Does Vitamin D Deficiency Cause Hypertension? Current Evidence from Clinical Studies and Potential Mechanisms

Vitamin D deficiency is widely prevalent across all ages, races, geographical regions, and socioeconomic strata. In addition to its important role in skeletal development and calcium homeostasis, several recent studies suggest its association with diabetes, hypertension, cardiovascular disease, certain types of malignancy, and immunologic dysfunction. Here, we review the current evidence regarding an association between vitamin D deficiency and hypertension in clinical and epidemiological studies. We also look into plausible biological explanations for such an association with the renin-angiotensin-aldosterone system and insulin resistance playing potential roles. Taken together, it appears that more studies in more homogeneous study populations are needed before a firm conclusion can be reached as to whether vitamin D deficiency causes or aggravates hypertension and whether vitamin D supplementation is safe and exerts cardioprotective effects. The potential problems with bias and confounding factors present in previous epidemiological studies may be overcome or minimized by well designed randomized controlled trials in the future

Incident Diabetes Complications among Women with type 1 diabetes based on Parity

Objectives To assess risk factors and incidence of diabetes complications in women with type 1 diabetes (T1D) based on parity. Research design/methods Data were collected from women (16–40 years old) in the T1D Exchange completing pregnancy/childbirth questionnaires during 2011–2013 and 2016–2018. Incidence of risk factors and diabetes complications were compared between women with a first pregnancy at/within 1-year of enrollment (n = 28) and never pregnant women by year 5 (n = 469). Results There was a trend for lower HbA1c (adjusted p = .14) and higher rates of overweight/obesity, triglyceride/HDL > 2, log (triglyercide/HDL), and hypertension among parous women compared with nulliparous women. There were no significant differences in rates of advanced nephropathy, albuminuria or cardiovascular disease. Conclusions Four-5 years after delivery, parous women with T1D tended to have lower HbA1c levels despite higher body mass indices and more frequent adverse lipid profiles and hypertension compared with nulliparous women. Further studies based on these trends are warranted

Prevalence and cardiometabolic associations of the glucocorticoid receptor gene polymorphisms N363S and Bcl1 in obese and non-obese black and white Mississippians

AbstrAct ObJEctIVE: Polymorphisms (sNP) in the glucocorticoid receptor (Gr) gene can alter sensitivity to glucocorticoids. Previous studies of the N363s and BclI sNP in the Gr gene have shown a metabolic syndrome phenotype in mostly non-African populations. the obesity phenotype of African Americans (AA) seems to be more severe than that of caucasians. DEsIGN: We aimed to assess the prevalence of N363s and BclI in obese and non-obese caucasian (n=26) and African (n=23) Mississippians (age: 23-63 years) to investigate associations with body composition (body mass index/bMI, waist-to-hip ratio), metabolic parameters (salivary cortisol, fasting glucose and insulin, hemoglobin A1c, fructosamine, HOMA-Ir index), and psychological stress perception (blood pressure/bP, perceived stress scale/Pss). rEsULts: All subjects were homozygous for wildtype N363N. BclI polymorphism genotype frequencies among the 23 AA were: homozygous cc (57%), GG (4%), and heterozygous cG (39%), and among the 26 white women: homozygous cc (35%), GG (19%), and heterozygous cG (46%). Linear and logistic regression analyses including a parsimonious model identified bMI as a statistically significant parameter between the two ethnic groups (bMI was 3.13 kg/m 2 higher in AA). Within the AA group, bMI, waist-to-hip ratio, log (HOMA-Ir), Pss scores, bP, and hyperlipidemia showed no statistically significant relationships for the BclI polymorphism. Pss scores were 15.2 for AA vs. 14.7 for white women (normal mean: 14.7 vs. 12.8). cONcLUsION: black Mississippians HORMONES 2012, 11(2):166-17

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Clustering of sebaceous gland carcinoma, papillary thyroid carcinoma and breast cancer in a woman as a new cancer susceptibility disorder: a case report

Abstract Introduction Multiple distinct tumors arising in a single individual or within members of a family raise the suspicion of a genetic susceptibility disorder. Case presentation We present the case of a 52-year-old Caucasian woman diagnosed with sebaceous gland carcinoma of the eyelid, followed several years later with subsequent diagnoses of breast cancer and papillary carcinoma of the thyroid. Although the patient was also exposed to radiation from a pipe used in the oil field industry, the constellation of neoplasms in this patient suggests the manifestation of a known hereditary susceptibility cancer syndrome. However, testing for the most likely candidates such as Muir-Torre and Cowden syndrome proved negative. Conclusion We propose that our patient's clustering of neoplasms either represents a novel cancer susceptibility disorder, of which sebaceous gland carcinoma is a characteristic feature, or is a variant of the Muir-Torre syndrome.</p

Calcium plus vitamin D supplementation and the risk of postmenopausal weight gain.

BackgroundObesity in the United States has increased significantly during the past several decades. The role of calcium in the maintenance of a healthy body weight remains controversial.MethodsA randomized, double-blinded, placebo-controlled trial was performed with 36 282 postmenopausal women, aged 50 to 79 years, who were already enrolled in the dietary modification and/or hormone therapy arms of the Women's Health Initiative clinical trial. Women were randomized at their first or second annual visit to receive a dose of 1000 mg of elemental calcium plus 400 IU of cholecalciferol (vitamin D) or placebo daily. Change in body weight was ascertained annually for an average of 7 years.ResultsWomen receiving calcium plus cholecalciferol supplements vs women receiving placebo had a minimal but consistent favorable difference in weight change (mean difference, -0.13 kg; 95% confidence interval, -0.21 to -0.05; P = .001). After 3 years of follow-up, women with daily calcium intakes less than 1200 mg at baseline who were randomized to supplements were 11% less likely to experience small weight gains (1-3 kg) and 11% less likely to gain more moderate amounts of weight (&gt;3 kg) (P for interaction for baseline calcium intake = .008).ConclusionCalcium plus cholecalciferol supplementation has a small effect on the prevention of weight gain, which was observed primarily in women who reported inadequate calcium intakes.Trial registrationclinicaltrials.gov Identifier: NCT00000611