Correction: Relationship between serum osteocalcin/undercarboxylated osteocalcin and type 2 diabetes: A systematic review/meta-analysis study protocol

The affiliations for the third author, Joshua R Lewis, were incomplete in the previous version of this manuscript..

Relationship between serum osteocalcin/undercarboxylated osteocalcin and type 2 diabetes: A systematic review/meta-analysis study protocol

INTRODUCTION: The global burden of type 2 diabetes (T2DM) is steadily increasing. Experimental studies have demonstrated that a novel hormone secreted by bone cells, osteocalcin (OC), can stimulate beta-cell proliferation and improve insulin sensitivity in mice. Observational studies in humans have investigated the relationship between OC and metabolic parameters, and T2DM. Importantly, few studies have reported on the undercarboxylated form of OC (ucOC), which is the putative active form of OC suggested to affect glucose metabolism. OBJECTIVES: We will conduct a systematic review and meta-analysis to: (1) compare the levels of serum OC and ucOC between T2DM and normal glucose-tolerant controls (NGC); (2) investigate the risk ratios between serum OC and ucOC, and T2DM; (3) determine the correlation coefficient between OC and ucOC and fasting insulin levels, homeostatic model assessment-insulin resistance, haemoglobin A1c and fasting glucose levels and (4) explore potential sources of between-study heterogeneity. The secondary objective is to compare the serum OC and ucOC between pre-diabetes (PD) and NGC and between T2DM and PD. HODS AND ANALYSIS: This study will report items in line with the guidelines outlined in preferred reporting items for systematic reviews and meta-analysis of observational studies in epidemiology. We will include observational studies (cohort, case-control and cross-sectional studies) and intervention studies with baseline data. Three databases (MEDLINE, EMBASE and SCOPUS) will be searched from inception until July 2018 without language restrictions. Two reviewers will independently screen the titles and abstracts and conduct a full-text assessment to identify eligible studies. Discrepancies will be resolved by consensus with a third reviewer. The risk of bias assessment will be conducted by two reviewers independently based on the Newcastle-Ottawa Scale. Potential sources of between-study heterogeneity will be tested using meta-regression/subgroup analyses. Contour-enhanced funnel plots and Egger\u27s test will be used to identify potential publication bias. ETHICS AND DISSEMINATION: Formal ethical approval is not required. We will disseminate the results to a peer-reviewed publication and conference presentation. PROSPERO REGISTRATION NUMBER: CRD42017073127

Effects of vitamin D status and supplements on anthropometric and biochemical indices in a clinical setting: A retrospective study

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Context: Obesity and low vitamin D status are linked. It is not clear that weight loss through lifestyle intervention is influenced by vitamin D status. Objective: The aim of this study was to investigate the effect of baseline vitamin D status and vitamin D supplementation on weight loss and associated parameters for participants on a weight loss program in a primary care setting. Design: A retrospective analysis of clinical records of patients who underwent an individually tailored weight loss program at a single dietetic clinic in Sydney, Australia. Setting: Primary care centers. Patients: 205 overweight and obese men and women aged from 18 to 50 years. Interventions: Patients were referred to a dietetic clinic for a weight loss program. Patients with low serum 25-hydroxyvitamin D (25(OH)D) concentrations at baseline were advised to increase sun exposure and take multivitamins supplemented with 2000 IU or 4000 IU per day of vitamin D3, according to the preference of their primary care physician. Main outcome measures: Clinical parameters of weight, height, waist circumference, and serum 25(OH)D, as well as blood pressure and fasting lipid profile were collected from both baseline and three-month follow-up consultations. Results: Subjects with sufficient baseline 25(OH)D levels (≥50 nmol/L) experienced significantly greater weight loss (−7.7 ± 5.9 kg vs. −4.2 ± 3.3 kg) and reductions in BMI (−2.6 ± 1.8 kg/m2 vs. −1.5 ± 1.1 kg/m2) and waist circumference (−5.2 ± 3.5 cm vs. −3.1 ± 3.1 cm) as compared with those who were vitamin D insufficient at baseline (p \u3c 0.001 for all). Vitamin D insufficient patients who were supplemented with daily 2000 IU or 4000 IU vitamin D experienced significantly greater decreases in weight (−5.3 ± 3.6 kg vs. −2.3 ± 1.6 kg), BMI (−1.9 ± 1.2 kg/m2 vs. −0.8 ± 0.6 kg/m2) and waist circumference (−4.2 ± 3.4 cm vs. −1.2 ± 1.3 cm) as compared with those not supplemented (p \u3c 0.001 for all). We also observed a greater decrease in low-density lipoprotein (LDL) cholesterol (−0.4 ± 0.5 mmol/L vs. −0.2 ± 0.5 mmol/L) in subjects insufficient at baseline and supplemented as compared with those insufficient at baseline and not supplemented (p \u3c 0.01). Conclusion: In a weight loss setting in a dietetic clinic, adequate vitamin D status at baseline, or achieved at three months through supplementation, was associated with significantly greater improvement of anthropometric measures. The study has implications for the management of vitamin D status in obese or overweight patients undergoing weight loss programs

