Body-mass index and mortality risk in U.S. blacks compared to whites.

OBJECTIVE: To compare body-mass index (BMI)-related mortality risk in U.S. Blacks vs. Whites as the relationship appears to differ across race/ethnicity groups. METHODS: Cross-sectional surveys of nationally representative samples of 11,934 Blacks and 59,741 Whites aged 35-75 in the National Health Interview Survey from 1997 to 2002 with no history of cardiovascular disease (CVD) or cancer were pooled. Mortality follow-up was available through 2006. BMI was calculated from self-reported height and weight. We used adjusted Cox regression analysis to adjust for potential confounders. RESULTS: Over 9 years of follow-up, there were 4303 deaths (1205 among never smokers). Age-adjusted mortality rates were higher in Blacks compared to Whites at BMI < 25 kg/m2 and showed no increase at higher levels of BMI. In men, adjusted hazard ratios for all-cause death rose in a similar fashion across upper BMI quintiles in Blacks and Whites; in women, however, BMI was positively associated with mortality risk in Whites, but inversely associated in Blacks (P interaction = 0.01). Racial disparities were amplified in subsidiary analyses that introduced a 12-month lag for mortality or focused on CVD mortality. CONCLUSIONS: The relationship of elevated BMI to mortality appeared weaker in US Blacks than in Whites, especially among women.

Body-Mass Index and All-Cause Mortality in US Adults With and Without Diabetes.

BACKGROUND: Previous studies found normal weight compared to overweight/obese adults with type 2 diabetes had a higher mortality risk, and body-mass index (BMI)-mortality studies do not typically account for baseline diabetes status. OBJECTIVE: To determine if diabetes influences the BMI-mortality relationship. DESIGN: Using a prospective study design, we analyzed data from a nationally representative sample of US adults participating in the National Health Interview Survey from 1997 to 2002, and followed for mortality through 2006. PARTICIPANTS: Excluding those with heart disease or cancer, our final analytic sample included 74,710 (34,805 never smoker) adults. MAIN MEASURES: BMI was calculated from self-reported height and weight. Diabetes status was based on self-reported diagnosis from a health professional. We used direct age standardization to calculate all-cause mortality rates and adjusted Cox models for all-cause mortality hazard ratios by BMI quintile; this was done separately for adults with diabetes and without diabetes. KEY RESULTS: Among never smokers, mean age was 50.1 years and 43 % were men. Mean BMI was 27.4 kg/m(2), 26 % were obese, and 2,035 (5 %) reported diagnosed diabetes. After 9 years, there were 4,355 deaths (754 of 4,740 with diabetes; 3,601 of 69,970 without) among 74,710 participants, and 1,238 (247 of 2,035 with diabetes; 991 of 32,770 without) among 34,805 never smokers. We observed a qualitative interaction with diabetes on the BMI-mortality relationship (p = 0.002). Death rates were substantially higher among participants with diabetes compared to those without diabetes across all BMI quintiles. However, death rates in participants with diabetes fell with increasing BMI quintile, while rates followed a J-shaped curve among those without diabetes. In adjusted Cox models, BMI was positively associated with mortality in adults without diabetes, but inversely associated with mortality among participants with diabetes. CONCLUSIONS: Mortality increased with increasing BMI in adults without diabetes, but decreased with increasing BMI among their counterparts with diabetes. Future studies need to be better designed to answer the question of whether normal weight adults with diabetes have a higher risk of mortality, by minimizing the possibility of reverse causation. Future studies should also account for prevalent diabetes in all investigations of the BMI-mortality relationship.

The association of plasma lactate with incident cardiovascular outcomes: the ARIC Study.

