05 for both). On the other hand, neither ambulatory nor clinic BP was affected by either dose of ramipril compared with the placebo group. There was no progression of UAER in the placebo group during the 2 years of the study. Analysis of covariance showed no differences in UAER between the three treatment groups at year 1 (P = 0.94) or year 2 (P = 0.97), after adjusting for baseline. Furthermore, there were no statistically significant changes from baseline UAER within any of the three treatment groups. CONCLUSIONS - Treatment with ramipril did not affect microalbuminuria or clinic or ambulatory BP in this study. On the basis of the present study, we question the clinical use of ACE inhibitors in stably normotensive patients with type 1 diabetes and microalbuminuria in whom a concomitant reduction in BP is not demonstrated.

  • 15. Brand, Judith S.
    et al.
    van der Schouw, Yvonne T.
    Onland-Moret, N. Charlotte
    Sharp, Stephen J.
    Ong, Ken K.
    Khaw, Kay-Tee
    Ardanaz, Eva
    Amiano, Pilar
    Boeing, Heiner
    Chirlaque, Maria-Dolores
    Clavel-Chapelon, Francoise
    Crowe, Francesca L.
    de Lauzon-Guillain, Blandine
    Duell, Eric J.
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Grioni, Sara
    Groop, Leif C.
    Kaaks, Rudolf
    Key, Timothy J.
    Nilsson, Peter M.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros, J. Ramon
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Slimani, Nadia
    Teucher, Birgit
    Tjonneland, Anne
    Tumino, Rosario
    van der A, Daphne L.
    Feskens, Edith J. M.
    Langenberg, Claudia
    Forouhi, Nita G.
    Riboli, Elio
    Wareham, Nicholas J.
    Age at Menopause, Reproductive Life Span, and Type 2 Diabetes Risk2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 4, p. 1012-1019Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk.

    RESEARCH DESIGN AND METHODS-Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied.

    RESULTS-Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04-1.69), 1.09 (0.90-1.31), 0.97 (0.86-1.10), and 0.85 (0.70-1.03) for women with menopause at ages <40, 40-44, 45-49, and >= 55 years, respectively, relative to those with menopause at age 50-54 years. The HR per SD younger age at menopause was 1.08 (1.02-1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [ 1.01-1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all > 0.05).

    CONCLUSIONS-Early menopause is associated with a greater risk of type 2 diabetes. Diabetes Care 36:1012-1019, 2013

  • 16. 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.

  • 17.
    Cardwell, Chris R
    et al.
    Queens University of Belfast, North Ireland .
    Stene, Lars C
    Norwegian Institute Public Heatlh, Norway Oslo University Hospital, Norway .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Rosenbauer, Joachim
    University of Dusseldorf, Germany .
    Cinek, Ondrej
    Charles University of Prague, Czech Republic University Hospital Motol, Czech Republic .
    Svensson, Jannet
    Herlev University Hospital, Denmark .
    Perez-Bravo, Francisco
    University of Chile, Chile .
    Memon, Anjum
    Brighton and Sussex Medical School and NHS Brighton and Hove, England .
    Gimeno, Suely G
    University of Federal Sao Paulo, Brazil .
    Wadsworth, Emma J K
    Cardiff University, Wales .
    Strotmeyer, Elsa S
    University of Pittsburgh, PA USA .
    Goldacre, Michael J
    University of Oxford, England .
    Radon, Katja
    Hospital Ludwig Maximilian University of Munich, Germany .
    Chuang, Lee-Ming
    National Taiwan University Hospital, Taiwan .
    Parslow, Roger C
    University of Leeds, England .
    Chetwynd, Amanda
    University of Lancaster, England .
    Karavanaki, Kyriaki
    University of Athens, Greece .
    Brigis, Girts
    Riga Stradins University, Latvia .
    Pozzilli, Paolo
    University of Campus Biomed, Italy .
    Urbonaite, Brone
    Lithuanian University of Health Science, Lithuania .
    Schober, Edith
    Medical University of Vienna, Austria .
    Devoti, Gabriele
    University of Salento, Italy .
    Sipetic, Sandra
    University of Belgrade, Serbia .
    Joner, Geir
    University of Oslo, Norway Oslo University Hospital, Norway .
    Ionescu-Tirgoviste, Constantin
    N Paulescu Institute Diabet, Romania .
    de Beaufort, Carine E
    Clin Pediat Luxembourg, Luxembourg .
    Harrild, Kirsten
    University of Aberdeen, Scotland .
    Benson, Victoria
    University of Oxford, England .
    Savilahti, Erkki
    University of Helsinki, Finland .
    Ponsonby, Anne-Louise
    Royal Childrens Hospital, Australia .
    Salem, Mona
    Ain Shams University, Egypt .
    Rabiei, Samira
    Shahid Beheshti University of Medical Science and Health Serv, Iran .
    C Patterson, Chris
    Queens University of Belfast, North Ireland .
    Breast-Feeding and Childhood-Onset Type 1 Diabetes A pooled analysis of individual participant data from 43 observational studies2012In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 35, no 11, p. 2215-2225Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. less thanbrgreater than less thanbrgreater thanRESEARCH DESIGN AND METHODS-Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. less thanbrgreater than less thanbrgreater thanRESULTS-Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for andgt;2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for andgt;3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for andgt;2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or andgt;3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I-2 = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for andgt;2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I-2 = 0%). Adjustments for potential confounders altered these estimates very little. less thanbrgreater than less thanbrgreater thanCONCLUSIONS-The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.

