Effect of Weight Loss, Exercise, or Both on Undercarboxylated Osteocalcin and Insulin Secretion in Frail, Obese Older Adults.
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ABSTRACT:
SUBMITTER: Colleluori G
PROVIDER: S-EPMC5603129 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
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Effect of Weight Loss, Exercise, or Both on Undercarboxylated Osteocalcin and Insulin Secretion in Frail, Obese Older Adults.
Colleluori Georgia G Napoli Nicola N Phadnis Uma U Armamento-Villareal Reina R Villareal Dennis T DT
Oxidative medicine and cellular longevity 20170823
<h4>Background</h4>Obesity exacerbates age-related decline in glucometabolic control. Undercarboxylated osteocalcin (UcOC) regulates pancreatic insulin secretion. The long-term effect of lifestyle interventions on UcOC and insulin secretion has not been investigated.<h4>Methods</h4>One hundred seven frail, obese older adults were randomized into the control (<i>N</i> = 27), diet (<i>N</i> = 26), exercise (<i>N</i> = 26), and diet-exercise (<i>N</i> = 28) groups for 1 year. Main outcomes included ...[more]
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Project description:BackgroundObesity exacerbates the age-related decline in physical function and causes frailty in older adults; however, the appropriate treatment for obese older adults is controversial.MethodsIn this 1-year, randomized, controlled trial, we evaluated the independent and combined effects of weight loss and exercise in 107 adults who were 65 years of age or older and obese. Participants were randomly assigned to a control group, a weight-management (diet) group, an exercise group, or a weight-management-plus-exercise (diet-exercise) group. The primary outcome was the change in score on the modified Physical Performance Test. Secondary outcomes included other measures of frailty, body composition, bone mineral density, specific physical functions, and quality of life.ResultsA total of 93 participants (87%) completed the study. In the intention-to-treat analysis, the score on the Physical Performance Test, in which higher scores indicate better physical status, increased more in the diet-exercise group than in the diet group or the exercise group (increases from baseline of 21% vs. 12% and 15%, respectively); the scores in all three of those groups increased more than the scores in the control group (in which the score increased by 1%) (P<0.001 for the between-group differences). Moreover, the peak oxygen consumption improved more in the diet-exercise group than in the diet group or the exercise group (increases of 17% vs. 10% and 8%, respectively; P<0.001); the score on the Functional Status Questionnaire, in which higher scores indicate better physical function, increased more in the diet-exercise group than in the diet group (increase of 10% vs. 4%, P<0.001). Body weight decreased by 10% in the diet group and by 9% in the diet-exercise group, but did not decrease in the exercise group or the control group (P<0.001). Lean body mass and bone mineral density at the hip decreased less in the diet-exercise group than in the diet group (reductions of 3% and 1%, respectively, in the diet-exercise group vs. reductions of 5% and 3%, respectively, in the diet group; P<0.05 for both comparisons). Strength, balance, and gait improved consistently in the diet-exercise group (P<0.05 for all comparisons). Adverse events included a small number of exercise-associated musculoskeletal injuries.ConclusionsThese findings suggest that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00146107.).
| S-EPMC3114602 | biostudies-literature
Project description:Osteocalcin in its undercarboxylated form (ucOC) may influence diabetes risk; however, its relationship with all-cause and cause-specific mortality is unclear. Whether other bone turnover markers (BTMs) are associated with mortality risk differently from ucOC also remains uncertain. Our aim was to determine associations of serum ucOC with all-cause and cause-specific mortality and compare these with the corresponding associations of serum total osteocalcin (TOC), procollagen type I N-propeptide (PINP), and collagen type 1 C-terminal cross-linked telopeptide (CTX) in older men. We conducted a prospective cohort study of 3871 community-dwelling men, aged 77.0 ± 3.6 years at baseline, followed for a median of 12.3 years. Exposure variables were ucOC, TOC, PINP, and CTX concentrations assayed in serum. Outcomes were incidence of all deaths and deaths due to cardiovascular disease (CVD) or cancer, ascertained using death registry data. Cox regression analyses adjusted for cardiovascular risk factors and prevalent CVD and for prevalent cancer in analyses of cancer-related mortality. Higher concentrations of ucOC, PINP, and CTX were associated with all-cause mortality (hazard ratio [HR] per 