Effects of combined calcium and vitamin D supplementation on insulin secretion, insulin sensitivity and β-cell function in multi-ethnic vitamin D-deficient adults at risk for type 2 diabetes: a pilot randomized, placebo-controlled trial

ObjectivesTo examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, &beta;-cell function, inflammation and metabolic markers.Design6-month randomized, placebo-controlled trial.ParticipantsNinety-five adults with serum 25-hydroxyvitamin D [25(OH)D] &le;55 nmol/L at risk of type 2 diabetes (with prediabetes or an AUSDRISK score &ge;15) were randomized. Analyses included participants who completed the baseline and final visits (treatment n = 35; placebo n = 45).InterventionDaily calcium carbonate (1,200 mg) and cholecalciferol [2,000&ndash;6,000 IU to target 25(OH)D &gt;75 nmol/L] or matching placebos for 6 months.MeasurementsInsulin sensitivity (HOMA2%S, Matsuda index), insulin secretion (insulinogenic index, area under the curve (AUC) for C-peptide) and &beta;-cell function (Matsuda index x AUC for C-peptide) derived from a 75 g 2-h OGTT; anthropometry; blood pressure; lipid profile; hs-CRP; TNF-&alpha;; IL-6; adiponectin; total and undercarboxylated osteocalcin.ResultsParticipants were middle-aged adults (mean age 54 years; 69% Europid) at risk of type 2 diabetes (48% with prediabetes). Compliance was &gt;80% for calcium and vitamin D. Mean serum 25(OH)D concentration increased from 48 to 95 nmol/L in the treatment group (91% achieved &gt;75 nmol/L), but remained unchanged in controls. There were no significant changes in insulin sensitivity, insulin secretion and &beta;-cell function, or in inflammatory and metabolic markers between or within the groups, before or after adjustment for potential confounders including waist circumference and season of recruitment. In a post hoc analysis restricted to participants with prediabetes, a significant beneficial effect of vitamin D and calcium supplementation on insulin sensitivity (HOMA%S and Matsuda) was observed.ConclusionsDaily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity, insulin secretion and &beta;-cell function in multi-ethnic adults with low vitamin D status at risk of type 2 diabetes. However, in participants with prediabetes, supplementation with vitamin D and calcium may improve insulin sensitivity.<br /

Adding marrow adiposity and cortical porosity to femoral neck areal bone mineral density improves the discrimination of women with nonvertebral fractures from controls

Advancing age is accompanied by a reduction in bone formation and remodeling imbalance, which produces microstructural deterioration. This may be partly caused by a diversion of mesenchymal cells towards adipocytes rather than osteoblast lineage cells. We hypothesized that microstructural deterioration would be associated with an increased marrow adiposity, and each of these traits would be independently associated with nonvertebral fractures and improve discrimination of women with fractures from controls over that achieved by femoral neck (FN) areal bone mineral density (aBMD) alone. The marrow adiposity and bone microstructure were quantified from HR‐pQCT images of the distal tibia and distal radius in 77 women aged 40 to 70 years with a recent nonvertebral fracture and 226 controls in Melbourne, Australia. Marrow fat measurement from HR‐pQCT images was validated using direct histologic measurement as the gold standard, at the distal radius of 15 sheep, with an agreement (R2 = 0.86, p < 0.0001). Each SD higher distal tibia marrow adiposity was associated with 0.33 SD higher cortical porosity, and 0.60 SD fewer, 0.24 SD thinner, and 0.72 SD more‐separated trabeculae (all p < 0.05). Adjusted for age and FN aBMD, odds ratios (ORs) (95% CI) for fracture per SD higher marrow adiposity and cortical porosity were OR, 3.39 (95% CI, 2.14 to 5.38) and OR, 1.79 (95% CI, 1.14 to 2.80), respectively. Discrimination of women with fracture from controls improved when cortical porosity was added to FN aBMD and age (area under the receiver‐operating characteristic curve [AUC] 0.778 versus 0.751, p = 0.006) or marrow adiposity was added to FN aBMD and age (AUC 0.825 versus 0.751, p = 0.002). The model including FN aBMD, age, cortical porosity, trabecular thickness, and marrow adiposity had an AUC = 0.888. Results were similar for the distal radius. Whether marrow adiposity and cortical porosity indices improve the identification of women at risk for fractures requires validation in prospective studies. © 2019 American Society for Bone and Mineral Research

Sun exposure and type 2 diabetes mellitus: Can sun exposure lower type 2 diabetes risk?