  • 18.
    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.

  • 19.
    Charalampopoulos, Dimitrios
    et al.
    UCL, England.
    Hermann, Julia M.
    Ulm Univ, Germany; German Ctr Diabet Res DZD, Germany.
    Svensson, Jannet
    Herlev Univ Hosp, Denmark.
    Skrivarhaug, Torild
    Oslo Univ Hosp, Norway.
    Maahs, David M.
    Stanford Univ, CA 94305 USA.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Warner, Justin T.
    Childrens Hosp Wales, Wales.
    Holl, Reinhard W.
    Ulm Univ, Germany; German Ctr Diabet Res DZD, Germany.
    Birkebaek, Niels H.
    Aarhus Univ Hosp, Denmark.
    Drivvoll, Ann K.
    Oslo Univ Hosp, Norway.
    Miller, Kellee M.
    Jaeb Ctr Hlth Res, FL USA.
    Svensson, Ann-Marie
    Ctr Registers Reg Vastra Gotaland, Sweden.
    Stephenson, Terence
    University College London, London, U.K..
    Hofer, Sabine E.
    Med Univ Innsbruck, Austria.
    Fredheim, Siri
    Herlev University Hospital, Herlev, Denmark.
    Kummernes, Siv J.
    Oslo Univ Hosp, Norway.
    Foster, Nicole
    Jaeb Ctr Hlth Res, FL USA.
    Hanberger, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Amin, Rakesh
    UCL, England.
    Rami-Merhar, Birgit
    Med Univ Vienna, Austria.
    Johansen, Anders
    Univ Copenhagen, Denmark.
    Dahl-Jorgensen, Knut
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Clements, Mark
    Childrens Mercy Hosp, MO 64108 USA; Univ Missouri Kansas City, MO USA; Univ Kansas, KS 66103 USA.
    Hanas, Ragnar
    NU Hosp Grp, Sweden; Univ Gothenburg, Sweden.
    Exploring Variation in Glycemic Control Across and Within Eight High-Income Countries: A Cross-sectional Analysis of 64,666 Children and Adolescents With Type 1 Diabetes2018In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 41, no 6, p. 1180-1187Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE International studies on childhood type 1 diabetes (T1D) have focused on whole-country mean HbA(1c) levels, thereby concealing potential variations within countries. We aimed to explore the variations in HbA(1c) across and within eight high-income countries to best inform international benchmarking and policy recommendations. RESEARCH DESIGN AND METHODS Data were collected between 2013 and 2014 from 64,666 children with T1D who were amp;lt; 18 years of age across 528 centers in Germany, Austria, England, Wales, U.S., Sweden, Denmark, and Norway. We used fixed-and random-effects models adjusted for age, sex, diabetes duration, and minority status to describe differences between center means and to calculate the proportion of total variation in HbA(1c) levels that is attributable to between-center differences (intraclass correlation [ICC]). We also explored the association between within-center variation and childrens glycemic control. RESULTS Sweden had the lowest mean HbA(1c) (59mmol/mol [7.6%]) and together with Norway and Denmark showed the lowest between-center variations (ICC amp;lt;= 4%). Germany and Austria had the next lowest mean HbA(1c) (61-62 mmol/mol [7.7-7.8%]) but showed the largest center variations (ICC similar to 15%). Centers in England, Wales, and the U.S. showed low-to-moderate variation around high mean values. In pooled analysis, differences between counties remained significant after adjustment for children characteristics and center effects (P value amp;lt; 0.001). Across all countries, children attending centers with more variable glycemic results had higher HbA(1c) levels (5.6mmol/mol [0.5%] per 5mmol/mol [0.5%] increase in center SD of HbA(1c) values of all children attending a specific center). CONCLUSIONS A tsimilar average levels of HbA(1c), countries display different levels of center variation. The distribution of glycemic achievement within countries should be considered in developing informed policies that drive quality improvement.

  • 20. Chatterjee, Saion
    et al.
    Peters, Sanne A. E.
    Woodward, Mark
    Mejia Arango, Silvia
    Batty, G. David
    Beckett, Nigel
    Beiser, Alexa
    Borenstein, Amy R.
    Crane, Paul K.
    Haan, Mary
    Hassing, Linda B.
    Hayden, Kathleen M.
    Kiyohara, Yutaka
    Larson, Eric B.
    Li, Chung-Yi
    Ninomiya, Toshiharu
    Ohara, Tomoyuki
    Peters, Ruth
    Russ, Tom C.
    Seshadri, Sudha
    Strand, Bjørn H.
    Walker, Rod
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Medical University, China .
    Huxley, Rachel R.
    Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men: A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia2016In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 39, no 2, p. 300-307Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a metaanalysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. RESEARCH DESIGN AND METHODS A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses. RESULTS Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45-1.80]; men: pooled RR 1.58 [95% CI 1.38-1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86-2.94) in women and 1.73 (95% CI 1.61-1.85) in men, and for nonvascular dementia, the RRs were 1.53 (95% CI 1.35-1.73) in women and 1.49 (95% CI 1.31-1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08-1.30]; P < 0.001). CONCLUSIONS Individuals with type 2 diabetes are at similar to 60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women.

