Prospective longitudinal studies evaluating the relevance of "Metabolically Healthy but Obese" (MHO) phenotype at risk for type 2 diabetes mellitus (T2D) and cardiovascular diseases are few and results are contradictory. As a representative of the general population, 1051 individuals were evaluated in 1997-1998 and re-evaluated after 6 years and 11 years. Subjects without known T2D were given an oral glucose tolerance test. Anthropometric and biochemical variables were measured. Four sets of criteria were considered to define MHO subjects besides body mass index ≥30 kg/m(2): A: Homeostatic Model of Assessment-Insulin Resistance Index (HOMA-IR) 40 mg/dL in men and high-density lipoprotein cholesterol >50 mg/dL in women, triglycerides <150 mg/dL, fasting glucose <110 mg/dL, and blood pressure ≤140/90 mm Hg; C: HOMA-IR <90th percentile, triglycerides <150 mg/dL, fasting glucose <110 mg/dL, and blood pressure ≤140/90 mm Hg; D: HOMA-IR <90th percentile, triglycerides <150 mg/dL, and fasting glucose <110 mg/dL. Subjects with T2D at baseline were excluded from the calculations of incidence of T2D. The baseline prevalence of MHO phenotype varied between 3.0% and 16.9%, depending on the set of criteria chosen. Metabolically nonhealthy obese subjects were at highest risk for becoming diabetic after 11 years of follow-up (odds ratio = 8.20; 95% confidence interval = 2.72-24.72; P < .0001). In MHO subjects the risk for becoming diabetic was lower than in metabolically nonhealthy obese subjects, but this risk remained significant (odds ratio = 3.13; 95% confidence interval = 1.07-9.17; P = .02). In subjects who lost weight during the study, the association between MHO phenotype and T2D incidence disappeared, even after adjusting for HOMA-IR. The results suggest that MHO is a dynamic concept that should be taken into account over time. As a clinical entity, it may be questionable.

Background: Transsexual persons afford a very suitable model to study the effect of sex steroids on uric acid metabolism. Design: This was a prospective study to evaluate the uric acid levels and fractional excretion of uric acid (FEUA) in a cohort of 69 healthy transsexual persons, 22 male-to-female transsexuals (MFTs) and 47 female-to-male transsexuals (FMTs). The subjects were studied at baseline and 1 and 2 yr after starting cross-sex hormone treatment. Results: The baseline levels of uric acid were higher in the MFT group. Compared with baseline, uric acid levels had fallen significantly after 1 yr of hormone therapy in the MFT group and had risen significantly in the FMT group. The baseline FEUA was greater in the FMT group. After 2 yr of cross-sex hormone therapy, the FEUA had increased in MFTs (P = 0.001) and fallen in FMTs (P = 0.004). In MFTs, the levels of uric acid at 2 yr were lower in those who had received higher doses of estrogens (P = 0.03), and the FEUA was higher (P = 0.04). The FEUA at 2 yr was associated with both the estrogen dose (P = 0.02) and the serum levels of estradiol-17β (P =0.03). In MFTs, a correlation was found after 2 yr of therapy between the homeostasis model assessment of insulin resistance and the serum uric acid (r = 0.59; P = 0.01). Conclusions: Serum levels of uric acid and the FEUA are altered in transsexuals as a result of cross-sex hormone therapy. The results concerning the MFT group support the hypothesis that the lower levels of uric acid in women are due to estrogen-induced increases in FEUA.

Activation of the PPAR gamma 2 gene (PPARG2) improves the action of insulin and its lipid metabolism. We examined the association between Pro12Ala polymorphism of PPARG2, type 2 diabetes mellitus (DM2), and peripheral insulin sensitivity in a population with a high intake of oleic acid. A cross-sectional, population-based study was undertaken in Pizarra, a small town in the province of Malaga in southern Spain. A total of 538 subjects, aged 18–65 y, were selected randomly from the municipal census. All subjects underwent a clinical, anthropometrical, and biochemical evaluation, including an oral glucose tolerance test and Pro12Ala polymorphism of PPARG2. Insulin resistance was measured by homeostasis model assessment. Those subjects with the Ala-12 allele had an odds ratio for impaired fasting glucose of 0.55, for impaired glucose tolerance of 0.59, and for DM2 of 0.30. The intake of monounsaturated fatty acids (MUFA) contributed to the variance of the homeostasis model assessment insulin resistance index (HOMA IR) (P = 0.04), with a 2-way interaction between the Ala-12 allele of PPARG2 and the intake of MUFA (P = 0.005). The results suggest the existence of an interaction between Pro12Ala polymorphism of PPARG2 and dietary MUFA, such that obese people with the Ala-12 allele have higher HOMA IR values, especially if their intake of MUFA is low.