We examined the association of plasma lactate at rest, a marker of oxidative capacity, with incident cardiovascular outcomes in 10,006 participants in the Atherosclerosis Risk in Communities (ARIC) Study visit 4 (1996-1998). We used Cox proportional-hazards models to estimate hazard ratios of incident coronary heart disease, stroke, heart failure, and all-cause mortality by quartiles of plasma lactate (Q1, ≤5.3 mg/dL; Q2, 5.4-6.6; Q3, 6.7-8.6; and Q4 ≥8.7). During a median follow-up time of 10.7 years, there were 1,105 coronary heart disease cases, 379 stroke cases, 820 heart failure cases, and 1,408 deaths. A significant graded relation between lactate level and cardiovascular events was observed in the demographically adjusted model (all P for trend < 0.001). After further adjustment for traditional and other potential confounders, the association remained significant for heart failure (Q4 vs. Q1: hazard ratio (HR) = 1.35, 95% confidence interval (CI): 1.07, 1.71) and all-cause mortality (HR = 1.27, 95% CI: 1.07, 1.51) (P for trend < 0.02 for these outcomes) but not for coronary heart disease (HR = 1.02, 95% CI: 0.84, 1.24) and stroke (HR = 1.26, 95% CI: 0.91, 1.75). The results for heart failure were robust across multiple subgroups, after further adjustment for N-terminal pro-B-type natriuretic peptide and after exclusion of participants with incident heart failure within 3 years. The independent associations of plasma lactate with heart failure and all-cause mortality suggest an important role for low resting oxidative capacity.

Quadriceps strength, quadriceps power, and gait speed in older U.S. adults with diabetes mellitus: results from the National Health and Nutrition Examination Survey, 1999-2002.

OBJECTIVES: To examine the independent association between diabetes mellitus (and its duration and severity) and quadriceps strength, quadriceps power, and gait speed in a national population of older adults. DESIGN: Cross-sectional nationally representative survey. SETTING: United States. PARTICIPANTS: Two thousand five hundred seventy-three adults aged 50 and older in the National Health and Nutrition Examination Survey 1999-2002 who had assessment of quadriceps strength. METHODS: Diabetes mellitus was ascertained according to questionnaire. Measurement of isokinetic knee extensor (quadriceps) strength was performed at 60º/s. Gait speed was assessed using a 20-foot walk test. Multiple linear regression analyses were used to assess the association between diabetes mellitus status and outcomes, adjusting for potential confounders or mediators. RESULTS: Older U.S. adults with diabetes mellitus had significantly slower gait speed (0.96 ± 0.02 m/s) than those without (1.08 ± 0.01 m/s; P < .001). After adjusting for demographic characteristics, weight, and height, diabetes mellitus was also associated with significantly lower quadriceps strength (-4.6 ± 1.9 Nm; P = .02) and power (-4.9 ± 2.0 W; P = .02) and slower gait speed (-0.05 ± 0.02 m/s; P = .002). Associations remained significant after adjusting for physical activity and C-reactive protein. After accounting for comorbidities (cardiovascular disease, peripheral neuropathy, amputation, cancer, arthritis, fracture, chronic obstructive pulmonary disease), diabetes mellitus was independently associated only with gait speed (-0.04 ± 0.02 m/s; P = .02). Diabetes mellitus duration in men and women was negatively associated with age-adjusted quadriceps strength (-5.7 and -3.5 Nm/decade of diabetes mellitus, respectively) and power (-6.1 and -3.8 W/decade of diabetes mellitus, respectively) (all P ≤ .001, no significant interactions according to sex). Glycosylated hemoglobin was not associated with outcomes after accounting for body weight. CONCLUSION: Older U.S. adults with diabetes mellitus have lower quadriceps strength and quadriceps power that is related to the presence of comorbidities and walk slower than those without diabetes mellitus. Future studies should investigate the relationship between hyperglycemia and subsequent declines in leg muscle function.

Elevated ALT and GGT predict all-cause mortality and hepatocellular carcinoma in Taiwanese male: a case-cohort study.

PURPOSE: Evidence indicates a positive association between liver enzymes and the risk of death in Western countries; however, the evidence in Asian populations is scarce. We investigated the association between liver enzymes and total, cardiovascular (CVD), cancer and hepatocellular carcinoma (HCC) mortality in a cohort of Taiwanese male free of cancer at baseline. METHODS: From 1996 to 2003, 54,751 Taiwanese male aged 40-80 years without cancer completed a health screening and were followed through 2005 (5.8 ± 2.5 years of follow-up). A random cohort of 3,961 male was selected to compare to 1,864 male who died. We used Cox proportional hazards regression models to assess the risk of all-cause, cardiovascular and cancer mortality associated with alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT). RESULTS: In this population, higher levels of ALT, AST and GGT were significantly associated with all-cause mortality [hazard ratio (HR) 1.2, 1.8 and 1.6 for ALT, AST and GGT, respectively; all p < 0.05], cancer mortality (HR 1.8-2.8) and HCC mortality (HR 5.5-36.1). GGT was significantly associated with CVD mortality (HR 1.2). CONCLUSIONS: In Taiwanese male free of cancer at baseline, elevations of ALT, AST and GGT were associated with future risk of all-cause death, all cancer and HCC mortality, independent of conventional risk factors, and could be used to identify male who would benefit from HCC screening.