Data from: Sleep duration is associated with vitamin D deficiency in older women living in Macao, China: A pilot cross-sectional study

Table 1.Characteristics of Macao population (n = 566) stratified by age. https://doi.org/10.1371/journal.pone.0229642.t001 Table 2. Sleep duration (h) and risk of serum 25OHD/L or 25OHD/L in older Macao residents (n = 204). https://doi.org/10.1371/journal.pone.0229642.t002 Table 3. Serum 25OHD/L or serum 25OHD/L risk stratified by duration of sleep (≤6h and \u3e6h) in older Macanese (n = 204). https://doi.org/10.1371/journal.pone.0229642.t003 Table 4. Studies investigating the association between sleep duration and vitamin D (serum 25OHD levels or dietary intake). https://doi.org/10.1371/journal.pone.0229642.t004 S1 Data. https://doi.org/10.1371/journal.pone.0229642.s00

Sleep duration is associated with vitamin D deficiency in older women living in Macao, China: A pilot cross-sectional study

© 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Chinese women are known to have both a high prevalence of metabolic syndrome (MetS) and vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) /l). Associations between sleep duration and circulating 25OHD have recently been reported but, to our knowledge, these associations have not been studied in older Chinese populations. We thus investigated whether sleep duration was associated with vitamin D status in a population from Macao, China, and whether sleep duration modified the association between MetS and vitamin D deficiency. In 207 older (\u3e55 years) Macanese, anthropometry, blood samples and validated questionnaires, including sleep duration and cardiovascular risk factors, were simultaneously collected. On multivariable categorical analyses, those women, not men, who had short sleep duration (≤6 hours (h)) were at a 2-fold risk for vitamin D deficiency (both /L and /L; OR = 1.94, 95%CI 1.29-2.92; OR = 2.05, 95%CI 1.06-3.98, respectively) and those who had longer sleep duration (\u3e8 h) were 3-fold more likely to have vitamin D deficiency (OR = 3.07, 95%CI 1.47-6.39; OR = 2.75, 95%CI 1.08- 7.00, respectively) compared to those with normal sleep duration (6-8 h). Both women and men with MetS were 2-fold more likely to have vitamin D deficiency (women: OR = 2.04, 95%CI 1.31-3.17; OR = 2.15, 95%CI 1.11-4.17, respectively; men: OR = 2.01, 95%CI 1.23-3.28; OR = 2.04, 95%CI 1.00-4.29, respectively). Moreover, women with both short sleep duration and MetS had an increased risk of vitamin D deficiency (OR = 3.26, 95%CI 1.10-9.64). These associations were not found in those with longer sleep. Men with longer sleep and MetS had a 5-fold risk of vitamin D deficiency (OR = 5.22; 95%CI 2.70-10.12). This association was non-significant for men with shorter sleep. We conclude that both short and long sleep duration were associated with vitamin D deficiency in older Chinese women. Further research is needed in larger cohorts or with intervention studies to further examine the associations between reduced sleep, metabolic syndrome and vitamin D deficiency

Skeletal muscle and the maintenance of vitamin d status

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Vitamin D, unlike the micronutrients, vitamins A, E, and K, is largely obtained not from food, but by the action of solar ultraviolet (UV) light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Since no defined storage organ or tissue has been found for vitamin D, it has been assumed that an adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D), which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into the blood. This uptake and release of 25(OH)D by muscle accounts for the very long half-life of this metabolite in the circulation. Since 25(OH)D concentration in the blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain an adequate vitamin D status in winter

The effects of acute exercise on bone turnover markers in middle-aged and older adults: A systematic review

© 2020 Elsevier Inc. Background: Bone turnover is the cellular machinery responsible for bone integrity and strength and, in the clinical setting, it is assessed using bone turnover markers (BTMs). Acute exercise can induce mechanical stress on bone which is needed for bone remodelling, but to date, there are conflicting results in regards to the effects of varying mechanical stimuli on BTMs. Objectives: This systematic review examines the effects of acute aerobic, resistance and impact exercises on BTMs in middle and older-aged adults and examines whether the responses are determined by the exercise mode, intensity, age and sex. Methods: We searched PubMed, SCOPUS, Web of Science and EMBASE up to 22nd April 2020. Eligibility criteria included randomised controlled trials (RCTs) and single-arm studies that included middle-aged (50 to 65 years) and older adults (\u3e65 years) and, a single-bout, acute-exercise (aerobic, resistance, impact) intervention with measurement of BTMs. PROSPERO registration number CRD42020145359. Results: Thirteen studies were included; 8 in middle-aged (n = 275, 212 women/63 men, mean age = 57.9 ± 1.5 years) and 5 in older adults (n = 93, 50 women/43 men, mean age = 68.2 ± 2.2 years). Eleven studies included aerobic exercise (AE, 7 middle-aged/4 older adults), and two included resistance exercise (RE, both middle-aged). AE significantly increased C-terminal telopeptide (CTX), alkaline phosphatase (ALP) and bone-ALP in middle-aged and older adults. AE also significantly increased total osteocalcin (tOC) in middle-aged men and Procollagen I Carboxyterminal Propeptide and Cross-Linked Carboxyterminal Telopeptide of Type I Collagen in older women. RE alone decreased ALP in older adults. In middle-aged adults, RE with impact had no effect on tOC or BALP, but significantly decreased CTX. Impact (jumping) exercise alone increased Procollagen Type 1 N Propeptide and tOC in middle-aged women. Conclusion: Acute exercise is an effective tool to modify BTMs, however, the response appears to be exercise modality-, intensity-, age- and sex-specific. There is further need for higher quality and larger RCTs in this area

