The influence of cholecystectomy and recurrent biliary events on the risk of post-pancreatitis diabetes mellitus: a nationwide cohort study in patients with first attack of acute pancreatitis.

BACKGROUND: It is unknown whether cholecystectomy for acute pancreatitis (AP) affects the risk of post-pancreatitis diabetes mellitus (PPDM). We aimed to investigate the associations between cholecystectomy, recurrent biliary events prior to cholecystectomy, and the risk of PPDM in patients with AP. METHODS: Using New Zealand nationwide data from 2007 to 2016, patients with first admission for AP were identified (n = 10,870). Cholecystectomy was considered as a time-dependent exposure. Timing of cholecystectomy was categorized as same-admission, readmission, and delayed cholecystectomy. Recurrent biliary events prior to cholecystectomy were identified. Multivariable Cox regression analyses were conducted. RESULTS: Among 2147 patients who underwent cholecystectomy, 141 (6.6%) developed PPDM. Overall, cholecystectomy was not significantly associated with the risk of PPDM (adjusted hazard ratio, 1.14; 95% confidence interval, 0.94-1.38). Delayed cholecystectomy was significantly associated with an increased risk of PPDM (adjusted hazard ratio, 1.36; 95% confidence interval, 1.01-1.83). Patients who had 2 or ≥3 recurrent biliary events prior to cholecystectomy were at a significantly increased risk of PPDM. CONCLUSION: Cholecystectomy in general was not associated with the risk of PPDM in patients with AP. Two or more repeated attacks of AP (or other biliary events) were associated with a significantly increased risk of PPDM.

Effect of Monthly High-Dose Vitamin D Supplementation on Acute Respiratory Infections in Older Adults: A Randomized Controlled Trial.

BACKGROUND: Although adults with low vitamin D status are at increased risk of acute respiratory infection (ARI), randomized controlled trials of vitamin D supplementation have provided inconsistent results. METHODS: We performed a randomized, double-blinded, placebo-controlled trial of 5110 adults aged 50-84 years. In 2011-2012, participants were randomized to an initial oral dose of 200 000 IU vitamin D3 followed by 100 000 IU monthly (n = 2558) or placebo (n = 2552) until late 2013 (median follow-up, 1.6 years). Participants reported upper and lower ARIs on monthly questionnaires. Cox models analyzed time to first ARI (upper or lower) by treatment group. RESULTS: Participants' mean age was 66 years and 58% were male; 83% were of European/other ethnicity, with the rest Maori, Polynesian, or South Asian. Mean (SD) baseline blood 25-hydroxyvitamin D [25(OH)D] level was 63 (24) nmol/L; 25% were <50 nmol/L. In a random sample (n = 441), vitamin D supplementation increased mean 25(OH)D to 135 nmol/L at 3 years, while those on placebo remained at 63 nmol/L. During follow-up, 3737 participants reported ≥1 ARI: 74.1% in the vitamin D group versus 73.7% in the placebo group. The hazard ratio for vitamin D compared with placebo was 1.01 (95% CI, 0.94, 1.07). Similar results were seen in most subgroups, including those with baseline 25(OH)D <50 nmol/L and in analyses of the upper/lower components of the ARI outcome. CONCLUSIONS: Monthly high-dose vitamin D supplementation does not prevent ARI in older adults with a low prevalence of profound vitamin D deficiency at baseline. Whether effects of daily or weekly dosing differ requires further study. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry, identifier ACTRN12611000402943.

Vitamin D supplementation increases adipokine concentrations in overweight or obese adults.

