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Association of fetuin-a with incident diabetes mellitus in community-living older adults: the cardiovascular health study.

ABSTRACT: BACKGROUND:The liver-secreted protein fetuin-A induces peripheral insulin resistance in vitro. In a pilot study, we observed that higher fetuin-A levels were associated with diabetes mellitus in older persons. However, this finding has not been confirmed in large cohorts. We sought to confirm the association of fetuin-A with incident diabetes mellitus in older persons and to determine whether the association differs by age, sex, and race and among persons with cardiovascular disease (CVD). METHODS AND RESULTS:Among 3710 community-living individuals ? 65 years of age without diabetes mellitus at baseline, fetuin-A was measured in serum collected in 1992 to 1993. Participants were followed up for 10.6 years (median) for incident diabetes mellitus. Cox regression models evaluated the association of fetuin-A with incident diabetes mellitus. Interaction terms evaluated heterogeneity by age, sex, race, and CVD. Mean age was 75 years; 60 were female; 15 were black; and 16 had CVD. Mean fetuin-A concentrations were 0.47 ± 0.10 g/L. During follow-up, 305 incident diabetes cases occurred. Each 0.10-g/L (SD)-greater fetuin-A was associated with 19 higher risk of diabetes mellitus (hazard ratio, 1.19; 95 confidence interval, 1.06-1.33) after adjustment for demographics, lifestyle factors, albumin, kidney function, and CVD. Further adjustment for potential mediators (body mass index, waist circumference, hypertension, lipids, and C-reactive protein) moderately attenuated the association (hazard ratio, 1.13; 95 confidence interval, 1.00-1.28). Results were similar by sex, race, and CVD status but were stronger in persons <75 years old (P for interaction=0.01). CONCLUSIONS:Higher fetuin-A is associated with incident diabetes mellitus in older persons regardless of sex, race, or prevalent CVD status. The association may be attenuated in those ? 75 years of age.

SUBMITTER: Ix JH

PROVIDER: S-EPMC3390925 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Association of fetuin-a with incident diabetes mellitus in community-living older adults: the cardiovascular health study.

Ix Joachim H JH Biggs Mary L ML Mukamal Kenneth J KJ Kizer Jorge R JR Zieman Susan J SJ Siscovick David S DS Mozzaffarian Dariush D Jensen Majken K MK Nelson Lauren L Ruderman Neil N Djousse Luc L

Circulation 20120417 19

<h4>Background</h4>The liver-secreted protein fetuin-A induces peripheral insulin resistance in vitro. In a pilot study, we observed that higher fetuin-A levels were associated with diabetes mellitus in older persons. However, this finding has not been confirmed in large cohorts. We sought to confirm the association of fetuin-A with incident diabetes mellitus in older persons and to determine whether the association differs by age, sex, and race and among persons with cardiovascular disease (CVD ...[more]

PMID: 22511752

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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:ImportanceThe prevalence of depressive symptoms among older adults has become an increasingly important public health priority. Elevated depressive symptoms are well documented among elderly people with cardiovascular disease (CVD), but studies conducted among Chinese adults are scarce.ObjectiveTo estimate the association between depressive symptoms and incident CVD among middle-aged and older Chinese adults.Design, setting, and participantsThe China Health and Retirement Longitudinal Study is an ongoing nationally representative prospective cohort study that was initiated in 2011. This cohort study included 12 417 middle-aged and older Chinese adults without heart disease and stroke at baseline. Statistical analysis was conducted from April 25, 2018, to December 13, 2018.ExposureDepressive symptoms were assessed using the validated 10-item of Center for Epidemiologic Studies Depression Scale.Main outcomes and measuresIncident CVD (ie, self-reported physician-diagnosed heart disease and stroke combined) was followed-up from June 1, 2011, to June 31, 2015. The Center for Epidemiologic Studies Depression Scale total score ranges from 0 to 30, with a score of 12 or more indicating elevated depressive symptoms.ResultsOf the 12 417 participants (mean [SD] age at baseline, 58.40 [9.51] years), 6113 (49.2%) were men. During the 4 years of follow-up, 1088 incident CVD cases were identified. Elevated depressive symptoms were independently associated with an increased CVD risk (adjusted hazard ratio, 1.39; 95% CI, 1.22-1.58) after adjusting for age, sex, residence, marital status, educational level, smoking status, drinking status, systolic blood pressure, and body mass index; history of diabetes, hypertension, dyslipidemia, and chronic kidney disease; and use of hypertension medications, diabetes medications, and lipid-lowering therapy. Of the 10 individual depressive symptoms measured by the Center for Epidemiologic Studies Depression Scale, only 2 symptoms, restless sleep (adjusted hazard ratio, 1.21; 95% CI, 1.06-1.39) and loneliness (adjusted hazard ratio, 1.21; 95% CI, 1.02-1.44), were significantly associated with incident CVD.Conclusions and relevanceElevated depressive symptoms overall and 2 individual symptoms (restless sleep and loneliness) were significantly associated with incident CVD among middle-aged and older Chinese adults.

