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Evidence is limited as to whether heritable risk of obesity varies throughout adulthood. Among >34,000 European Americans, aged 18-100 years, from multiple U.S. studies in the Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we examined evidence for heterogeneity in the associations of five established obesity risk variants (near FTO, GNPDA2, MTCH2, TMEM18, and NEGR1) with BMI across four distinct epochs of adulthood: 1) young adulthood (ages 18-25 years), adulthood (ages 26-49 years), middle-age adulthood (ages 50-69 years), and older adulthood (ages [greater than or equal to] 70 years); or 2) by menopausal status in women and stratification by age 50 years in men. Summary-effect estimates from each meta-analysis were compared for heterogeneity across the life epochs. We found heterogeneity in the association of the FTO (rs8050136) variant with BMI across the four adulthood epochs (P = 0.0006), with larger effects in young adults relative to older adults (β [SE] = 1.17 [0.45] vs. 0.09 [0.09] kg/[m.sup.2], respectively, per A allele) and smaller intermediate effects. We found no evidence for heterogeneity in the association of GNPDA2, MTCH2, TMEM18, and NEGR1 with BMI across adulthood. Genetic predisposition to obesity may have greater effects on body weight in young compared with older adulthood for FTO, suggesting changes by age, generation, or secular trends. Future research should compare and contrast our findings with results using longitudinal data., In the past 5 years, genome-wide association studies have identified common genetic loci associated with BMI (in kilograms per meters squared) mainly in European populations (1-4). It has been suggested [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2010.06.016 Byline: Hilary A. Tindle (a), Bennet Omalu (b), Anita Courcoulas (a), Marsha Marcus (a), Jennifer Hammers (c), Lewis H. Kuller (a) Keywords: Bariatric surgery; Public health; Suicides Abstract: Bariatric surgery is recognized as the treatment of choice for class III obesity (body mass index [greater than or equal to]40) and has been increasingly recommended for obese patients. Prior research has suggested an excess of deaths due to suicide following bariatric surgery, but few large long-term follow-up studies exist. We examined postbariatric surgery suicides by time since operation, sex, age, and suicide death rates as compared with US suicide rates. Author Affiliation: (a) University of Pittsburgh, Pittsburgh, Pa (b) University of California, Davis (c) Office of Chief Medical Examiner, The City of New York, New York Article Note: (footnote) Funding: This publication was made possible by a grant from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research (KL2 RR024154-05, Dr. Tindle). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on NCRR is available at http://www.ncrr.nih.gov/. Information on Re-engineering the Clinical Research Enterprise can be obtained from http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp., Conflict of Interest: There are no conflicts of interest to report., Author: All authors had access to the data and had a role in writing the manuscript.

OBJECTIVE--To examine the relationship of parity with diabetes and markers of glucose homeostasis in older women. RESEARCH DESIGN AND METHODS--We used data from the female participants in the Cardiovascular Health [...]

Background: The associations of serum omega-6 (n-6) fatty acids with lipoprotein subclasses at the population level are uncertain. Objective: We aimed to examine associations between major n-6 fatty acids lie, linoleic acid (LA, 18:2n-6) and arachidonic acid (AA, 20:4n-6)] and the lipoprotein subclasses VLDL, LDL, and HDL. Design: We conducted a cross-sectional study in 1098 participants using population-based data from US white, Japanese American, Japanese, and Korean men aged 40-49 y. Serum fatty acids were analyzed by capillary gas-liquid chromatography. Lipoprotein subclasses were measured by nuclear magnetic resonance spectroscopy. Multiple linear regression models as a function of each fatty acid were used after adjustment for age, population, body mass index, pack-years of smoking, alcohol consumption, diabetes, hypertension, and omega-3 (n-3) and trans fatty acids. Results: Serum LA was inversely associated with large VLDL ([beta] = -0.62, P < 0.001), total LDL ([beta] = -22.08, P < 0.001), and small LDL ([beta] = -31.89, P < 0.001) particle concentrations and VLDL size ([beta] = -0.72, P < 0.001). Serum LA was positively associated with large HDL particle concentration ([beta] = 0.21, P < 0.001) and HDL size ([beta] = 0.03, P < 0.001). The patterns of association of AA with large VLDL and large HDL particle concentrations were comparable with those of LA. Conclusions: At the population level, higher serum concentrations of LA were significantly associated with lower concentrations of total LDL particles. Higher serum concentrations of LA and AA were significantly associated with a lower concentration of large VLDL particles and a higher concentration of large HDL particles. These associations were consistent across the population groups. This trial was registered at clinicaltrials.gov as NCT00069797. doi: 10.3945/ajcn.2009.28500.

