Elevated In Vivo Insulin Clearance in Pima Indians with Non-insulin-dependent Diabetes Mellitus

In vivo insulin clearance in 10 subjects with non-insulin-dependent diabetes mellitus (NIDDM) has been compared with clearance in eight equally obese nondiabetic control subjects by two different methods. The first approach consisted of determining the metabolic clearance rates of exogenously infused insulin (MCR,) during hyperins Ulinemic (100 mU/m² min) glucose clamp studies. The results indicated that mean (± SEM) MCR, was 1.4-fold greater in the diabetic subjects (436 ± 22 ml m² min) than in the controls (325 ± 24 ml/m²min, P < 0.005), resulting in a lower steady-state plasma insulin concentration in the diabetic (255 ± 8 μU/ml) compared with the nondiabetic subjects (329 ± 29 μU/ ml, P < 0.001). The impact of NIDDM on insulin removal rates was also estimated by a second method in which extraction of endogenously secreted insulin (EXT₁) in response to an oral glucose load was calculated from the integrated area above basal of plasma insulin (∫IRI) and of plasma C-peptide (∫CPR), an estimate of β-cell secretion. The results demonstrated that fractional extraction of endogenously secreted insulin (EXT₁ = 100 [{∫CPR - ∫IRI}/∫CPR]) was also 1.2-fold greater for diabetic subjects (88.9 ± 2.5%) than for nondiabetic controls (72.0 ± 2.8%, P < 0.001). Finally, these two independent measurements of in vivo insulin removal rates (MCR, and EXT₁) were significantly correlated with each other (r = 0.71, P < 0.002). These observations are consistent with the view that elevated insulin clearance may contribute to the postchallenge hypoinsulinemia of NIDDM in Pima Indians.