@article {1210, title = {Association between adiposity in midlife and older age and risk of diabetes in older adults.}, journal = {JAMA}, volume = {303}, year = {2010}, month = {2010 Jun 23}, pages = {2504-12}, abstract = {

CONTEXT: Adiposity is a well-recognized risk factor for type 2 diabetes among young and middle-aged adults, but the relationship between body composition and type 2 diabetes is not well described among older adults.

OBJECTIVE: To examine the relationship between adiposity, changes in adiposity, and risk of incident type 2 diabetes in adults 65 years of age and older.

DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study (1989-2007) of 4193 men and women 65 years of age and older in the Cardiovascular Health Study. Measures of adiposity were derived from anthropometry and bioelectrical impedance data at baseline and anthropometry repeated 3 years later.

MAIN OUTCOME MEASURE: Incident diabetes was ascertained based on use of antidiabetic medication or a fasting glucose level of 126 mg/dL or greater.

RESULTS: Over median follow-up of 12.4 years (range, 0.9-17.8 years), 339 cases of incident diabetes were ascertained (7.1/1000 person-years). The adjusted hazard ratio (HR) (95\% confidence interval [CI]) of type 2 diabetes for participants in the highest quintile of baseline measures compared with those in the lowest was 4.3 (95\% CI, 2.9-6.5) for body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), 3.0 (95\% CI, 2.0-4.3) for BMI at 50 years of age, 4.2 (95\% CI, 2.8-6.4) for weight, 4.0 (95\% CI, 2.6-6.0) for fat mass, 4.2 (95\% CI, 2.8-6.2) for waist circumference, 2.4 (95\% CI, 1.6-3.5) for waist-hip ratio, and 3.8 (95\% CI, 2.6-5.5) for waist-height ratio. However, when stratified by age, participants 75 years of age and older had HRs approximately half as large as those 65 to 74 years of age. Compared with weight-stable participants (+/-2 kg), those who gained the most weight from 50 years of age to baseline (> or = 9 kg), and from baseline to the third follow-up visit (> or = 6 kg), had HRs for type 2 diabetes of 2.8 (95\% CI, 1.9-4.3) and 2.0 (95\% CI, 1.1-3.7), respectively. Participants with a greater than 10-cm increase in waist size from baseline to the third follow-up visit had an HR of type 2 diabetes of 1.7 (95\% CI, 1.1-2.8) compared with those who gained or lost 2 cm or less.

CONCLUSION: Among older adults, overall and central adiposity, and weight gain during middle age and after the age of 65 years are associated with risk of diabetes.

}, keywords = {Adiposity, Age Factors, Aged, Body Mass Index, Diabetes Mellitus, Type 2, Female, Humans, Incidence, Male, Prospective Studies, Risk Factors, United States, Weight Gain}, issn = {1538-3598}, doi = {10.1001/jama.2010.843}, author = {Biggs, Mary L and Mukamal, Kenneth J and Luchsinger, Jos{\'e} A and Ix, Joachim H and Carnethon, Mercedes R and Newman, Anne B and de Boer, Ian H and Strotmeyer, Elsa S and Mozaffarian, Dariush and Siscovick, David S} } @article {1257, title = {Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S. adults: a cohort study.}, journal = {Ann Intern Med}, volume = {153}, year = {2010}, month = {2010 Dec 21}, pages = {790-9}, abstract = {

BACKGROUND: Palmitoleic acid (cis-16:1n-7), which is produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative.

OBJECTIVE: To investigate whether circulating trans-palmitoleate is independently related to lower metabolic risk and incident type 2 diabetes.

DESIGN: Prospective cohort study from 1992 to 2006.

SETTING: Four U.S. communities.

PATIENTS: 3736 adults in the Cardiovascular Health Study.

MEASUREMENTS: Anthropometric characteristics and levels of plasma phospholipid fatty acids, blood lipids, inflammatory markers, and glucose-insulin measured at baseline in 1992 and dietary habits measured 3 years earlier. Multivariate-adjusted models were used to investigate how demographic, clinical, and lifestyle factors independently related to plasma phospholipid trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). Findings were validated for metabolic risk factors in an independent cohort of 327 women.

RESULTS: In multivariate analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate levels. Higher trans-palmitoleate levels were associated with slightly lower adiposity and, independently, with higher high-density lipoprotein cholesterol levels (1.9\% across quintiles; P = 0.040), lower triglyceride levels (-19.0\%; P < 0.001), a lower total cholesterol-HDL cholesterol ratio (-4.7\%; P < 0.001), lower C-reactive protein levels (-13.8\%; P = 0.05), and lower insulin resistance (-16.7\%, P < 0.001). Trans-palmitoleate was also associated with a substantially lower incidence of diabetes, with multivariate hazard ratios of 0.41 (95\% CI, 0.27 to 0.64) and 0.38 (CI, 0.24 to 0.62) in quintiles 4 and 5 versus quintile 1 (P for trend < 0.001). Findings were independent of estimated dairy consumption or other fatty acid dairy biomarkers. Protective associations with metabolic risk factors were confirmed in the validation cohort.

