Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

AIMS/HYPOTHESIS: Vasopressin plays a role in osmoregulation, glucose homeostasis and inflammation. Therefore, plasma copeptin, the stable C-terminal portion of the precursor of vasopressin, has strong potential as a biomarker for the cardiometabolic syndrome and diabetes. Previous results were contradictory, which may be explained by differences between men and women in responsiveness of the vasopressin system. The aim of this study was to evaluate the usefulness of copeptin for prediction of future type 2 diabetes in men and women separately. METHODS: From the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 4,063 women and 3,909 men without diabetes at baseline were included. A total of 208 women and 288 men developed diabetes during a median follow-up of 7.7 years. RESULTS: In multivariable-adjusted models, we observed a stronger association of copeptin with risk of future diabetes in women (OR 1.49 [95% CI 1.24, 1.79]) than in men (OR 1.01 [95% CI 0.85, 1.19]) (p (interaction) < 0.01). The addition of copeptin to the Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) clinical model improved the discriminative value (C-statistic,+0.007, p = 0.02) and reclassification (integrated discrimination improvement [IDI] = 0.004, p < 0.01) in women. However, we observed no improvement in men. The additive value of copeptin in women was maintained when other independent predictors, such as glucose, high sensitivity C-reactive protein (hs-CRP) and 24 h urinary albumin excretion (UAE), were included in the model. CONCLUSIONS/INTERPRETATION: The association of plasma copeptin with the risk of developing diabetes was stronger in women than in men. Plasma copeptin alone, and along with existing biomarkers (glucose, hs-CRP and UAE), significantly improved the risk prediction for diabetes in women

An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology

BACKGROUND: In humans, serotonin has typically been investigated as a neurotransmitter. However, serotonin also functions as a hormone across animal phyla, including those lacking an organized central nervous system. This hormonal action allows serotonin to have physiological consequences in systems outside the central nervous system. Fluctuations in estrogen levels over the lifespan and during ovarian cycles cause predictable changes in serotonin systems in female mammals. DISCUSSION: We hypothesize that some of the physiological effects attributed to estrogen may be a consequence of estrogen-related changes in serotonin efficacy and receptor distribution. Here, we integrate data from endocrinology, molecular biology, neuroscience, and epidemiology to propose that serotonin may mediate the effects of estrogen. In the central nervous system, estrogen influences pain transmission, headache, dizziness, nausea, and depression, all of which are known to be a consequence of serotonergic signaling. Outside of the central nervous system, estrogen produces changes in bone density, vascular function, and immune cell self-recognition and activation that are consistent with serotonin's effects. For breast cancer risk, our hypothesis predicts heretofore unexplained observations of the opposing effects of obesity pre- and post-menopause and the increase following treatment with hormone replacement therapy using medroxyprogesterone. SUMMARY: Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation

How useful are prescribing indicators based on the DU90% method to distinguish the quality of prescribing between pharmacotherapy audit meetings with different levels of functioning?

Item does not contain fulltextOBJECTIVES: The objective of the study was to assess the association between the quality of drug prescribing based on three indicator types derived from the DU90% method and different levels of functioning in pharmacotherapy audit meetings (PTAMs). MATERIALS AND METHODS: The level of functioning in PTAMs in 2004 was assessed by a standard questionnaire. Data on prescriptions in 2004 by the GPs participating in the included PTAMs were extracted from the database of the Foundation for Pharmaceutical Statistics. Three types of DU90% indicators were computed for the seven mostly prescribed drug classes. With univariate and multivariate analyses of variance, differences in the results of three types of indicators for each of the seven drug classes were assessed according to the levels of PTAMs. RESULTS: For 84 PTAMs with varying levels of functioning, we found no association between the level of PTAM and the quality of prescribing for any of the indicators within the seven drug classes. In general, results gained of all PTAMs seemed to be high in quality for the aspects measured. CONCLUSIONS: It is difficult to define indicators based on the DU90% method, which can readily distinguish differences in the quality of drug prescribing between PTAMs with different levels of functioning. Indicators for prescribing should specifically meet relevant items in the quality of prescribing for certain drug classes. Items for classification of PTAM levels may need some reconsideration

Inhaled Corticosteroids and the Occurrence of Oral Candidiasis:A Prescription Sequence Symmetry Analysis

<p>The primary aim of the study was to gain insight into the relative risk of clinically relevant oral candidiasis following inhaled corticosteroid (ICS) initiation over time. A secondary aim was to analyse the influence of patient characteristics and co-medication on the occurrence of this adverse effect.</p><p>Drug prescription data from 1994 to 2011 were retrieved from the IADB.nl database. To study the influence of ICS use on occurrence of oral candidiasis, a prescription symmetry analysis was used, including patients using medication for oral candidiasis up to 1 year before or after ICS initiation. The relative risk was calculated by dividing the number of patients receiving medication for oral candidiasis after ICS initiation by the number of patients receiving the same medication before ICS initiation. Sub-analyses were conducted to compare the relative risks at several time points after ICS initiation and to account for therapy persistence by only including chronic users of ICS. A multivariate logistic regression model was used to identify predictive factors.</p><p>A total of 52,279 incident users of ICS therapy were identified, of which 1,081 received medication for oral candidiasis up to 1 year before or after ICS initiation. A total of 701 patients received medication for oral candidiasis after ICS initiation, while 361 received these medications in the reversed sequence, resulting in a sequence ratio (SR) of 1.94 (95 % CI 1.71-2.21). In the first 3 months after ICS initiation, the SR was 2.72 (95 % CI 2.19-3.38) and then decreased to 1.47 (95 % CI 1.11-1.95) 9-12 months after ICS initiation. Predictive factors were higher daily dose of ICS and concomitant use of oral corticosteroids.</p><p>This study found a significant and clinically relevant increased number of patients receiving medication for oral candidiasis in the first year after therapy initiation with ICS. Relative risk is highest in the first 3 months, but remains increased up to at least 1 year after ICS initiation. This study stresses the need for patient education and inhalation instruction.</p>