Leptin and variables of body adiposity, energy balance, and insulin resistance in a population-based study

OBJECTIVE - Leptin is thought to play a key role in the control of body weight. There is a complex interrelationship between leptin and insulin or insulin resistance, but it is unknown how leptin is regulated. We therefore explored, in a large population-based study of 2,484 Caucasian subjects aged 50-74 years, the relationship between leptin and variables of body adiposity, energy balance, and insulin resistance. RESEARCH DESIGN AND METHODS - Leptin was measured by means of a radioimmunoassay. Multiple linear regression analyses were performed with leptin as dependent variable and age, sex, BMI, waist circumference, daily energy intake, physical activity, smoking, hypertension, fasting triglyceride concentrations, HDL cholesterol, fasting plasma glucose, and fasting plasma insulin concentrations as independent variables (determinants). RESULTS - Leptin concentrations were found to be four times higher in women than in men. Effect modification between sex and potential determinants was expected, and the analyses were performed separately for women and men. BMI was the strongest determinant of leptin in women and waist circumference the strongest determinant in men. BMI, waist circumference, insulin, and triglyceride concentrations were independently and significantly (P < 0.05) associated with leptin, while inverse associations were shown for smoking and daily energy intake (borderline significance). CONCLUSIONS - This study confirms the relationship between insulin and leptin and, in addition, suggests a relationship between triglyceride concentrations and leptin independent of sex, BMI, waist circumference, and insulin

Hyperproinsulinaemia in impaired glucose tolerance is associated with a delayed insulin reponse to glucose

In subjects with impaired glucose tolerance hyperproinsulinaemia has been shown to be predictive for progression to Type II (non-insulin- dependent) diabetes mellitus. These findings are often interpreted as early indicators of an impaired beta-cell function. The aim of our study was to assess the potential determinants of hyperproinsulinaemia in subjects with impaired glucose tolerance. The study group consisted of 110 subjects, 45-74 years of age with mean 2 h plasma glucose concentrations between 8.6 and 11.1 mmol/l following two oral glucose tolerance tests. Subsequently, the hyperglycaemic clamp technique (10 mmol/l, with a priming infusion of 20% glucose solution, 150 mg/kg) was used to assess the beta-cell function (time needed to reach the insulin peak) and insulin sensitivity (M/I value: glucose metabolised divided by insulin response, 150-180 min). Results showed that the intact-proinsulin:insulin ratio increased with increasing time needed to reach the insulin peak (0.065, 0.079 and 0.101; time needed to reach the insulin peak ≤ 5 min, 5 to 15 min, > 15 min; p < 0.05). The split- proinsulin:insulin ratio showed a similar association with the time needed to reach the insulin peak. These associations were independent of age, sex, body mass index and waist:hip ratio. In conclusion, this study shows that relative hyperproinsulinaemia is associated with an impaired beta-cell function in a study group of subjects with impaired glucose tolerance selected after two oral glucose tolerance tests

Sex Steroids Affect Triglyceride Handling, Glucose-Dependent Insulinotropic Polypeptide, and Insulin Sensitivity

OBJECTIVE- To evaluate metabolic effects of sex steroids in nonfasting and fasting conditions, independent from changes in body composition. RESEARCH DESIGN AND METHODS- A randomized clinical trial was performed to create contrasting sex steroid levels in healthy young men: by letrozole (aromatase inhibitor) to lower estradiol (E-2) and increase testosterone (group T, n = 10) versus letrozole plus E-2 patches to lower T and raise E-2 (group E, n = 10). Mixed meals and hyperinsulinemic-euglycemic clamps were performed before and after a 1-week treatment period. RESULTS- Following intervention, the postprandial triglyceride response displayed a diverging response with a decline in group T and an increase in group E; the postprandial glucose-dependent insulinotropic polypeptide (GIP) response increased in group T. Insulin sensitivity increased in group T but remained unaltered in group E. CONCLUSIONS- In healthy young men, short-term changes in sex steroids affect postprandial triglyceride and GIP response and insulin sensitivity.Signal transduction in aging related disease