PURPOSE: Vitamin D regulates adipokine production in vitro; however, clinical trials have been inconclusive. We conducted secondary analyses of a randomized controlled trial to examine whether vitamin D supplementation improves adipokine concentrations in overweight/obese and vitamin D-deficient adults. METHODS: Sixty-five individuals with a BMI ≥ 25 kg/m2 and 25-hydroxyvitamin D (25(OH)D) ≤ 50 nmol/L were randomized to oral cholecalciferol (100,000 IU single bolus followed by 4,000 IU daily) or matching placebo for 16 weeks. We measured BMI, waist-to-hip ratio, % body fat (dual X-ray absorptiometry), serum 25(OH)D (chemiluminescent immunoassay) and total adiponectin, leptin, resistin, and adipsin concentrations (multiplex assay; flow cytometry). Sun exposure, physical activity, and diet were assessed using questionnaires. RESULTS: Fifty-four participants completed the study (35M/19F; mean age = 31.9 ± 8.5 years; BMI = 30.9 ± 4.4 kg/m2). After 16 weeks, vitamin D supplementation increased 25(OH)D concentrations compared with placebo (57.0 ± 21.3 versus 1.9 ± 15.1 nmol/L, p < 0.001). There were no differences between groups for changes in adiponectin, leptin, resistin, or adipsin in unadjusted analyses (all p > 0.05). After adjustment for baseline values, season, sun exposure, and dietary vitamin D intake, there was a greater increase in adiponectin (ß[95%CI] = 13.7[2.0, 25.5], p = 0.02) and leptin (ß[95%CI] = 22.3[3.8, 40.9], p = 0.02) in the vitamin D group compared with placebo. Results remained significant after additional adjustment for age, sex, and % body fat (p < 0.02). CONCLUSIONS: Vitamin D may increase adiponectin and leptin concentrations in overweight/obese and vitamin D-deficient adults. Further studies are needed to clarify the molecular interactions between vitamin D and adipokines and the clinical implications of these interactions in the context of obesity. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT02112721.

Risk of Mortality and Hospitalization After Post-Pancreatitis Diabetes Mellitus vs Type 2 Diabetes Mellitus: A Population-Based Matched Cohort Study.

OBJECTIVES: To investigate the risk of mortality and hospitalization in individuals with post-pancreatitis diabetes mellitus (PPDM) compared with those with type 2 diabetes mellitus (T2DM). METHODS: Using nationwide hospital discharge data on pancreatitis and diabetes in New Zealand (n = 231,943), a total of 959 individuals with PPDM were identified. For each individual with PPDM, 10 age- and sex-matched individuals with T2DM were randomly selected. Multivariable Cox regression analysis was conducted, and the risk was expressed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: A total of 3,867 deaths occurred among 10,549 study individuals. Individuals with PPDM had all-cause mortality rate at 80.5 (95% CI, 70.3-90.6) per 1,000 person-years, which was higher compared with T2DM individuals (adjusted HR, 1.13 (95% CI, 1.00-1.29); absolute excess risk, 14.8 (95% CI, 4.5-25.2) per 1,000 person-years). Compared with T2DM, PPDM was associated with higher risks of mortality from cancer (adjusted HR, 1.44; 95% CI, 1.13-1.83), infectious disease (adjusted HR, 2.52; 95% CI, 1.69-3.77), and gastrointestinal disease (adjusted HR, 2.56; 95% CI, 1.64-4.01). Individuals with PPDM vs T2DM were also at significantly higher risks of hospitalization for chronic pulmonary disease, moderate to severe renal disease, and infectious disease. CONCLUSIONS: Individuals with PPDM have higher risk of mortality and hospitalization compared with individuals with T2DM. Guidelines for management of PPDM need to be developed with a view to preventing excess deaths and hospitalizations in individuals with PPDM.

Diabetes knowledge of primary health care and specialist nurses in a major urban area.

AIM AND OBJECTIVES: To examine trends since a previous 2006-2008 survey in diabetes knowledge held by primary health care nurses and their use of national diabetes guidelines, perceived ability to advise diabetes patients and preferences for further diabetes education. BACKGROUND: The obesity epidemic has led to a rapid increase in the prevalence of prediabetes and type 2 diabetes and to greater expectations for an expanded role for primary health care nurses in the prevention and community management of diabetes. DESIGN: Cross-sectional survey using a self-administered questionnaire and telephone interview and adheres to the STROBE guidelines. METHODS: All nurses who provide community-based care in a major urban area were identified, and stratified by group, prior to random selection to participate in the study. A total of 1,416 practice, district (home care) and specialist nurses were identified who provide community-based care. Of the 459 who were randomly selected, 336 (73%) participated in 2016 and were compared with a representative sample of 287 nurses surveyed in 2006-2008. RESULTS: Compared with nurses in 2006-2008, significantly more nurses in 2016 used diabetes guidelines, knew that stroke was a diabetes-related complication, had a greater understanding of the pathology of diabetes and reported having sufficient knowledge to advise patients on laboratory results and improving outcomes through lifestyle changes. Despite these improvements, in 2016, only 24% of nurses could state that stroke was a complication of type 2 diabetes, only 37% felt sufficiently knowledgeable to advise patients on medications, and <20% could state that hypertension, smoking and the dyslipidaemia profile were important modifiable risk factors. CONCLUSION: There have been improvements in nurse's knowledge but gaps remain for cardiovascular outcomes and associated modifiable risk factors and medication management. RELEVANCE TO CLINICAL PRACTICE: Education programmes should focus on improving cardiovascular risk management in patients with type 2 diabetes.