  • 21.
    Dahlquist, G G
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Primary and secondary prevention strategies of pre-type 1 diabetes. Potentials and pitfalls.1999In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 22 Suppl 2, p. B4-6Article in journal (Refereed)
    Abstract [en]

    Over the past decade, a large part of type 1 diabetes research has focused on the possibility of preventing the disease. The objective of this article is to analyze which potential and pitfalls different preventive strategies may involve from the individual, epidemiological, and ethical perspectives. Two potential prevention strategies are considered: l) to try to arrest or delay an already ongoing immune destruction of the beta-cells, and 2) to try to intervene with exposures that may initiate this process. In addition to the potential effects of immune modulation, this prevention strategy depends on screening for risk markers. There are inherent ethical problems with screening because of the introduction of awareness of risk in healthy individuals and also because false positivity, the rate of which differs tremendously in high- and low-risk groups. Because of these latter circumstances, the most promising low-risk preventive treatments presently used in trials, i.e., nicotinamide and insulin, will probably only be feasible in high-risk groups, such as family members, though this group covers only 10-15% of potential cases. The second strategy aiming at eradicating environmental initiators of the beta-cell destruction will avoid the problem of screening and approach a total population at risk. Potential risk factors, such as food components (cow's milk proteins, gliadin or nitroso products) or different viruses, are indicated by animal and epidemiological studies. So far, however, no single environmental risk factor has been proven to be necessary and certainly not sufficient for the disease causation, and the etiological fractions estimated in population-based studies are low. It is concluded that more basic research is warranted before effective and safe prevention can be introduced for type 1 diabetes. Most probably, different preventive strategies must be applied to different groups and populations and in different phases of the beta-cell destruction.

  • 22.
    Dahlquist, G G
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Boman, J E
    Juto, P
    Enteroviral RNA and IgM antibodies in early pregnancy and risk for childhood-onset IDDM in offspring.1999In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 22, no 2, p. 364-5Article in journal (Refereed)
  • 23.
    Dahlquist, G G
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Patterson, C
    Soltesz, G
    Perinatal risk factors for childhood type 1 diabetes in Europe. The EURODIAB Substudy 2 Study Group.1999In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 22, no 10, p. 1698-702Article in journal (Refereed)
    Abstract [en]

    Different perinatal events are associated with an increased risk of type 1 diabetes. The effect of maternal-child blood group incompatibility is strong and indicates a true effect that must be further explored.

  • 24.
    Dahlquist, Gisela G
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Forsberg, Jenny
    Hagenfeldt, Lars
    Boman, Jens
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Increased prevalence of enteroviral RNA in blood spots from newborn children who later developed type 1 diabetes: a population-based case-control study.2004In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 27, no 1, p. 285-6Article in journal (Refereed)
  • 25.
    Dahlquist, Gisela
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kallen, Bengt
    Indications that phototherapy is a risk factor for insulin-dependent diabetes.2003In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, no 1, p. 247-8Article in journal (Refereed)
  • 26.
    Dahlquist, Gisela
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Patterson, Christopher C.
    Centre for Public Health, Queen’s University, Belfast, Northern Ireland .
    Incidence of Type 1 Diabetes in Sweden Among Individuals Aged 0-34 Years, 1983-2007: An analysis of time trends2011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, no 8, p. 1754-1759Article in journal (Refereed)
    Abstract [en]

    Objective: To clarify whether the increase in childhood type 1 diabetes is mirrored by a decrease in older age-groups, resulting in younger age at diagnosis.

    Research design and methods: We used data from two prospective research registers, the Swedish Childhood Diabetes Register, which included case subjects aged 0–14.9 years at diagnosis, and the Diabetes in Sweden Study, which included case subjects aged 15–34.9 years at diagnosis, covering birth cohorts between 1948 and 2007. The total database included 20,249 individuals with diabetes diagnosed between 1983 and 2007. Incidence rates over time were analyzed using Poisson regression models.

    Results: The overall yearly incidence rose to a peak of 42.3 per 100,000 person-years in male subjects aged 10–14 years and to a peak of 37.1 per 100,000 person-years in female subjects aged 5–9 years and decreased thereafter. There was a significant increase by calendar year in both sexes in the three age-groups <15 years; however, there were significant decreases in the older age-groups (25- to 29-years and 30- to 34-years age-groups). Poisson regression analyses showed that a cohort effect seemed to dominate over a time-period effect.

    Conclusions: Twenty-five years of prospective nationwide incidence registration demonstrates a clear shift to younger age at onset rather than a uniform increase in incidence rates across all age-groups. The dominance of cohort effects over period effects suggests that exposures affecting young children may be responsible for the increasing incidence in the younger age-groups.

