Reduced insulin-mediated glucose uptake by euglycemic clamp in offspring of patients with type 2 diabetes.

Abstract

Family studies point to an important genetic element in the genesis of type 2 diabetes. A variety of metabolic abnormalities have been documented in offspring of patients with type 2 diabetes. It has not been shown, however, at what age reduced insulin sensitivity is demonstrable using the sensitive the euglycemic clamp technique. To address this issue we screened 425 consecutive type 2 diabetic patients and examined all available (n = 48) normotensive, normoglycemic, non-smoking offspring (mean age 31.4+/-0.9 years) and compared them to 22 healthy offspring of non-diabetic parents (controls). The two groups were of similar age and BMI. Measurements in offspring and controls included baseline IRI, tissue glucose uptake (TGU, using euglycemic hyperinsulinemic clamp technique), and 24 hour ambulatory blood pressure (ABP). TGU was significantly (p < 0.001) lower in offspring of diabetic parents (338.8+/-19.9 (mol/kg/min) when compared to controls (516.6+/-22.2 micromol/kg/min). 24 h systolic ABP was significantly higher (p < 0.02) in propositi compared to controls (121.2+/-2.2 mm Hg and 113.8+/-1.7 mm Hg, respectively). No difference in triglycerides concentration was found. A borderline negative correlation was observed, however, between triglyceride levels and TGU (R = -0.48, p < 0.001). TGU was not related to the presence or absence of diabetic nephropathy in the parents. We conclude: Insulin resistance and various facets of the metabolic syndrome are demonstrable even at age 30 years in young non-obese, normotensive offspring of patients with type 2 diabetes. These disturbances are not related to the presence of microvascular complications in parents.