The association between vitamin D concentration and pain: a systematic review and meta-analysis.

OBJECTIVE: Pain-related conditions, such as chronic widespread pain and fibromyalgia, are major burdens for individuals and the health system. Evidence from previous research on the association between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and pain is conflicting. Thus, we aimed to determine if there is an association between mean 25(OH)D concentration (primary aim), or proportion of hypovitaminosis D (secondary aim), and pain conditions in observational studies. DESIGN: Published observational research on 25(OH)D concentration and pain-related conditions was systematically searched for in electronic sources (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) and a random-effects meta-analysis was conducted on included studies. RESULTS: Eighty-one observational studies with a total of 50 834 participants were identified. Compared with controls, mean 25(OH)D concentration was significantly lower in patients with arthritis (mean difference (MD): -12·34 nmol/l; P<0·001), muscle pain (MD: -8·97 nmol/l; P=0·003) and chronic widespread pain (MD: -7·77 nmol/l; P<0·001), but not in patients with headache or migraine (MD: -2·53 nmol/l; P=0·06). The odds of vitamin D deficiency was increased for arthritis, muscle pain and chronic widespread pain, but not for headache or migraine, compared with controls. Sensitivity analyses revealed similar results. CONCLUSIONS: A significantly lower 25(OH)D concentration was observed in patients with arthritis, muscle pain and chronic widespread pain, compared with those without. These results suggest that low 25(OH)D concentrations may be associated with pain conditions.

Vitamin D3 supplementation in adults with bronchiectasis: A pilot study.

Vitamin D supplementation prevents acute respiratory infections and, through modulating innate and adaptive immunity, could have a potential role in bronchiectasis management. The primary aims of this pilot study were to assess serum 25-hydroxyvitamin D (25(OH)D) levels in New Zealand adults with bronchiectasis, and their 25(OH)D levels after vitamin D3 supplementation. Adults with bronchiectasis received an initial 2.5 mg vitamin D3 oral loading dose and 0.625 mg vitamin D3 weekly for 24 weeks. The primary outcome was serum 25(OH)D levels before and after vitamin D3 supplementation. Secondary outcomes (time to first infective exacerbation, exacerbation frequency, spirometry, health-related quality of life measures, sputum bacteriology and cell counts and chronic rhinosinusitis) were also assessed. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12612001222831). The initial, average 25(OH)D level was 71 nmol/L (95% confidence interval (CI): [58, 84]), rising to 218 nmol/L (95% CI: [199, 237]) at 12 weeks and 205 nmol/L (95% CI: [186, 224]) at 24 weeks. The initial serum cathelicidin level was 25 nmol/L (95% CI: [17, 33]), rising to 102 nmol/L (95% CI: [48, 156]) at 12 weeks and 151 nmol/L (95% CI: [97, 205]) at 24 weeks. Over the 24-week study period, we observed statistically significant changes of 1.11 (95% CI: [0.08, 2.14]) in the Leicester Cough Questionnaire and -1.97 (95% CI: [-3.71, -0.23]) in the Dartmouth COOP charts score. No significant adverse effects were recorded. Many New Zealand adults with bronchiectasis have adequate 25(OH)D levels. Weekly vitamin D3 supplementation significantly improved 25(OH)D levels.

A short history of phototherapy, vitamin D and skin disease.