     

  • 27. Dawed, Adem Y.
    et al.
    Zhou, Kaixin
    van Leeuwen, Nienke
    Mahajan, Anubha
    Robertson, Neil
    Koivula, Robert
    Elders, Petra J. M.
    Rauh, Simone P.
    Jones, Angus G.
    Holl, Reinhard W.
    Stingl, Julia C.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Skåne University Hospital, Malmö, Lund University, Malmö, Sweden; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA .
    McCarthy, Mark I.
    't Hart, Leen M.
    Pearson, Ewan R.
    Variation in the Plasma Membrane Monoamine Transporter (PMAT) (Encoded by SLC29A4) and Organic Cation Transporter 1 (OCT1) (Encoded by SLC22A1) and Gastrointestinal Intolerance to Metformin in Type 2 Diabetes: An IMI DIRECT Study2019In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 42, no 6, p. 1027-1033Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Gastrointestinal adverse effects occur in 20-30% of patients with metformin-treated type 2 diabetes, leading to premature discontinuation in 5-10% of the cases. Gastrointestinal intolerance may reflect localized high concentrations of metformin in the gut. We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects.

    RESEARCH DESIGN AND METHODS: The study included 286 severe metformin-intolerant and 1,128 metformin-tolerant individuals from the IMI DIRECT (Innovative Medicines Initiative: DIabetes REsearCh on patient straTification) consortium. We assessed the association of patient characteristics, concomitant medication, and the burden of mutations in the SLC29A4 and SLC22A1 genes on odds of intolerance.

    RESULTS: Women (P < 0.001) and older people (P < 0.001) were more likely to develop metformin intolerance. Concomitant use of transporter-inhibiting drugs increased the odds of intolerance (odds ratio [OR] 1.72, P < 0.001). In an adjusted logistic regression model, the G allele at rs3889348 (SLC29A4) was associated with gastrointestinal intolerance (OR 1.34, P = 0.005). rs3889348 is the top cis-expression quantitative trait locus for SLC29A4 in gut tissue where carriers of the G allele had reduced expression. Homozygous carriers of the G allele treated with transporter-inhibiting drugs had more than three times higher odds of intolerance compared with carriers of no G allele and not treated with inhibiting drugs (OR 3.23, P < 0.001). Use of a genetic risk score derived from rs3889348 and SLC22A1 variants found that the odds of intolerance were more than twice as high in individuals who carry three or more risk alleles compared with those carrying none (OR 2.15, P = 0.01).

    CONCLUSIONS: These results suggest that intestinal metformin transporters and concomitant medications play an important role in the gastrointestinal adverse effects of metformin.

  • 28. 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.

  • 29.
    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.

  • 30. Ekberg, Karin
    et al.
    Brismar, Tom
    Johansson, Bo-Lennart
    Lindström, Per
    Juntti-Berggren, Lisa
    Norrby, Anders
    Berne, Christian
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    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. © 2007 by the American Diabetes Association.

  • 31. 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.

  • 32.
    Ekelund, Ulf
    et al.
    Medical Research Council Epidemiology Unit, Cambridge, U.K..
    Franks, Paul
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sharp, Stephen
    Medical Research Council Epidemiology Unit, Cambridge, U.K..
    Brage, Søren
    Medical Research Council Epidemiology Unit, Cambridge, U.K..
    Wareham, Nicholas J.
    Medical Research Council Epidemiology Unit, Cambridge, U.K..
    Increase in physical activity energy expenditure is associated with reduced metabolic risk independent of change in fatness and fitness2007In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 30, no 8, p. 2101-2106Article in journal (Refereed)
    Abstract [en]

    Objective: We sought to examine whether change in physical activity energy expenditure (PAEE) is associated with change in metabolic risk factors and whether this association is independent of change in fat mass and aerobic fitness.

    Research design and methods: In a population-based sample of 176 men and 217 women followed prospectively for 5.6 years, we measured PAEE by individually calibrated heart rate monitoring, aerobic fitness, total body fat (fat mass), and metabolic risk factors (blood pressure, fasting triglycerides, HDL cholesterol, insulin, and 2-h glucose) at baseline and follow-up.

    Results: A 100 J · kg fat-free mass (FFM)−1 · min−1 increase in PAEE from baseline to follow-up reduced triglycerides by 3.5% (95% CI 0.03–5.7) in men and 3.2% (0.02–5.4) in women, fasting insulin by 5.3% (1.0–7.5) in men and women, and 2-h glucose by 3.2% (0.3–5.3) in men and 3.1% (0.3–5.2) in women, after adjustment for sex, age, smoking status, aerobic fitness, baseline phenotype, and change in fat mass. In general, the magnitudes of association for change in fat mass with metabolic risk factors were two to three times stronger than for PAEE.

    Conclusions: Increasing levels of physical activity may protect against metabolic disease even in the absence of improved aerobic fitness and reduced body fatness. Therefore, the combination of increasing levels of physical activity and avoidance of gain in fat mass is likely to be the most successful approach for preventing cardiovascular and metabolic disease.

