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

Abstract

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 (MCRI) during hyperinsulinemic (100 mU/m2/min) glucose clamp studies. The results indicated that mean (+/- SEM) MCRI was 1.4-fold greater in the diabetic subjects (436 +/- 22 ml/m2/min) than in the controls (325 +/- 24 ml/m2/min, P less than 0.005), resulting in a lower steady-state plasma insulin concentration in the diabetic (255 +/- 8 microU/ml) compared with the nondiabetic subjects (329 +/- 29 microU/ml, P less than 0.001). The impact of NIDDM on insulin removal rates was also estimated by a second method in which extraction of endogenously secreted insulin (EXTI) 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 beta-cell secretion. The results demonstrated that fractional extraction of endogenously secreted insulin (EXTI = 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 less than 0.001). Finally, these two independent measurements of in vivo insulin removal rates (MCRI and EXTI) were significantly correlated with each other (r = 0.71, P less than 0.002). These observations are consistent with the view that elevated insulin clearance may contribute to the postchallenge hypoinsulinemia of NIDDM in Pima Indians.

Correlates of insulin clearance in apparently healthy non-obese Japanese men

“…First, we did not perform a pancreatic clamp to completely suppress endogenous insulin secretion throughout the experiment (basal period and clamp). To take this fact into consideration, we adjusted the calculation of MCRI according to the suppression of C-peptide level using a previously published method 30, 31 . Second, we recruited only Japanese in this study, thus our results may not be applicable to other ethnic groups.…”

Relationship of insulin clearance and secretion to insulin sensitivity in non‐diabetic Mexican Americans

“…Vasquez et al have reported that obese Pima Indians with type I1 diabetes have increased clearance of insulin relative to obese non-diabetic Indians [27], thus partially explaining the low post glucose challenge insulin concentrations in the former. It would be of considerable interest to follow the non-diabetic Pima Indians to determine whether the clearance of insulin changes after the onset of the diabetic state or, alternatively, whether clearance of insulin (as well as insulin sensitivity [5]) predicts the onset of type I1 diabetes.…”

Kinetic Models for Insulin Disappearance from Plasma in Type I Diabetic Patients

“…Studies of the kinetics of insulin in diabetes as compared to the normal state have given conflicting results: the insulin disappearance rate from the blood stream has been reported to be increased (Navalesi et al 1983;Vasquez et a/. 1985), unchanged (Silvers et al 1969;Brskov & Christensen 1969;Genuth 1972;Navalesi et al 1978;McGuire et al 1979;Del Prato et al 1983) or decreased (Stimmler et al 1972;Frost et Gray et a/.…”