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Lifestyle programs that reduce health risks and support weight loss (WL) in older adults face adherence and attendance challenges due to reduced energy requirements, impaired mobility, lack of transportation, and low social support. Tailored lifestyle and weight management programs are needed to better support healthy aging for older adults. Here, we developed and piloted an age-adapted, remotely delivered modification of the Diabetes Prevention Program (DPP). The modification includes age-appropriate goals, visuals, and examples; flexible dietary composition; remote classroom and fitness-monitoring technology; and standardized online classroom materials employing pedagogical and behavior change theory. The modifications were designed to safeguard fidelity and to boost adherence, engagement, and knowledge integration, with the convenience of a fully remote WL program for diverse older adults. Six-month pilot data are presented from older adults (55–85 years, body mass index (BMI) 27–39.9 kg/m2, N = 20) randomly allocated to an online DPP intervention with weight, diet, and activity monitored remotely, or into a waitlisted control. The intervention achieved 100% attendance and adherence to self-monitoring. The intervention group mean (±SD) body weight change was −9.5% (±4.1); 90% lost ≥ 5%. By contrast, the control group gained 2.4% (±1.8). Once thought incompatible with older adults, remote interventions are feasible for older adults and can support fidelity, adherence, engagement, and clinically significant WL. Standardized materials are provided for future implementation. [ABSTRACT FROM AUTHOR]

Background Data suggest an association between GH secretion and circulating levels of the myokine irisin and inflammatory cytokinesIL-6 and high-sensitivity C-reactive protein (hsCRP). The impact of GH secretagogues on these markers is unknown. Objectives To determine the effect of treatment with the GH secretagogue anamorelin on 12-month changes in serum irisin, IL-6, and hsCRP levels and to assess whether baseline irisin levels modulate the glycemic response to treatment with anamorelin. Methods This is an ancillary study in 26 older adults with osteosarcopenia who participated in a 12-month trial examining the effect of anamorelin 100 mg/day vs placebo on musculoskeletal outcomes. Serum irisin, IL-6, and hsCRP were measured at baseline and 12 months. Results Treatment with anamorelin, compared with placebo, did not significantly alter irisin levels [12-month change = 0.50 ± 1.2 (SD) ng/mL in anamorelin group and −0.08 ± 2.3 ng/mL in placebo; P =.191]. Baseline irisin levels were not significantly correlated with 2-month change in fasting glucose levels in the anamorelin group (r = −0.222, P =.46) or the placebo group (r = 0.30, P =.34); however, the slopes of the 2 regression lines describing the relationship by group tended to differ (P =.0547). Anamorelin treatment for 12 months had no significant effect on serum IL-6 or hsCRP levels. Conclusion In this small sample of older adults with osteosarcopenia, treatment with the GH secretagogue anamorelin did not significantly alter levels of irisin, IL-6, or hsCRP. Higher baseline irisin levels may attenuate the glycemic response to anamorelin treatment; however, a larger study is needed to confirm this possibility. [ABSTRACT FROM AUTHOR]

Context: Anamorelin, a ghrelin receptor agonist known to stimulate the pulsatile release of GH from the pituitary, has the potential to improve musculoskeletal health in adults with osteosarcopenia. Objective: To determine the effect of anamorelin treatment for 1 year on muscle mass and strength and on biochemical markers of bone turnover in adults with osteosarcopenia (OS). Design: Randomized, placebo-controlled, 1-year anamorelin intervention trial Setting: The Bone Metabolism Laboratory at the USDA Nutrition Center at Tufts University. Participants: 26 men and women, age 50 years and older, with OS. Main outcome measures: Muscle mass by D3-creatine dilution and lean body mass (LBM) and bone mineral density (BMD) by dual-energy X-ray absorptiometry, muscle strength, serum IGF-1, and bone turnover markers, serum procollagen 1 intact N-terminal (P1NP), and C-terminal telopeptide (CTX). Results: Anamorelin did not have a significant effect on muscle mass or LBM; it significantly increased knee flexion torque at 240°/s by 20% (P = .013) and had a similar nonstatistically significant effect on change in knee extension; it increased bone formation (P1NP) by 75% (P = .006) and had no significant effect on bone resorption (CTX) or BMD. Serum IGF-1 increased by 50% in the anamorelin group and did not change in the placebo group (P = .0001 for group difference). Conclusion: In this pilot study, anamorelin did not significantly alter muscle mass; however, it may potentially improve lower extremity strength and bone formation in addition to increasing circulating IGF-1 levels in adults with OS. Further study of anamorelin in this population is warranted. [ABSTRACT FROM AUTHOR]