OBJECTIVE--A loss of skeletal muscle mass is frequently observed in older adults. The aim of the study was to investigate the impact of type 2 diabetes on the changes in [...]

Background: The association of serum polyunsaturated fatty acids (PUFAs) with lipids in different populations is not known. Objective: Our aim was to examine the association of serum n--6 (omega-6) or n--3 (omega-3) PUFAs with triglycerides or HDL-cholesterol concentrations in 261 white, 285 Japanese, and 212 Japanese American men aged 4049 y. Design: We used a population-based cross-sectional study. Of the original sample (n = 926), those taking lipid-lowering medications or who had diabetes (n = 168) were excluded. Serum fatty acids were analyzed by capillary gas-liquid chromatography. Multiple regression models as a function of tertile groups of each PUFA were used. Results: Serum n--6 PUFAs were significantly inversely associated with triglycerides across populations after adjustment for age, body mass index, pack-years of smoking, and ethanol consumption [[beta] = -0.39 (P < 0.001), -0.38 (P < 0.001), and -0.33 (P < 0.001) in whites, Japanese, and Japanese Americans, respectively]. Marine n--3 PUFAs were significantly inversely associated with triglycerides across populations [[beta] = -0.15 (P < 0.001), -0.22 (P < 0.001), and - 0.13 (P < 0.001) in whites, Japanese, and Japanese Americans, respectively]. n--6 PUFAs were significantly positively associated with HDL cholesterol in whites ([beta] = 4.49, P < 0.001) and Japanese ([beta] = 3.73, P < 0.01). Marine n--3 PUFAs were significantly positively associated with HDL cholesterol in Japanese ([beta] = 2.15, P < 0.05), and eicosapentaenoic acid was significantly positively associated with HDL cholesterol in whites ([beta] = 2.68, P < 0.01). Conclusion: Serum n--6 and n--3 PUFAs are inversely associated with triglycerides across populations.

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1532-5415.2008.02056.x Byline: Diane G. Ives (*), Paulraj Samuel ([dagger]), Bruce M. Psaty ([double dagger]s.[parallel]#), Lewis H. Kuller (*) Keywords: death certificates; mortality; vital statistics Abstract: OBJECTIVES: To compare nosologist coding of underlying cause of death according to the death certificate with adjudicated cause of death for subjects aged 65 and older in the Cardiovascular Health Study (CHS). DESIGN: Observational. SETTING: Four communities: Forsyth County, North Carolina (Wake Forest University); Sacramento County, California (University of California at Davis); Washington County, Maryland (Johns Hopkins University); and Pittsburgh, Pennsylvania (University of Pittsburgh). PARTICIPANTS: Men and women aged 65 and older participating in CHS, a longitudinal study of coronary heart disease and stroke, who died through June 2004. MEASUREMENTS: The CHS centrally adjudicated underlying cause of death for 3,194 fatal events from June 1989 to June 2004 using medical records, death certificates, proxy interviews, and autopsies, and results were compared with underlying cause of death assigned by a trained nosologist based on death certificate only. RESULTS: Comparison of 3,194 CHS versus nosologist underlying cause of death revealed moderate agreement except for cancer (kappa=0.91, 95% confidence interval (CI)=0.89-0.93). kappas varied according to category (coronary heart disease, kappa=0.61, 95% CI=0.58-0.64; stroke, kappa=0.59, 95% CI=0.54-0.64; chronic obstructive pulmonary disease, kappa=0.58, 95% CI=0.51-0.65; dementia, kappa=0.40, 95% CI=0.34-0.45; and pneumonia, kappa=0.35, 95% CI=0.29-0.42). Differences between CHS and nosologist coding of dementia were found especially in older ages in the sex and race categories. CHS attributed 340 (10.6%) deaths due to dementia, whereas nosologist coding attributed only 113 (3.5%) to dementia as the underlying cause. CONCLUSION: Studies that use only death certificates to determine cause of death may result in misclassification and potential bias. Changing trends in cause-specific mortality in older individuals may be a function of classification process rather than incidence and case fatality. Author Affiliation: (*)Department of Epidemiology, Center for Aging and Population Health ([dagger])Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania ([double dagger])Departments of Medicine (s.)Epidemiology ([parallel])Health Sciences, University of Washington, Seattle, Washington; and (#)Center for Health Sciences, Group Health, Seattle, Washington. Article note: Address correspondence to Diane G. Ives, Department of Epidemiology, Center for Aging and Population Health, 130 North Bellefield Avenue Rm 541, University of Pittsburgh, Pittsburgh, PA 15213. E-mail: ivesd@edc.pitt.edu

