[en] In a double-blind, randomized, cross-over study, the metabolic effects of a short treatment with metformin (2 x 850 mg day-1 for 2 days and 850 mg 1 h before evaluation) were compared to those of placebo in 15 obese subjects (BMI: 33.2 +/- 0.9 kg m-2), with abdominal distribution of adipose tissue and impaired glucose tolerance. An intravenous glucose tolerance test (0.3 g glucose kg-1) was performed after each period of treatment. Areas under the curve (AUC0-180 min) were calculated for plasma glucose, insulin, and C-peptide levels. Glucose tolerance was estimated by the coefficient of glucose assimilation (KG). Insulin sensitivity (SI) and glucose effectiveness (SG) indices were calculated using Bergman's minimal model. Insulin secretion rate (ISR) was determined by deconvolution of plasma C-peptide levels and insulin metabolic clearance rate (MCR) was estimated by dividing AUC 1SR by AUC insulin. Fasting plasma insulin levels were reduced after metformin (89.3 +/- 15.9 vs 112.4 +/- 24.3 pmol l-1; p = 0.04). AUC glucose, KG and SG were similar in both tests. However, AUC insulin was reduced (39.7 +/- 6.5 vs 51.8 +/- 10.4 nmol min l-1; p = 0.02), while SI (6.98 +/- 1.14 vs 4.61 +/- 0.42 10(-5) min-1 pmol-1 l; p = 0.03) and insulin MCR (715 +/- 116 vs 617 +/- 94 ml min-1 m-2; p = 0.03) were increased after metformin. The demonstration that metformin rapidly improves insulin sensitivity should encourage further research to evaluate the long-term effects of metformin in android obese subjects with impaired oral glucose tolerance.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Scheen, André ; Université de Liège - ULiège > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques - Médecine interne générale
Letiexhe, Michel ; Centre Hospitalier Universitaire de Liège - CHU > Diabétologie,nutrition, maladies métaboliques
Lefebvre, Pierre ; Centre Hospitalier Universitaire de Liège - CHU > Diabétologie,nutrition, maladies métaboliques
Language :
English
Title :
Short administration of metformin improves insulin sensitivity in android obese subjects with impaired glucose tolerance.
Publication date :
1995
Journal title :
Diabetic Medicine: A Journal of the British Diabetic Association
Beck‐Nielsen H., Groop LC (1994) Metabolic and genetic characterization of prediabetic states. Sequence of events leading to non‐insulin‐dependent diabetes mellitus. Journal of Clinical Investigation 94:1714-1721.
Phillips DIW, Clark PM, Hales CN, Osmond C. (1994) Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion. Diabetic Med 11:286-292.
Reaven GM (1988) Role of insulin resistance in human disease. Diabetes 37:1595-1607.
Martin BC, Warram JH, Krolewski AS, Bergman RN, Soeldner JS, Kahn CR (1992) Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25‐year follow‐up study. Lancet 340:925-929.
Scheen AJ, Lefèbvre PJ (1992) Assessment of insulin sensitivity in vivo. Application to the study of type 2 diabetes. Horm Res 38:19-27.
Bailey CJ (1992) Biguanides and NIDDM. Diabetes Care 15:755-772.
Hermann LS, Melander A. (1992) Biguanides: basic aspects and clinical uses. International Textbook of Diabetes Mellitus , Alberti KGMM, DeFronzo RA, Keen H., Zimmet P.,. Chichester:, Wiley; 773-795.
Alberti KGMM, Gries FA (1988) Management of non‐insulin‐dependent diabetes mellitus in Europe. A consensus view. Diabetic Med 5:275-281.
Scheen AJ, Lefebvre PJ (1993) Pharmacological treatment of the obese diabetic patients. Diabete Metab 19:547-559.
Widen EIM, Eriksson JG, Groop LC (1992) Metformin normalizes nonoxidative glucose metabolism in insulin‐resistant normoglycemic first‐degree relatives of patients with NIDDM. Diabetes 41:354-358.
Hollenbeck CB, Johnston P., Varasteh BB, Chen YDI, Reaven GM (1991) Effects of metformin on glucose, insulin and lipid metabolism in patients with mild hypertriglyceridaemia and non‐insulin dependent diabetes by glucose tolerance test criteria. Diabete Metab 17:483-489.
Fendri S., Debussche X., Puy H., Vincent O., Marcelli JM, Dubreuil A. (1993) Metformin effects on peripheral sensitivity to insulin in non diabetic obese subjects. Diabete Metab 19:245-249.