Ferric carboxymaltose (FCM)-induced hypophosphatemia is seen in up to 75% of patients receiving this therapy for iron deficiency anemia. Hypophosphatemia has been attributed to increased circulating levels of fibroblast growth factor-23 (FGF23), the transcription of which is upregulated in an iron-deficient state. However, hypophosphatemia typically resolves within 12 weeks of FCM administration. Here, we present a case of unusually prolonged hypophosphatemia that developed after treatment with FCM in a 39-year-old female with autosomal dominant polycystic kidney disease (ADPKD) but normal renal function. Workup was significant for low tubular reabsorption of phosphate and inappropriately normal FGF23. Genetic disorders of hypophosphatemia and a FGF23-secreting tumor were ruled out. Treatment with calcitriol was required for nearly 3.5 years. The prolonged hypophosphatemia was attributed to underlying ADPKD because these patients demonstrate inappropriately elevated FGF23 levels for the degree of severity of reduced glomerular filtration rate. However, the stimulus driving FGF23 secretion in these patients is incompletely understood. Elevated FGF23 in the kidney suppresses renal tubular phosphate reabsorption and 1α-hydroxylase activity ultimately leading to hypophosphatemia. We conclude that our patient was at a high risk of developing hypophosphatemia because of underlying ADPKD, and FCM was the likely precipitant to identify this underlying process. [ABSTRACT FROM AUTHOR]

Objective: Lifestyle interventions have had limited effectiveness in work sites when evaluated in randomized trials. This study assessed the effectiveness of a novel lifestyle intervention for weight loss (Healthy Weight for Living [HWL]) implemented with or without meal replacements (MR) in work sites. HWL used a new behavioral approach emphasizing reducing hunger and building healthy food preferences, and, unlike traditional lifestyle interventions, it did not require calorie counting. Methods: Twelve work sites were randomized to an 18‐month intervention (n = 8; randomization within work sites to HWL, HWL + MR) or 6‐month wait‐listed control (n = 4). Participants were employees with overweight or obesity (N = 335; age = 48 [SD 10] years; BMI = 33 [6] kg/m2; 83% female). HWL was group‐delivered in person or by videoconference. The primary outcome was 6‐month weight change; secondary outcomes included weight and cardiometabolic risk factors measured at 6, 12, and 18 months in intervention groups. Results: Mean 6‐month weight change was −8.8% (95% CI: −11.2% to −6.4%) for enrollees in HWL and −8.0% (−10.4% to −5.5%) for HWL + MR (p < 0.001 for both groups vs. controls), with no difference between interventions (p = 0.40). Clinically meaningful weight loss (≥5%) was maintained at 18 months in both groups (p < 0.001). Conclusions: A new lifestyle intervention approach, deliverable by videoconference with or without MR, supported clinically impactful weight loss in employees. [ABSTRACT FROM AUTHOR]

Introduction: This study sought to examine the effect of vitamin D3 (VD3) 3200 IU/d, calcifediol (HyD) 20mcg/d, or placebo on intramyonuclear vitamin D receptor (VDR) concentration, muscle fiber cross-sectional area (FCSA), and muscle satellite cell activation. Materials and methods: It was conducted on a subset of the VD3 (n = 12), HyD (n = 11), and placebo (n = 13) groups who participated in the 6-month randomized controlled HyD Osteopenia Study in postmenopausal women. Baseline and 6-month vastus lateralis muscle cross sections were probed for VDR, fiber type I and II, and PAX7 (satellite cell marker) using immunofluorescence. Results: Baseline mean ± SD age was 61 ± 4 years and serum 25-hydroxyvitamin D (25OHD) level was 55.1 ± 22.8 nmol/L. Baseline characteristics did not differ significantly by group. Six-month mean ± SD 25OHD levels were 138.7 ± 22.2 nmol/L (VD3), 206.8 ± 68.8 nmol/L (HyD), and 82.7 ± 36.1 nmol/L (placebo), ANOVA P < 0.001. There were no significant group differences in 6-month change in VDR concentration (ANOVA P = 0.227). Mean ± SD percent 6-month changes in type I FCSA were 20.5 ± 32.7% (VD3), − 6.6 ± 20.4% (HyD), and − 0.3 ± 14.0% (placebo, ANOVA P = 0.022). Type II FCSA or PAX7 concentration did not change significantly by group (all P > 0.358). Conclusion: This study demonstrated no significant change in intramyonuclear VDR in response to either form of vitamin D vs. placebo. Type I FCSA significantly increased with VD3, but not with HyD at 6 months. As type I fibers are more fatigue resistant than type II, enlargement in type I suggests potential for improved muscle endurance. Although HyD resulted in the highest 25OHD levels, no skeletal muscle benefits were noted at these high levels. Clinical trial: NCT02527668. [ABSTRACT FROM AUTHOR]