The earliest record between sun exposure and skin disease goes back five millennia to the ancient Egyptians. The modern scientific era of medical light therapy and skin diseases started in 1877 when Downs and Blunt reported that exposure to light inhibited fungal growth in test tubes. Continuing research generated a growing medical interest in the potential the effects of light to treat and cure skin diseases considered as parasitic. This culminated in the awarding of the 1903 Nobel Prize in Medicine to Niels Finsen for his pioneering work showing that light could successfully treat cutaneous mycobacterium tuberculosis (lupus vulgaris), a disfiguring disorder common at the time. Cod liver oil was used as a folk remedy to treat rickets prior to 1789 in Manchester, UK and sunlight was published as the cure for this disease in 1921. The work by Hess and Weinstock in 1925 showed that food irradiated with ultraviolet (UV) light prevented rickets in rats, which paved the way for the discovery of vitamin D. The range of skin diseases treated by light therapy increased in the following years, to the point where a 1932 review by the American Medical Association on the use of UV therapy in dermatology listed 34 skin conditions for which UV radiation may be useful. This period coincided with the development of sanatoria in Europe and North America which used heliotherapy for the treatment of tuberculosis. UV therapy and vitamin D continued to be used successfully for the treatment of tuberculosis up to the 1950s when it was superseded by more effective antibiotics. Modern phototherapy developed in the 1980s with the discovery of the action spectrum for psoriasis leading to the development of narrow band UVB. Subsequently a biological mechanism by which UV light and vitamin D treated tuberculosis was identified in 2006. This involves activation of human macrophages via toll-like receptors to upregulate the vitamin D receptor gene resulting in induction of the antimicrobial peptide cathelicidin. The role of UV light and vitamin D in the treatment of skin diseases is currently an active area of research.

Effect of waist circumference on the association between serum 25-hydroxyvitamin D and serum lipids: results from the National Health and Nutrition Examination Survey 2001-2006.

OBJECTIVE: To examine the interaction between waist circumference (WC) and serum 25-hydroxyvitamin D (25(OH)D) level in their associations with serum lipids. DESIGN: Cross-sectional study. The associations of serum 25(OH)D with total cholesterol, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), LDL-C:HDL-C and TAG were examined using multiple linear regression. Effect modification by WC was assessed through cross-product interaction terms between 25(OH)D and WC categories (abdominal overweight, 80-<88 cm in females/94-<102 cm in males; abdominal obesity, ≥88 cm in females/≥102 cm in males). SETTING: The US National Health and Nutrition Examination Survey waves 2001-2006. SUBJECTS: Non-pregnant fasting participants (n 4342) aged ≥20 years. RESULTS: Lower 25(OH)D levels were significantly associated with lower HDL-C levels as well as with higher LDL-C:HDL-C and TAG levels in abdominally obese participants, but not in abdominally overweight or normal-waist participants. In contrast, lower 25(OH)D levels were associated with lower levels of total cholesterol and LDL-C in abdominally overweight and normal-waist participants only, but this association was only partly significant. However, a significant difference in the association between 25(OH)D and the lipids according to WC category was found only for LDL-C:HDL-C (P for interaction=0·02). CONCLUSIONS: Our results from this large, cross-sectional sample suggest that the association between lower 25(OH)D levels and an unfavourable lipid profile is stronger in individuals with abdominal obesity than in those with abdominal overweight or a normal WC.

Factors associated with photoprotection by body clothing coverage, particularly in non-summer months, among a New Zealand community sample.

Clothing coverage is important for reducing skin cancer risk, but may also influence vitamin D sufficiency, so associated plausible predictors require investigation. Volunteers (18 to 85 years), with approximately equal numbers by sex and four ethnicity groups, were recruited in cities from two latitude bands: Auckland (36.9°S) and Dunedin (45.9°S). Baseline questionnaire, anthropometric and spectrophotometer skin colour data were collected and weather data obtained. Percent body coverage was calculated from eight week diary records. Potential independent predictors (unadjusted p < 0.25) were included in adjusted models. Participants (n = 506: Auckland n = 334, Dunedin n = 172; mean age 48.4 years) were 62.7% female and had a median body clothing coverage of 81.6% (IQR 9.3%). Dunedin was cooler, less windy and had lower UVI levels than Auckland. From the fully adjusted model, increased coverage occurred in non-summer months (despite adjusting for weather), among Dunedin residents and Asians (compared to Europeans), during the middle of the day, with a dose response effect observed for greater age. Reduced coverage was associated with Pacific ethnicity and greater time spent outdoors. Additionally, higher temperatures were associated with reduced coverage, whereas increased cloud cover and wind speed were associated with increased coverage. Although the only potentially modifiable factors associated with clothing coverage were the time period and time spent outdoors, knowledge of these and other associated factors is useful for the framing and targeting of health promotion messages to potentially influence clothing coverage, facilitate erythema avoidance and maintain vitamin D sufficiency.