Body mass index and colon cancer screening: a systematic review and meta-analysis.

BACKGROUND: Obesity is associated with increased colon cancer mortality and lower rates of mammography and Pap testing. METHODS: We conducted a systematic review to determine whether obesity is associated with lower rates of colon cancer screening. We searched the PubMed, CINAHL, and Cochrane Library databases. Two investigators reviewed citations, abstracts, and articles independently. Two investigators abstracted study information sequentially and evaluated quality independently using standardized forms. We included all studies in our qualitative syntheses. We used random effects meta-analyses to combine those studies providing screening results by the following body mass index (BMI) categories: Normal, 18.5-24.9 kg/m(2) (reference); overweight, 25-29.9 kg/m(2); class I obesity, 30-34.9 kg/m(2); class II obesity, 35-39.9 kg/m(2); and class III obesity, ≥ 40 kg/m(2). RESULTS: Of 5,543 citations, we included 23 articles. Almost all studies were cross-sectional and ascertained BMI and screening through self-report. BMI was not associated with colon cancer screening overall. The subgroup of obese white women reported lower rates of colon cancer screening compared with those with a normal BMI with combined ORs (95% CI) of 0.87 (0.82-0.93), 0.80 (0.65-0.99), and 0.73 (0.58-0.94) for class I, II, and III obesity, respectively. Results were similar among white men with class II obesity. CONCLUSIONS: Overall, BMI was not associated with colon cancer screening. Obese white men and women may be less likely to undergo colon cancer screening compared with those with a normal BMI. IMPACT: Further investigation of this disparity may reduce the risk of obesity-related colon cancer death.

Primary prevention of type 2 diabetes: integrative public health and primary care opportunities, challenges and strategies.

Type 2 diabetes imposes a large and growing burden on the public's health. This burden, combined with the growing evidence for primary prevention from randomized controlled trials of structured lifestyle programs leads to recommendations to include caloric reduction, increased physical activity and specific assistance to patients in problem solving to achieve modest weight loss as well as pharmacotherapy. These recommendations demand exploration of new ways to implement such primary prevention strategies through more integrated community organization, medical practice and policy. The US experience with control of tobacco use and high blood pressure offers valuable lessons for policy, such as taxation on products, and for practice in a variety of settings, such as coordination of referrals for lifestyle supports. We acknowledge also some notable exceptions to their generalizability. This paper presents possible actions proposed by an expert panel, summarized in Table 1 as recommendations for immediate action, strategic action and research. The collaboration of primary care and public health systems will be required to make many of these recommendations a reality. This paper also provides information on the progress made in recent years by the Division of Diabetes Translation at the US Centers for Disease Control and Prevention (CDC) to implement or facilitate such integration of primary care and public health for primary prevention.

Glycated hemoglobin and cancer incidence and mortality in the Atherosclerosis in Communities (ARIC) Study, 1990-2006.

Diabetes is a risk factor for many cancers; chronic hyperglycemia is hypothesized to be, in part, explanatory. We evaluated the association between glycated hemoglobin, a time-integrated glycemia measure, and cancer incidence and mortality in nondiabetic and diabetic men and women. We conducted a prospective study of 12,792 cancer-free participants attending the second visit (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) Study. We measured glycated hemoglobin in whole-blood samples using HPLC. Incident cancers were ascertained from registries and hospital records through 2006. We estimated multivariable-adjusted hazard ratios (HR) of cancer incidence and mortality for nondiabetic participants with values ≥ 5.7% (elevated), nondiabetic participants with <5.0% (low) and diabetic participants all compared with nondiabetic participants with 5.0-5.6% (normal). We ascertained 2,349 incident cancer cases and 887 cancer deaths. Compared with nondiabetic women with normal glycated hemoglobin, nondiabetic women with elevated values had an increased risk of cancer incidence (HR:1.24; 95% CI:1.07,1.44) and mortality (HR:1.58; 95% CI:1.23,2.05) as did diabetic women (incidence, HR:1.30; 95% CI:1.06,1.60, mortality, HR:1.96; 95% CI:1.40,2.76). Nondiabetic women with low values also had increased risk. Diabetic women with good glycemic control (<7.0%) had a lower cancer risk than those with higher values. Glycated hemoglobin in nondiabetic and diabetic men, and diabetes were not statistically significantly associated with total cancer risk. Our findings support the hypothesis that chronic hyperglycemia, even in the nondiabetic range, increases cancer risk in women. Maintaining normal glycated hemoglobin overall, and good glycemic control among diabetic adults, may reduce the burden of cancer, especially in women.

