Increased Basal Glucose Production and Utilization in Nondiabetic First-Degree Relatives of Patients With NIDDM

To characterize the abnormalities in basal glucose homeostasis in people who are at increased risk for non-insulin-dependent diabetes mellitus (NIDDM), we measured the rates of basal hepatic glucose output (HGO), glucose disappearance, and metabolic clearance of glucose (MCR) in 27 nondiabetic first-degree relatives of NIDDM patients and 16 age-, sex-, and weight-matched healthy control subjects with no family history of NIDDM. Mean fasting plasma glucose was significantly lower (P < 0.05) in control subjects (mean ± SE 77 ± 2 mg/dl) than in relatives (84 ± 2 mg/dl). Mean basal insulin levels were not significantly different between relatives and control subjects (10.0 ± 1.5 vs. 7.7 ± 1.0 μU/ml). Mean basal HGO was significantly lower in control subjects compared with relatives (1.83 ± 0.07 vs. 2.20 ± 0.10 mg · kg⁻¹ · min⁻¹ P < 0.05). Mean MCR was similar in relatives (2.58 ± 0.12 mg · kg⁻¹ · min⁻¹) and control subjects (2.35 ± 0.09 mg · kg⁻¹ · min⁻¹). In summary, this study demonstrates that basal hepatic glucose production and glucose utilization are increased in glucose-tolerant first-degree relatives compared with healthy control subjects. We conclude that impaired basal hepatic glucose regulation rather than glucose disposal is present as an early defect in glucose-tolerant first-degree relatives of NIDDM patients.