Hepatic insulin removal following oral glucose loading in nonobese subjects with mild Type II diabetes mellitus.

Abstract

This study has concentrated on evaluating the possible contributions of changes in liver uptake to glucose intolerance. Insulin secretion was simultaneously monitored. The level of hepatic uptake of insulin during basal conditions and after glucose loading was assessed in non-obese subjects with mild diabetes and compared to that of a healthy control group. It was demonstrated that metabolic clearance of insulin was identical under basal conditions (13.1 $\pm$ 1.5 ml kg$\sp{-1}$ml$\sp{-1}$--controls and 13.6 $\pm$ 2.0 ml kg$\sp{-1}$ml$\sp{-1}$--subjects with mild diabetes). Both the metabolic clearance rate and hepatic extraction of insulin fell by 20% in the control group following the glucose load (10.5 $\pm$ 1.5 ml kg$\sp{-1}$ml$\sp{-1}$ 139 $\pm$ 9%, n.s). However, the decrease in the group of subjects with mild diabetes was found to be approximately 50% (p 0.05). The ratios of the integrated insulin to C-peptide concentrations (in arbitrary units) showed a close relationship to the decline in the fractional hepatic extraction after glucose loading. It was found to be 0.21 $\pm$ 0.03 for the control group and 0.38 $\pm$ 0.05 for the subjects with mild diabetes (p 0.05). These ratios also demonstrated a correlation with a degree of glucose intolerance expressed as the integrated glucose concentrations for each subject (r = 0.6). The increase in the levels of circulating insulin resulted primarily from the fall in the hepatic insulin extraction, because based on the C-peptide data, there was no significant increase in the insulin secretion. The integrated insulin concentrations were 100% greater in the glucose intolerant group when compared with controls (137 $\pm$ 24 vs. 73 $\pm$ 12), while there was no significant difference in the integrated C-peptide concentrations (369 $\pm$ 51 vs. 340 $\pm$ 28). It is suggested, therefore that the decrease in insulin removal by the liver, and not hypersecretion can explain the hyperinsulinemia seen in the patients with mild diabetes which were studied here and therefore could be one of the early defects in this disease. (Abstract shortened by UMI.)