  • 33.
    Elding Larsson, Helena
    et al.
    Lund University.
    Vehik, Kendra
    University of S Florida.
    Bell, Ronny
    Wake Forest University.
    Dabelea, Dana
    Colorado School Public Heatlh.
    Dolan, Lawrence
    University of Cincinnati.
    Pihoker, Catherine
    University of Washington.
    Knip, Mikael
    Tampere University Hospital.
    Veijola, Riitta
    University of Oulu.
    Lindblad, Bengt
    University of Gothenburg.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Holl, Reinhard
    University of Ulm.
    J Haller, Michael
    University of Florida.
    Reduced Prevalence of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Young Children Participating in Longitudinal Follow-Up2011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, no 11, p. 2347-2352Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-Young children have an unacceptably high prevalence of diabetic ketoacidosis (DKA) at the clinical diagnosis of type I. diabetes. The aim of this study was to determine whether knowledge of genetic risk and close follow-up for development of islet autoantibodies through participation in The Environmental Determinants of Diabetes in the Young (TEDDY) study results in lower prevalence of DKA at diabetes onset in children aged andlt;2 and andlt;5 years compared with population-based incidence studies and registries. less thanbrgreater than less thanbrgreater thanRESEARCH DESIGN AND METHODS-Symptoms and laboratory data collected on TEDDY participants diagnosed with type 1 diabetes between 2004 and 2010 were compared with data collected during the similar periods from studies and registries in all TEDDY-participating countries (U.S., SEARCH for Diabetes in Youth Study; Sweden, Swediabkids; Finland, Finnish Pediatric Diabetes Register; and Germany, Diabetes Patienten Verlaufsdokumenation [DPV] Register). less thanbrgreater than less thanbrgreater thanRESULTS-A total of 40 children younger than age 2 years and 79 children younger than age 5 years were diagnosed with type 1 diabetes in TEDDY as of December 2010. In children andlt;2 years of age at onset, DKA prevalence in TEDDY participants was significantly lower than in all comparative registries (German DPV Register, P andlt; 0.0001; Swediabkids, P = 0.02; SEARCH, P andlt; 0.0001; Finnish Register, P andlt; 0.0001). The prevalence of DKA in TEDDY children diagnosed at andlt;5 years of age (13.1%) was significantly lower compared with SEARCH (36.4%) (P andlt; 0.0001) and the German DPV Register (32.2%) (P andlt; 0.0001) but not compared with Swediabkids or the Finnish Register. less thanbrgreater than less thanbrgreater thanCONCLUSIONS-Participation in the TEDDY study is associated with reduced risk of DMA at diagnosis of type 1 diabetes in young children.

  • 34. 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.

  • 35. Elks, Cathy E.
    et al.
    Ong, Ken K.
    Scott, Robert A.
    van der Schouw, Yvonne T.
    Brand, Judith S.
    Wark, Petra A.
    Amiano, Pilar
    Balkau, Beverley
    Barricarte, Aurelio
    Boeing, Heiner
    Fonseca-Nunes, Ana
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Lunds universitet.
    Grioni, Sara
    Halkjaer, Jytte
    Kaaks, Rudolf
    Key, Timothy J.
    Khaw, Kay Tee
    Mattiello, Amalia
    Nilsson, Peter M.
    Overvad, Kim
    Palli, Domenico
    Quiros, J. Ramon
    Rinaldi, Sabina
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Romieu, Isabelle
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Tormo, Maria-Jose
    Tumino, Rosario
    Daphne, L. Van der A.
    Forouhi, Nita G.
    Sharp, Stephen J.
    Langenberg, Claudia
    Riboli, Elio
    Wareham, Nicholas J.
    Age at Menarche and Type 2 Diabetes Risk The EPIC-InterAct study2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 11, p. 3526-3534Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Younger age at menarche, a marker of pubertal timing in girls, is associated with higher risk of later type 2 diabetes. We aimed to confirm this association and to examine whether it is explained by adiposity. RESEARCH DESIGN AND METHODS The prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from 26 research centers across eight European countries. We tested the association between age at menarche and incident type 2 diabetes using Prentice-weighted Cox regression in 15,168 women (n = 5,995 cases). Models were adjusted in a sequential manner for potential confounding and mediating factors, including adult BMI. RESULTS Mean menarcheal age ranged from 12.6 to 13.6 years across InterAct countries. Each year later menarche was associated with 0.32 kg/m(2) lower adult BMI. Women in the earliest menarche quintile (8-11 years, n = 2,418) had 70% higher incidence of type 2 diabetes compared with those in the middle quintile (13 years, n = 3,634), adjusting for age at recruitment, research center, and a range of lifestyle and reproductive factors (hazard ratio [HR], 1.70; 95% CI, 1.49-1.94; P < 0.001). Adjustment for BMI partially attenuated this association (HR, 1.42; 95% CI, 1.18-1.71; P < 0.001). Later menarche beyond the median age was not protective against type 2 diabetes. CONCLUSIONS Women with history of early menarche have higher risk of type 2 diabetes in adulthood. Less than half of this association appears to be mediated by higher adult BMI, suggesting that early pubertal development also may directly increase type 2 diabetes risk.