1 standard deviation increase: ucOC 1.12, 95% confidence interval [CI] 1.06-1.18, p < 0.001; PINP HR = 1.06, 95% CI 1.01-1.11, p = 0.009; CTX HR = 1.13, 95% CI 1.08-1.19, p < 0.001), but TOC was not associated. Similar results were found after excluding men with an incident fracture during follow-up. Higher ucOC and CTX were associated with CVD mortality (ucOC HR per 1 SD increase 1.13, 95% CI 1.05-1.22, p = 0.001; CTX HR = 1.12, 95% CI 1.04-1.20, p = 0.003), but this result was not significant in competing risks analysis. Higher CTX was also associated with cancer mortality (HR = 1.12, 95% CI 1.01-1.23, p = 0.024). In conclusion, in older men, higher bone turnover, assessed by BTMs including ucOC, is a biomarker for all-cause mortality risk. Undercarboxylated osteocalcin was a more informative biomarker for this outcome than TOC. Higher CTX was associated with all-cause and cancer-related mortality. Further evaluation of causality and potential underlying mechanisms is warranted. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
| S-EPMC9540459 | biostudies-literature
Project description:BackgroundObesity impairs cognition and health-related quality of life (HRQOL) in older adults; however, the appropriate treatment of obese older adults remains controversial.ObjectiveThe objective was to determine the independent and combined effects of weight loss and exercise on cognition, mood, and HRQOL in obese older adults.DesignOne hundred seven frail, obese older adults were randomly assigned to a control, weight-management (diet), exercise, or weight-management-plus-exercise (diet-exercise) group for 1 y. In this secondary analysis, main outcomes were Modified Mini-Mental State Examination (3MS) and total Impact of Weight on Quality of Life-Lite (IWQOL) scores. Other outcomes included Word Fluency Test, Trail Making Test Parts A and B, and Geriatric Depression Scale (GDS) scores.ResultsScores on the 3MS improved more in the diet (mean ± SE: 1.7 ± 0.4), exercise (2.8 ± 0.4), and diet-exercise (2.9 ± 0.4) groups than in the control group (0.1 ± 0.4) (between-group P = 0.0001-0.04); scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group. Scores on the Word Fluency Test improved more in the exercise (4.1 ± 0.8) and diet-exercise (4.2 ± 0.7) groups than in the control group (-0.8 ± 0.8; both P = 0.001). For the Trail Making Test Part A, scores in the diet-exercise group (-11.8 ± 1.9) improved more than in the control group (-0.8 ± 1.9) (P = 0.001); a similar finding was observed for the Trail Making Test Part B. Scores on the IWQOL improved more in the diet (7.6 ± 1.6), exercise (10.1 ± 1.6), and diet-exercise (14.0 ± 1.4) groups than in the control group (0.3 ± 1.6) (P = 0.0001-0.03); scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group. In the diet-exercise group, peak oxygen consumption and strength changes were independent predictors of 3MS changes; weight and strength changes were independent predictors of IWQOL changes. GDS scores did not change.ConclusionsWeight loss and exercise each improve cognition and HRQOL, but their combination may provide benefits similar to exercise alone. These findings could inform practice guidelines with regard to optimal treatment strategies for obese older adults. This trial was registered atclinicaltrials.govas NCT00146107.
| S-EPMC4144098 | biostudies-literature
Project description:Osteocalcin has been considered to be an important regulator of energy metabolism in type 2 diabetes mellitus (T2DM). However, the mechanism underlying the involvement of uncarboxylated osteocalcin in the vascular complications of T2DM is not fully understood. In the present study, we analyzed the potential correlations between uncarboxylated osteocalcin and macro- or microangiopathic complications in subjects with T2DM and tested the impact of uncarboxylated osteocalcin on insulin resistance in human umbilical vein endothelial cells (HUVECs). The results showed that the serum levels of uncarboxylated osteocalcin were lower in subjects with vascular complications of T2DM. Univariate correlation analyses revealed negative correlations between uncarboxylated osteocalcin and waist-to-hip ratio, HbA1c, and HOMA-IR. In in vitro experiments, insulin resistance was induced by applying tunicamycin to HUVECs. Uncarboxylated osteocalcin not only markedly reduced the phosphorylations of PERK and eIF2α, but also elevated the phosphorylations of IRS-1 and Akt, resulting in improvement of insulin signal transduction via PI3K/Akt/NF-κB signaling in HUVECs. Therefore, there is a possible relationship between uncarboxylated osteocalcin and the vascular complications of T2DM. Uncarboxylated osteocalcin partially improves insulin signal transduction via PI3K/Akt/NF-κB signaling in tunicamycin-induced HUVECs, suggesting osteocalcin as a potential treatment for the vascular complications of T2DM.
