Vitamin D and Gestational Diabetes Mellitus

Type 2 Diabetes Mellitus (T2DM) was characteristically an adult-onset illness until recently, when it became recognized as an increasing problem among youth in conjunction with escalating rates and associated risks of pediatric. Youth-onset T2DM is associated with a range of psychosocial risk factors, and research underscores the relevancy of depressive symptoms and quality of life factors in illness diagnosis, management and prognosis. This review paper summarizes available findings on depression and health-related quality of life for youth-onset T2DM, and provides recommendations for clinical practice and a conceptual framework for further studies.     

Vitamin D and Vascular Disease: The Current and Future Status of Vitamin D Therapy in Hypertension and Kidney Disease

Over the past decade, vitamin D has generated considerable interest as potentially having important effects on the vasculature and the kidney. Animal and human data indicate that vitamin D suppresses the activity of the renin-angiotensin system and improves endothelial function. Observational studies in humans suggest that low 25-hydroxyvitamin D (25[OH]D) levels are associated with a higher risk of hypertension. However, findings from randomized trials of vitamin D supplementation (with cholecalciferol or ergocalciferol) to lower blood pressure are inconsistent, possibly stemming from variability in study population, sample size, vitamin D dose, and duration. Supplementation with activated vitamin D (i.e., 1,25-dihydroxyvitamin D or analogues) in patients with chronic kidney disease reduces urine albumin excretion, an important biomarker for future decline in renal function. These studies are reviewed, with special emphasis on recent findings. Definitive studies are warranted to elucidate the effects of vitamin D supplementation on mechanisms of hypertension and kidney disease.     

Hypovitaminosis D in Chronic Kidney Disease

Background and objectives: Recent studies show high prevalence of suboptimal 25-hydroxyvitamin D levels in chronic kidney disease patients. This study sought to test the hypothesis that the prevalence of 25-hydroxyvitamin D deficiency is significantly higher in chronic kidney disease patients and, in diabetic nephropathy, low serum 25-hydroxyvitamin D is associated with abnormal serum parathyroid hormone, bone mineral density, and coronary artery calcification.Design, setting, participants, & measurements: Study A used data from the Third National Health and Nutrition Examination Survey. Study B was a post hoc analysis of an observational study of coronary artery calcification in non–dialysis-dependent diabetic nephropathy.Results: In study A, the adjusted odds for 25-hydroxyvitamin D deficiency were 32% higher in chronic kidney disease patients. This higher prevalence of 25-hydroxyvitamin D deficiency, however, could not be explained by differences in total vitamin D intakes. The consequences of suboptimal 25-hydroxyvitamin D levels were analyzed in 146 patients with diabetic nephropathy. The significant, inverse relationship between serum 25-hydroxyvitamin D and parathyroid hormone levels was attenuated to a nonsignificant level on multivariate adjustment. There was a significant, inverse relationship between bone mineral density and coronary artery calcification scores; neither was independently associated with serum 25-hydroxyvitamin D. The serum 25-hydroxyvitamin D levels declined modestly in 72 patients studied after 12.4 ± 0.4 mo.Conclusions: 25-Hydroxyvitamin D deficiency is more common in chronic kidney disease, but this higher prevalence is unlikely to be a result of lower vitamin D intakes. The consequences of suboptimal 25-hydroxyvitamin D levels remain to be definitively elucidated.Vitamin D is important for maintaining bone health and muscle function (1). Serum 25 hydroxyvitamin D (25OHD) levels are a sensitive marker of the total body vitamin D stores. Epidemiologic and interventional studies suggest that serum 25OHD levels of at least 30 ng/ml are probably necessary to ensure optimal bone health and muscle function (1,2). Using this threshold, a large proportion of elderly, nursing home residents, dark-skinned people, and individuals who require hospitalization are either vitamin D insufficient (15 to 30 ng/ml) or deficient (<15 ng/ml) (1,3,4). In the absence of data from individuals with chronic kidney disease (CKD), the Kidney Disease Outcomes Quality Initiative (KDOQI) workgroup extrapolated these data to make opinion-based recommendations to maintain serum 25OHD levels >30 ng/ml in patients with stage 3 or 4 CKD (5). Numerous studies have demonstrated that the vast majority of non–dialysis-dependent patients with CKD have suboptimal 25OHD levels (6–9); however, none of these studies included a sufficiently large sample of control subjects to determine whether CKD is independently associated with a higher prevalence of suboptimal 25OHD levels. Moreover, secondary hyperparathyroidism and reduced bone mineral density (BMD)—the most common consequences of suboptimal 25OHD levels in the general population—are often present in patients with CKD. There is a paucity of data evaluating the role of 25OHD in the reduced BMD in CKD.We undertook this study to test the hypothesis that CKD is an independent predictor of 25OHD deficiency in a random sample of community-dwelling individuals of the United States using the Third National Health and Nutrition Survey (NHANES III; study A); this may, in part, be accounted for by lower daily vitamin D intakes. Furthermore, in a cohort of patients with diabetes and diabetic nephropathy (DN), we sought to determine the effects of suboptimal 25OHD levels on bone health (elevated serum parathyroid hormone (PTH) levels and reduced BMD) and coronary artery calcification (CAC) scores (study B).     

