@article {1380, title = {Association of fetuin-a with incident diabetes mellitus in community-living older adults: the cardiovascular health study.}, journal = {Circulation}, volume = {125}, year = {2012}, month = {2012 May 15}, pages = {2316-22}, 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 {\textpm} 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.

}, keywords = {African Continental Ancestry Group, Age Distribution, Aged, Aged, 80 and over, alpha-2-HS-Glycoprotein, Body Mass Index, C-Reactive Protein, Cardiovascular Diseases, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Humans, Incidence, Life Style, Lipids, Male, Pilot Projects, Prevalence, Proportional Hazards Models, Residence Characteristics, Risk Factors, Sex Distribution}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.111.072751}, author = {Ix, Joachim H and Biggs, Mary L and Mukamal, Kenneth J and Kizer, Jorge R and Zieman, Susan J and Siscovick, David S and Mozzaffarian, Dariush and Jensen, Majken K and Nelson, Lauren and Ruderman, Neil and Djouss{\'e}, Luc} } @article {5860, title = {Hemoglobin A1c and arterial and ventricular stiffness in older adults.}, journal = {PLoS One}, volume = {7}, year = {2012}, month = {2012}, pages = {e47941}, abstract = {

OBJECTIVE: Arterial and ventricular stiffening are characteristics of diabetes and aging which confer significant morbidity and mortality; advanced glycation endproducts (AGE) are implicated in this stiffening pathophysiology. We examined the association between HbA(1c), an AGE, with arterial and ventricular stiffness measures in older individuals without diabetes.

RESEARCH DESIGN \& METHODS: Baseline HbA(1c) was measured in 830 participants free of diabetes defined by fasting glucose or medication use in the Cardiovascular Health Study, a population-based cohort study of adults aged >= 65 years. We performed cross-sectional analyses using baseline exam data including echocardiography, ankle and brachial blood pressure measurement, and carotid ultrasonography. We examined the adjusted associations between HbA(1c) and multiple arterial and ventricular stiffness measures by linear regression models and compared these results to the association of fasting glucose (FG) with like measures.

RESULTS: HbA(1c) was correlated with fasting and 2-hour postload glucose levels (r = 0.21; p<0.001 for both) and positively associated with greater body-mass index and black race. In adjusted models, HbA(1c) was not associated with any measure of arterial or ventricular stiffness, including pulse pressure (PP), carotid intima-media thickness, ankle-brachial index, end-arterial elastance, or left ventricular mass (LVM). FG levels were positively associated with systolic, diastolic and PP and LVM.

CONCLUSIONS: In this sample of older adults without diabetes, HbA(1c) was not associated with arterial or ventricular stiffness measures, whereas FG levels were. The role of AGE in arterial and ventricular stiffness in older adults may be better assessed using alternate AGE markers.

}, keywords = {Adult, African Continental Ancestry Group, Aged, Ankle Brachial Index, Arteries, Blood Glucose, Blood Pressure, Body Mass Index, Cross-Sectional Studies, Fasting, Female, Genetic Association Studies, Glycated Hemoglobin A, Glycation End Products, Advanced, Heart Ventricles, Humans, Male, Middle Aged, Ultrasonography, Vascular Stiffness}, issn = {1932-6203}, doi = {10.1371/journal.pone.0047941}, author = {Zieman, Susan J and Kamineni, Aruna and Ix, Joachim H and Barzilay, Joshua and Djouss{\'e}, Luc and Kizer, Jorge R and Biggs, Mary L and de Boer, Ian H and Chonchol, Michel and Gottdiener, John S and Selvin, Elizabeth and Newman, Anne B and Kuller, Lewis H and Siscovick, David S and Mukamal, Kenneth J} } @article {6210, title = {The influence of sex on cardiovascular outcomes associated with diabetes among older black and white adults.}, journal = {J Diabetes Complications}, volume = {28}, year = {2014}, month = {2014 May-Jun}, pages = {316-22}, abstract = {

AIMS: It is unknown whether sex differences in the association of diabetes with cardiovascular outcomes vary by race. We examined sex differences in the associations of diabetes with incident congestive heart failure (CHF) and coronary heart disease (CHD) between older black and white adults.

METHODS: We analyzed data from the Cardiovascular Health Study (CHS), a prospective cohort study of community-dwelling individuals aged >=65 from four US counties. We included 4817 participants (476 black women, 279 black men, 2447 white women and 1625 white men). We estimated event rates and multivariate-adjusted hazard ratios for incident CHF, CHD, and all-cause mortality by Cox regression and competing risk analyses.

RESULTS: Over a median follow-up of 12.5years, diabetes was more strongly associated with CHF among black women (HR, 2.42 [95\% CI, 1.70-3.40]) than black men (1.39 [0.83-2.34]); this finding did not reach statistical significance (P for interaction=0.08). Female sex conferred a higher risk for a composite outcome of CHF and CHD among black participants (2.44 [1.82-3.26]) vs. (1.44 [0.97-2.12]), P for interaction=0.03). There were no significant sex differences in the HRs associated with diabetes for CHF among whites, or for CHD or all-cause mortality among blacks or whites. The three-way interaction between sex, race, and diabetes on risk of cardiovascular outcomes was not significant (P=0.07).

CONCLUSIONS: Overall, sex did not modify the cardiovascular risk associated with diabetes among older black or white adults. However, our results suggest that a possible sex interaction among older blacks merits further study.

}, keywords = {African Continental Ancestry Group, Age Factors, Aged, Aged, 80 and over, Cohort Studies, Coronary Disease, Diabetes Complications, European Continental Ancestry Group, Female, Heart Failure, Humans, Incidence, Longitudinal Studies, Male, Prospective Studies, Regression Analysis, Retrospective Studies, Risk Factors, Sex Factors, Survival Rate}, issn = {1873-460X}, doi = {10.1016/j.jdiacomp.2013.12.004}, author = {Vimalananda, Varsha G and Biggs, Mary L and Rosenzweig, James L and Carnethon, Mercedes R and Meigs, James B and Thacker, Evan L and Siscovick, David S and Mukamal, Kenneth J} }