Serum leptin concentration in moderate and severe obesity: relationship with clinical, anthropometric and metabolic factors

OBJECTIVE: To study clinical, anthropometric and metabolic determinants of serum leptin concentrations in a series of patients with a wide range of ob esity. SUBJECTS: 400 patients, 116 males and 284 females, aged 44 +/- 12.3 years w ith body mass index (BMI) ranging from 31 to 82 kg/m(2) (mean 41.4 +/- 7.1) , MEASUREMENTS: Energy intake by 7-day recall, resting energy expenditure (RE E) by indirect calorimetry, body composition determined by bioelectrical im pedance; C index, an anthropometric index of abdominal fat distribution, an d waist-hip ratio (WHR), blood glucose serum leptin concentrations, total c holesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, uric acid, and insulin concentrations HOMA IRI (homeostastis model assessment o f insulin resistance index). RESULTS: Leptin concentrations were higher in obese than in normal subjects and in females than in males without differences between diabetic and non- diabetic patients; leptin concentrations were not related to age and showed a strong negative association with energy intake only in the group of wome n with BMI less than 40. Leptin concentrations showed a direct correlation with BMI and body fat values (expressed either as percentage of total body mass or absolute fat mass) independent of age and sex. After adjustment for fat mass, leptin values higher than predicted were found in women whereas concentrations lower than predicted were found predominantly in men. Leptin showed an inverse correlation with WHR and C-index, the latter persisting also after correction for gender and fat mass. REE, but not REE/kg fat-free mass (FFM) was inversely related to leptin also after correction for sex a nd absolute fat mass. Leptin concentrations were directly associated with H OMA IRI, insulin and HDL cholesterol and inversely associated with triglyce rides and uric acid. The relationship of leptin with HOMA IRI was still evi dent after adjusting for sex but was lost when absolute fat mass was added to the model; HDL cholesterol and triglycerides appeared to be variables in dependent of leptin concentrations even when both sex and fat mass were add ed to the model. CONCLUSIONS: In a large group of obese patients (half of whom had severe ob esity, gender, BMI and fat mass accounted for the largest proportion of ser um leptin concentrations variability. We found that in obese subjects there is an effect of fat distribution on leptin concentrations and that, after excluding variability due to absolute fat mass, patients with a greater amo unt of abdominal fat have relatively low leptin concentrations which in tur n relates to a metabolic profile compatible with an increased cardiovascula r risk. Women with milder obesity may retain some degree of control of food intake by leptin.