Response to Cardiac Resynchronization Therapy Across Chronic Kidney Disease Stages

IntroductionLimited data are available concerning the effect of severe chronic kidney disease (CKD) on the response to cardiac resynchronization therapy (CRT) because these patients are commonly excluded from trials. Therefore, we aimed to assess the effect of CRT on renal function, reverse remodeling and outcome across all stages of CKD in a large patient population of recipients of CRT.MethodsWe retrospectively evaluated 798 consecutive patients with heart failure who were undergoing CRT implantation between October 2008 and September 2016. Renal function data were available at baseline and at 6 months following CRT. Remodeling based on left ventricular end diastolic volume/left ventricular ejection fraction (LVESV/LVEF) and clinical outcome was assessed using a combined endpoint of all-cause mortality and hospitalization because of heart failure.ResultsMedian baseline estimated glomerular filtration rate was 62.8 (43.6–77.8) mL/min/1.73 m². Of the patients, 33.6% were in CKD stage 3, 11.0% in stage 4 and 1.1% in stage 5. LVEF and LVESV improved across all CKD stages; however, patients with CKD stages 1 and 2 exhibited a greater degree of improvement in LVEF (median 15% vs 10%, P < 0.001) and LVESV (median –37.2% vs –29.9%, P < 0.001) compared to patients with CKD stages 3–5. Despite a greater degree of reverse remodeling in CKD stages 1 and 2, the most accurate cut-off of remodeling predicting good clinical outcome was lower for patients with CKD stage 3–5, respectively: 5.5% vs 9.5% (LVEF) and –6.67% vs –12.41% (LVESV).ConclusionsCRT results in reverse remodeling across all stages of CKD, although to a lesser extent in patients with renal dysfunction (CKD stage 3–5). However, patients with CKD derive benefit on outcome at a lesser degree of remodeling.     

Everolimus Eluting Stents in Patients with Diabetes Mellitus and Chronic Kidney Disease: Insights from the TUXEDO Trial

