Insulin production rate, hepatic insulin retention and splanchnic carbohydrate metabolism after oral glucose ingestion in hyperinsulinaemic Type 2 (non-insulin-dependent) diabetes mellitus

Publisher Website
Google Scholar
Abstract
To differentiate peripheral and hepatic insulin resistance in hyperinsulinaemic overweight Type 2 (non-insulin-dependent) diabetic patients (n = 17; 143±4% ideal body weight; mean±SEM) arterial concentrations and splanchnic exchange of glucose, pyruvate, lactate, non-esterified fatty acids, β-hydroxybutyrate and acetoacetate, as well as the insulin production rate, were determined before and during oral glucose loads of 25 g or 100 g. Insulin production rate, hepatic insulin retention and splanchnic exchange of glucose and metabolites were estimated by means of the hepatic venous catheter technique. In the basal state insulin production rate was greater in overweight Type 2 diabetic patients (2.57±0.28 pmol.kg-1. min-1) than in healthy control subjects (1.68±0.17 pmol.kg-1. min-1; pp < 0.05), but was below normal with 100 g glucose (p < 0.01). Relative insulin trapping by the splanchnic bed in the diabetic patients was 54±3%, not different from normal. Following a 100 g glucose load, splanchnic insulin retention fell by 20% in the patients, and less consistently so in healthy controls. Splanchnic glucose output was normal in the diabetic patients both in the basal state and after glucose ingestion although the induced arterial blood glucose levels were greater in the diabetic patients than in control subjects (p < 0.005). Splanchnic output of pyruvate (p < 0.025), lactate (p < 0.01), and β-hydroxybutyrate (p < 0.005) were greater in the basal state in the diabetic patients than in healthy subjects. However, no difference in splanchnic exchange was seen between the two groups in their metabolites' respective response to glucose ingestion. These data suggest that obese hyperinsulinaemic Type 2 diabetic patients may represent a subgroup of diabetic patients with predominantly peripheral, but compensated hepatic, insulin resistance being associated with an increased basal insulin production rate which only exhausts after ingestion of a large glucose load.