Healthy lifestyles are associated with better vitamin D status in community-dwelling older men: The Health In Men Study (HIMS)

Objective: Older people are more prone to vitamin D deficiency than younger populations. Individual lifestyle factors have been associated with vitamin D status. We examined the influence of a combination of lifestyle factors on vitamin D status in older men. Participants and Measurements: In a population-based cohort study of older men (age ≥65 years), a lifestyle score was calculated from eight prudent health-related behaviours (smoking, exercise, alcohol, fish and meat consumption, adding salt, milk choices and obesity) collected via questionnaire at baseline. Blood samples were collected 5 years afterwards to measure plasma 25-hydroxyvitamin D (25OHD) levels. Associations between lifestyles and the likelihood of having plasma 25OHD levels of ≥75 versus <75 nmol/L and ≥50 versus <50 nmol/L were tested using logistic regression models. Results: Of the 2717 men analysed, mean plasma 25OHD was 69.0 ± 23.5 nmol/L, with 20.7% having plasma 25OHD <50 nmol/L. Men engaging in ≥4 healthy lifestyle behaviours had 20% higher odds of plasma 25OHD ≥75 nmol/L (adjusted OR = 1.20, 95% CI: 1.01−1.45) compared to those with <4 healthy behaviours. No association was found for 25OHD ≥50 nmol/L. Higher physical activity was the only individual component significantly associated with vitamin D sufficiency (highest vs. lowest quintiles of physical activity, adjusted OR = 2.01, 95% CI: 1.47−2.74 for 25OHD ≥50 nmol/L, adjusted OR = 2.35, 95% CI: 1.81−3.06 for 25OHD ≥75 nmol/L). Conclusion: Multiple healthy lifestyle behaviours are associated with better vitamin D status in older men. Further work is needed to determine the effects of promoting healthy lifestyle behaviours, including physical activity, on vitamin D sufficiency

Association between circulating osteocalcin and cardiometabolic risk factors following a 4-week leafy green vitamin K-rich diet

© 2020 S. Karger AG, Basel. Copyright: All rights reserved. Background: Evidence suggests that lower serum undercarboxylated osteocalcin (ucOC) may be negatively associated with cardiometabolic health. We investigated whether individuals with a suppression of ucOC following an increase in dietary vitamin K1 exhibit a relative worsening of cardiometabolic risk factors. Materials and Methods: Men (n = 20) and women (n = 10) aged 62 ± 10 years participated in a randomized, controlled, crossover study. The primary analysis involved using data obtained from participants following a high vitamin K1 diet (HK; 4-week intervention of increased leafy green vegetable intake). High and low responders were defined based on the median percent reduction (30%) in ucOC following the HK diet. Blood pressure (resting and 24 h), arterial stiffness, plasma glucose, lipid concentrations, and serum OC forms were assessed. Results: Following the HK diet, ucOC and ucOC/tOC were suppressed more (p \u3c 0.01) in high responders (41 and 29%) versus low responders (12 and 10%). The reduction in ucOC and ucOC/tOC was not associated with changes in blood pressure, arterial stiffness, plasma glucose, or lipid concentrations in the high responders (p \u3e 0.05). Discussion/Conclusion: Suppression of ucOC via consumption of leafy green vegetables has no negative effects on cardiometabolic health, perhaps, in part, because of cross-talk mechanisms

Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism

Long-term glucocorticoid treatment is associated with numerous adverse outcomes, including weight gain, insulin resistance, and diabetes; however, the pathogenesis of these side effects remains obscure. Glucocorticoids also suppress osteoblast function, including osteocalcin synthesis. Osteocalcin is an osteoblast-specific peptide that is reported to be involved in normal murine fuel metabolism. We now demonstrate that osteoblasts play a pivotal role in the pathogenesis of glucocorticoid-induced dysmetabolism. Osteoblast-targeted disruption of glucocorticoid signaling significantly attenuated the suppression of osteocalcin synthesis and prevented the development of insulin resistance, glucose intolerance, and abnormal weight gain in corticosterone-treated mice. Nearly identical effects were observed in glucocorticoid-treated animals following heterotopic (hepatic) expression of both carboxylated and uncarboxylated osteocalcin through gene therapy, which additionally led to a reduction in hepatic lipid deposition and improved phosphorylation of the insulin receptor. These data suggest that the effects of exogenous high-dose glucocorticoids on insulin target tissues and systemic energy metabolism are mediated, at least in part, through the skeleton.NHMRC Grants 402462 and 63281