Reduced primary care respiratory infection visits following pregnancy and infancy vitamin D supplementation: a randomised controlled trial.

AIM: To determine whether vitamin D supplementation reduces primary care visits for acute respiratory infection (ARI). METHODS: A randomised, double-blind, placebo-controlled trial was conducted in New Zealand and powered to determine the vitamin D dose needed to achieve normal vitamin D status during infancy. Healthy pregnant women, from 27 weeks' gestation to birth, and their infants, from birth to age 6 months, were assigned to placebo or one of the two dosages of daily oral vitamin D3 . Woman/infant pairs were randomised to placebo/placebo, 1000 IU/400 IU or 2000 IU/800 IU. For this ad hoc analysis, the primary care records of enrolled children were audited to age 18 months. RESULTS: Two hundred and sixty pregnant women were randomised to placebo (n = 87), lower-dose (n = 87) or higher-dose (n = 86) vitamin D3 . In comparison with the placebo group (99%), the proportion of children making any ARI visits was smaller in the higher-dose (87%, p = 0.004), but not the lower-dose vitamin D3 group (95%, p = 0.17). The median number of ARI visits/child was less in the higher-dose vitamin D3 group from age 6-18 months (placebo 4, lower dose 3, higher dose 2.5; p = 0.048 for higher-dose vitamin D3 vs. placebo). CONCLUSION: Vitamin D3 supplementation during pregnancy and infancy reduces primary care visits for ARI during early childhood.

Arterial stiffness and incident chronic kidney disease: a large population-based cohort study.

BACKGROUND/AIMS: Evidence from large population-based cohorts as to the association of arterial stiffness and incident chronic kidney disease (CKD) is mixed. This large population-based study aimed to investigate whether arterial stiffness, assessed oscillometrically, was associated with incident CKD. METHODS: The study population comprised 4838 participants from the Vitamin D Assessment (ViDA) Study without known CKD (mean ± SD age = 66 ± 8). Arterial stiffness was assessed from 5 April, 2011 to 6 November, 2012 by way of aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure. Incident CKD was determined by linkage to national hospital discharge registers. Cox proportional hazards regression was used to assess the risk of CKD in relation to chosen arterial stiffness measures over the continuum and quartiles of values. RESULTS: During a mean ± SD follow-up of 10.5 ± 0.4 years, 376 participants developed incident CKD. Following adjustment for potential confounders, aortic pulse wave velocity (hazard ratio (HR) per SD increase 1.69, 95% CI 1.45-1.97), estimated carotid-femoral pulse wave velocity (HR per SD increase 1.84, 95% CI 1.54-2.19), and aortic pulse pressure (HR per SD increase 1.37, 95% CI 1.22-1.53) were associated with the incidence of CKD. The risk of incident CKD was, compared to the first quartile, higher in the fourth quartile of aortic pulse wave velocity (HR 4.72, 95% CI 2.69-8.27; Ptrend < 0.001), estimated carotid-femoral pulse wave velocity (HR 4.28, 95% CI 2.45-7.50; Ptrend < 0.001) and aortic pulse pressure (HR 2.71, 95% CI 1.88-3.91; Ptrend < 0.001). CONCLUSIONS: Arterial stiffness, as measured by aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure may be utilised in clinical practice to help identify people at risk of future CKD. TRIAL REGISTRATION: www.anzctr.org.au identifier:ACTRN12611000402943.

Increased risk of cardiovascular and renal disease, and diabetes for all women diagnosed with gestational diabetes mellitus in New Zealand-A national retrospective cohort study.

