Does glibenclamide influence the clearance of insulin and glucose uptake in patients with type 2 diabetes mellitus?

Abstract

Sulphonylureas have been proposed to decrease the clearance of insulin based on the finding that they increase peripheral insulin concentrations more than C-peptide concentrations. However, direct evidence for such an effect has so far been lacking. The aim of this study was to investigate whether glibenclamide affects clearance of insulin in Type 2 diabetic patients. Nine patients with Type-2 diabetes participated in the study. Insulin clearance and glucose metabolism was assessed with a 240 min euglycaemic insulin clamp in combination with infusion of somatostatin (400μgh⁻¹) to completely suppress endogenous insulin secretion. Either saline or glibenclamide was infused throughout the clamp in random order. During both the glibenclamide and the saline protocol the C-peptide level declined to < 0.07nmoll⁻¹ within 150 min, indicating that insulin secretion was completely suppressed. However, peripheral clamp insulin concentrations remained similar during both saline and glibenclamide protocols (3374±258 vs. 3350±265 pmoll⁻¹ × 240 min, p = NS). There was no significant difference in the metabolic clearance rate of insulin during the glibenclamide compared to the saline experiment neither during the first 120min (796±36 vs. 757±34mlm⁻²min⁻¹) nor during the last 2h of the clamp (780±43 vs. 724±35mlm⁻²min⁻¹). Total glucose metabolism during the first two (14±2 vs. 15±2μmolkg⁻¹ min⁻¹) and the last 2h of the clamp was similar both during saline and glibenclamide infusions (27±4 vs. 28±4μmolkg⁻¹ min⁻¹).

It is concluded that glibenclamide does not decrease the clearance of insulin in patients with Type-2 diabetes and has no direct effect on total glucose uptake when endogenous insulin secretion is inhibited by somatosatin.

Key Words:

• euglycaemic clamp
• insulin clearance
• insulin sensitivity
• glibenclamide
• Type 2 diabetes