  • 36.
    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)
  • 37.
    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.

  • 38.
    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.

  • 39. Estampador, Angela C.
    et al.
    Pomeroy, Jeremy
    Renstrom, Frida
    Nelson, Scott M.
    Mogren, Ingrid
    Persson, Margareta
    Dalarna University, School of Education, Health and Social Studies, Caring Science/Nursing.
    Sattar, Naveed
    Domellof, Magnus
    Franks, Paul W.
    Infant body composition and adipokine concentrations in relation to maternal gestational weight gain2014In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 37, no 5, p. 1432-1438Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE. To investigate associations of maternal gestational weight gain and body composition and their impact on offspring body composition and adipocytokine, glucose, and insulin concentrations at age 4 months.

    RESEARCH DESIGN AND METHODS. This was a prospective study including 31 mother-infant pairs (N = 62). Maternal body composition was assessed using doubly labeled water. Infant body composition was assessed at 4 months using air displacement plethysmography, and venous blood was assayed for glucose, insulin, adiponectin, interleukin-6 (IL-6), and leptin concentrations.

    RESULTS. Rate of gestational weight gain in midpregnancy was significantly associated with infant fat mass (r = 0.41, P = 0.03); rate of gestational weight in late pregnancy was significantly associated with infant fat-free mass (r = 0.37, P = 0.04). Infant birth weight was also strongly correlated with infant fat-free mass at 4 months (r = 0.63, P = 0.0002). Maternal BMI and maternal fat mass were strongly inversely associated with infant IL-6 concentrations (r = -0.60, P = 0.002 and r = -0.52, P = 0.01, respectively). Infant fat-free mass was inversely related to infant adiponectin concentrations (r = -0.48, P = 0.008) and positively correlated with infant blood glucose adjusted for insulin concentrations (r = 0.42, P = 0.04). No significant associations for leptin were observed.

    CONCLUSIONS. Timing of maternal weight gain differentially impacts body composition of the 4-month-old infant, which in turn appears to affect the infant's glucose and adipokine concentrations.

  • 40.
    Estampador, Angela C.
    et al.
    Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden .
    Pomeroy, Jeremy
    Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden ; Phoenix Epidemiology and Clinical Research Branch, National Institutes of Health, Phoenix, AZ .
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden .
    Nelson, Scott M.
    Reproductive and Maternal Medicine, Faculty of Medicine, University of Glasgow, Glasgow, U.K..
    Mogren, Ingrid
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Persson, Margareta
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Dalarna University, School of Health and Social Studies, Falun, Sweden.
    Sattar, Naveed
    British Heart Foundation Cardiovascular Research Center, University of Glasgow, Glasgow, U.K..
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden ; Department of Nutrition, Harvard School of Public Health, Boston, MA.
    Infant body composition and adipokine concentrations in relation to maternal gestational weight gain2014In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 37, no 5, p. 1432-1438Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate associations of maternal gestational weight gain and body composition and their impact on offspring body composition and adipocytokine, glucose, and insulin concentrations at age 4 months. RESEARCH DESIGN AND METHODS: This was a prospective study including 31 mother-infant pairs (N = 62). Maternal body composition was assessed using doubly labeled water. Infant body composition was assessed at 4 months using air displacement plethysmography, and venous blood was assayed for glucose, insulin, adiponectin, interleukin-6 (IL-6), and leptin concentrations. RESULTS: Rate of gestational weight gain in midpregnancy was significantly associated with infant fat mass (r = 0.41, P = 0.03); rate of gestational weight in late pregnancy was significantly associated with infant fat-free mass (r = 0.37, P = 0.04). Infant birth weight was also strongly correlated with infant fat-free mass at 4 months (r = 0.63, P = 0.0002). Maternal BMI and maternal fat mass were strongly inversely associated with infant IL-6 concentrations (r = -0.60, P = 0.002 and r = -0.52, P = 0.01, respectively). Infant fat-free mass was inversely related to infant adiponectin concentrations (r = -0.48, P = 0.008) and positively correlated with infant blood glucose adjusted for insulin concentrations (r = 0.42, P = 0.04). No significant associations for leptin were observed. CONCLUSIONS: Timing of maternal weight gain differentially impacts body composition of the 4-month-old infant, which in turn appears to affect the infant's glucose and adipokine concentrations.