LIMITATION: Results could be affected by measurement error or residual confounding.

CONCLUSION: Circulating trans-palmitoleate is associated with lower insulin resistance, presence of atherogenic dyslipidemia, and incident diabetes. Our findings may explain previously observed metabolic benefits of dairy consumption and support the need for detailed further experimental and clinical investigation.

PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

}, keywords = {Adiposity, Aged, C-Reactive Protein, Cholesterol, Cholesterol, HDL, Dairy Products, Diabetes Mellitus, Type 2, Fatty Acids, Monounsaturated, Feeding Behavior, Female, Humans, Incidence, Insulin Resistance, Male, Prospective Studies, Risk Factors, Triglycerides, United States}, issn = {1539-3704}, doi = {10.7326/0003-4819-153-12-201012210-00005}, author = {Mozaffarian, Dariush and Cao, Haiming and King, Irena B and Lemaitre, Rozenn N and Song, Xiaoling and Siscovick, David S and Hotamisligil, G{\"o}khan S} } @article {1254, title = {Measures of adiposity and future risk of ischemic stroke and coronary heart disease in older men and women.}, journal = {Am J Epidemiol}, volume = {173}, year = {2011}, month = {2011 Jan 01}, pages = {10-25}, abstract = {

The relation between measures of general and central adiposity and individual cardiovascular endpoints remains understudied in older adults. This study investigated the association of measures of body size and composition with incident ischemic stroke or coronary heart disease (1989-2007) in 3,754 community-dwelling US adults aged 65-100 years. Standardized anthropometry and bioelectric impedance measurements were obtained at baseline. Body mass index at age 50 years (BMI50) was calculated on the basis of recalled weight. Although only waist/hip ratio was significantly associated with ischemic stroke in quintile analysis in women, dichotomized body mass index (BMI) (>= 30 kg/m{\texttwosuperior}) was the only significant predictor in men. For coronary heart disease, there were significant positive adjusted associations for all adiposity measures, without interaction by sex. This was true for both quintiles and conventional cutpoints for obesity, although BMI-defined overweight (25-29.9 kg/m{\texttwosuperior} was significant at midlife but not at baseline. Strengths of association for extreme quintiles (quintile 5 vs. quintile 1) were broadly comparable, but the highest effect estimates were for waist/hip ratio (hazard ratio = 1.56, 95\% confidence interval: 1.25, 1.94) and BMI50 (hazard ratio = 1.71, 95\% confidence interval: 1.37, 2.14), both of which remained significant after adjustment for mediators, BMI, or each other. Whether these differences translate to better risk prediction will require meta-analytical approaches, as will determination of prognostic cutpoints.

}, keywords = {Adiposity, Age Factors, Aged, Aged, 80 and over, Brain Ischemia, Coronary Disease, Female, Humans, Incidence, Male, Middle Aged, Obesity, Prevalence, Retrospective Studies, Risk Factors, Sex Factors, United States}, issn = {1476-6256}, doi = {10.1093/aje/kwq311}, author = {Kizer, Jorge R and Biggs, Mary L and Ix, Joachim H and Mukamal, Kenneth J and Zieman, Susan J and de Boer, Ian H and Mozaffarian, Dariush and Barzilay, Joshua I and Strotmeyer, Elsa S and Luchsinger, Jos{\'e} A and Elkind, Mitchell S V and Longstreth, W T and Kuller, Lewis H and Siscovick, David S} } @article {1344, title = {Adiposity and incident heart failure in older adults: the cardiovascular health study.}, journal = {Obesity (Silver Spring)}, volume = {20}, year = {2012}, month = {2012 Sep}, pages = {1936-41}, abstract = {

While several studies have reported a positive association between overall adiposity and heart failure (HF) risk, limited and inconsistent data are available on the relation between central adiposity and incident HF in older adults. We sought to examine the association between waist circumference (WC) and incident HF and assess whether sex modifies the relation between WC and HF. Prospective study using data on 4,861 participants of the Cardiovascular Health Study (1989-2007). HF was adjudicated by a committee using information from medical records and medications. We used Cox proportional hazard models to compute hazard ratio (HR). The mean age was 73.0 years for men and 72.3 years for women; 42.5\% were men and 15.3\% were African Americans. WC was positively associated with an increased risk of HF: each standard deviation of WC was associated with a 14\% increased risk of HF (95\% CI: 3\%-26\%) in a multivariable model. There was not a statistically significant sex-by-WC interaction (P = 0.081). BMI was positively associated with incident HF (HR: 1.22 (95\% CI: 1.15-1.29) per standard deviation increase of BMI); however, this association was attenuated and became nonstatistically significant upon additional adjustment for WC (HR: 1.09 (95\% CI: 0.99-1.21)). In conclusion, a higher WC is associated with an increased risk of HF independent of BMI in community-living older men and women.

