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Vitamin D plays a critical role in many physiological functions, including calcium metabolism and musculoskeletal health. This commentary aims to explore the intricate relationships among skin complexion, race, and 25-hydroxyvitamin D (25[OH]D) levels, focusing on challenges the Endocrine Society encountered during clinical practice guideline development. Given that increased melanin content reduces 25(OH)D production in the skin in response to UV light, the guideline development panel addressed the potential role for 25(OH)D screening in individuals with dark skin complexion. The panel discovered that no randomized clinical trials have directly assessed vitamin D related patient-important outcomes based on participants' skin pigmentation, although race and ethnicity often served as presumed proxies for skin pigmentation in the literature. In their deliberations, guideline panel members and selected Endocrine Society leaders underscored the critical need to distinguish between skin pigmentation as a biological variable and race and ethnicity as socially determined constructs. This differentiation is vital to maximize scientific rigor and, thus, the validity of resulting recommendations. Lessons learned from the guideline development process emphasize the necessity of clarity when incorporating race and ethnicity into clinical guidelines. Such clarity is an essential step toward improving health outcomes and ensuring equitable healthcare practices. [ABSTRACT FROM AUTHOR]

Background Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain. Objective To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing. Methods A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined "empiric supplementation" as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D. Results The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D–containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity. Conclusion The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits. [ABSTRACT FROM AUTHOR]

Context Low vitamin D status is common and is associated with various common medical conditions. Objective To support the development of the Endocrine Society's Clinical Practice Guideline on Vitamin D for the Prevention of Disease. Methods We searched multiple databases for studies that addressed 14 clinical questions prioritized by the guideline panel. Of the 14 questions, 10 clinical questions assessed the effect of vitamin D vs no vitamin D in the general population throughout the lifespan, during pregnancy, and in adults with prediabetes; 1 question assessed dosing; and 3 questions addressed screening with serum 25-hydroxyvitamin D (25[OH]D). The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess certainty of evidence. Results Electronic searches yielded 37 007 citations, from which we included 151 studies. In children and adolescents, low-certainty evidence suggested reduction in respiratory tract infections with empiric vitamin D. There was no significant effect on select outcomes in healthy adults aged 19 to 74 years with variable certainty of evidence. There was a very small reduction in mortality among adults older than 75 years with high certainty of evidence. In pregnant women, low-certainty evidence suggested possible benefit on various maternal, fetal, and neonatal outcomes. In adults with prediabetes, moderate certainty of evidence suggested reduction in the rate of progression to diabetes. Administration of high-dose intermittent vitamin D may increase falls, compared to lower-dose daily dosing. We did not identify trials on the benefits and harms of screening with serum 25(OH)D. Conclusion The evidence summarized in this systematic review addresses the benefits and harms of vitamin D for the prevention of disease. The guideline panel considered additional information about individuals' and providers' values and preferences and other important decisional and contextual factors to develop clinical recommendations. [ABSTRACT FROM AUTHOR]

In recent years, vitamin D has been received increased attention due to the resurgence of vitamin D deficiency and rickets in developed countries and the identification of extraskeletal effects of vitamin D, suggesting unexpected benefits of vitamin D in health and disease, beyond bone health. The possibility of extraskeletal effects of vitamin D was first noted with the discovery of the vitamin D receptor (VDR) in tissues and cells that are not involved in maintaining mineral homeostasis and bone health, including skin, placenta, pancreas, breast, prostate and colon cancer cells, and activated T cells. However, the biological significance of the expression of the VDR in different tissues is not fully understood, and the role of vitamin D in extraskeletal health has been a matter of debate. This report summarizes recent research on the roles for vitamin D in cancer, immunity and autoimmune diseases, cardiovascular and respiratory health, pregnancy, obesity, erythropoiesis, diabetes, muscle function, and aging.

We examined the cross-sectional association between plasma 25-hydroxyvitamin D [25(OH)D] and markers of the insulin resistant phenotype. Plasma 25(OH)D concentrations were measured in 808 nondiabetic participants of the Framingham Offspring Study. Outcome measures included fasting and 2-h post 75-g oral glucose tolerance test (OGTT) glucose and insulin; these were used to calculate the homeostatic model assessment-insulin resistance (HOMA IR) and insulin sensitivity index ([ISI.sub.0,120]). We also measured plasma adiponectin, triacylglycerol, and HDL cholesterol concentrations as markers of the insulin-resistant phenotype. After adjusting for age, sex, BMI, waist circumference, and current smoking status, plasma 25(OH)D concentration was inversely associated with fasting plasma glucose and insulin concentrations, and HOMA-IR. Compared with the participants in the lowest tertile category of plasma 25(OH)D, those in the highest tertile category had a 1.6% lower concentration of fasting plasma glucose (P-trend = 0.007), 98% lower concentration of fasting plasma insulin (P-trend = 0.001), and 12.7% lower HOMA-I R score (P-trend < 0.001). After adjusting for age and sex, plasma 25(OH)D was positively associated with [ISI.sub.0,120], plasma adiponectin, and HDL cholesterol and inversely associated with plasma triacylglycerol, but these associations were no longer significant after further adjustment for BMI, waist circumference, and current smoking status. 25(OH)D and 2-h post-OGTT glucose were not associated. Among adults without diabetes, vitamin D status was inversely associated with surrogate fasting measures of insulin resistance. These results suggest that vitamin D status may be an important determinant for type 2 diabetes mellitus.