  • 41.
    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)
  • 42.
    Franks, Paul W.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pearson, Ewan
    Florez, Jose C.
    Gene-Environment and Gene-Treatment Interactions in Type 2 Diabetes2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 5, p. 1413-1421Article, review/survey (Refereed)
  • 43. Goedecke, Julia H
    et al.
    Dave, Joel A
    Faulenbach, Mirjam V
    Utzschneider, Kristina M
    Lambert, Estelle V
    West, Sacha
    Collins, Malcolm
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Walker, Brian R
    Seckl, Jonathan R
    Kahn, Steven E
    Levitt, Naomi S
    Insulin response in relation to insulin sensitivity: an appropriate beta-cell response in black South African women.2009In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 32, no 5, p. 860-855Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The purpose of this study was to characterize differences in the acute insulin response to glucose (AIR(g)) relative to insulin sensitivity (S(I)) in black and white premenopausal normoglycemic South African women matched for body fatness. RESEARCH DESIGN AND METHODS: Cross-sectional analysis including 57 black and white South African women matched for BMI, S(I), AIR(g), and the disposition index (AIR(g) x S(I)) were performed using a frequently sampled intravenous glucose tolerance test with minimal model analysis, and similar measures were analyzed using an oral glucose tolerance test (OGTT). Body composition was assessed by dual-energy X-ray absorptiometry and computed tomography. RESULTS: S(I) was significantly lower (4.4 +/- 0.8 vs. 9.4 +/- 0.8 and 2.9 +/- 0.8 vs. 6.0 +/- 0. 8 x 10(-5) min(-1)/[pmol/l], P < 0.001) and AIR(g) was significantly higher (1,028 +/- 255 vs. 352 +/- 246 and 1,968 +/- 229 vs. 469 +/- 246 pmol/l, P < 0.001), despite similar body fatness (30.9 +/- 1.4 vs. 29.7 +/- 1.3 and 46.8 +/- 1.2 vs. 44.4 +/- 1.3%) in the normal-weight and obese black women compared with their white counterparts, respectively. Disposition index, a marker of beta-cell function, was not different between ethnic groups (3,811 +/- 538 vs. 2,966 +/- 518 and 3,646 +/- 485 vs. 2,353 +/- 518 x 10(-5) min, P = 0.10). Similar results were obtained for the OGTT-derived measures. CONCLUSIONS: Black South African women are more insulin resistant than their white counterparts but compensate by increasing their insulin response to maintain normal glucose levels, suggesting an appropriate beta-cell response for the level of insulin sensitivity.

  • 44. Greenbaum, Carla
    et al.
    Mandrup-Poulsen, Thomas
    Friedenberg McGee, Paula
    Battelino, Tadej
    Haastert, Burkhard
    Ludvigsson, Johnny
    The Biostatistics Center, Rockville, Maryland.
    Pozzilli, Paolo
    Lachin, John M
    Kolb, Hubert
    and the European C-peptide Trial Study Group, The Type 1 Diabetes Trial Net Research Group
    Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes2008In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, no 10, p. 1966-1971Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Beta-cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. RESEARCH DESIGN AND METHODS: In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects completed 348 tests (up to 3 each) with either two MMTTs or two GSTs. RESULTS: Among individuals with up to 4 years' duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were highly reproducible, the MMTT was significantly more so (R(2) = 0.96 for peak C-peptide response). Overall, the majority of subjects preferred the MMTT, and there were few adverse events. Some older subjects preferred the shorter duration of the GST. Nausea was reported in the majority of GST studies, particularly in the young age-group. CONCLUSIONS: The MMTT is preferred for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.

  • 45. 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.

  • 46. 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.

  • 47.
    Hanberger, Lena
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindblad, Bengt
    Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    AlC in children and adolescents with diabetes in relation to certain clinical parameters - The Swedish Childhood Diabetes Registry SWEDIABKIDS2008In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, no 5, p. 927-929Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - We explored the relationship between AlC and insulin regimen, duration of diabetes, age, sex, and BMI as well as the differences between clinical mean AlC levels at pediatric diabetes clinics in Sweden. RESEARCH DESIGN AND METHODS - Data from 18,651 clinical outpatient visits (1,033 girls and 1,147 boys) at 20 pediatric clinics during 2001 and 2002 registered in the Swedish Childhood Diabetes Registry SWEDIABKIDS, a national quality registry, were analyzed. RESULTS - AlC was < 7.0% (target value similar to 8% per Diabetes Control and Complications Trial/National Glycohemoglobin Standardization Program standards) at 35% of the visits. Girls had significantly higher mean AlC than boys during adolescence. High mean AlC was correlated with high mean insulin dose, long duration of diabetes, and older age. Mean AlC varied between clinics (6.8-8.2%). Differences between centers could not be explained by differences in diabetes duration, age, BMI, or insulin dose. CONCLUSIONS - Adolescents with a high insulin dose and a long duration of diabetes, especially girls, need to be focused on, Differences in mean values between centers remained inexplicable and require further investigation.

  • 48.
    Hanås, Ragnar
    et al.
    Department of Pediatrics, Uddevalla Hospital, Uddevalla.
    Carlsson, Sten
    Department of Medical Physics, Uddevalla Hospital, Uddevalla.
    Frid, Anders
    Department of Internal Medicine, University of Lund, Lund.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Unchanged Insulin Absorption After 4 Days' Use of Subcutaneous Indwelling Catheters for Insulin Injections1997In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 20, no 4, p. 487-490Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Since 1985, we have used indwelling catheters (Insuflon, Maersk Medical, Lynge, Denmark; Chronimed, Minnetonka, MN) to lessen pain when injecting insulin. However, some patients experience a rise in blood glucose after using indwelling catheters for a few days. We therefore studied the absorption of 125I-labeled insulin when using indwelling catheters.