}, keywords = {Adiposity, Aged, Aging, Body Fat Distribution, Body Mass Index, Female, Heart Failure, Humans, Incidence, Independent Living, Male, Obesity, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Factors, Sex Factors, United States, Waist Circumference}, issn = {1930-739X}, doi = {10.1038/oby.2011.320}, author = {Djouss{\'e}, Luc and Bartz, Traci M and Ix, Joachim H and Zieman, Susan J and Delaney, Joseph A and Mukamal, Kenneth J and Gottdiener, John S and Siscovick, David S and Kizer, Jorge R} } @article {6062, title = {Circulating 25-hydroxyvitamin D is associated with insulin resistance cross-sectionally but not longitudinally in older adults: The Cardiovascular Health Study.}, journal = {Metabolism}, volume = {62}, year = {2013}, month = {2013 Dec}, pages = {1788-94}, abstract = {

BACKGROUND: Despite extensive study, the role of vitamin D in insulin resistance and secretion remains unclear.

OBJECTIVE: To examine the cross-sectional and longitudinal relationships between 25-hydroxyvitamin D (25(OH)D) concentrations and indices of insulin resistance and secretion in older adults.

METHODS AND RESULTS: Among 2134 participants of the Cardiovascular Health Study who were free from cardiovascular disease, we measured serum 25(OH)D concentrations in samples collected in 1992-1993. We examined insulin resistance and secretion using Homeostasis Model Assessment (HOMA) estimates cross-sectionally and among 1469 participants who had repeated HOMA measures four years later (1996-1997). In cross-sectional analysis, each 10 ng/mL increment in 25(OH)D concentration was associated with a 0.09 lower adjusted HOMA-IR [95\% CI (-0.17, -0.02), p=0.01]. However, baseline 25(OH)D concentrations were not associated with change in HOMA-IR over 4 years of follow up (p=0.48). 25(OH)D concentrations were not associated with insulin secretion, as determined by HOMA-β, in either cross-sectional or longitudinal analysis.

CONCLUSIONS: Circulating 25(OH)D concentrations are associated with lower insulin resistance in cross-sectional but not longitudinal analyses. Whether this reflects residual confounding in cross-sectional analyses or the short-term nature of the relationship between vitamin D and insulin sensitivity will require trials with repeated measures of these factors.

}, keywords = {Adiposity, Aged, Anthropometry, Cardiovascular Diseases, Cross-Sectional Studies, Exercise, Female, Humans, Hydroxycholecalciferols, Inflammation, Insulin, Insulin Resistance, Longitudinal Studies, Male, Middle Aged, Obesity, Risk Factors, Surveys and Questionnaires}, issn = {1532-8600}, doi = {10.1016/j.metabol.2013.07.008}, author = {Danziger, John and Biggs, Mary L and Niemi, Matt and Ix, Joachim H and Kizer, Jorge R and Djouss{\'e}, Luc and de Boer, Ian H and Siscovick, David S and Kestenbaum, Bryan and Mukamal, Kenneth J} } @article {5994, title = {Risk factors for type 2 diabetes mellitus preceded by β-cell dysfunction, insulin resistance, or both in older adults: the Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {177}, year = {2013}, month = {2013 Jun 15}, pages = {1418-29}, chapter = {1418}, abstract = {

Insulin resistance (IR) and pancreatic β-cell dysfunction lead to type 2 diabetes mellitus (DM). We tested whether risk factors would differ for DM that was preceded predominantly by IR, β-cell dysfunction, or both among 4,384 older adults (mean age, 72.7 (standard deviation, 5.6) years) in the Cardiovascular Health Study, which was conducted in North Carolina, California, Maryland, and Pennsylvania (1989-2007). When evaluating established risk factors, we found older age, greater adiposity, higher systolic blood pressure, a lower high-density lipoprotein cholesterol level, a higher triglyceride level, and a lower alcohol intake to be independently associated with greater IR but, conversely, with better β-cell function (P < 0.001). The prospective associations between some risk factors and incident DM varied significantly depending on whether DM was preceded predominantly by IR, β-cell dysfunction, or both. For example, obesity and lower high-density lipoprotein cholesterol levels were positively associated with DM preceded predominantly by IR (hazard ratio (HR) = 5.02, 95\% confidence interval (CI): 2.81, 9.00; and HR = 1.97, 95\% CI: 1.32, 2.93, respectively), with a significant association with and an insignificant trend toward a lower risk of DM preceded predominantly by β-cell dysfunction (HR = 0.33, 95\% CI: 0.14, 0.80; and HR = 0.78, 95\% CI: 0.43, 1.39, respectively). In conclusion, among older adults, DM risk factors were differentially associated with DM preceded predominantly by IR or β-cell dysfunction. Biologic and clinical implications of putative subtypes of DM require further investigation.

}, keywords = {Adiposity, Age Factors, Aged, Aged, 80 and over, Aging, Alcohol Drinking, Blood Pressure, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Humans, Incidence, Insulin Resistance, Insulin-Secreting Cells, Lipids, Male, Prospective Studies, Risk Factors, Socioeconomic Factors, United States}, issn = {1476-6256}, doi = {10.1093/aje/kws440}, author = {Imamura, Fumiaki and Mukamal, Kenneth J and Meigs, James B and Luchsinger, Jos{\'e} A and Ix, Joachim H and Siscovick, David S and Mozaffarian, Dariush} }