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- Title
Elevated Levels of Retinol Binding Protein 4 Correlate with Hyperglycemia and Cardiovascular Risk Factors Independently of Insulin Sensitivity in Offspring of Type 2 Diabetic Subjects.
- Authors
Zemany, Laura; Graham, Timothy E.; Zilinskaite, Jone P.; Vättinen, Markku; Pihlajamäki, Jussi; Smith, Ulf; Kahn, Barbara B.; Laakso, Markku
- Abstract
Serum levels of retinol binding protein 4 (RBP4) are increased in insulin resistant states. We measured RBP4 levels in 240 non-diabetic offspring of type 2 diabetic subjects. Offspring had the following measurements: oral glucose tolerance test (OGTT), intravenous glucose tolerance test (IVGTT), euglycemic hyperinsulinemic clamp, and CT scan to evaluate subcutaneous and intra-abdominal fat. Mean age was 36.5±6.4 years, mean BM126±5 kg/m². No statistically significant differences in serum RBP4 levels were found between subjects with normoglycemia (n=170, mean RBP4 25.6 µg/ml), impaired fasting glucose (n=47, RBP4 27.4 µg/ml) and impaired glucose tolerance (n=23, RBP4 26.7 µg/ml). RBP4 levels correlated positively with BMI (p=0.007), systolic (p=0.022) and diastolic (p=0.02 l) blood pressure, fasting glucose (p=0.004) and insulin (p=0.029), 1st phase insulin response in an IVGTT (p=0.009), plasma glucose (p<0.001) and insulin (p=0.005) area under the curve during OGTT, total and LDL cholesterol (p<0.001), total triglycerides (p<0.001), and intra-abdominal fat area (13<0.001). RBP4 levels correlated inversely with whole body glucose uptake (WBGU) (p=0.003) and HDL cholesterol (p=0.027). In multivariate linear regression analysis including RBP4 levels, age, BMI, WBGU, and 1st phase insulin response as independent variables and glucose AUC in OGTT as the dependent variable, RBP4 levels were associated with glucose AUC in OGTT (p=0.006) independently of other variables. Genetic analysis of 900 Caucasian nondiabetic offspring of type 2 diabetic subjects revealed that several SNPs in the RBP4 gene are associated with circulating glucose levels from 10 to 60 min during an IVGTT. In sum, high serum RBP4 levels are associated with components of the metabolic syndrome in nonobese, nondiabetic subjects. High RBP4 is also associated with hyperglycemia, evaluated by glucose AUC in OGTT, independently of age, BMI, insulin sensitivity and insulin secretion in offspring of type 2 diabetic patients. In conclusion, genetic and metabolic data suggest that RBP4 may regulate insulin action on hepatic glucose output. Furthermore, RBP4 is a convenient marker to assess risk of diabetes and cardiovascular disease in subjects in whom the risk might otherwise be overlooked.
- Publication
Diabetes, 2007, Vol 56, pA378
- ISSN
0012-1797
- Publication type
Academic Journal