    RESEARCH DESIGN AND METHODS Five men and five women participated (age 18–25 years, C-peptide negative, HbA1c 9.0 ± 1.0% [mean ± SD, DCA-2000 method], diabetes duration 5–21 [median 9.5] years). After thyroid blockage with potassium iodide, we injected 5IU of 125I-labeled short-acting insulin subcutaneously in the abdomen (“ordinary injection”) and 5 IU on the contralateral side through an indwelling catheter (“catheter injection”). The injection/insertion area was free of lipohyper- and lipohypotrophies. Disappearance rate was measured for 180 min with a gamma camera. The patients injected all premeal injections of short-acting insulin through the same indwelling catheter in the following 4 days. The investigation procedure was repeated day 3 and 5.

    RESULTS We found no statistically or clinically (95% CI) significant difference in residual activity of 125I-insulin after 60 min or in time for 50% of the injected depot to disappear (T-50%) among catheter injections on day 1, 3, and 5; ordinary injections on days 1, 3, and 5; or catheter and ordinary injections on days 1, 3, and 5, respectively. HbA1c correlated both to T-50% (r = 0.73, P = 0.016) and residual activity of 125I-insulin after 60 min (r = 0.69, P = 0.028), indicating that patients with a slower absorption will have a less ideal metabolic control when using premeal bolus injections.

    CONCLUSIONS We conclude that using indwelling subcutaneous catheters for insulin injections for up to 4 days does not affect the absorption of short-acting insulin.

  • 49.
    Hanås, Ragnar
    et al.
    Department of Pediatrics, Uddevalla Hospital, Uddevalla.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Metabolic Control Is Not Altered When Using Indwelling Catheters for Insulin Inactions1994In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 17, no 7, p. 716-718Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To determine if the use of indwelling catheters for insulin injections affects the long- and short-term metabolic control of insulin-dependent diabetes mellitus (IDDM).

    RESEARCH DESIGN AND METHODS Sixteen children and adolescents 9–20 years of age were included in a randomized 10-week crossover study using indwelling catheters (Insuflon, Pharma-Plast, Lynge, Denmark; CHRONIMED, Minnetonka, Minnesota) for insulin injections. Their diabetes duration was 7.5 ± 3.3 years (range 2–14), and they used multiple injection therapy with 4–5 doses/day. C-peptide was <0.15 nM fasting and ≤0.30 nM postprandial.

    RESULTS We found no significant difference between those with and without Insuflon in degree of metabolic control reflected by HbA1c (with Insuflon, 7.3 ± 2.6%; without, 7.1 ± 2.2%), 24-h profiles of blood glucose and free insulin, 24-h samples of glucosuria, or ketonuria. Weight, insulin doses per kilogram per 24 h, and insulin antibodies were all the same in the two groups.

    CONCLUSIONS The long- and short-term metabolic control of IDDM was not altered by the use of indwelling catheters for insulin injections. Insuflon can be offered as an alternative to patients with IDDM who find regular injections uncomfortable.

  • 50. Hare, Matthew JL
    et al.
    Magliano, Dianna J
    Zimmet, Paul Z
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Joonas, Noorjehan
    Pauvaday, Vassen
    Larhubarbe, Jose
    Tuomilehto, Jaakko
    Kowlessur, Sudhir
    Alberti, K George MM
    Shaw, Jonathan E
    Glucose-independent ethnic differences in HbA(1c), in people without known diabetes2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 6, p. 1534-1540Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To determine whether glucose-independent differences in HbA(1c) exist between people of African, South Asian, and Chinese ethnicities.

    RESEARCH DESIGN AND METHODS Data from 6,701 people aged 19-78 years, without known diabetes, from Mauritius, and participating in the population-based Non-Communicable Disease Surveys of the main island and the island of Rodrigues were included. Participants were African (n = 1,219 from main island, n = 1,505 from Rodrigues), South Asian (n = 3,820), and Chinese (n = 157). Survey data included HbA(1c), plasma glucose during oral glucose tolerance testing (OGTT), anthropometry, demographics, and medical and lifestyle history.

    RESULTS Mean HbA(1c), after adjustment for fasting and 2-h plasma glucose and other factors known to influence HbA(1c), was higher in Africans from Rodrigues (6.1%) than in South Asians (5.7%, P < 0.001), Chinese (5.7%, P < 0.001), or Africans from the main island of Mauritius (5.7%, P < 0.001). The age-standardized prevalence of diabetes among Africans from Rodrigues differed substantially depending on the diagnostic criteria used [OGTT 7.9% (95% CI 5.8-10.0); HbA(1c) 17.3% (15.3-19.2)]. Changing diagnostic criteria resulted in no significant change in the prevalence of diabetes within the other ethnic groups.

    CONCLUSIONS People of African ethnicity from Rodrigues have higher HbA(1c) than those of South Asian or African ethnicity from the main island of Mauritius for reasons not explained by plasma glucose during an OGTT or traditional factors known to affect glycemia. Further research should be directed at determining the mechanism behind this disparity and its relevance to clinical outcomes.

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