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]

Context: Supplementation with vitamin D has the potential to both reduce and increase risk of falling, and parathyroid hormone (PTH) may contribute to fall risk. Objective: To assess the associations of intra-trial mean circulating levels of 25-hydroxyvitamin D [25(OH)D] and PTH on incident falls in healthy older adults. Design: Observational within a clinical trial. Setting: The Bone Metabolism Laboratory at the USDA Nutrition Center at Tufts University. Participants: 410 men and women age ≥65 years who participated in the 3-year Boston STOP IT trial to determine the effect of supplementation with 700 IU of vitamin D3 plus calcium on incident falls (secondary endpoint). Intra-trial exposures of 25(OH)D and PTH were calculated as the mean of biannual measures up to and including the first fall. Main outcome measures: Incidence of first fall. Results: Intra-trial mean 25(OH)D was significantly associated with risk of falling in a U-shaped pattern; the range associated with minimal risk of falling was approximately 20 to 40 ng/mL. PTH was not significantly associated with risk of falling. Conclusions: The findings highlight the importance of maintaining the circulating 25(OH)D level between 20 and 40 ng/mL, the range that is also recommended for bone health. At PTH levels within the normal range, there was no detectible independent association of PTH with fall risk. [ABSTRACT FROM AUTHOR]

This document is a response to a letter from Wagner et al regarding a case report on FGF23-mediated hypophosphatemia secondary to ferric carboxymaltose (FCM) use. The authors address concerns raised by Wagner et al and provide further explanation of the underlying pathophysiology. They discuss the role of FGF23 and PTH in driving hypophosphatemia, as well as the potential contribution of the PKD1 mutation. The authors also mention a study that suggests a correlation between elevated ferritin levels and FGF23-induced hypophosphatemia. They conclude that treatment with calcitriol successfully prevented significant bone mineral losses in their patient. No funding or disclosures are reported. [Extracted from the article]

The objective of the present investigation was to determine whether energy restriction (ER) influences expression of skeletal muscle-specific microRNA (miRNA) in circulation (c-myomiR) and whether changes in c-myomiR are associated with rates of whole body protein synthesis. Sixteen older (64 ~ 2 yr) overweight (28.5 ~ 1.2 kg/m²) men enrolled in this 35-day controlled feeding trial. A 7-day weight maintenance (WM) period was followed by 28 days of 30% ER. Whole body protein turnover was determined from [15N]glycine enrichments in 24-h urine collections, and c-myomiR (miR-1-3p, miR-133a-3p, miR-133b, and miR-206) expression was assessed from serum samples by RT-quantitative PCR upon completion of the WM and ER periods. Participants lost 4.4 ~ 0.3 kg body mass during ER (P < 0.05). After 28 days of ER, miR-133a and miR-133b expression was upregulated (P < 0.05) compared with WM. When all four c-myomiR were grouped as c-myomiR score (sum of the median fold change of all myomiR), overall expression of c-myomiR was higher (P < 0.05) at ER than WM. Backward linear regression analysis of whole body protein synthesis and breakdown and carbohydrate, fat, and protein oxidation determined protein synthesis to be the strongest predictor of c-myomiR score. An inverse association (P < 0.05) was observed with ER c-myomiR score and whole body protein synthesis (r=-0.729, r²=-0.530). Findings from the present investigation provide evidence that upregulation of c-myomiR expression profiles in response to short-term ER is associated with lower rates of whole body protein synthesis. [ABSTRACT FROM AUTHOR]