| S-EPMC5427815 | biostudies-literature
Project description:BACKGROUND:Obesity causes frailty in older adults; however, weight loss might accelerate age-related loss of muscle and bone mass and resultant sarcopenia and osteopenia. METHODS:In this clinical trial involving 160 obese older adults, we evaluated the effectiveness of several exercise modes in reversing frailty and preventing reduction in muscle and bone mass induced by weight loss. Participants were randomly assigned to a weight-management program plus one of three exercise programs - aerobic training, resistance training, or combined aerobic and resistance training - or to a control group (no weight-management or exercise program). The primary outcome was the change in Physical Performance Test score from baseline to 6 months (scores range from 0 to 36 points; higher scores indicate better performance). Secondary outcomes included changes in other frailty measures, body composition, bone mineral density, and physical functions. RESULTS:A total of 141 participants completed the study. The Physical Performance Test score increased more in the combination group than in the aerobic and resistance groups (27.9 to 33.4 points [21% increase] vs. 29.3 to 33.2 points [14% increase] and 28.8 to 32.7 points [14% increase], respectively; P=0.01 and P=0.02 after Bonferroni correction); the scores increased more in all exercise groups than in the control group (P<0.001 for between-group comparisons). Peak oxygen consumption (milliliters per kilogram of body weight per minute) increased more in the combination and aerobic groups (17.2 to 20.3 [17% increase] and 17.6 to 20.9 [18% increase], respectively) than in the resistance group (17.0 to 18.3 [8% increase]) (P<0.001 for both comparisons). Strength increased more in the combination and resistance groups (272 to 320 kg [18% increase] and 288 to 337 kg [19% increase], respectively) than in the aerobic group (265 to 270 kg [4% increase]) (P<0.001 for both comparisons). Body weight decreased by 9% in all exercise groups but did not change significantly in the control group. Lean mass decreased less in the combination and resistance groups than in the aerobic group (56.5 to 54.8 kg [3% decrease] and 58.1 to 57.1 kg [2% decrease], respectively, vs. 55.0 to 52.3 kg [5% decrease]), as did bone mineral density at the total hip (grams per square centimeter; 1.010 to 0.996 [1% decrease] and 1.047 to 1.041 [0.5% decrease], respectively, vs. 1.018 to 0.991 [3% decrease]) (P<0.05 for all comparisons). Exercise-related adverse events included musculoskeletal injuries. CONCLUSIONS:Of the methods tested, weight loss plus combined aerobic and resistance exercise was the most effective in improving functional status of obese older adults. (Funded by the National Institutes of Health; LITOE ClinicalTrials.gov number, NCT01065636 .).
| S-EPMC5552187 | biostudies-literature
Project description:We reported that weight loss induces bone loss which is prevented by exercise training; however, the mechanism for this observation remains unclear. Sclerostin, an inhibitor of bone formation, has been found to increase in states of unloading and may mediate the changes in bone metabolism associated with weight loss and exercise. The objective of the study was to determine the effect of lifestyle intervention in obese older adults on sclerostin levels, and on hip geometry parameters. A total of 107 obese (body mass index [BMI] ? 30?kg/m(2)) older (?65 years) adults were randomly assigned to control, diet, exercise, and combined diet-exercise for 1 year. Sclerostin levels were measured by ELISA at baseline, 6 months, and 12 months, while hip geometry parameters were obtained from bone mineral density (BMD) images done by dual-energy X-ray absorptiometry using hip structure analysis at baseline and 12 months. Both the diet and diet-exercise groups had significant decreases in body weight (-9.6% and -9.4%, respectively), whereas weight was stable in the exercise and control groups. Sclerostin levels increased significantly and progressively in the diet group (6.6%?±?1.7% and 10.5%?±?1.9% at 6 and 12 months, respectively, all p?<?0.05), whereas they were unchanged in the other groups; in particular, they were stable in the diet-exercise group (0.7%?±?1.6% and 0.4%?±?1.7% at 6 and 12 months, respectively, all p?=?0.05). Hip geometry parameters showed significant decreases in cross-sectional area, cortical thickness, and BMD; and increases in buckling ratio at the narrow neck, intertrochanter, and femoral shaft. These negative changes on bone geometry were not observed in the diet-exercise group. Significant correlations between changes in sclerostin and changes in certain hip geometry parameters were also observed (p?<?0.05). In conclusion, the increase in sclerostin levels with weight loss that was prevented by exercise may partly mediate the negative effects of weight loss on bone metabolism and the osteoprotective effect of exercise training.