BACKGROUND: Gestational diabetes mellitus increases the risk of developing type 2 diabetes. The aim of this study is to compare cardiometabolic and renal outcomes for all women in New Zealand with gestational diabetes (2001-2010) with women without diabetes, 10-20 years following delivery. METHODS: A retrospective cohort study, utilizing a national dataset providing information for all women who gave birth between 1 January 2001 and 31 December 2010 (n = 604 398). Adolescent girls <15 years, women ≥50 years and women with prepregnancy diabetes were excluded. In total 11 459 women were diagnosed with gestational diabetes and 11 447 were matched (for age and year of delivery) with 57 235 unexposed (control) women. A national hospital dataset was used to compare primary outcomes until 31 May 2021. RESULTS: After controlling for ethnicity, women with gestational diabetes were significantly more likely than control women to develop diabetes-adjusted hazard ratio (HR) 20.06 and 95% confidence interval (CI) 18.46-21.79; a first cardiovascular event 2.19 (1.86-2.58); renal disease 6.34 (5.35-7.51) and all-cause mortality 1.55 (1.31-1.83), all p values <.0001. The HR and 95% CI remained similar after controlling for significant covariates: diabetes 18.89 (17.36-20.56), cardiovascular events 1.79 (1.52-2.12), renal disease 5.42 (4.55-6.45), and all-cause mortality 1.44 (1.21-1.70). When time-dependent diabetes was added to the model, significance remained for cardiovascular events 1.33 (1.10-1.61), p = .003 and renal disease 2.33 (1.88-2.88), p < .0001 but not all-cause mortality. CONCLUSIONS: Women diagnosed with gestational diabetes have an increased risk of adverse cardiometabolic and renal outcomes. Findings highlight the importance of follow-up screening for diabetes, cardiovascular risk factors, and renal disease.

Arterial Stiffness and Incident Glaucoma: A Large Population-Based Cohort Study.

PURPOSE: To investigate whether arterial stiffness, assessed oscillometrically, is associated with incident glaucoma in the Vitamin D Assessment (ViDA) Study cohort, aged 50 to 84 years. DESIGN: Prospective, population-based cohort study. METHODS: Arterial stiffness was assessed in 4,713 participants without known glaucoma (mean ± SD age = 66 ± 8 years) from 5 April 2011 to 6 November 2012 by way of aortic PWV (aPWV), estimated carotid-femoral PWV (ePWV) and aortic PP (aPP). Incident glaucoma was identified through linkage to national prescription and hospital discharge registers. Relative risks of glaucoma for each arterial stiffness measure were estimated by Cox proportional hazards regression, over the continuum of values and by quartiles. RESULTS: During a mean ± SD follow-up of 10.5±0.4 years, 301 participants developed glaucoma. Arterial stiffness, as measured by aPWV (Hazard ratio (HR) per SD increase, 1.36, 95% CI 1.14-1.62) and ePWV (HR per SD increase, 1.40, 95% CI 1.14-1.71) but not aPP (HR per SD increase, 1.06, 95% CI 0.92-1.23) was associated with incident glaucoma. When arterial stiffness was analyzed as a categorical variable, the highest quartiles of aPWV (HR, 2.62, 95% CI 1.52-4.52; Ptrend = .007), ePWV (HR, 2.42, 95%CI 1.37-4.27; Ptrend = .03), and aPP (HR, 1.68, 95%CI 1.10-2.5; Ptrend = .02) were associated with the development of glaucoma. CONCLUSIONS: Arterial stiffness measured with a simple oscillometric device predicted the development of glaucoma and could potentially be used in clinical practice to help identify people at risk of this condition. It may also present a new therapeutic research avenue, including in respect of systemic antihypertensives.

A Systematic Review Supporting the Endocrine Society Clinical Practice Guidelines on Vitamin D.

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.

Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline.

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.

Sizing the association between lifestyle behaviours and fatness in a large, heterogeneous sample of youth of multiple ethnicities from 4 countries.