ABSTRACT The acid load accompanying modern diets may have adverse effects on bone and muscle metabolism. Treatment with alkaline salts of potassium can neutralize the acid load, but the optimal amount of alkali is not established. Our objective was to determine the effectiveness of two doses of potassium bicarbonate (KHCO3) compared with placebo on biochemical markers of bone turnover, and calcium and nitrogen (N) excretion. In this double-blind, randomized, placebo-controlled study, 244 men and women age 50 years and older were randomized to placebo or 1 mmol/kg or 1.5 mmol/kg of KHCO3 daily for 3 months; 233 completed the study. The primary outcomes were changes in 24-hour urinary N-telopeptide (NTX) and N; changes in these measures were compared across the treatment groups. Exploratory outcomes included 24-hour urinary calcium excretion, serum amino-terminal propeptide of type I procollagen (P1NP), and muscle strength and function assessments. The median administered doses in the low-dose and high-dose groups were 81 mmol/day and 122 mmol/day, respectively. When compared with placebo, urinary NTX declined significantly in the low-dose group ( p = 0.012, after adjustment for baseline NTX, gender, and change in urine creatinine) and serum P1NP declined significantly in the low-dose group ( p = 0.004, adjusted for baseline P1NP and gender). Urinary calcium declined significantly in both KHCO3 groups versus placebo ( p < 0.001, adjusted for baseline urinary calcium, gender, and changes in urine creatinine and calcium intake). There was no significant effect of either dose of KHCO3 on urinary N excretion or on the physical strength and function measures. KHCO3 has favorable effects on bone turnover and calcium excretion and the lower dose appears to be the more effective dose. Long-term trials to assess the effect of alkali on bone mass and fracture risk are needed. © 2015 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

In this review, we summarize current evidence for a direct effect of vitamin D on skeletal muscle. A number of studies identify the receptor for 1,25'dihydroxyvitamin-Di (vitamin D receptor (VDR)) and the enzyme CYP27B1 ( I-a-hydroxylase) in muscle. We hypothesize that vitamin D acts on myocytes via the VDR, and we examine proposed effects on myocyte proliferation, differentiation, growth, and inflammation. [ABSTRACT FROM AUTHOR]

Objective: Serum sclerostin levels have been reported to be inversely associated with serum 25OHD levels, but the effect of vitamin D and calcium supplementation on serum sclerostin levels is unknown. This study was carried out to determine whether vitamin D and calcium supplementation altered serum sclerostin levels in healthy older adults. Design: We measured serum sclerostin levels at baseline and after 2 years in 279 men and women who participated in a placebo-controlled vitamin D (700 IU/day) and calcium (500 mg/day) intervention trial carried out in men and women aged ⩾65 years. Method: Serum sclerostin levels were measured using the MesoScale Discovery chemiluminescence assay. Results: In the men, sclerostin levels increased over 2 years by 4.11±1.81 ng/l (13.1%) in the vitamin D plus calciumsupplemented group and decreased by 3.16±1.78 ng/l (10.9%) in the placebo group (P=0.005 for difference in change). Adjustments for the season of measurement, baseline physical activity levels, baseline serum sclerostin levels, and total body bone mineral content did not substantially alter the changes. In the women, there was no significant group difference in change in serum sclerostin levels either before or after the above-mentioned adjustments. In both the sexes, vitamin D and calcium supplementation significantly increased serum ionized calcium levels and decreased parathyroid hormone levels. Conclusion: Men and women appear to have different serum sclerostin responses to vitamin D and calcium supplementation. The reason for this difference remains to be determined. [ABSTRACT FROM AUTHOR]