A prospective study of the associations between treated diabetes and cancer outcomes.

OBJECTIVE: To quantify the association of treated diabetes with cancer incidence and cancer mortality as well as cancer case fatality and all-cause mortality in adults who subsequently develop cancer and to calculate attributable fractions due to diabetes on various cancer outcomes. RESEARCH DESIGN AND METHODS: Prospective data on 599 diabetic and 17,681 nondiabetic adults from the CLUE II (Give Us a Clue to Cancer and Heart Disease) cohort in Washington County, Maryland, were analyzed. Diabetes was defined by self-reported use of diabetes medications at baseline. Cancer incidence was ascertained using county and state cancer registries. Mortality data were obtained from death certificates. RESULTS: From 1989 to 2006, 116 diabetic and 2,365 nondiabetic adults developed cancer, corresponding to age-adjusted incidence of 13.25 and 10.58 per 1,000 person-years, respectively. Adjusting for age, sex, education, BMI, smoking, hypertension treatment, and high cholesterol treatment using Cox proportional hazards regression, diabetes was associated with a higher risk of incident cancer (hazard ratio 1.22 [95% CI 0.98-1.53]) and cancer mortality (1.36 [1.02-1.81]). In individuals who developed cancer, adults with diabetes had a higher risk of cancer case fatality (1.34 [1.002-1.79]) and all-cause mortality (1.61 [1.29-2.01]). For colorectal, breast, and prostate cancers, the attributable fractions resulting from diabetes were larger for cancer fatality and mortality than cancer incidence. CONCLUSIONS: In this prospective cohort, diabetes appears to exert a greater influence downstream on the risk of mortality in people with cancer than on upstream risk of incident cancer.

Non-alcoholic fatty liver disease and mortality among US adults: prospective cohort study.

OBJECTIVE: To evaluate the association between non-alcoholic fatty liver disease and all cause and cause specific mortality in a representative sample of the US general population. DESIGN: Prospective cohort study. SETTING: US Third National Health and Nutrition Examination Survey (NHANES III: 1988-94) with follow-up of mortality to 2006. PARTICIPANTS: 11,371 adults aged 20-74 participating in the Third National Health and Nutrition Examination Survey, with assessment of hepatic steatosis. MAIN OUTCOME MEASURE: Mortality from all causes, cardiovascular disease, cancer, and liver disease (up to 18 years of follow-up). RESULTS: The prevalence of non-alcoholic fatty liver disease with and without increased levels of liver enzymes in the population was 3.1% and 16.4%, respectively. Compared with participants without steatosis, those with non-alcoholic fatty liver disease but normal liver enzyme levels had multivariate adjusted hazard ratios for deaths from all causes of 0.92 (95% confidence interval 0.78 to 1.09), from cardiovascular disease of 0.86 (0.67 to 1.12), from cancer of 0.92 (0.67 to 1.27), and from liver disease of 0.64 (0.12 to 3.59). Compared with participants without steatosis, those with non-alcoholic fatty liver disease and increased liver enzyme levels had adjusted hazard ratios for deaths from all causes of 0.80 (0.52 to 1.22), from cardiovascular disease of 0.59 (0.29 to 1.20), from cancer of 0.53 (0.26 to 1.10), and from liver disease of 1.17 (0.15 to 8.93). CONCLUSIONS: Non-alcoholic fatty liver disease was not associated with an increased risk of death from all causes, cardiovascular disease, cancer, or liver disease.

Glycated hemoglobin and the risk of kidney disease and retinopathy in adults with and without diabetes.

