Acute effect of glimepiride on insulin-stimulated glucose metabolism in glucose-tolerant insulin-resistant offspring of patients with type 2 diabetes.
OBJECTIVE
This study addressed whether acute infusion of glimepiride influences glucose metabolism independent of its effect on insulin secretion.


METHODS
Ten healthy, glucose-tolerant but insulin-resistant probands were subjected to a placebo-controlled, double-blind, cross-over study. Each individual received infusions of either 0.15 mol/l saline or glimepiride in randomized order on two separate occasions. A three-step hyperinsulinemic (0.5, 1.0, and 1.5 mU. kg(-1). min(-1))-euglycemic glucose clamp was performed on both occasions to determine insulin sensitivity. Glimepiride-induced insulin secretion was inhibited by octreotide. Endogenous glucose production and glucose elimination were measured with the "hot" glucose infusion method using U-[(13)C]glucose as tracer. Glucose oxidation was determined from indirect calorimetry. Lipolysis was evaluated by measurements of nonesterified fatty acid (NEFA) and glycerol concentration and measurement of glycerol production.


RESULTS
Plasma glucose and insulin concentrations were not significantly different between glimepiride or saline infusions. There was a significant increase in the rate of glucose infusion necessary to maintain euglycemia during infusion of glimepiride during the low- (12.2 +/- 1.1 vs. 16.1 +/- 1.7 micro mol. kg(-1). min(-1)) and intermediate-dose insulin infusion (24.4 +/- 1.7 vs. 30.0 +/- 2.8 micro mol. kg(-1). min(-1)). This was explained by an increased rate of glucose elimination and to a lesser degree by a decrease in glucose production. Glucose oxidation rate was not different. NEFA and glycerol concentration and glycerol production were equally suppressed.


CONCLUSIONS
Glimepiride improves peripheral glucose uptake and decreases endogenous glucose production independent of its insulin secretagogue action. The effects shown in this acute study are, however, too small to be considered therapeutically beneficial for the individual patient.
Overkamp
Dietrich
D
Department of Internal Medicine IV, Tübingen, Germany. dietrih.overkamp@med.uni-tuebingen.de
Volk
Annette
A
Maerker
Elke
E
Heide
Peter E
PE
Wahl
Hans G
HG
Rett
Kristian
K
Häring
Hans U
HU
D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D009679:Nuclear Family; D012016:Reference Values; D013453:Sulfonylurea Compounds / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; C057619:glimepiride