ABSTRACT It is sometimes assumed that dietary fat is required for vitamin D absorption, although the impact of different amounts of dietary fat on vitamin D absorption is not established. This study was conducted to determine whether the presence of a meal and the fat content of the meal influences vitamin D absorption or the 25-hydroxyvitamin D [25(OH)D] response to supplemental vitamin D3. Based on earlier studies in rats we postulated that absorption would be greatest in the low-fat meal group. Sixty-two healthy older men and women were randomly assigned to one of three meal groups: no meal, high-fat meal, or low-fat meal; each was given a monthly 50,000 IU vitamin D3 supplement with the test breakfast meal (or after a fast for the no-meal group) and followed for 90 days. Plasma vitamin D3 was measured by liquid chromatography-mass spectroscopy (LC/MS) before and 12 hours after the first dose; plasma 25(OH)D was measured by radioimmunoassay at baseline and after 30 and 90 days. The mean 12-hour increments in vitamin D3, after adjusting for age and sex, were 200.9 nmol/L in the no-meal group, 207.4 nmol/L in the high-fat meal group, and 241.1 nmol/L in the low-fat meal group ( p = 0.038), with the increase in the low-fat group being significantly greater than the increases in the other two groups. However, increments in 25(OH)D levels at 30 and 90 days did not differ significantly in the three groups. We conclude that absorption was increased when a 50,000 IU dose of vitamin D was taken with a low-fat meal, compared with a high-fat meal and no meal, but that the greater absorption did not result in higher plasma 25(OH)D levels in the low-fat meal group. [ABSTRACT FROM AUTHOR]

Background: The reliability of estimating muscle fiber cross-sectional area (measure of muscle fiber size) and fiber number from only a subset of fibers in rat hindlimb muscle cross-sections has not been systematically evaluated. This study examined the variability in mean estimates of fiber cross-sectional area as a function of the number of fibers measured, and tested whether counting a subset of fibers in a cross-section could predict total fiber number in middle-aged rats. Results: Soleus and extensor digitorum longus (EDL) muscle cross-sections from 23-month-old, male Fisher 344 x Brown Norway rats were stained for myofibrillar ATPase activity to identify muscle fiber type (either type I [slow-twitch] or II [fast-twitch]) and laminin to facilitate fiber cross-sectional measurements. We outlined the circumference of 1000 to 1600 single muscle fibers for measurement of fiber cross-sectional area within muscle sections. Mean type I fiber cross-sectional area was based on soleus muscle sections which were predominantly composed of type I muscle fibers. Mean type II fiber cross-sectional area was based on EDL muscle sections which were predominantly composed of type II muscle fibers. A bootstrapping resampling technique demonstrated that variability in sampling distribution of mean type I and II fiber cross-sectional areas decreased and gradually stabilized as the number of fibers measured increased with large declines in variability occurring at numbers below 150 fibers. Coefficients of variation for bootstrapped mean type I fiber cross-sectional areas were lower than for type II. In the same muscle sections, total fiber number was compared to fiber numbers within 1, 2, 3, and 4 fixed field areas (10x magnification; 1000 x 1500 pixels in size/field) on the cross-section. Fiber numbers from 3 to 4 fields (approximating 15 to 20% of the cross-section) provided a reasonably predictive value of total fiber number (r=0.57-0.59, P=0.003). Conclusions: These data describe a pattern of improved precision in estimating mean fiber cross-sectional area as sample size of fibers measured increases to at least 150 in this rat model. Counting 15-20% of the fibers in cross-sections provides a reasonably reliable estimate of the total fiber number. [ABSTRACT FROM AUTHOR]

Abstract: This review aims to summarize current knowledge on the role of vitamin D in skeletal muscle tissue and function. Vitamin D deficiency can cause a myopathy of varying severity. Clinical studies have indicated that vitamin D status is positively associated with muscle strength and physical performance and inversely associated with risk of falling. Vitamin D supplementation has shown to improve tests of muscle function, reduce falls, and possibly impact on muscle fiber composition and morphology in vitamin D deficient older adults. Molecular mechanisms of vitamin D action on muscle tissue include genomic and non-genomic effects via a receptor present in muscle cells. Genomic effects are initiated by binding of 1,25-dihydroxyvitamin D [1,25(OH)2D] to its nuclear receptor, which results in changes in gene transcription of mRNA and subsequent protein synthesis. Non-genomic effects of vitamin D are rapid and mediated through a cell surface receptor. Knockout mouse models of the vitamin D receptor provide insight into understanding the direct effects of vitamin D on muscle tissue. Recently, VDR polymorphisms have been described to affect muscle function. Parathyroid hormone which is strongly linked with vitamin D status also may play a role in muscle function; however, distinguishing its role from that of vitamin D has yet to be fully clarified. Despite the enormous advances in recent decades, further research is needed to fully characterize the exact underlying mechanisms of vitamin D action on muscle tissue and to understand how these cellular changes translate into clinical improvements in physical performance. [Copyright &y& Elsevier]