OBJECTIVE: Glycated hemoglobin was recently recommended for use as a diagnostic test for diabetes. We examined the association between 2010 American Diabetes Association diagnostic cut points for glycated hemoglobin and microvascular outcomes (chronic kidney disease, end-stage renal disease [ESRD], and retinopathy) and formally tested for the presence of risk thresholds in the relationships of glycated hemoglobin with these outcomes. RESEARCH DESIGN AND METHODS: Prospective cohort and cross-sectional analyses of 11,357 participants (773 with a history of diagnosed diabetes) from the Atherosclerosis Risk in Communities (ARIC) Study. RESULTS: During a median of 14 years of follow-up of individuals without diagnosed diabetes at baseline, clinical categories of glycated hemoglobin were associated with risk of chronic kidney disease, with adjusted hazard ratios (HRs) of 1.12 (0.94-1.34) and 1.39 (1.04-1.85) for glycated hemoglobin 5.7-6.4% and ≥6.5%, respectively, as compared with <5.7% (P trend = 0.002). The corresponding HRs for ESRD were 1.51 (0.82-2.76) and 1.98 (0.83-4.73), respectively (P trend = 0.047). In the absence of diagnosed diabetes, glycated hemoglobin was cross sectionally associated with the presence of moderate/severe retinopathy, with adjusted odds ratios of 1.42 (0.69-2.92) and 2.91 (1.19-7.11) for glycated hemoglobin 5.7-<6.5% and ≥6.5%, respectively, compared with <5.7% (P trend = 0.011). Risk associations were stronger among individuals with a history of diabetes. We did not observe significant thresholds in the associations of glycated hemoglobin with kidney disease risk or retinopathy. CONCLUSIONS: These data from a community-based, biracial population support the use of new 2010 American Diabetes Association glycated hemoglobin cut points for the diagnosis of diabetes.

Diabetes mellitus and breast cancer outcomes: a systematic review and meta-analysis.

PURPOSE: The goal of this study was to perform a systematic review and meta-analysis to examine the effect of pre-existing diabetes on breast cancer-related outcomes. METHODS: We searched EMBASE and MEDLINE databases from inception through July 1, 2009, using search terms related to diabetes mellitus, cancer, and prognostic outcome. Studies were included if they reported a prognostic outcome by diabetes status, evaluated a cancer population, and contained original data published in the English language. We performed a meta-analysis of pre-existing diabetes and its effect on all-cause mortality in patients with breast cancer and qualitatively summarized other prognostic outcomes. RESULTS: Of 8,828 titles identified, eight articles met inclusion/exclusion criteria and described outcomes in patients with breast cancer and diabetes. Pre-existing diabetes was significantly associated with all-cause mortality in six of seven studies. In a meta-analysis, patients with breast cancer and diabetes had a significantly higher all-cause mortality risk (pooled hazard ratio [HR], 1.49; 95% CI, 1.35 to 1.65) compared with their nondiabetic counterparts. Three of four studies found pre-existing diabetes to be associated with more advanced stage at presentation. Diabetes was also associated with altered regimens for breast cancer treatment and increased toxicity from chemotherapy. CONCLUSION: Compared with their nondiabetic counterparts, patients with breast cancer and pre-existing diabetes have a greater risk of death and tend to present at later stages and receive altered treatment regimens. Studies are needed to investigate pathophysiologic interactions between diabetes and breast cancer and determine whether improvements in diabetes care can reduce mortality in patients with breast cancer.

Associations of obesity measures with subtypes of ischemic stroke in the ARIC Study.

BACKGROUND: Associations between obesity and lacunar, nonlacunar thrombotic, and cardioembolic stroke are not firmly established. METHODS: Body mass index (BMI), waist circumference, and waist-to-hip ratio (WHR) were recorded at baseline between 1987 and 1989 in the Atherosclerosis Risk in Communities (ARIC) Study for 13 549 black and white adults who were aged from 45 to 64 years and had no history of cardiovascular disease or cancer. The incidence of ischemic stroke subtypes was ascertained from surveillance of hospital records over a median follow-up of 16.9 years. Cox proportional hazards regression analyses adjusted for age, sex, race, education, smoking status and cigarette years, usual ethanol intake, and leisure time sports index were used to estimate hazard ratios (HRs). RESULTS: The ARIC sample at baseline was 43.8% men and 27.3% blacks; mean age was 53.9 years. Mean BMI, waist circumference, and WHR were 27.7 kg/m(2), 96.8 cm, and 0.92, respectively. The associations of lacunar (n = 138), nonlacunar (n = 338), and cardioembolic (n = 122) ischemic stroke incidence with obesity measures were all generally positive and linear. The HRs for the highest versus lowest quintile of the 3 obesity measures ranged from 1.43-2.21 for lacunar stroke, 1.90-2.16 for nonlacunar stroke, and 2.37-2.91 for cardioembolic stroke. CONCLUSIONS: Although different pathophysiological mechanisms may exist, the incidences of lacunar, nonlacunar, and cardioembolic stroke were all significantly positively associated with the degree of obesity, regardless of the measure used.

