Michel Letiexhe

Short Administration of Metformin Improves Insulin Sensitivity in Android Obese Subjects with Impaired Glucose Tolerance

In a double‐blind, randomized, cross‐over study, the metabolic effects of a short treatment with metformin (2 times 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 Bergmans 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 ISR by AUC insulin. Fasting plasma insulin levels were reduced after metformin (89.3 ± 15.9 vs 112.4 ± 24.3 pmol I−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 I−1; p = 0.02), while SI (6.98 ± 1.14 vs 4.61 ± 0.42 10−5 min−1 pmol−1 I; 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.

Intact cross-talk between insulin secretion and insulin action after postgastroplasty recovery of ideal body weight in severely obese patients.

Most reports investigating the hormonal and metabolic effects of bariatric surgery studied obese subjects after partial weight loss only. Nevertheless, all studies showed significant improvements of insulin secretion, action, clearance and inhibition of its own secretion, although the parallel kinetics of all these changes remained questionable. Using the intravenous glucose tolerance test, we demonstrated a full normalization of insulin secretion, action on glucose metabolism and clearance in eight obese women who recovered and maintained ideal body weight following gastroplasty. Reciprocal changes were observed between postglucose acute insulin secretion and insulin-mediated glucose disposal so that the so-called disposition index (product of these two variables) remained unchanged after vs before gastroplasty in those individuals with normal glucose tolerance. These favourable results should encourage obtaining a drastic and sustained weight loss in patients with severe obesity at risk of developing type II diabetes.

Plasma leptin levels, insulin secretion, clearance and action on glucose metabolism in anorexia nervosa.

From a metabolic point of view, anorexia nervosa may be viewed as a mirror image of obesity. We compared insulin secretion, clearance and action on glucose metabolism during an intravenous glucose tolerance test in nine women with anorexia nervosa and in nine age-matched normal-weight controls. Insulin secretion (ISR) was derived by decon volution of plasma C-peptide levels, insulin clearance (MCRI) was obtained by dividing the area under the curve (AUC0-180 min) of ISR by the corresponding AUC of plasma insulin levels insulin sensitivity (SI) and glucose effectiveness index (SG) were calculated by Bergman’s minimal model. The anorectic women had markedly lower BMI values (13.7±0.6 vs 23.2±0.8 kg/m2, p<0.0001) and serum basal leptin levels (2.8±0.6 vs 8.9±1.8 ng/mL, p=0.005) than control women. The anorectic women exhibited clear-cut lower fasting and post-glucose plasma insulin levels but similar corresponding plasma C-peptide concentrations when compared to controls. Consequently, ISR was similar in both groups while MCRI was significantly increased in anorexia nervosa (MCRI: 3320±881 vs 822±79 mL…min-1.m-2, p<0.02). The index SI tended to be higher in anorectic women than in normal-weight subjects, but withou reaching the level of statistical significance because of a high between-subject variability (20.2±5.7 vs 12.5±2.2 10-5…min-1/pmol…L-1, NS). The index SG was similar in both groups (0.022±0.004 vs 0.018±0.002 min-1, NS). In conclusion, low plasma insulin levels observed in women with anorexia nervosa result from high MCRI rather than from depressed insulin secretion. Insulin sensitivity is not systematically increased and glucose effectiveness is unchanged in anorectic women when compared to normal-weight controls.