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1532-5415.2008.01856.x Byline: Caterina Rosano (*), Anne B. Newman (*), Ronit Katz ([dagger]), Calvin H. Hirsch ([double dagger]), Lewis H. Kuller (*) Keywords: digit symbol substitution test score; gait speed; mortality and disability Abstract: OBJECTIVES: To determine whether, in well-functioning older adults, a lower score on the Digit Symbol Substitution Test (DSST) and slower gait are associated with greater risk of mortality and of developing incident disability independent of other risk factors, including brain structural abnormalities (white matter hyperintensities, brain infarcts, ventricular enlargement) and whether the combination of varying levels of DSST score and gait speed are associated with a greater risk of mortality and disability than low DSST or slow gait alone. DESIGN: Observational cohort study. SETTING: Community. PARTICIPANTS: Three thousand one hundred fifty-six (43% men, 29% black, mean age 70.4) participants in the Cardiovascular Health Study (CHS), free from stroke and physical disability and with a modified Mini-Mental State Examination (3MS) score of 80 or higher. MEASUREMENTS: Total mortality and incident disability (self-report of any difficulty performing one or more of the six activities of daily living) ascertained over a median follow-up time of 8.4 years. RESULTS: By the end of follow-up, 704 participants had died and 1,096 had incident disability. In Cox proportional hazards models adjusted for age, sex, race, education, cardiovascular disease, and brain magnetic resonance imaging abnormalities, lower DSST score and slower gait remained significantly associated with greater risk of mortality and of incident disability. Mortality rates were higher in those who had both low DSST score ( CONCLUSION: In well-functioning older adults, low DSST score and slow gait, alone or in combination, could be risk factors for mortality and for developing disability, independent of other risk factors, including measures of brain integrity. Author Affiliation: (*)Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennylvania ([dagger])Department of Biostatistics, Collaborative Health Studies Coordinating Center, University of Washington, Seattle, Washington ([double dagger])Department of Medicine and Public Health Sciences, School of Medicine, University of California Davis Medical Center, Sacramento, California. Article note: Address correspondence to Caterina Rosano, MD, MPH, 130 North Bellefield Avenue, Room 507, Pittsburgh, PA 15213. E-mail: rosanoc@edc.pitt.edu

Background: Although obesity is strongly associated with diabetes, the greater prevalence of diabetes in persons of African ancestry than in those of other ancestries cannot be explained simply by differences in total or central adiposity. Objective: We examined whether skeletal muscle composition is associated with diabetes in 1249 men of African ancestry aged [greater than or equal to] 40 y. Design: Anthropometry and fasting serum glucose were measured, and lower-leg skeletal muscle composition was assessed with peripheral quantitative computerized tomography (pQCT). Results: The prevalence of diabetes in this population was high (21%). We observed an age-associated adipose tissue remodeling in skeletal muscle and greater intermuscular (IMAT) and lesser subcutaneous (SAT) adipose tissue area with advancing age (P < 0.0001). Multivariate stepwise logistic regression identified more IMAT and less SAT to be significantly associated with a greater prevalence of diabetes. Even among normal-weight men [body mass index (BMI; in kg/[m.sup.2]) < 25], diabetic men had significantly (P = 0.01) more IMAT than did those without diabetes. Greater IMAT was also associated with a greater prevalence of hyperglycemia in men with a family history of diabetes than in those without such history (P for interaction = 0.02). Conclusions: These findings underscore the independent associations of subcutaneous and intermuscular fat among men of African ancestry, an effect that may be modified by a family history of diabetes. Further studies are needed to identify the genetic and physiologic mechanisms that influence the distribution and remodeling of adipose tissue in skeletal muscle with aging.'

