Adiponectinemia, glucose status, insulin secretion and insulin resistance in obese women: influence of weight loss 1) To compare variation in adiponectin levels, in insulin secretion / insulin resistance indexes, and in anthropometric parameters in obese women during weight loss program, according to their initial status; 2) To compare metabolic status changes in obese women during weight loss program, according to their initial status; 3) To assess the association between changes in adiponectin levels and changes ininsulin secretion and insulin resistance indexes with those in anthropometric parameters. AIMS

METHODS 100 premenopausal obese women characterized for anthropometric parameters (BMI, waist, WHR, total fat mass) fasting venous blood sample collection + classic 75g OGTT a. one index of insulin resistance: homeostatic model assessment of insulin resistance (HOMA-IR); b. one of insulin sensitivity: Matsuda formula; c. two insulin secretion indexes: homeostatic model assessment of beta cell (HOMA%beta) and insulinogenic index (INS-i). Women entered in a weight loss program and were reassessed for all parameters after 6 and 12 months. Total population Metabolic status groups Normoglycemia Intermediate hyperglycemia Diabetes p N Age (years)34.1±8.234± ± ± BMI (kg/m 2 )43.6±843.2± ±848.1± Fat mass (kg)54± ±14.251± ± Waist circ.(cm)117.7± ± ± ± Waist:hip ratio0.88± ± ± ± Adiponectin (μg/ml)6.86± ± ± ± HOMA-IR4.42± ± ± ±5.04<0.001 Matsuda formula3.69± ± ± ± HOMA%beta262.1± ± ±206121± INS-i24.2± ± ±195.2±

RESULTS Parameters variation (%) Between month 0 and month 6 (N=86)Between month 0 and month 12 (N=67) Normoglycemia Intermediate hyperglycemia DiabetespNormoglycemia Intermediate hyperglycemia Diabetesp Weight Fat mass Waist WHR Adiponectin P<0.001 Metabolic status at month 6 Normoglycemia Intermediate hyperglycemia DiabetesTOTAL Metabolic status at month 0Normoglycemia Intermediate hyperglycemia Diabetes 1539 TOTAL P<0.001 Metabolic status at month 12 Normoglycemia Intermediate hyperglycemia Diabetes TOTA L Metabolic status at month 0Normoglycemia Intermediate hyperglycemia Diabetes 2338 TOTAL

RESULTS rprp ∆Weight∆Fat mass∆Waist∆WHR∆Adiponectin Variations between month 0 and month 6 ∆HOMA-IR < < < ∆Matsuda < < < * ∆HOMA%beta ∆INS-i < ∆Adiponectin rprp ∆Weight∆Fat mass∆Waist∆WHR∆Adiponectin Variations between month 0 and month 12 ∆HOMA-IR < < < < * ∆Matsuda ∆HOMA%beta ∆INS-i ∆Adiponectin < < < * Correlation present after adjustment for anthropometric parameters

As expected we demonstrated higher insulin secretion and lower insulin resistance indexes in normoglycemic obese women. In weight loss programs, obese women lose fat mass (with a subsequently increase in insulin sensitivity and insulin secretion) independently from their initial metabolic status. Adiponectin levels parallels insulin sensitivity indexes during the process of weight reduction, independently from the amount of fat mass loss. That might indicate a direct insulin-sensitizing effect of adiponectin.