Background/objectives: Routine use of vitamin D supplements has increased substantially in the United States. However, the safety and tolerability of long-term use of high-dose vitamin D are not known. We assessed the safety and tolerability of high-dose, daily vitamin D3 in the vitamin D and type 2 diabetes (D2d) study.Subjects/methods: In total, 2423 overweight/obese persons with prediabetes were randomized in a double-blind manner to either 4000 IU of vitamin D3 (the tolerable upper intake level for adults by the National Academy of Medicine) taken daily or matching placebo. All participants were included in this analysis. Incident adverse events (AE) were ascertained 4 times a year at in-person visits (twice a year) and interim remote encounters (twice a year) and were defined as untoward or unfavorable medical occurrences. Serious adverse events (SAE) included death, life-threatening events, and hospitalizations.Results: A total of 8304 AEs occurred during 3 years of follow-up and were less frequent in the vitamin D group compared to placebo (Incidence Rate Ratio [IRR] = 0.94; 95% Confidence Interval (CI) 0.90, 0.98). The overall frequency of protocol-specified AEs of interest, which included nephrolithiasis, hypercalcemia, hypercalciuria, or low estimated glomerular filtration rate, was low and did not differ by group. There were no significant between-group differences in total SAEs (IRR = 0.96 (0.81, 1.14)).Conclusion: Vitamin D3 supplementation at 4000 IU per day was safe and well tolerated among overweight/obese participants at high risk for diabetes who were appropriately monitored for safety. In this population, this dose of vitamin D3 did not increase risk of AEs or SAEs, including those previously associated with vitamin D such as hypercalcemia, hypercalciuria, or nephrolithiasis.Clinical Trial Registration: ClinicalTrials.gov NCT01942694, prospectively registered September 16, 2013. [ABSTRACT FROM AUTHOR]

A study was conducted on adults with type 2 diabetes in order to understand the effectiveness of incretin-based therapy. The results conclude that incretin-based therapy is a suitable and effective therapy

There is considerable uncertainty over whether any one dietary pattern broadly facilitates weight loss or maintenance of weight loss, and current dietary guidelines recommend a spectrum of dietary composition for the general population. However, emerging evidence suggests that specific dietary compositions may work better for identifiable groups of overweight/ obese individuals based on their individual metabolic status. In particular, characteristics of insulin dynamics, such as insulin sensitivity or insulin secretion status, may interact with diets that vary in macronutrient composition to influence the weight loss achieved with a hypocaloric diet. Key words: dietary composition, insulin secretion, insulin sensitivity, weight loss

The relative contribution of circulating glucose to meal-to-meal variability in energy intake is not known. In 8 free-living young (median age 26.5 y) women with healthy body weight (median BMI 22.2 kg/[m.sup.2]), we measured glucose in the interstitial space by an automated monitoring procedure (continuous glucose monitoring system, CGMS[TM]) for up to 3 consecutive days (mean 706 glucose readings per subject). We examined the association between interstitial glucose (which lags blood glucose by ~10 min), self-reported hunger, satiety, desire for a meal, and nutrient intakes. Participants reported consuming a typical Western diet (59% carbohydrate, 27% fat, 14% protein). Median (interquartile range) interstitial glucose was 5.2 mmol/L (4.7-5.8). Using repeated-measures techniques in univariate analyses, desire for a meal (r = 0.45, P < 0.0001), hunger (r = 0.37, P = 0.0002), satiety (r = -0.40, P < 0.0001), low interstitial absolute mean glucose up to 25 min before eating (r = -0.23, P = 0.02), and a large decline in glucose between 40 and 5 min before eating (r = -0.17, P = 0.08) were all associated with meal energy intake. In multivariate regression analyses, desire for a meal (P < 0.0001) and hunger (P = 0.02) were the strongest independent contributors to meal energy intake, whereas absolute mean glucose measured in the period 15 to 0 min before eating was marginally significant (P = 0.08). In conclusion, absolute glucose level is a significant predictor of energy intake in nonobese women. However, desire for a meal and hunger are quantitatively more important, emphasizing the importance of both glucose signals and nonglucose (internal or environmental) factors in within-subject variability in energy intake. In addition, the CGMS may have utility in understanding the role of circulating glucose in energy regulation in free-living subjects under a wide range of different nutritional conditions. KEY WORDS: * glucose * energy * hunger * satiety * free-living