Human obesity. Studies of treatment, leptin and the metabolic syndrome

Abstract

Aims: To evaluate very low calorie diets (VLCD) in obesity treatment and elucidate leptin's role in the response to severe caloric restriction. To analyse relations between metabolic variables, body composition and liver tests and the interplay between mental distress, socio-demographic variables and cardiovascular risk factors in obesity. Methods: 113 obese were randomised to two years of hypocaloric diet, with or without initial VLCD. 121 obese were randomised to three different initial 16 week VLCD periods followed by hypocaloric diet: either strict VLCD, with or without week one as inpatients, or VLCD plus two minor weekly meals. Blood was sampled from obese subjects before, during and after a VLCD-driven weight reduction and analysed for leptin, insulin, cortisol and thyroid hormones. Relations between maintained weight loss after 48 weeks, baseline levels and changes in hormone levels were analysed. Cross-sectional associations between liver tests, body composition, metabolic variables and alcohol intake were examined and structural equation modelling was applied to investigate relations between body mass index (BMI), visceral adipose tissue (VAT), metabolic variables, mental health and socio-economic variables. Results and conclusions: Two treatment years resulted in significant weight losses with (9.2kg), or without (6.3kg) VLCD. In men there was a significant difference between treatment strategies, 15.5 vs. 5.3kg. Strict VLCD resulted in greater weight losses than the more liberal approach but there was no benefit initiating VLCD in hospital. Low baseline leptin levels and large leptin declines were related to large weight reductions after 48 weeks. There were no, or only weak, relations between changes in leptin and insulin, cortisol and thyroid hormones indicating that leptin might be less important for the human response to semi-starvation. Elevated aminotransferases were positively and reduced bilirubin negatively related to VAT and insulin and might be viewed as additional characteristics of the metabolic syndrome. BMI was the main determinant of VAT. BMI and VAT were main determinants of insulin, while depression, education and physical inactivity had less impact. Insulin and VAT were central determinants of other cardiovascular risk factors. This indicates that BMI should not be underestimated when evaluating the pathogenesis of disturbed metabolism in the obese.