The primary objective of this study was to investigate the potential synergy between low doses of L-carnitine tartrate and creatine monohydrate to induce muscle protein synthesis and anabolic pathway activation in primary human myoblasts. In addition, the effects of Lipid multi-particulates (LMP) formulation on creatine stability and bioavailability were assessed in rodents and healthy human subjects. When used individually, L-carnitine tartrate at 50 µM and creatine monohydrate at 0.5 µM did not affect myoblast protein synthesis and signaling. However, when combined, they led to a significant increase in protein synthesis. Increased AKT and RPS6 phosphorylation were observed with 50 µM L-carnitine tartrate 5 µM creatine in combination in primary human myoblasts. When Wistar rats were administered creatine with LMP formulation at either 21 or 51 mg/kg, bioavailability was increased by 27% based on the increase in the area under the curve (AUC) at a 51 mg/kg dose compared to without LMP formulation. Tmax and Cmax were unchanged. Finally, in human subjects, a combination of LMP formulated L-carnitine at 500 mg (from L-carnitine tartrate) with LMP formulated creatine at 100, 200, or 500 mg revealed a significant and dose-dependent increase in plasma creatine concentrations. Serum total L-carnitine levels rose in a similar manner in the three combinations. These results suggest that a combination of low doses of L-carnitine tartrate and creatine monohydrate may lead to a significant and synergistic enhancement of muscle protein synthesis and activation of anabolic signaling. In addition, the LMP formulation of creatine improved its bioavailability. L-carnitine at 500 mg and LMP-formulated creatine at 200 or 500 mg may be useful for future clinical trials to evaluate the effects on muscle protein synthesis. [ABSTRACT FROM AUTHOR]

With aging there is a chronic low-grade metabolic-acidosis that may exacerbate negative protein balance during weight loss. The objective of this randomized pilot study was to assess the impact of 90 mmol∙day−1 potassium bicarbonate (KHCO3) versus a placebo (PLA) on 24-h urinary net acid excretion (NAE), nitrogen balance (NBAL), and whole-body ammonia and urea turnover following short-term diet-induced weight loss. Sixteen (KHCO3; n = 8, PLA; n = 8) older (64 ± 4 years) overweight (BMI: 28.5 ± 2.1 kg∙day−1) men completed a 35-day controlled feeding study, with a 7-day weight-maintenance phase followed by a 28-day 30% energy-restriction phase. KHCO3 or PLA supplementation began during energy restriction. NAE, NBAL, and whole-body ammonia and urea turnover (15N-glycine) were measured at the end of the weight-maintenance and energy-restriction phases. Following energy restriction, NAE was −9.8 ± 27.8 mmol∙day−1 in KHCO3 and 43.9 ± 27.8 mmol∙day−1 in PLA (p < 0.05). No significant group or time differences were observed in NBAL or ammonia and urea turnover. Ammonia synthesis and breakdown tended (p = 0.09) to be higher in KHCO3 vs. PLA following energy restriction, and NAE was inversely associated (r = −0.522; p < 0.05) with urea synthesis in all subjects. This pilot study suggests some benefit may exist with KHCO3 supplementation following energy restriction as lower NAE indicated higher urea synthesis. [ABSTRACT FROM AUTHOR]

A response by Lisa Ceglia and colleagues to a letter to the editor about their article "Meta-Analysis: Efficacy and Safety of Inhaled Insulin Therapy in Adults With Diabetes Mellitus," in a previous issue is presented.