| S-EPMC3361603 | biostudies-literature
Project description:ContextAnimal studies indicate that osteocalcin (OC), particularly the undercarboxylated isoform (unOC), affects insulin sensitivity and secretion, but definitive data from humans are lacking.ObjectiveThe objectives of the study were to determine whether total OC and unOC are independently associated with insulin sensitivity and β-cell response in overweight/obese adults; whether glucose tolerance status affects these associations; and whether the associations are independent of bone formation, as reflected in procollagen type 1 amino propeptide (P1NP).Design, setting, and participantsThis was a cross-sectional study conducted at a university research center involving 63 overweight/obese adults with normal (n = 39) or impaired fasting glucose (IFG; n = 24).Main outcome measuresSerum concentrations of total/undercarboxylated OC and P1NP were assessed by RIA; insulin sensitivity was determined by iv glucose tolerance test (S(I)-IVGTT), liquid meal test (S(I) meal), and homeostasis model assessment of insulin resistance; β-cell response to glucose [basal β-cell response to glucose; dynamic β-cell response to glucose; static β-cell response to glucose; and total β-cell response to glucose] was derived using C-peptide modeling of meal test data; and intraabdominal adipose tissue was measured using computed tomography scanning.ResultsMultiple linear regression, adjusting for intraabdominal adipose tissue and P1NP, revealed that total OC was positively associated with S(I)-iv glucose tolerance test (P < .01) in the total sample. OC was not associated with S(I) meal or homeostasis model assessment of insulin resistance. In participants with IFG, unOC was positively associated with static β-cell response to glucose and total β-cell response to glucose (P < .05), independent of insulin sensitivity.ConclusionsIn overweight/obese individuals, total OC may be associated with skeletal muscle but not hepatic insulin sensitivity. unOC is uniquely associated with β-cell function only in individuals with IFG. Further research is needed to probe the causal inference of these relationships and to determine whether indirect nutrient sensing pathways underlie these associations.
| S-EPMC3701277 | biostudies-literature
Project description:BACKGROUND:Muscles and bones are interconnected. Recent studies suggest that undercarboxylated osteocalcin from bone may affect muscle mass and strength. There are, however, no prospective human data on this relationship. METHODS:We previously treated patients with hypoparathyroidism with intact Parathyroid Hormone (PTH) or placebo in a six-month randomized, placebo-controlled trial and demonstrated a marked increase in undercarboxylated osteocalcin (ucOC) in the PTH-treated group. We therefore investigated if this increase correlated with changes in muscle mass, strength or function. Primarily, the muscle mass using Dual energy X-ray Absorptiometry (DXA) was measured and the maximal voluntary isometric muscle strength at the upper and lower extremities, using dynamometry, was assessed. Furthermore, repeated chair stands test, Timed Up and Go test were performed and postural stability using a stadiometer was assessed. Finally, the relationship between change in ucOC or the ratio of the changes in ucOC and total OC (ucOC%/OC%) and different measures of muscle function were analyzed, using regression analyses. RESULTS:The findings indicated that ucOC%/OC% was positively and significantly associated with percentage change in max force production during elbow extension (? = 0.28, P = 0.034), however, all other associations were non-significant. CONCLUSIONS:Given the number of statistical tests that were carried out, our one significant finding may represent a false positive. Thus the results do not support the role of ucOC in muscle function in humans with hypoparathyroidism. Our results are inconsistent with previous data from a human cross-sectional study; however, cross-sectional studies, do not allow for inference of causality. The analyses should be repeated in larger, randomized trials including healthy individuals.
| S-EPMC5138377 | biostudies-literature
Project description:Osteocalcin (OCN) was the most abundant noncollagen protein and considered as an endocrine factor. However, the functions of Undercarboxylated osteocalcin (ucOCN) on osteoclast and bone resorption are not well understood. In the present study, preosteoclast RAW264.7 cells and bone marrow mononuclear cells (BMMs) were treated with ucOCN purified from prokaryotic bacteria. Our results showed that ucOCN attenuated the proliferation of RAW264.7 cells with a concentration dependant manner by MTS assay. Scrape wounding assay revealed the decreased motility of RAW264.7 cells after ucOCN treatment. RT-qPCR results manifested the inhibitory effects of ucOCN on the expression of osteoclastic marker genes in RAW264.7 cells during inducing differentiation of RANKL. It was also observed that ucOCN inhibited the formation of multinucleated cells from RAW264.7 cells and BMMs detected by TRAP staining. The number and area of bone resorb pits were also decreased after treatment with ucOCN during their osteoclast induction by toluidine blue staining. The formation and integrity of the osteoclast actin ring were impaired by ucOCN by immunofluorescent staining. Time dependant treatment of ucOCN during osteoclastic induction demonstrated the inhibitory effects mainly occurred at the early stage of osteoclastogenesis. Signaling analysis of luciferase activity of the CRE or SRE reporter and ERK1/2 phosphorylation showed the selective inhibitor or siRNA of Gprc6a (a presumptive ucOCN receptor) could attenuate the promotion of ucOCN on CRE-luciferase activity. Taken together, we provided the first evidence that ucOCN had negative effects on the early differentiation and bone resorption of osteoclasts via Gprc6a.
| S-EPMC7934677 | biostudies-literature
Project description:IntroductionThe 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.ObjectivesWe 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 analysisThis 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's test will be used to identify potential publication bias.Ethics and disseminationFormal ethical approval is not required. We will disseminate the results to a peer-reviewed publication and conference presentation.Prospero registration numberCRD42017073127.
| S-EPMC6429918 | biostudies-literature