Neighborhood and weight-related health behaviors in the Look AHEAD (Action for Health in Diabetes) study.

BACKGROUND: Previous studies have shown that neighborhood factors are associated with obesity, but few studies have evaluated the association with weight control behaviors. This study aims to conduct a multi-level analysis to examine the relationship between neighborhood SES and weight-related health behaviors. METHODS: In this ancillary study to Look AHEAD (Action for Health in Diabetes) a trial of long-term weight loss among individuals with type 2 diabetes, individual-level data on 1219 participants from 4 clinic sites at baseline were linked to neighborhood-level data at the tract level from the 2000 US Census and other databases. Neighborhood variables included SES (% living below the federal poverty level) and the availability of food stores, convenience stores, and restaurants. Dependent variables included BMI, eating patterns, weight control behaviors and resource use related to food and physical activity. Multi-level models were used to account for individual-level SES and potential confounders. RESULTS: The availability of restaurants was related to several eating and weight control behaviors. Compared to their counterparts in neighborhoods with fewer restaurants, participants in neighborhoods with more restaurants were more likely to eat breakfast (prevalence Ratio [PR] 1.29 95% CI: 1.01-1.62) and lunch (PR = 1.19, 1.04-1.36) at non-fast food restaurants. They were less likely to be attempting weight loss (OR = 0.93, 0.89-0.97) but more likely to engage in weight control behaviors for food and physical activity, respectively, than those who lived in neighborhoods with fewer restaurants. In contrast, neighborhood SES had little association with weight control behaviors. CONCLUSION: In this selected group of weight loss trial participants, restaurant availability was associated with some weight control practices, but neighborhood SES was not. Future studies should give attention to other populations and to evaluating various aspects of the physical and social environment with weight control practices.

Postoperative mortality in cancer patients with preexisting diabetes: systematic review and meta-analysis.

OBJECTIVE: Diabetes appears to increase risk for some cancers, but the association between preexisting diabetes and postoperative mortality in cancer patients is less clear. Our objective was to systematically review postoperative mortality in cancer patients with and without preexisting diabetes and summarize results using meta-analysis. RSEARCH DESIGN AND METHODS: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica Database (EMBASE) for articles published on or before 1 July 2009, including references of qualifying articles. We included English language investigations of short-term postoperative mortality after initial cancer treatment. Titles, abstracts, and articles were reviewed by at least two independent readers. Study population and design, results, and quality components were abstracted with standard protocols by one reviewer and checked for accuracy by additional reviewers. RESULTS: Of 8,828 titles identified in our original search, 20 articles met inclusion criteria for qualitative systematic review. Of these, 15 reported sufficient information to be combined in meta-analysis. Preexisting diabetes was associated with increased odds of postoperative mortality across all cancer types (OR = 1.85 [95% CI 1.40-2.45]). The risk associated with preexisting diabetes was attenuated but remained significant when we restricted the meta-analysis to models that controlled for confounders (1.51 [1.13-2.02]) or when we accounted for publication bias using the trim and fill method (1.52 [1.13-2.04]). CONCLUSIONS: Compared with their nondiabetic counterparts, cancer patients with preexisting diabetes are approximately 50% more likely to die after surgery. Future research should investigate physiologic pathways to mortality risk and determine whether improvements in perioperative diabetes care can reduce postoperative mortality.

Association between increasing levels of hemoglobin A1c and coronary atherosclerosis in asymptomatic individuals without diabetes mellitus.

