Insulin resistance in nondiabetic morbidly obese patients: Effect of bariatric surgery

Objective: To evaluate insulin action on substrate use and insulinemia in nondiabetic class III obese patients before and after weight loss induced by bariatric surgery. Research Methods and Procedures: Thirteen obese patients (four men/nine women; BMI = 56.3 +/- 2.7 kg/m(2)) and 13 lean subjects (five men/eight women; BMI = 22.4 +/- 0.5 kg/m(2)) underwent euglycemic clamp, oral glucose tolerance test, and indirect calorimetry. The study was carried out before (Study 1) and after (similar to40% relative to initial body weight; Study II) weight loss induced by Roux-en-Y Gastric bypass with silastic ring surgery. Results: The obese patients were insulin resistant (whole-body glucose use = 19.7 +/- 1.5 vs. 51.5 +/- 2.4 mumol/min per kilogram fat-free mass, p < 0.0001) and hyperinsulinemic in the fasting state (332 +/- 86 vs. 85 +/- 5 pM, p < 0.0001) and during the oral glucose tolerance test compared with the lean subjects. Fasting plasma insulin normalized after weight loss, whereas whole-body glucose use increased (35.5 +/- 3.7 mumol/min per kilogram fat-free mass, p < 0.05 vs. Study 1). The higher insulin clearance of obese did not change during the follow-up period. Insulin-induced glucose oxidation and nonoxidative glucose disposal were lower in the obese compared with the lean group (all p < 0.05). In Study 11, the former increased slightly, whereas nonoxidative glucose disposal reached values similar to those of the control group. Fasting lipid oxidation was higher in the obese than in the control group and did not change significantly in Study II. The insulin effect on lipid oxidation was slightly improved (p = 0.01 vs. Study 1). Discussion: The rapid weight loss after surgery in obese class III patients normalized insulinemia and improved insulin sensitivity almost entirely due to glucose storage, whereas fasting lipid oxidation remained high.11121495150

Normal insulin sensitivity in lean offspring of obese parents

Objective: Offspring of diabetic or hypertensive patients are insulin resistant at a prediabetic/prehypertensive stage. We tested the hypothesis that insulin action may be impaired in the offspring of obese nondiabetic parents. Research Methods and Procedures: Twenty-one lean offspring of nonobese subjects [(OL) 22+/-3 years of age] were matched to 23 lean offspring of obese subjects (OOb) by gender distribution, age, BMI, and waist circumference. Anthropometry, oral glucose tolerance, in vivo insulin sensitivity [by a euglycemic insulin clamp (6 pmol/min per kilogram(FFM); where FFM represents fat-free mass)], and thermogenesis (by indirect calorimetry) were measured in each subject. The study subjects were from a population of 267 nuclear families (one offspring and both his/her parents) in which there was statistically significant (chi(2)=30.2, p=0.001) concordance of BMI between parents and offspring. Results: In comparing OOb with OL, no statistically significant difference or trend toward a difference was detected in fasting plasma glucose and insulin concentrations, glucose and insulin responses to oral glucose, insulin sensitivity [metabolism value=45+/-12 (OOb) vs. 47+/-17 mumol/min per kilogram(FFM) (OL)], insulin-induced inhibition of protein and lipid oxidation, stimulation of glucose oxidation and nonoxidative glucose disposal, respiratory quotient, resting energy expenditure, and glucose-induced thermogenesis. Discussion: The metabolic similarity between lean offspring of obese parents and those of nonobese parents Suggests that insulin resistance and its correlates are not co-inherited with the predisposition to develop obesity

Lack of insulin inhibition on insulin secretion in non-diabetic morbidly obese patients

OBJECTIVE: Insulin inhibition of insulin secretion has been described in normal lean subjects. In this study, we examined whether this phenomenon also occurs in the morbidly obese who often have severe peripheral insulin resistance. SUBJECTS: Twelve obese patients, normotolerant to glucose (8F/4M, body mass index (BMI) = 54.8 +/-2.5 kg/m(2), 39y) and 16 lean control subjects (10F/6M, BMI = 22.0 +/-0.5 kg/m(2), 31y). DESIGN AND MEASUREMENTS: An experimental study using various parameters, including an euglycemic hyperinsulinemic clamp (280pmol/min/m(2) of body surface), an oral glucose tolerance test (OGTT), electrical bioimpedance and indirect calorimetry. RESULTS: The obese subjects were insulin resistant (M = 19.8 +/-1.6 vs 48.7 +/-2.6 mu mol/min kg FFM, P < 0.0001) and hyperinsulinemic in the fasted state and after glucose ingestion. Fasting plasma C-peptide levels (obese 1425 +/- 131 pmol/l vs lean 550 +/- 63 pmol/l; P < 0.0001) decreased less during the clamp in the obese groups (-16.9 +/-6.9% vs -43.0 +/-5.6% relative to fasting values; P = 0.007). In the lean group, the C-peptide decrease during the clamp (percentage variation) was related to insulin sensitivity, M/FFM (r = 0.56, P = 0.03), even after adjustment for the clamp glucose variation. CONCLUSION: We conclude that, in lean subjects, insulin inhibits its own secretion, and this may be related to insulin sensibility. This response is blunted in morbidly obese patients and may have a role in the pathogenesis of fasting hyperinsulinemia in these patients.25679880