© 2015 Catherine Shore-LorentiBackground: Lower serum 25-hydroxyvitamin D (25OHD) levels have been consistently associated with increased type 2 diabetes mellitus (T2DM) prevalence and incidence in systematic reviews and meta-analyses of observational studies, however this association has not consistently been replicated in vitamin D supplementation trials. This disparity may be due to a number of different factors: lack of power in the trials due to small sample size, insufficient duration of dosing, baseline vitamin D or glycaemic status differing between studies, low supplementation compliance or insufficient vitamin D dose. Alternatively, lower 25OHD levels may be a product, rather than a cause of ill-health, or they may share pathology earlier in life or in disease progression so that supplementing with vitamin D in adulthood has no effect on disease outcome. This body of work presents another explanation: given that sun exposure is the most influential contributor to serum 25OHD levels, observational studies may be reporting an effect of sun exposure, rather than vitamin D, on T2DM. Therefore vitamin D supplementation trials may be failing to capture any additional benefits of sun exposure through non-vitamin D pathways. The aim of this body of work was to investigate the possible association between sun exposure and T2DM endpoints reported in scientific literature as well as in an original analysis. A major objective of the original analysis was to determine whether or not any association found between sun exposure and T2DM incidence was through non-vitamin D pathways. Methods: Following a literature review, a systematic review of observational studies reporting on associations between sun exposure variables and T2DM-related endpoints was conducted. The potential of an association between sun exposure- measured using ambient ultraviolet radiation (UVR), and five-year cumulative incidence of T2DM was explored using a prospective, national diabetes cohort (AusDiab). A causal mediation analysis was undertaken to explore whether or not there were effects of ambient UVR on cumulative T2DM incidence, via non-vitamin D pathways. Results: The systematic review revealed that high-level evidence for an association between sun exposure and T2DM-related outcomes was lacking. There was moderate-level evidence for greater sun exposure reducing T2DM incidence. The opposite was found in the original analysis using the AusDiab cohort: ambient UVR was associated with increased T2DM incidence (OR=1.17, 95% CI: 1.01-1.36, p=0.04). This association was independent of an effect of age, sex, body mass index, physical activity, ethnicity, smoking status and serum 25OHD levels, but was likely to be confounded by area-level determinants of health due to the nature of the exposure variable. The major limitations of this work were that the sun exposure measures were suboptimal. Time-of-year measures were the most common sun exposure variables contained in the systematic review, and ambient UVR at the site of participant recruitment was the proxy for sun exposure in the original analysis. Conclusion: There is likely to be a complex relationship between sun exposure and T2DM. The direction of the association between sun exposure and T2DM incidence, as well as delineation of the mechanistic pathways through which this association may exist, are yet to be confirmed. Future studies are encouraged to use person-level sun exposure measurements, and findings from such studies may influence sun protection policy

Metabolic Syndrome and Its Associations with Components of Sarcopenia in Overweight and Obese Older Adults

Ageing, obesity and the metabolic syndrome (MetS) may all contribute to poor muscle health (sarcopenia). This study aimed to determine the cross-sectional associations between MetS (International Diabetes Federation classification) and sarcopenia (revised European Working Group on Sarcopenia in Older People definition) in 84 overweight and obese older adults. Components of sarcopenia included muscle strength (hand grip and leg extension), physical performance (stair climb test and short physical performance battery (SPPB), including gait speed and repeated chair stands time), muscle mass (appendicular lean mass (ALM), dual-energy X-ray absorptiometry), muscle size (peripheral quantitative computed tomography-determined calf and forearm cross-sectional area (CSA)) and muscle quality (muscle density and strength normalised to lean mass). Waist circumference was associated with greater muscle size, but poorer leg extension strength, chair stands and stair climb time, gait speed, SPPB scores and muscle quality measures (all p &lt; 0.05). MetS was positively associated with ALM and forearm muscle CSA, and negatively associated with muscle quality measures and chair stands time (all p &lt; 0.05). MetS is associated with larger muscle size, yet poorer muscle quality in overweight and obese older adults. Assessments of muscle function and quality should be considered for obese older adults and those with MetS

