Vitamin D status is not related to insulin resistance in different phenotypes of moderate obesity.

Low plasma 25-hydroxy-vitamin D (25OHD) and high levels of parathyroid hormone (PTH) are associated with obesity and could play a role in the occurrence of complications such as insulin resistance. The objective of the study was to evaluate whether the relationship between 25OHD status and phosphocalcic parameters differs between metabolically healthy obese (MHO) and insulin-resistant obese (IRO). This cross-sectional study included 158 consecutive adults (121 females) with obesity (body mass index (BMI) 35.15 ± 2.8 kg/m2), aged 43.21 ± 13.6 years. Serum 25OHD, calcemia, phosphatemia, PTH, plasma lipids, fasting plasma glucose, insulin levels, and body composition were measured. Participants were classified as MHO (n = 65) or IRO (n = 93) based on homeostatic model assessment insulin-resistance value. IRO patients had a higher BMI (p = 0.001), waist circumference (p = 0.03), and trunk fat mass (p = 0.007) than MHO patients. Mean HbA1c (p = 0.03), triglycerides (p = 0.02), and hsCRP (p = 0.04) plasmatic levels were increased in the IRO group. No between-group difference was found on 25OHD, PTH, calcium, or phosphorus plasmatic levels. Only age-predicted 25OHD levels were identified among IRO participants, whereas no factors were identified in MHO. No predictive factors of PTH plasmatic level were identified in the IRO and MHO groups. Although MHO and IRO patients have different metabolic profiles, we did not detect any difference regarding either 25OHD or PTH. Insulin resistance was not a predictive factor of vitamin D status. Our results confirm the absence of link between vitamin D status and insulin resistance in moderate obesity.

Procalcitonin, an Independent Marker of Abdominal Fat Accumulation in Obese Patients.

BACKGROUND: Circulating procalcitonin (PCT) is an inflammatory marker produced by several cell types including adipose tissue following cytokine stimulation. A low-grade inflammation is well recognized in obese patients with insulin resistance but data on PCT levels in obese patients remain scarce. The aim of our study was to evaluate the link between plasma PCT concentration and metabolic parameters of obesity. METHODS: Measurements of biological parameters and total body scan using dual-energy x-ray were performed in all non-diabetic adult patients with a body mass index ≥ 30 kg/m² hospitalized for metabolic and physical assessment of their obesity since January 2010. RESULTS: Elevated plasma PCT levels of the 295 patients included were associated with degree of obesity (OR = 2.76 [1.26-6.03] class III vs. class I obesity), waist circumference (OR = 4.20 [1.98-8.92], highest vs. lowest tercile), and trunk-to-total fat ratio (OR = 6.75 [2.12-21.4], highest vs. lowest tercile). Interestingly, no significant as- sociation between the highest PCT levels and hsCRP (OR = 1.33 [0.68-2.26]) or IR (OR = 1.26 [0.67-2.37]) was found. CONCLUSIONS: Our results showed that plasma PCT levels were independently associated with central adiposity assessed by clinical and imaging assessment, but not with insulin resistance in obese patients.

Impact of obesity on bone mass throughout adult life: Influence of gender and severity of obesity.

BACKGROUND: Obesity improves areal bone mineral density (aBMD). However, it is unknown whether gender, ageing or the severity of obesity could modulate this effect and whether different bone sites are similarly affected. OBJECTIVE: The aim of this observational study was to model the aBMD variation in obese patients from peak bone period to old age according to gender, bone localisation and severity of obesity. SUBJECTS AND METHODS: Five hundred and four obese patients (363 women, 72%) with a mean BMI of 38.5 ± 6.0 kg/m2, aged from 18.1 to 81.9 years (mean age 49.6 ± 14.6 years) were recruited. The whole body (WB), hip, lumbar spine (L1­L4) and one-third radius aBMDs were determined using dual-energy x-ray absorptiometry (DXA). RESULTS: Z-scores were significantly increased, above the age- and gender-related mean, both for women and men at WB (respectively 0.79 SD and 0.32 SD), hip (1.09 SD and 1.06 SD), one-third radius (1.70 SD and 0.45 SD) and L1­L4 levels (0.86 SD for women only). The improvement of Z-scores was significantly more marked in women compared to men at all bone sites, hip excepted. Furthermore, differences compared with normal values were significantly accentuated by ageing, without noticeable gender effect. In women, regardless of BMI and bone site, Z-scores were higher than normal values, this difference being most marked at WB, L1­L4 and hip levels for obese patients with a BMI above 40 kg/m2. Lean mass, but not fat mass, was independently associated with aBMD in men and women. CONCLUSION: This study demonstrated for the first time that obesity induces an improvement of aBMD, which is modulated by bone site location, severity of obesity, age and gender. The accentuation of peak bone mass combined with a reduction of bone loss rate with ageing may explain why obese patients present a lower prevalence of osteoporosis.

Leukotriene production is increased in abdominal obesity.

Obesity is a major risk factor for insulin resistance and type-2 diabetes. A chronic low grade inflammatory state has been described during obesity and associated with insulin resistance pathogenesis. Results from animal studies are in favor of a role of the leukotriene (LT) pathway in obesity induced-insulin resistance. However, there is a paucity of data regarding this association in human obesity. Therefore, the aim of this study was to investigate whether LT production was associated with insulin resistance and other metabolic parameters in a cohort of obese subjects. Forty-six (70% females) obese subjects (BMI≧30 kg/m2) without known diabetes and without inflammatory disease (CRP<10 mg/l) were included. Median age was 44 years (16-80) with a median BMI of 36.8 kg/m2 (30-51). Insulin resistance was evaluated by HOMA-IR index and glucose tolerance test. Urinary LTE4 (U-LTE4) concentration was measured by enzyme immune assay. Screening for obstructive sleep apnea was performed. There was a positive association of U-LTE4 with waist to hip ratio, systolic blood pressure and HOMA-IR in univariate analysis. Further, waist to hip ratio remained the only parameter significantly correlated with U-LTE4, in adjusted multivariate analysis. Taken together, these results confirm the previously established notion of chronic low grade inflammation in obesity and further suggests a role for the LT pathway in obesity-associated development of insulin resistance in humans.

Steroidogenic factor-1 (SF-1) gene mutation as a frequent cause of primary amenorrhea in 46,XY female adolescents with low testosterone concentration.

BACKGROUND: Primary amenorrhea due to 46,XY disorders of sex differentiation (DSD) is a frequent reason for consultation in endocrine and gynecology clinics. Among the genetic causes of low-testosterone primary amenorrhea due to 46,XY DSD, SRY gene is reported to be frequently involved, but other genes, such as SF1 and WT1, have never been studied for their prevalence. METHODS: We directly sequenced SRY, SF1 and WT1 genes in 15 adolescent girls with primary amenorrhea, low testosterone concentration, and XY karyotype, to determine the prevalence of mutations. We also analyzed the LH receptor gene in patients with high LH and normal FSH concentrations. RESULTS: Among the 15 adolescents with primary amenorrhea and low testosterone concentration, we identified two new SRY mutations, five new SF1 mutations and one new LH receptor gene mutation. Our study confirms the 10-15% prevalence of SRY mutations and shows the high prevalence (33%) of SF1 abnormalities in primary amenorrhea due to 46,XY DSD with low plasma testosterone concentration. CONCLUSIONS: The genetic analysis of low-testosterone primary amenorrhea is complex as several factors may be involved. This work underlines the need to systematically analyze the SF1 sequence in girls with primary amenorrhea due to 46,XY DSD and low testosterone, as well as in newborns with 46,XY DSD.