Insulin regulation of leptin synthesis and secretion in humans: the model of myotonic dystrophy

OBJECTIVE Myotonic dystrophy (MyD) is a systemic disorder in which insulin resistance is well recognized. In the present study we have characterized p lasma leptin levels in patients with MyD and in age, sex and body mass inde x (BMI) matched controls and assessed the influence of leptin on the clinic al manifestations of MyD. DESIGN AND PATIENTS Body composition, plasma leptin, fasting and post-oral glucose tolerance test insulin, IGF-I and IGFBP3 were studied in 34 MyD pat ients and 33 controls. MEASUREMENTS Body composition was measured using a bioelectrical impedance analyzer, and circulating levels of insulin, leptin, IGF-I, IGFBP3 were mea sured by IRMA or PIA. Insulin sensitivity was modelled according to a homeo stasis model assessment (HOMA) computer-solved model. RESULTS Percentage body fat was higher in patients than in controls (25.6 /- 2.28% vs 18.8 +/- 1.53%, P=0.013). Insulin levels, both fasting and afte r oral glucose were higher in patients than in controls, and insulin sensit ivity was lower in patients than in controls. Serum leptin was higher in pa tients than in controls (20.98 +/- 3.11% mu g/l vs 10.4 +/- 1.31 mu g/l, P = 0.004), and higher in women than in men, both in patients and in controls . In patients, leptin levels were correlated with age, BMI, fasting insulin , insulin area under curve and lower insulin sensitivity, whereas leptin le vels were not correlated with body fat or other parameters of body composit ion. In controls, leptin levels were correlated with BMI and body fat. The results were evaluated using logistic regression models for each of the 2 p opulations. In the model of MyD, insulin resistance and age correctly ident ified higher leptin levels in relation to controls out of 87.88% of patient s, and in the model of controls male sex with a negative correlation and BM I correctly identified their leptin levels out of 84.33% cases. CONCLUSIONS These findings show that MyD provides a different model of lept in regulation in humans, and suggest that in MyD patients there are correla tions between leptin and insulin resistance and age, irrespective of body f at. In contrast, leptin levels in controls, correlate with sex and BMI. The data on leptin in this population of patients can not be related aetiologi cally to the muscle disease itself.