OBJECTIVE--Mitochondrial uncoupling proteins (UCPs) are involved in body weight regulation and glucose homeostasis. Genetic variants in the UCP2-UCP3 gene cluster, located on chromosome 11q13, may play a significant role in the development of type 2 diabetes. RESEARCH DESIGN AND METHODS--We conducted a comprehensive assessment of common single nucleotide polymorphisms (SNPs) at the 70-kb UCP2-UCP3 gene cluster in relation to type 2 diabetes risk in a prospective, case-control study nested in the Women's Health Initiative Observational Study, an ethnically diverse cohort of postmenopausal women including Caucasian, African, Hispanic, and Asian American subjects. We genotyped 14 tag SNPs in 1,584 incident type 2 diabetes case and 2,198 control subjects matched by age, ethnicity, clinical center, time of blood draw, and length of follow-up. RESULTS--We identified a haplotype set (rs591758-rs668514-rs647126-rs1800006, spanning the UCP2-UCP3 intergenic and UCP3 regions) as significantly associated with greater type 2 diabetes risk (nominal P = 0.0011, permutation P = 0.046) in Caucasian women, especially among overweight Caucasians (BMI >25 kg/[m.sup.2]) (nominal P = 0.0006, permutation P = 0.032). Compared with the most common haplotype (h1010 as the referent), haplotype h0001 (19.5% in control subjects) had odds ratios of 2.0 (95% CI 1.13-3.37) in Caucasians and 3.8 (1.44-9.93) in Caucasian overweight women. Similar haplotype-type 2 diabetes association was also observed among Hispanic women who were overweight. CONCLUSIONS--These findings suggest a role of UCP2-UCP3 gene cluster haplotypes in diabetes; in particular, the effects of the high-risk haplotypes were more apparent in overweight Caucasian women. These data warrant further confirmation in future prospective and experimental studies., Uncoupling proteins (UCPs) are members of the super family of anion carrier proteins located in the inner membrane of mitochondria (1). Among the five UCP homologues, UCP1-UCP5 (2), UCP2 and [...]

OBJECTIVE--The homeostasis model assessment (HOMA), based on plasma levels of fasting glucose and insulin, has been widely validated and applied for quantifying insulin resistance and β-cell function. However, prospective data [...]

OBJECTIVE--It has been shown that adults with either long-standing type 1 or type 2 diabetes had lower skeletal muscle strength than nondiabetic adults in cross-sectional studies. The aim of the [...]

Diabetes is an emblematic example of a heterogeneous disease. Systemic inflammation has emerged as a prominent factor in the type 2 diabetes pathoetiology, but it remains ill-defined in type 1 diabetes. There is a wide spectrum of associations between inflammatory responses and diabetic syndromes. At one end of this spectrum, there is type 1 diabetes for which there is convincing evidence that chronic inflammation of pancreatic islets is a central aspect of disease pathogenesis. At the opposite end, is type 2 diabetes that is clearly associated with systemic inflammation, which could be either the cause or simply mark the underlying pathology. Accumulating evidence has substantiated that a subgroup of adult patients clinically diagnosed with type 2 diabetes exhibit autoantibody responses to islet autoantigens. The presence of these immunologic abnormalities is associated with a severe insulin secretory defect and the absence of signs of systemic inflammation as documented by plasma C-reactive protein and fibrinogen levels that are comparable with those of control populations. Islet autoantibody evaluation should be part of the diagnostic assessment for clinically diagnosed type 2 diabetes not only because it might predict the rate of progression to insulin requirement in adult populations but also to identify a pathogenically distinct disease phenotype characterized by the absence of systemic inflammation and its related disorders. A more appropriate characterization of this subgroup of clinically diagnosed type 2 diabetes, diabetes of autoimmune pathogenesis, will promote future research into the etiology, natural history, and treatment., Diabetes is a heterogeneous dysregulation of carbohydrate metabolism, and there is no doubt that we are in the midst of an epidemic of this disease. The pathogenic equation for diabetes [...]

