Metformin improves peripheral but not hepatic insulin action in obese patients with type II diabetes.
Nine obese patients with Type II diabetes mellitus were examined in a double-blind cross-over study. Metformin 0.5 g trice daily or placebo were given for 4 weeks. At the end of each period fasting and day-time postprandial values of plasma glucose, insulin, C-peptide and lactate were determined, and in vivo insulin action was assessed using the euglycemic clamp in combination with [3-3H]glucose tracer technique. Metformin treatment significantly reduced mean day-time plasma glucose levels (10.2 +/- 1.2 vs 11.4 +/- 1.2 mmol/l, P less than 0.01) without enhancing mean day-time plasma insulin (43 +/- 4 vs 50 +/- 7 mU/l, NS) or C-peptide levels (1.26 +/- 0.12 vs 1.38 +/- 0.18 nmol/l, NS). Fasting plasma lactate was unchanged (1.57 +/- 0.16 vs 1.44 +/- 0.11 mmol/l, NS), whereas mean day-time plasma lactate concentrations were slightly increased (1.78 +/- 0.11 vs 1.38 +/- 0.11 mmol/l, P less than 0.01). The clamp study revealed that metformin treatment was associated with an enhanced insulin-mediated glucose utilization (370 +/- 38 vs 313 +/- 33 mg.m-2.min-1, P less than 0.01), whereas insulin-mediated suppression of hepatic glucose production was unchanged. Also basal glucose clearance was improved (61.0 +/- 5.8 vs 50.6 +/- 2.8 ml.m-2.min-1, P less than 0.05), whereas basal hepatic glucose production was unchanged (81 +/- 6 vs 77 +/- 4 mg.m-2.min-1, NS).


CONCLUSIONS
1) Metformin treatment in obese Type II diabetic patients reduces hyperglycemia without changing the insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Hother-Nielsen
O
O
Department of Internal Medicine, Aarhus Amtssygehus, Denmark.
Schmitz
O
O
Andersen
P H
PH
Beck-Nielsen
H
H
Pedersen
O
O
D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D002940:Circadian Rhythm; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005215:Fasting; D006801:Humans; D007328:Insulin / Q000097:blood*; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000188:drug therapy*
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; D008687:Metformin