Background: Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown.Methods: We randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.7 to 6.4%) and no diagnostic criteria for diabetes to receive 4000 IU per day of vitamin D3 or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508.Results: A total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups.Conclusions: Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; D2d ClinicalTrials.gov number, NCT01942694.). [ABSTRACT FROM AUTHOR]

Several studies suggest that neutralizing acid load in the diet with alkali had favorable effects on intermediate markers of musculoskeletal health. We examined whether alkali supplementation with potassium bicarbonate [(KHCO 3 ); 81 mmol/d; n = 12] vs placebo (n = 12) for 84 days altered serum microRNAs, potential biomarkers associated with innumerable biological processes including bone and muscle metabolism. Serum microRNAs, urinary net acid excretion (UNAE), urinary N -telopeptide (UNTX), urinary calcium (UCa), urinary nitrogen (UN), glomerular filtration rate, serum procollagen type 1 amino-terminal propeptide (P1NP), serum insulin-like growth factor-1 (IGF-1), and its serum binding protein IGFBP3 were measured at baseline and day 84. Baseline characteristics and measurements were similar in the two treatment groups. Eighty-four-day changes in UNAE differed by group (KHCO 3 , -47 ± 9 mmol; placebo, -5 ± 5 mmol; P < 0.01). KHCO 3 significantly reduced UNTX, UCa, and serum P1NP but did not affect UN, serum IGF-1, or IGFBP3 levels compared with placebo over 84 days. Fold change in serum circulating microRNA (c-miR)-133b differed significantly by group (KHCO 3 , 2.26 ± 0.85; placebo, -1.23 ± 0.69; P < 0.01); there was a similar trend in c-miR-21-5p. Fold changes in c-miR-133b and c-miR-21-5p were inversely associated with changes in UNAE and UNTX; fold change in c-miR-21-5p was inversely associated with change in UCa, with a similar trend with c-miR-133b. In summary, reducing renal acid load with KHCO 3 was associated with increased expressions of c-miR-133b and c-miR-21-5p. Furthermore, increases in c-miRNA-133b and c-miR-21-5p were inversely associated with bone resorption markers UNTX and UCa consistent with potential beneficial effects on bone in older adults. However, the broader significance of c-miRNAs as musculoskeletal biomarkers is still under investigation, and larger studies are needed to verify these preliminary results.

Unlabelled: Transient hypocalcemia after thyroidectomy is not uncommon and the risk increases with the extent of neck surgery. We report a case of severe and prolonged hypocalcemia after total thyroidectomy complicated by thoracic duct injury. Hypoparathyroidism and thoracic duct injury are potential complications following total thyroidectomy with extensive lymph node dissection. This case suggested that having both conditions may complicate treatment of hypoparathyroid-induced hypocalcemia by way of losses of calcium and vitamin D in the chyle leak., Learning Points: This report highlights chyle leak as an uncommon cause of prolonged hypocalcemia in patients who have undergone extensive neck surgery.Chyle has an electrolyte concentration similar to that of plasma.Medical treatment options for a chyle leak include fat-free oral diet or parenteral nutrition without oral intake, pharmacological treatment (primarily octreotide).

It is sometimes assumed that dietary fat is required for vitamin D absorption, although the impact of different amounts of dietary fat on vitamin D absorption is not established. This study was conducted to determine whether the presence of a meal and the fat content of the meal influences vitamin D absorption or the 25-hydroxyvitamin D [25(OH)D] response to supplemental vitamin D3 . Based on earlier studies in rats we postulated that absorption would be greatest in the low-fat meal group. Sixty-two healthy older men and women were randomly assigned to one of three meal groups: no meal, high-fat meal, or low-fat meal; each was given a monthly 50,000 IU vitamin D3 supplement with the test breakfast meal (or after a fast for the no-meal group) and followed for 90 days. Plasma vitamin D3 was measured by liquid chromatography-mass spectroscopy (LC/MS) before and 12 hours after the first dose; plasma 25(OH)D was measured by radioimmunoassay at baseline and after 30 and 90 days. The mean 12-hour increments in vitamin D3 , after adjusting for age and sex, were 200.9 nmol/L in the no-meal group, 207.4 nmol/L in the high-fat meal group, and 241.1 nmol/L in the low-fat meal group (p = 0.038), with the increase in the low-fat group being significantly greater than the increases in the other two groups. However, increments in 25(OH)D levels at 30 and 90 days did not differ significantly in the three groups. We conclude that absorption was increased when a 50,000 IU dose of vitamin D was taken with a low-fat meal, compared with a high-fat meal and no meal, but that the greater absorption did not result in higher plasma 25(OH)D levels in the low-fat meal group., (Copyright © 2013 American Society for Bone and Mineral Research.)