Effects of combined calcium and vitamin D supplementation on insulin secretion, insulin sensitivity and ?-cell function in multi-ethnic vitamin D-deficient adults at risk for type 2 diabetes: A pilot randomized, placebo-controlled tria

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Calf muscle density in independently associated with physical function in overweight and obese older adults

Objectives: To determine whether associations of calf muscle density with physical function are independent of other determinants of functional decline in overweight and obese older adults. Methods: This was a secondary analysis of a cross-sectional study of 85 community-dwelling overweight and obese adults (mean±SD age 62.8±7.9 years; BMI 32.3±6.1 kg/m2; 58% women). Peripheral quantitative computed tomography assessed mid-calf muscle density (66% tibial length) and dual-energy X-ray absorptiometry determined visceral fat area. Fasting glucose, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and C-reactive protein (CRP) were analysed. Physical function assessments included hand grip and knee extension strength, balance path length (computerised posturography), stair climb test, Short Physical Performance Battery (SPPB) and self-reported falls efficacy (Modified Falls Efficacy Scale; M-FES). Results: Visceral fat area, not muscle density, was independently associated with CRP and fasting glucose (B=0.025; 95% CI 0.009-0.042 and B=0.009; 0.001-0.017, respectively). Nevertheless, higher muscle density was independently associated with lower path length and stair climb time, and higher SPPB and M-FES scores (all P < 0.05). Visceral fat area, fasting glucose and CRP did not mediate these associations. Conclusions: Higher calf muscle density predicts better physical function in overweight and obese older adults independent of insulin resistance, visceral adiposity or inflammation. © 2018, International Society of Musculoskeletal and Neuronal Interactions

Mean baseline values and the mean absolute changes in anthropometry and blood pressure in the treatment and placebo group.

<p>Baseline data are presented as mean (SD).</p><p>*A multivariate 2-factor repeated-measures regression analysis was used to assess time effects and time by treatment effect interactions on all outcome variables after adjustment for the variables that were different between treatment groups at baseline. Numbers in brackets represent unadjusted <i>P</i> values.</p>†<p><i>P</i>&lt;0.1 for the difference between groups at baseline (unpaired <i>t</i> test or Wilcoxon, as appropriate).</p><p>DBP, diastolic blood pressure; SBP, systolic blood pressure; WC, waist circumference.</p><p>Mean baseline values and the mean absolute changes in anthropometry and blood pressure in the treatment and placebo group.</p

Mean baseline and 6 month values and the mean absolute changes in insulin sensitivity, insulin secretion and β-cell function in the treatment and placebo group.

<p>Baseline and 6 month data are presented as mean (SD).</p><p>*A multivariate 2-factor repeated-measures regression analysis was used to assess time effects and time by treatment effect interactions on all outcome variables after adjustment for the variables that were different between treatment groups at baseline. Numbers in brackets represent unadjusted <i>P</i> values.</p>†<p>Logarithmically-transformed variables.</p>‡<p>Calculated by multiplying Matsuda index by AUC for C-peptide.</p><p>AUC, area under the curve; HOMA2%S, Homeostasis Model Assessment 2 index of insulin sensitivity.</p><p>Mean baseline and 6 month values and the mean absolute changes in insulin sensitivity, insulin secretion and β-cell function in the treatment and placebo group.</p

Flowchart showing participant enrollment, allocation, follow-up and analysis.

<p>Flowchart showing participant enrollment, allocation, follow-up and analysis.</p