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

Family studies point to an important genetic element in the genesis of type 2 diabetes. A variety of metabolic abnormalities have been documented in o ffspring 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 cons ecutive type 2 diabetic patients and examined all available (n = 48) normot ensive, 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 an d controls included baseline IRI, tissue glucose uptake (TGU, using euglyce mic hyperinsulinemic clamp technique), and 24 hour ambulatory blood pressur e (ABP). TGU was significantly (p < 0.001) lower in offspring of diabetic p arents (338.8 +/- 19.9 (mol/kg/min) when compared to controls (516.6 +/- 22 .2 mu mol/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 H g, respectively). No difference in triglycerides concentration was found. A borderline negative correlation was observed, however, between triglycerid e levels and TGU (R = -0.48, p < 0.001). TGU was not related to the presenc e or absence of diabetic nephropathy in the parents. We conclude: Insulin resistance and various facets of the metabolic syndrom e are demonstrable even at age 30 years in young non-obese, normotensive of fspring of patients with type 2 diabetes. These disturbances are not relate d to the presence of microvascular complications in parents.