OBJECTIVE--We evaluated whether psychosocial factors that are related to cardiovascular disease and type 2 diabetes predict prospectively the risk for the metabolic syndrome using the different clinical criteria available for [...]

OBJECTIVE--There is increased stiffness of the large central arteries in type 2 diabetic patients, and obesity is a risk factor. However, the effect of intentional weight loss on arterial stiffness [...]

OBJECTIVE--To examine the long-term association of metabolic syndrome with mortality among those at high risk for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS--A total of 10,950 Multiple Risk Factor Intervention [...]

A study assessing the incidence of pneumonia amongst community-dwelling elderly persons is presented. The study also examines the risk factors and the mortality rates of pneumonia. The correlation of cardiovascular diseases with the risk factors for pneumonia is also examined.

A study using the medical history of elderly patients with coronary artery diseases, peripheral arterial diseases and noninvasive markers of cardiovascular disease for forecasting the onset of dementia and Alzheimer's disease is presented.

A study on subclinical brain magnetic resonance imaging abnormalities in active elderly persons indicates greater possibility of such persons developing physical disabilities and deteriorating motor functions.

A study on the elderly persons with higher levels of coronary artery calcification is presented. It is observed that these patients are more likely to show greater level of severity in magnetic resonance imaging abnormalities. These patients are also more prone to dementia.

Background: Weight loss and increased physical exercise reduce the risk for diabetes in people with impaired glucose tolerance. Randomized trial evidence on the effect of these interventions on people without impaired glucose tolerance is lacking. Objective: To examine the influence of a comprehensive intervention program on the risk for developing diabetes in men without impaired glucose tolerance and in a post hoc subgroup analysis by baseline cigarette smoking status. Design: Randomized, controlled trial. Setting: 22 clinical centers for the Multiple Risk Factor Intervention Trial (MRFIT). Participants: 12 866 men age 35 to 57 years at risk for cardiovascular disease were randomly assigned to either a special intervention or usual care group and followed for 6 to 7 years; this report focuses on 11 827 men without diabetes or impaired glucose tolerance at entry for whom follow-up glucose measurements were available. Measurements: Cardiovascular disease risk factors, fasting blood glucose levels, and diabetes medication history were assessed before randomization and annually. Intervention: Men in the special intervention group were counseled to change diet (reduce saturated fat, cholesterol, and calorie intake), to stop smoking, and to increase physical activity. Blood pressure was treated more intensively in the special intervention group than in the usual care group. Results: 11.5% of the special intervention group and 10.8% of the usual care group developed diabetes over 6 years of follow-up (hazard ratio, 1.08 [95% CI, 0.96 to 1.20]). The special intervention-usual care hazard ratio for diabetes was 1.26 (CI, 1.10 to 1.45) among smokers (63%) and 0.82 (CI, 0.68 to 0.98) among nonsmokers (37%). These estimates differed significantly (P = 0.0003). Weight gain after smoking cessation and the use of antihypertensive drugs may have counterbalanced the beneficial effect of the lifestyle intervention for the special intervention group smokers, while the lifestyle intervention was beneficial among nonsmokers. Limitations: Principal findings are based on a post hoc sub-group analysis. Conclusions: In nonsmokers, an intervention program that included nutrition counseling to produce reductions in weight, serum cholesterol, and (along with antihypertensive medication) blood pressure reduced the risk for diabetes.

The relationship between baseline measures of serum lipoproteins and incident hypertension in older adults is examined. Results indicated that the older adults with abnormal serum lipoproteins were at an increased risk of developing hypertension.

