Can dysglycemia in OGTT be predicted by baseline parameters in patients with PCOS?

Background: Polycystic ovary syndrome (PCOS) is considered a risk factor for the development of type 2 diabetes mellitus (T2DM). However, which is the most appropriate way to evaluate dysglycemia in women with PCOS and who are at increased risk are as yet unclear. Aim of the study: To determine the prevalence of T2DM, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) in PCOS women and potential factors to identify those at risk. Subjects and methods: The oral glucose tolerance test (OGTT), biochemical/hormonal profile, and ovarian ultrasound data from 1614 Caucasian women with PCOS and 362 controls were analyzed in this cross-sectional multicenter study. The data were categorized according to age and BMI. Results: Dysglycemia (T2DM, IGT, and IFG according to World Health Organization criteria) was more frequent in the PCOS group compared to controls: 2.2% vs 0.8%, P = 0.04; 9.5% vs 7.4%, P = 0.038; 14.2% vs 9.1%, P = 0.002, respectively. OGTT was essential for T2DM diagnosis, since in 88% of them basal glucose values were inconclusive for diagnosis. The presence of either T2DM or IFG was irrespective of age (P = 0.54) and BMI (P = 0.32), although the latter was associated with IGT (P = 0.021). There was no impact of age and BMI status on the prevalence of T2DM or IFG. Regression analysis revealed a role for age, BMI, fat deposition, androgens, and insulin resistance for dysglycemia. However, none of the factors prevailed as a useful marker employed in clinical practice. Conclusions: One-third of our cohort of PCOS women with either T2DM or IGT displayed normal fasting glucose values but without confirming any specific predictor for dysglycemic condition. Hence, the evaluation of glycemic status using OGTT in all women with PCOS is strongly supported.

The association of glucocorticoid receptor polymorphism with metabolic outcomes in menopausal women with adrenal incidentalomas.

OBJECTIVES: To investigate whether BclI polymorphism in the glucocorticoid receptor gene influences hypothalamic-pituitary-adrenal (HPA) axis regulation, body composition and metabolic parameters in women with adrenal incidentalomas (AIs). STUDY DESIGN: A cross-sectional study. MAIN OUTCOME MEASURES: We analyzed 106 women with AIs. Insulin resistance was assessed using a homeostasis model while HPA activity was assessed using dexamethasone suppression tests (DST), basal ACTH, urinary free cortisol, and midnight serum cortisol level. Body composition was analyzed using dual-energy X-ray absorptiometry. DNA was obtained from peripheral blood leucocytes and BclI polymorphism was detected using PCR, RFLP and DNA sequencing. RESULTS: BclI carriers in comparison with those with wild-type BclI had less suppressed cortisol after DST-0.5 mg (126.4 ± 111.4 vs 80.9 ± 75.7 nmol/l, p = 0.026) and had a lower prevalence of impaired glucose tolerance and of type 2 diabetes mellitus (T2DM). BclI carriers had a higher percentage of leg fat mass (FM), lower left-sided limb muscle mass and a decline in total lean body mass. Duration of menopause remained a strong predictor of appendicular lean mass index (ALMI) (ß=-0.125, p = 0.034). BclI polymorphism was significantly associated with sum of legs FM percentage (ß=0.327, p = 0.048). T2DM was negatively associated with BclI polymorphism, after adjusting for age, truncal FM, ALMI, and sum of legs FM (OR=0.158, 95%CI 0.031-0.806, p = 0.027). CONCLUSIONS: BclI polymorphism is associated with tissue-specific glucocorticoid sensitivity, relative glucocorticoid resistance of the HPA axis and peripheral adipose tissue, and glucocorticoid hypersensitivity at the muscle level. By modulating glucocorticoid and insulin sensitivity, BclI polymorphism appears to reduce the risk of T2DM in women with AIs.

Quality of life in patients with polyneuropathy associated with different types of monoclonal gammopathy of undetermined significance.

Polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS-PNP) has a chronic and slowly progressive course but can lead to significant disability and reduced quality of life (QoL). The aim of this study was to analyze QoL in MGUS-PNP patients and to determine its predictors. Our study included 51 patients diagnosed with MGUS-PNP (23.5% with IgM, 66.7% IgG or IgA, 7.8% undetermined paraprotein, 2.0% light chains). QoL was assessed using the SF-36 questionnaire. The Medical Research Council Sum Score (MRC-SS), INCAT disability and sensory scores, ataxia score, Krupp's Fatigue Severity Scale and Beck's Depression Inventory were also used. Total SF-36 score was 50.0 ± 21.4 and no difference was observed between IgM and IgG/IgA MGUS-PNP. Physical composite score was worse than mental (44.4 ± 21.4 vs. 54.5 ± 20.9). Following factors showed correlation with SF-36 total score in univariate analysis: INCAT disability score, MRC-SS, INCAT sensory score, level of ataxia, fatigue and depression (p < 0.01). Significant predictors of worse SF-36 total score in our MGUS-PNP patients were depression (ß = - 0.46, p < 0.01), fatigue (ß = - 0.32, p < 0.01) and INCAT disability score (ß = - 0.27, p < 0.01). QoL in MGUS-PNP is equally affected in patients with different types of paraprotein. MGUS-PNP patients with more severe functional disability, fatigue and depression need special attention of clinicians since they could be at higher risk to have worse QoL. This should be taken into account when treating subjects with MGUS-PNP.