1. 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

2. 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 N100711910 Age (years)34.1±8.234±8.534.9±7.633.8±7.20.904 BMI (kg/m 2 )43.6±843.2±7.942.7±848.1±7.50.16 Fat mass (kg)54±15.153.4±14.251±18.163.8±12.90.078 Waist circ.(cm)117.7±15.2116.1±13.6116.7±18.8131.5±12.50.009 Waist:hip ratio0.88±0.080.86±0.070.89±0.080.95±0.070.001 Adiponectin (μg/ml)6.86±3.217.35±3.465.73±2.15.54±2.320.056 HOMA-IR4.42±3.653.29±2.165.35±3.8710.64±5.04<0.001 Matsuda formula3.69±2.544.27±2.662.51±1.331.32±0.330.001 HOMA%beta262.1±174.9281.9±169.2263.6±206121±61.20.023 INS-i24.2±20.227.1±20.421.3±195.2±4.20.01

3. 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-5.5 -6.10.978-7.3-7.2-14.10.36 Fat mass-8.3-5.8-12.70.53-10.1-8.2-22.30.245 Waist-4.1-4.5-3.70.959-5.5-4.5-11.80.294 WHR-2.1-1.70.184-1.3-4.50.36 Adiponectin+29.3+35.2+11.80.4+30.6+38.6+11.60.591 P<0.001 Metabolic status at month 6 Normoglycemia Intermediate hyperglycemia DiabetesTOTAL Metabolic status at month 0Normoglycemia 562058 Intermediate hyperglycemia 154019 Diabetes 1539 TOTAL 7211986 P<0.001 Metabolic status at month 12 Normoglycemia Intermediate hyperglycemia Diabetes TOTA L Metabolic status at month 0Normoglycemia 471048 Intermediate hyperglycemia 74011 Diabetes 2338 TOTAL 568367

4. RESULTS rprp ∆Weight∆Fat mass∆Waist∆WHR∆Adiponectin Variations between month 0 and month 6 ∆HOMA-IR 0.458 <0.001 0.579 <0.001 0.475 <0.001 0.13 0.282 -0.142 0.241 ∆Matsuda -0.468 <0.001 -0.521 <0.001 -0.473 <0.001 -0.333 0.006 0.361 0.003* ∆HOMA%beta 0.118 0.337 0.106 0.392 0.128 0.298 0.009 0.943 0.116 0.347 ∆INS-i -0.385 0.001 -0.379 0.002 -0.427 <0.001 -0.385 0.001 0.239 0.051 ∆Adiponectin -0.2 0.066 -0.135 0.220 -0.178 0.103 -0.11 0.318 rprp ∆Weight∆Fat mass∆Waist∆WHR∆Adiponectin Variations between month 0 and month 12 ∆HOMA-IR 0.772 <0.001 0.76 <0.001 0.792 <0.001 0.547 <0.001 -0.367 0.02* ∆Matsuda -0.476 0.003 -0.442 0.005 -0.479 0.002 -0.393 0.015 0.129 0.454 ∆HOMA%beta 0.203 0.198 0.199 0.206 0.184 0.244 0.026 0.868 0.022 0.895 ∆INS-i -0.24 0.147 -0.257 0.119 -0.212 0.201 -0.204 0.219 0.185 0.28 ∆Adiponectin -0.57 <0.001 -0.568 <0.001 -0.448 <0.001 -0.139 0.274 * Correlation present after adjustment for anthropometric parameters

5. 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.