BACKGROUND: The magnitude of the relationship between lifestyle risk factors for obesity and adiposity is not clear. The aim of this study was to clarify this in order to determine the level of importance of lifestyle factors in obesity aetiology. METHODS: A cross-sectional analysis was carried out on data on youth who were not trying to change weight (n = 5714), aged 12 to 22 years and from 8 ethnic groups living in New Zealand, Australia, Fiji and Tonga. Demographic and lifestyle data were measured by questionnaires. Fatness was measured by body mass index (BMI), BMI z-score and bioimpedance analysis, which was used to estimate percent body fat and total fat mass (TFM). Associations between lifestyle and body composition variables were examined using linear regression and forest plots. RESULTS: TV watching was positively related to fatness in a dose-dependent manner. Strong, dose-dependent associations were observed between fatness and soft drink consumption (positive relationship), breakfast consumption (inverse relationship) and after-school physical activity (inverse relationship). Breakfast consumption-fatness associations varied in size across ethnic groups. Lifestyle risk factors for obesity were associated with percentage differences in body composition variables that were greatest for TFM and smallest for BMI. CONCLUSIONS: Lifestyle factors were most strongly related to TFM, which suggests that studies that use BMI alone to quantify fatness underestimate the full effect of lifestyle on adiposity. This study clarifies the size of lifestyle-fatness relationships observed in previous studies.

Small doses from artificial UV sources elucidate the photo-production of vitamin D.

To clarify the relation between UV exposure and vitamin D status, 201 volunteers wore personal electronic UV dosimeters during daylight hours, to record their UV exposure over a 10 week period when ambient UV levels were significantly less than the summer maxima. Blood samples to determine serum 25-hydroxyvitamin D3 [25(OH)D3] levels were taken at the end of week 4 and week 8. Participants were then given a single full-body exposure of approximately 2 SED from one of four artificial UV sources with different spectral outputs and a further blood sample taken at study completion, nominally week 10. The artificial UV exposure reversed the mean seasonal decline in 25(OH)D3. Increases in 25(OH)D3 from week 8 to week 10 were related to total UV exposure, including the ambient sun exposures. These exposures were weighted by the erythemal action spectrum and separately for three different action spectra for pre-vitamin D production. For the erythema weighting function, 25(OH)D3 increased 1.78 ± 0.25 nmol per litre per SED, a value consistent with other studies. Any differences due to age, BMI, gender, and skin reflectance were not statistically significant. Ethnicity differences were the only significant factor, with Asians producing the least vitamin D, and Maori the most. There was no statistically significant improvement in consistency between sources for any of the three pre-vitamin weightings compared with that for erythema. Further work is needed to verify which vitamin D action spectrum is most appropriate. Nevertheless, these small doses of UV from artificial sources were helpful in quantifying the relationship between UV exposure and vitamin D status among the New Zealand population.

Association of arterial stiffness and neuropathy in diabetes: a systematic review and meta-analysis.

Evidence is still emerging on the relationships of arterial stiffness with cardiac autonomic neuropathy (CAN) and peripheral neuropathy (PN). To our knowledge no systematic reviews or meta-analyses of these associations have been published. The purpose of our review was to assess the association of arterial stiffness with each type of neuropathy. Medline and Embase were systematically searched for observational studies of arterial stiffness and neuropathy.The systematic review of 60 studies (25 for CAN and 37 for PN), 59 including people with diabetes, showed arterial stiffness overall was higher in people with neuropathy than people without neuropathy. Forty-three studies were included in the meta-analysis. For CAN (19 studies), arterial stiffness was increased in people with neuropathy compared with without, as measured by pulse wave velocity (PWV) (mean difference: 1.32 m/s, 95% CI 0.82 to 1.81, p<0.00001), pulse pressure (PP) (mean difference: 6.25 mmHg, 95% CI 4.51 to 7.99, p<0.00001) or augmentation index (mean difference: 5.52%, 95% CI 3.46 to 7.58, p<0.0001). For PN (26 studies), arterial stiffness was increased in people with neuropathy compared with those without, as measured by PWV (mean difference: 1.22 m/s, 95% CI 0.87 to 1.58, p<0.00001) or PP (mean difference: 4.59 mmHg, 95% CI 2.96 to 6.22, p<0.00001). Only two cohort studies were located so the temporality of the association between arterial stiffness and neuropathy remains unclear. Increased arterial stiffness is associated with CAN and PN.PROSPERO registration number: CRD42019129563.