title: Plasma homocysteine concentrations in young individuals at increased risk of type 2 diabetes are associated with subtle differences in glomerular filtration rate but not with insulin resistance.
abstract: Plasma homocysteine levels are elevated in individuals with type 2 diabetes contributing to the increased cardiovascular risk of these patients. As insulin resistance is a key feature in type 2 diabetic patients, hyperhomocysteinemia might be a consequence of insulin resistance. We studied this hypothesis in 839 individuals(male: 302, female: 537, mean age: 37.5 years) with a higher prevalence of insulin resistance (positive family history of type 2 diabetes, history of gestational diabetes, overweight). Subjects with overt type 2 diabetes or known kidney disease were excluded from the study. Mean plasma homocysteine concentration was 8.9 micromol/l (95% RCI 4.8-14.9). Adjusted for age and sex we could not find a significant correlation between homocysteine levels and BMI, insulin levels, or the insulin sensitivity-index (r = 0.35; p = 0.48). Furthermore, after a successful lifestyle intervention resulting in a significant decrease in BMI, body fat content and improved insulin sensitivity (p < 0.0001 each) no differences in homocysteine concentrations could be achieved. However,in the cross-sectional analysis we found a significant and independent, negative correlation between glomerular filtration rate (GFR) and homocysteine levels (r = -0.37; p < 0.0001). In conclusion, our study did not reveal a significant association between levels of homocysteine and insulin resistance in a population with an increased risk for type 2 diabetes. However, plasma homocysteine levels were related to subtle differences in kidney function at this early stage.
authors.affiliation: Department of Endocrinology, Diabetology, Nephrology, Angiology, and Clinical Chemistry, University Hospital of Internal Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: S A
authors.initials: SA
authors.lastname: Schäfer
authors.forename: K
authors.initials: K
authors.lastname: Müssig
authors.forename: N
authors.initials: N
authors.lastname: Stefan
authors.forename: H-U
authors.initials: HU
authors.lastname: Häring
authors.forename: A
authors.initials: A
authors.lastname: Fritsche
authors.forename: B M
authors.initials: BM
authors.lastname: Balletshofer
mesh_terms: D000328:Adult; D000367:Age Factors; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D005260:Female; D005919:Glomerular Filtration Rate; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D040242:Risk Reduction Behavior; D013223:Statistics as Topic
chemical_list: D007328:Insulin; D006710:Homocysteine