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1.
Diabet Med ; 32(2): 198-205, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25345799

ABSTRACT

AIMS: To investigate whether the presence of glutamic acid decarboxylase (GAD) autoantibodies post-partum in women with prior gestational diabetes mellitus was associated with changes in metabolic characteristics, including ß-cell function and insulin sensitivity. METHODS: During 1997-2010, 407 women with gestational diabetes mellitus were offered a 3-month post-partum follow-up including anthropometrics, serum lipid profile, HbA1c and GAD autoantibodies, as well as a 2-h oral glucose tolerance test (OGTT) with blood glucose, serum insulin and C-peptide at 0, 30 and 120 min. Indices of insulin sensitivity and insulin secretion were estimated to assess insulin secretion adjusted for insulin sensitivity, disposition index (DI). RESULTS: Twenty-two (5.4%) women were positive for GAD autoantibodies (GAD+ve) and the remainder (94.6%) were negative for GAD autoantibodies (GAD-ve). The two groups had similar age and prevalence of diabetes mellitus. Women who were GAD+ve had significantly higher 2-h OGTT glucose concentrations during their index-pregnancy (10.5 vs. 9.8 mmol/l, P = 0.001), higher fasting glucose (5.2 vs. 5.0 mmol/l, P = 0.02) and higher 2-h glucose (7.8 vs. 7.1 mmol/l, P = 0.05) post-partum. Fasting levels of C-peptide and insulin were lower in GAD+ve women compared with GAD-ve women (520 vs. 761 pmol/l, P = 0.02 and 33 vs. 53 pmol/l, P = 0.05) Indices of insulin sensitivity were similar in GAD+ve and GAD-ve women, whereas all estimates of DI were significantly reduced in GAD+ve women. CONCLUSION: GAD+ve women had higher glucose levels and impaired insulin secretion adjusted for insulin sensitivity (DI) compared with GAD-ve women. The combination of OGTT and GAD autoantibodies post-partum identify women with impaired ß-cell function. These women should be followed with special focus on development of Type 1 diabetes.


Subject(s)
Autoantibodies/analysis , Autoimmune Diseases/diagnosis , Diabetes Mellitus, Type 1/diagnosis , Diabetes, Gestational/physiopathology , Glutamate Decarboxylase/immunology , Insulin-Secreting Cells/metabolism , Insulin/metabolism , Adult , Autoimmune Diseases/epidemiology , Autoimmune Diseases/etiology , Autoimmune Diseases/immunology , Biomarkers/blood , Cohort Studies , Denmark/epidemiology , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/etiology , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/etiology , Diabetes Mellitus, Type 2/immunology , Diabetes, Gestational/blood , Diabetes, Gestational/immunology , Diagnosis, Differential , Early Diagnosis , Female , Follow-Up Studies , Glutamate Decarboxylase/antagonists & inhibitors , Humans , Insulin/blood , Insulin Resistance , Insulin Secretion , Insulin-Secreting Cells/immunology , Postpartum Period , Pregnancy , Prevalence , Prospective Studies
2.
Diabetologia ; 55(2): 340-8, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22095239

ABSTRACT

AIMS/HYPOTHESIS: There is substantial evidence that mitochondrial dysfunction is linked to insulin resistance and is present in several tissues relevant to the pathogenesis of type 2 diabetes. Here, we examined whether common variation in genes involved in oxidative phosphorylation (OxPhos) contributes to type 2 diabetes susceptibility or influences diabetes-related metabolic traits. METHODS: OxPhos gene variants (n = 10) that had been nominally associated (p < 0.01) with type 2 diabetes in a recent genome-wide meta-analysis (n = 10,108) were selected for follow-up in 3,599 type 2 diabetic and 4,956 glucose-tolerant Danish individuals. A meta-analysis of these variants was performed in 11,729 type 2 diabetic patients and 43,943 non-diabetic individuals. The impact on OGTT-derived metabolic traits was evaluated in 5,869 treatment-naive individuals from the Danish Inter99 study. RESULTS: The minor alleles of COX10 rs9915302 (p = 0.02) and COX5B rs1466100 (p = 0.005) showed nominal association with type 2 diabetes in our Danish cohort. However, in the meta-analysis, none of the investigated variants showed a robust association with type 2 diabetes after correction for multiple testing. Among the alleles potentially associated with type 2 diabetes, none negatively influenced surrogate markers of insulin sensitivity in non-diabetic participants, while the minor alleles of UQCRC1 rs2228561 and COX10 rs10521253 showed a weak (p < 0.01 to p < 0.05) negative influence on indices of glucose-stimulated insulin secretion. CONCLUSIONS/INTERPRETATION: We cannot rule out the possibility that common variants in or near OxPhos genes may influence beta cell function in non-diabetic individuals. However, our quantitative trait studies and a sufficiently large meta-analysis indicate that common variation in proximity to the examined OxPhos genes is not a major cause of insulin resistance or type 2 diabetes.


Subject(s)
Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Electron Transport Complex IV/genetics , Genetic Variation , Insulin Resistance , Oxygen/chemistry , Polymorphism, Single Nucleotide , Alleles , Case-Control Studies , Denmark , Diabetes Mellitus, Type 2/genetics , Glucose/metabolism , Humans , Mitochondria/metabolism , Models, Biological , Models, Genetic , Oxidative Phosphorylation , Phosphorylation , Quantitative Trait Loci
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