Project description:BackgroundNo evidence-based recommendations regarding optimal breakfast frequency and timing and type 2 diabetes mellitus (T2DM) exist for older adults because of limited studies.ObjectivesWe sought to prospectively assess relations between breakfast frequency and timing and T2DM risk among older adults and determine whether these depended on sex or cardiometabolic risk factors.MethodsWeekly breakfast frequency and usual daily breakfast time were assessed by questionnaire at baseline in 3747 older adults (aged ≥ 65 y) from the Cardiovascular Health Study (CHS) who were free of cancer and T2DM and followed for 17.6 y. Multivariable-adjusted hazard ratios (aHRs) with 95% CIs estimated from Cox proportional hazards models were used to quantify associations with T2DM.ResultsMost CHS participants (median age: 74 y; IQR: 71-78 y) consumed breakfast daily (85.5%), and 73% had their first daily eating occasion between 07:00 and 09:00, both of which were associated with higher socioeconomic status, factors that are indicative of a healthier lifestyle, and lower levels of cardiometabolic risk indicators at baseline. During follow-up, 547 T2DM cases were documented. No strong evidence was observed linking breakfast frequency and risk of T2DM. Compared with participants whose breakfast timing (first eating occasion of the day) was 07:00-09:00, those who broke fast after 09:00 had an aHR for T2DM of 0.71 (95% CI: 0.51, 0.99). This association was present in participants with impaired fasting glucose at baseline (aHR: 0.61; 95% CI: 0.39, 0.95) but not in those without (aHR: 0.83; 95% CI: 0.50, 1.38). No associations between eating frequency or timing and T2DM were observed within other prespecified subgroups.ConclusionsEating breakfast daily was not associated with either higher or lower risk of T2DM in this cohort of older adults, whereas a later (after 09:00) daily first eating occasion time was associated with lower T2DM risk in participants with impaired fasting glucose at baseline.This trial was registered at clinicaltrials.gov as NCT00005133.

Project description:BackgroundType 2 diabetes mellitus (T2D) confers a two- to three-fold increased risk of cardiovascular disease (CVD). However, the mechanisms underlying increased CVD risk among people with T2D are only partially understood. We hypothesized that a genetic association study among people with T2D at risk for developing incident cardiovascular complications could provide insights into molecular genetic aspects underlying CVD.MethodsFrom 16 studies of the Cohorts for Heart & Aging Research in Genomic Epidemiology (CHARGE) Consortium, we conducted a multi-ancestry time-to-event genome-wide association study (GWAS) for incident CVD among people with T2D using Cox proportional hazards models. Incident CVD was defined based on a composite of coronary artery disease (CAD), stroke, and cardiovascular death that occurred at least one year after the diagnosis of T2D. Cohort-level estimated effect sizes were combined using inverse variance weighted fixed effects meta-analysis. We also tested 204 known CAD variants for association with incident CVD among patients with T2D.ResultsA total of 49,230 participants with T2D were included in the analyses (31,118 European ancestries and 18,112 non-European ancestries) which consisted of 8,956 incident CVD cases over a range of mean follow-up duration between 3.2 and 33.7 years (event rate 18.2%). We identified three novel, distinct genetic loci for incident CVD among individuals with T2D that reached the threshold for genome-wide significance (P<5.0×10-8): rs147138607 (intergenic variant between CACNA1E and ZNF648) with a hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.15 - 1.32, P=3.6×10-9, rs11444867 (intergenic variant near HS3ST1) with HR 1.89, 95% CI 1.52 - 2.35, P=9.9×10-9, and rs335407 (intergenic variant between TFB1M and NOX3) HR 1.25, 95% CI 1.16 - 1.35, P=1.5×10-8. Among 204 known CAD loci, 32 were associated with incident CVD in people with T2D with P<0.05, and 5 were significant after Bonferroni correction (P<0.00024, 0.05/204). A polygenic score of these 204 variants was significantly associated with incident CVD with HR 1.14 (95% CI 1.12 - 1.16) per 1 standard deviation increase (P=1.0×10-16).ConclusionsThe data point to novel and known genomic regions associated with incident CVD among individuals with T2D.

Dataset Information

Association of fetuin-a with incident diabetes mellitus in community-living older adults: the cardiovascular health study.

Publications

Association of fetuin-a with incident diabetes mellitus in community-living older adults: the cardiovascular health study.

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