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No Evidence of Association Between Undercarboxylated Osteocalcin and Incident Type 2 Diabetes.

ABSTRACT: Mouse models suggest that undercarboxylated osteocalcin (ucOC), produced by the skeleton, protects against type 2 diabetes development, whereas human studies have been inconclusive. We aimed to determine if ucOC or total OC is associated with incident type 2 diabetes or changes in fasting glucose, insulin resistance (HOMA-IR), or beta-cell function (HOMA-Beta). A subcohort (n = 338; 50% women; 36% black) was identified from participants without diabetes at baseline in the Health, Aging, and Body Composition Study. Cases of incident type 2 diabetes (n = 137) were defined as self-report at an annual follow-up visit, use of diabetes medication, or elevated fasting glucose during 8 years of follow-up. ucOC and total OC were measured in baseline serum. Using a case-cohort design, the association between biomarkers and incident type 2 diabetes was assessed using robust weighted Cox regression. In the subcohort, linear regression models analyzed the associations between biomarkers and changes in fasting glucose, HOMA-IR, and HOMA-Beta over 9 years. Higher levels of ucOC were not statistically associated with increased risk of incident type 2 diabetes (adjusted hazard ratio = 1.06 [95% confidence interval, 0.84-1.34] per 1 standard deviation [SD] increase in ucOC). Results for %ucOC and total OC were similar. Adjusted associations of ucOC, %ucOC, and total OC with changes in fasting glucose, HOMA-IR, and HOMA-Beta were modest and not statistically significant. We did not find evidence of an association of baseline undercarboxylated or total osteocalcin with risk of incident type 2 diabetes or with changes in glucose metabolism in older adults. © 2022 American Society for Bone and Mineral Research (ASBMR).

SUBMITTER: Babey ME

PROVIDER: S-EPMC10441038 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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No Evidence of Association Between Undercarboxylated Osteocalcin and Incident Type 2 Diabetes.

Babey Muriel E ME Ewing Susan K SK Strotmeyer Elsa S ES Napoli Nicola N Schafer Anne L AL Vittinghoff Eric E Gundberg Caren M CM Schwartz Ann V AV

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20220227 5

Mouse models suggest that undercarboxylated osteocalcin (ucOC), produced by the skeleton, protects against type 2 diabetes development, whereas human studies have been inconclusive. We aimed to determine if ucOC or total OC is associated with incident type 2 diabetes or changes in fasting glucose, insulin resistance (HOMA-IR), or beta-cell function (HOMA-Beta). A subcohort (n = 338; 50% women; 36% black) was identified from participants without diabetes at baseline in the Health, Aging, and Body ...[more]

PMID: 35118705

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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.

Project description:BackgroundObesity is a well-known risk factor for type 2 diabetes mellitus (T2DM). Studies have shown that the Chinese visceral adiposity index (CVAI), a novel visceral adiposity indicator, is positive associated with the risk of T2DM in the Chinese population. This study aimed to investigate the correlation between CVAI and incident T2DM in a Japanese population.MethodsWe performed a secondary analysis of open-access data from a retrospective cohort study. This study included 15,464 participants who received regular medical examinations at Murakami Memorial Hospital. All participants underwent a questionnaire survey, physical examination, and blood biochemical testing at baseline. The main outcome was new-onset T2DM during follow-up. Cox regression analysis and Kaplan-Meier analysis were used to analyze the risk of CVAI on T2DM, and we conducted smooth curve fitting. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of CVAI, body mass index (BMI), and waist circumference (WC) for incident T2DM.ResultsDuring a median follow-up time of 5.39 years, 373 new-onset T2DM events were observed. Kaplan-Meier curves showed that the incidence of T2DM increased as the CVAI increased (log-rank χ 2 = 187.1076 and 129.6067 in males and females, respectively, both P <0.001). After adjustment for covariates, per 1 increase of CVAI was associated with a 1.0133-fold and 1.0246-fold higher risk of incident T2DM in males and females, respectively (both P <0.001). Those individuals in the top CVAI quartile group had the highest risk of new-onset T2DM (HR = 3.1568 and 5.8415 in males and females, respectively, both P <0.05). A nonlinear relationship was identified by the smooth fitting curve between CVAI and T2DM events in both genders. ROC analysis indicated that CVAI had better predictive power than BMI and WC in both genders.ConclusionOur results demonstrate that CVAI was significantly associated with an increased risk of new-onset T2DM in Japanese adults.

Project description:BackgroundLow circulating concentrations of 25-hydroxyvitamin D (25[OH]D), a marker of vitamin D status, are associated with an increased risk of type 2 diabetes, but whether this association is causal remains unclear. We aimed to estimate the unconfounded, causal association between 25(OH)D concentration and risk of type 2 diabetes using a mendelian randomisation approach.MethodsUsing several data sources from populations of European descent, including type 2 diabetes cases and non-cases, we did a mendelian randomisation analysis using single nucleotide polymorphisms (SNPs) within or near four genes related to 25(OH)D synthesis and metabolism: DHCR7 (related to vitamin D synthesis), CYP2R1 (hepatic 25-hydroxylation), DBP (also known as GC; transport), and CYP24A1 (catabolism). We assessed each SNP for an association with circulating 25(OH)D concentration (5449 non-cases; two studies), risk of type 2 diabetes (28 144 cases, 76 344 non-cases; five studies), and glycaemic traits (concentrations of fasting glucose, 2-h glucose, fasting insulin, and HbA1c; 46 368 non-cases; study consortium). We combined these associations in a likelihood-based mendelian randomisation analysis to estimate the causal association of 25(OH)D concentration with type 2 diabetes and the glycaemic traits, and compared them with that from a meta-analysis of data from observational studies (8492 cases, 89 698 non-cases; 22 studies) that assessed the association between 25(OH)D concentration and type 2 diabetes.FindingsAll four SNPs were associated with 25(OH)D concentrations (p<10(-6)). The mendelian randomisation-derived unconfounded odds ratio for type 2 diabetes was 1·01 (95% CI 0·75-1·36; p=0·94) per 25·0 nmol/L (1 SD) lower 25(OH)D concentration. The corresponding (potentially confounded) relative risk from the meta-analysis of data from observational studies was 1·21 (1·16-1·27; p=7·3 × 10(-19)). The mendelian randomisation-derived estimates for glycaemic traits were not significant (p>0·25).InterpretationThe association between 25(OH)D concentration and type 2 diabetes is unlikely to be causal. Efforts to increase 25(OH)D concentrations might not reduce the risk of type 2 diabetes as would be expected on the basis of observational evidence. These findings warrant further investigations to identify causal factors that might increase 25(OH)D concentration and also reduce the risk of type 2 diabetes.FundingUK Medical Research Council Epidemiology Unit and European Union Sixth Framework Programme.

Dataset Information

No Evidence of Association Between Undercarboxylated Osteocalcin and Incident Type 2 Diabetes.

Publications

No Evidence of Association Between Undercarboxylated Osteocalcin and Incident Type 2 Diabetes.

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