Bergman RN, Phillips LS, Cobelli C. (1981) Physiologic evaluation of factors controlling glucose tolerance in man. Measurement of insulin sensitivity and B‐cell glucose sensitivity from the response to intravenous glucose. J Clin Invest 68:1456-1467.
Duysinx BC, Scheen AJ, Gérard PL, Letiexhe M., Paquot N., Lefèbvre PJ (1994) Measurement of insulin sensitivity by the minimal model method using a simplified intravenous glucose tolerance test: validity and reproducibility. Diabete Metab 20:425-432.
Hales CN, Randle PJ (1963) Immunoassay of insulin with insulin‐antibody precipitate. Biochem J 88:137-146.
Heding LG (1975) Radioimmunological determination of human C‐peptide in serum. Diabetologia 11:541-548.
Okabe H., Uji Y., Nagashima K., Noma A. (1980) Enzymatic determination of free fatty acids in serum. Clin Chem 26:1540-1543.
Keal J., Somogyi A. (1986) Rapid and sensitive high‐performance liquid chromatographic assay for metformin in plasma and urine using ion‐pair extraction techniques. J Chromatogr 378:503-508.
Polonsky KS, Given BD, Hirsch L., Shapiro EJ, Tillil H., Beebe C. (1988) Quantitative study of insulin secretion and clearance in normal and obese subjects. J Clin Invest 81:435-441.
Van Cauter E., Mestrez F., Sturis J., Polonsky KS (1992) Estimation of insulin secretion rate from C‐peptide levels. Diabetes 41:368-377.
Letiexhe MR, Scheen AJ, Gérard PL, Desaive C., Lefèbvre PJ (1994) Insulin secretion, clearance and action before and after gastroplasty in severely obese subjects. Int J Obesity 18:295-300.
Castillo MJ, Scheen AJ, Letiexhe MR, Lefèbvre PJ (1994) How to measure insulin clearance. Diabetes Metab Rev 10:119-150.
Bergman RN (1989) Towards physiological understanding of glucose tolerance. Minimal‐model approach. Diabetes 38:1512-1527.
Scheen AJ, Paquot N., Castillo MJ, Lefèbvre PJ (1994) How to measure insulin action in vivo. Diabetes Metab Rev 10:151-158.
Zerbe GO (1979) Randomization analysis of the completely randomized design extended to growth and response curves. Journal of the American Statistical Association 74:215-221.
Giugliano D., de Rosa N., Di Maro G., Marfella R., Acampora R., Buoninconti R. (1993) Metformin improves glucose, lipid metabolism, and reduces blood pressure in hypertensive, obese women. Diabetes Care 16:1387-1390.
Landin K., Tengborn L., Smith U. (1991) Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors. J Internal Med 229:181-187.
Saad MF, Anderson RL, Laws A., Watanabe RM, Kades WW, Chen Y‐DI (1994) A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance. Diabetes 43:1114-1121.
Perriello G., Misericordia P., Volpi E., Santucci A., Santucci C., Ferrannini E. (1994) Acute antihyperglycemic mechanisms of metformin in NIDDM. Evidence for suppression of lipid oxidation and hepatic glucose production. Diabetes 43:920-928.
Haffner SM, Stern MP, Watanabe RN, Bergman RN (1992) Relationship of insulin clearance and secretion to insulin sensitivity in non‐diabetic Mexican Americans. Eur J Clin Invest 22:147-153.
Letiexhe MR, Scheen AJ, Gérard PL, Desaive C., Lefèbvre PJ (1995) Post‐gastroplasty recovery of ideal body weight normalizes glucose and insulin metabolism in obese women. J Clin Endocrinol Metab 80:364-369.
DeFronzo RA, Ferrannini E. (1991) Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14:173-194.
Nagi DK, Yudkin JS (1993) Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. Diabetes Care 16:621-629.
Vague, Juhan‐Vague I., Alessi MC, Badier C., Valadier J. (1987) Metformin decreases the high plasminogen activator inhibition capacity, plasma insulin and triglyceride levels in non‐diabetic obese subjects. Thromb Haemost 57:326-328.
Taylor SI, Accili D., Imai Y. (1994) Insulin resistance or insulin deficiency. Which is the primary cause of NIDDM?. Diabetes 43:735-740.
O'Rahilly S., Hattersley A., Vaag A., Gray H. (1994) Insulin resistance as the major cause of impaired glucose tolerance‐: a self‐fulfilling prophesy?. Lancet 344:585-589.