Parathyroid Hormone and Insulin Resistance in Distinct Phenotypes of Severe Obesity: A Cross-Sectional Analysis in Middle-Aged Men and Premenopausal Women

Abstract

High levels of PTH are reported in obese individuals and related to increased cardiometabolic risk. Our objective was to evaluate whether the relationship between PTH, insulin resistance, and related metabolic parameters differ between metabolically healthy obese (MHO) and insulin-resistant obese (IRO) subjects. We conducted a cross-sectional study among patients evaluated for bariatric surgery in our University Hospital. Patients initially included were 174 severely obese subjects (114 women, aged 40 ± 5 yr, body mass index of 45 ± 6 kg/m(2)) without diabetes, chronic kidney disease, or hyperparathyroidism. MHO (n = 43) and IRO (n = 86) subjects were identified according to quartiles of insulin resistance. Fasting and postload glucose, insulin, total and high-density lipoprotein cholesterol, triglycerides, creatinine, calcium, phosphorus, PTH, 25-hydroxyvitamin D (25OHD), fibrinogen, and high-sensitivity C-reactive protein were assessed. Insulin sensitivity index was derived from a 75-g oral glucose tolerance test. Fat distribution and bone mineral density were assessed with dual-energy x-ray absorptiometry. Although 25OHD levels were higher in MHO than in IRO subjects [72.23 (59.41-80.36) vs. 52.36 (41.98-62.57) nmol/liter, P = 0.002], PTH levels were comparable between groups (74.4 ± 13.2 vs. 72.1 ± 15.1 ng/liter, P = 0.34). No differences in serum calcium, phosphorus, bone mineral density, and renal function were detected. An independent inverse association between 25OHD and insulin resistance was seen in both groups. In contrast to IRO subjects, after adjusting for covariates, PTH levels were unrelated to insulin sensitivity index, fasting and postload glucose, insulin, and high-sensitivity C-reactive protein in MHO subjects. MHO and IRO subjects show comparably high levels of circulating PTH, which are not associated with insulin resistance and related metabolic parameters in MHO subjects. Most of the associations observed in IRO subjects appear to be mediated by greater truncal fat mass.