BackgroundPatients with diabetes and those with chronic kidney disease (CKD) are at increased risk of cardiovascular events. Everolimus eluting stents (EES) have been shown to be superior to paclitaxel eluting stents (PES) in patients with diabetes. However, it is not known if EES is as beneficial in diabetic patients with CKD compared with those without CKD.Methods and resultsPatients enrolled in the TUXEDO-India trial, which is a clinical trial of patients with diabetes and coronary artery disease (CAD) randomly assigned to EES vs. thin-strut PES (Taxus Element), with data on baseline renal function were selected. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² using the Cockcroft–Gault formula. Primary outcome was target vessel failure (TVF-defined as cardiac death, TV myocardial infarction (MI) or ischemia driven TV revascularization) at 1 year. Various secondary outcomes including stent thrombosis were evaluated.Among the 1821 patients with diabetes included in this analysis, 344 (19%) had CKD. In a propensity score adjusted analysis, patients with CKD had a significant increase in MACE (HR = 2.02; 95% CI 1.17–3.50; P = 0.01); death/MI/TVR (HR = 1.99; 95% CI 1.18–3.34; P = 0.009); death/MI (HR = 2.31; 95% CI 1.30–4.08; P = 0.004); cardiac death/MI (HR = 2.40; 95% CI 1.31–4.42; P = 0.005); death (HR = 2.88; 95% CI 1.35–6.13; P = 0.006) driven by an increase in cardiac death (HR = 3.33; 95% CI 1.42–7.83; P = 0.006) when compared with those without CKD. However, stent related events (TV-MI, TVR, TLR and stent thrombosis) were not different between CKD and non CKD groups. A significant interaction between CKD status and stent type (EES vs. PES) was noted for the outcomes of TVF (P_interaction = 0.046), MACE (P_interaction = 0.02), cardiac death or MI (P_interaction = 0.05), non-target vessel related MI (P_interaction = 0.04), non-Q-wave MI (P_interaction = 0.03) and deaths/MI/TVR (P_interaction = 0.04) such that EES was superior to PES in the non-CKD cohort but not in the CKD cohort.ConclusionsIn subjects with diabetes, CKD is an independent predictor of adverse cardiovascular outcomes including increased risk of death driven largely by non-stent related events. While EES was superior to PES in patients without CKD, this was not the case in those with CKD (Clinical Trials Registry-India number, CTRI/2011/06/001830).     

Acute Kidney Injury Following Aortic Valve Replacement in Patients Without Chronic Kidney Disease

BackgroundThe data on acute kidney injury (AKI) in patients without chronic kidney disease (CKD) after transcatheter aortic valve replacement (TAVR) are limited. The study sought to compare the incidence of AKI and its impact on 5-year mortality after TAVR and surgical aortic valve replacement (SAVR) in patients without CKD.MethodsThis registry included data from 6463 consecutive patients who underwent TAVR or SAVR. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m². AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. For sensitivity analysis, propensity-score matching between TAVR and SAVR was performed.ResultsThe study included 4555 consecutive patients (TAVR, n = 1215 and SAVR, n = 3340) without CKD. Propensity-score matching identified 542 pairs. Patients who underwent TAVR had a significantly lower incidence of AKI in comparison to those who underwent SAVR (unmatched 4.7% vs 16.4%, P < 0.001, multivariable analysis: odds ratio, 0.29, 95% confidence interval [CI], 0.20-0.41; matched 5.9% vs 19.0%, P < 0.001). Patients with AKI had significantly increased 5-year mortality compared with those without AKI (unmatched 36.0% vs 19.1%, log-rank P < 0.001; matched 36.3% vs 24.0%, log-rank P < 0.001). The adjusted hazard ratios for 5-year mortality were 1.58 (95% CI, 1.20-2.08) for AKI grade 1, 3.27 (95% CI, 2.09-5.06) for grade 2, and 4.82 (95% CI, 2.93-8.04) for grade 3.ConclusionsTAVR in patients without CKD was associated with a significantly less frequent incidence of AKI compared with SAVR. AKI significantly increased the risk of 5-year mortality after either TAVR or SAVR, and increasing severity of AKI was incrementally associated with 5-year mortality.     

Vitamin D,Insulin Resistance,and Type 2 Diabetes

Vitamin D deficiency has become a major public health problem in the United States and worldwide due to its increasing prevalence and potential health risks. There is growing evidence from experimental studies that vitamin D is essential for pancreatic insulin secretion and peripheral insulin action through binding to the vitamin D receptor (VDR). Observational evidence, primarily from cross-sectional studies, has shown that low dietary vitamin D intake or vitamin D levels are inversely related to glucose intolerance, insulin resistance, decreased insulin secretion, as well as prevalence of the metabolic syndrome. Population genetic data for an association between VDR gene polymorphisms and type 2 diabetes have been sparse and yielded inconsistent results. Prospective data, although limited, tend to support an inverse association between serum 25(OH) vitamin D levels and incident type 2 diabetes. Direct evidence from randomized trials on the effect of vitamin D supplements on insulin homeostasis, however, remains limited. Future well-designed randomized clinical trials are warranted to address the potential beneficial effect of vitamin D supplementation on preventing type 2 diabetes.