Markers of humoral islet cell autoimmunity, such as autoantibodies (AAs) against the 65-kDa isoform of GAD (GAD65), serve as determinants of risk for autoimmune diabetes. Despite the high prevalence of diabetes in U.S. racial and ethnic minority adult populations, little is known concerning the prevalence of GAD65 AA in these groups. We estimated the prevalence of GAD65 AA in 1,064 diabetic and 1,036 nondiabetic participants who were 40-90 years of age from the Third National Health and Nutrition Examination Survey (NHANES III), which provides a representative ethnic sample of the U.S. diabetic population. The prevalence of GAD65 AA was higher in diabetic participants compared with nondiabetic participants in non-Hispanic whites (n -920; 6.3% vs. 2.0%; P = 0.001) and non-Hispanic blacks (n = 534; 3.7% vs. 1.3%; P = 0.08) but not in Mexican Americans (n = 646; 1.2% vs. 2.6%; P = 0.18). Among diabetic non-Hispanic whites and non-Hispanic blacks, being GAD65 AA positive was associated with lower BMI and C-peptide (P < 0.05). These results may reflect the outcome of an autoimmune process leading to β-cell destruction/dysfunction in non-Hispanic white and non-Hispanic black adult diabetic patients as it occurs in a similar manner in type 1 diabetes. Among diabetic Mexican Americans, the lower prevalence of GAD65 AA suggests a lower frequency of autoimmune-related diabetes., The prevalence of diabetes (diagnosed and undiagnosed) in adults ≥ 20 years of age in the U.S. was estimated to be 7.8% in the period between 1998 and 1994 based [...]

OBJECTIVE--Moderate weight loss is recommended for overweight and obese patients with type 2 diabetes, and conjunctive use of weight loss medication has been advocated. The current study examined weight loss-dependent [...]

OBJECTIVE--The aim of this study was to examine the role of comorbid conditions and body composition in the association between diabetes and subclinical functional limitation, an indication of early functional [...]

OBJECTIVE--To evaluate racial differences and factors associated with worse glycemic control in well-functioning older individuals with type 2 diabetes. Our hypothesis was that glycemic control would be worse among black [...]

Background: Little is known about the relation of the dietary intake of n-3 polyunsaturated fatty acids, ie, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from fatty fish and [alpha]-linolenic acid from vegetable oils, with ischemic heart disease among older adults. Objective: We investigated the associations of plasma phospholipid concentrations of DHA, EPA, and [alpha]-linolenic acid as biomarkers of intake with the risk of incident fatal ischemic heart disease and incident nonfatal myocardial infarction in older adults. Design: We conducted a case-control study nested in the Cardiovascular Health Study, a cohort study of adults aged [greater than or equal to] 65 y. Cases experienced incident fatal myocardial infarction and other ischemic heart disease death (n = 54) and incident nonfatal myocardial infarction (n = 125). Matched controls were randomly selected (n = 179). We measured plasma phospholipid concentrations of n-3 polyunsaturated fatty acids in blood samples drawn [approximately equal to] 2 y before the event. Results: A higher concentration of combined DHA and EPA was associated with a lower risk of fatal ischemic heart disease, and a higher concentration of [alpha]-linolenic acid with a tendency to lower risk, after adjustment for risk factors [odds ratio: 0.32 (95% CI: 0.13, 0.78; P = 0.01) and 0.52 (0.24, 1.15; P = 0.1), respectively]. In contrast, n-3 polyunsaturated fatty acids were not associated with nonfatal myocardial infarction. Conclusions: Higher combined dietary intake of DHA and EPA, and possibly [alpha]-linolenic acid, may lower the risk of fatal ischemic heart disease in older adults. The association of n-3 polyunsaturated fatty acids with fatal ischemic heart disease, but not with nonfatal myocardial infarction, is consistent with possible antiarrhythmic effects of these fatty acids. KEY WORDS Fatty acids, n-3 fatty acids, phospholipids, ischemic heart disease, myocardial infarction, nested case-control studies, docosahexaenoic acid, eicosapentaenoic acid, older adults, Cardiovascular Health Study