BACKGROUND: Earlier studies have shown an association between high-normal glucose and increasing glycosylated hemoglobin (HbA1c) levels and cardiovascular events. The objective of this investigation was to study the association between increasing levels of HbA1c in asymptomatic individuals without diabetes mellitus (DM) and coronary plaque characteristics. METHODS: The study population consisted of 1043 asymptomatic Korean individuals without DM who underwent 64-slice cardiac computed tomography angiography as part of a health screening evaluation. We excluded 147 individuals with known history of DM and/or fasting glucose of at least 126 mg/dl, no HbA1c data, or missing risk factor information. The associations between coronary atherosclerosis and plaque subtype burden with increasing HbA1c levels were assessed using multivariable regression analyses. RESULTS: The final study population consisted of 906 individuals without DM (mean age: 49+/-9 years, 62% males); 19 and 9% of the population had any and two or more segments with coronary plaque, respectively. Unadjusted analysis showed a positive association between increasing levels of HbA1c and the number of coronary segments with any (P<0.001) and with mixed coronary plaques (P<0.0001). The association persisted even when traditional risk factors were taken into account. No significant relationship was found between increasing HbA1c levels and the burden of noncalcified or calcified plaque. CONCLUSION: Increasing levels of HbA1c in asymptomatic individuals without DM are associated with the presence of coronary atherosclerosis, but more specifically with the presence and burden of mixed coronary plaques. Elements of plaque instability have been associated with mixed coronary plaques.

Race- and sex-specific associations of obesity measures with ischemic stroke incidence in the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND PURPOSE: Studies have suggested differences in the association between obesity and ischemic stroke in black versus white populations. In this study, we explored ischemic stroke risk in relation to a variety of obesity measures by sex and race. METHODS: Using data from the Atherosclerosis Risk in Communities Study, we obtained information on body mass index, waist circumference, and waist-to-hip ratio from 13 549 black and white participants who were aged 45 to 65 years between 1987 and 1989. All were free of cardiovascular disease and cancer at baseline. Incident strokes over a median follow-up of 16.9 years were ascertained from hospital records. RESULTS: Although crude incidence rates of ischemic stroke varied more than 3-fold by race and sex, the relationship between higher measures of obesity and ischemic stroke risk was positive and linear across all groups. The crude incidence of ischemic stroke was 1.2 per 1000 person-years for white women with the lowest body mass index, ranging up to 8.0 per 1000 person-years for black men with the highest body mass index. Hazard ratios for the highest versus lowest quintile of body mass index, waist circumference, and waist-to-hip ratio ranged from 1.43 to 3.19, indicating increased stroke risk associated with obesity, however it was measured, even after adjustment for potential confounders. Additional adjustment for factors that may mediate the relationship, such as diabetes and hypertension, significantly attenuated the associations, suggesting that these factors may explain much of the stroke risk associated with obesity. CONCLUSIONS: Degree of obesity, defined by body mass index, waist circumference, or waist-to-hip ratio, was a significant risk factor for ischemic stroke regardless of sex or race.

Smoking, smoking cessation, and risk for type 2 diabetes mellitus: a cohort study.

BACKGROUND: Cigarette smoking is an established predictor of incident type 2 diabetes mellitus, but the effects of smoking cessation on diabetes risk are unknown. OBJECTIVE: To test the hypothesis that smoking cessation increases diabetes risk in the short term, possibly owing to cessation-related weight gain. DESIGN: Prospective cohort study. SETTING: The ARIC (Atherosclerosis Risk in Communities) Study. PATIENTS: 10,892 middle-aged adults who initially did not have diabetes in 1987 to 1989. MEASUREMENTS: Smoking was assessed by interview at baseline and at subsequent follow-up. Incident diabetes was ascertained by fasting glucose assays through 1998 and self-report of physician diagnosis or use of diabetes medications through 2004. RESULTS: During 9 years of follow-up, 1254 adults developed type 2 diabetes. Compared with adults who never smoked, the adjusted hazard ratio of incident diabetes in the highest tertile of pack-years was 1.42 (95% CI, 1.20 to 1.67). In the first 3 years of follow-up, 380 adults quit smoking. After adjustment for age, race, sex, education, adiposity, physical activity, lipid levels, blood pressure, and ARIC Study center, compared with adults who never smoked, the hazard ratios of diabetes among former smokers, new quitters, and continuing smokers were 1.22 (CI, 0.99 to 1.50), 1.73 (CI, 1.19 to 2.53), and 1.31 (CI, 1.04 to 1.65), respectively. Further adjustment for weight change and leukocyte count attenuated these risks substantially. In an analysis of long-term risk after quitting, the highest risk occurred in the first 3 years (hazard ratio, 1.91 [CI, 1.19 to 3.05]), then gradually decreased to 0 at 12 years. LIMITATION: Residual confounding is possible even with meticulous adjustment for established diabetes risk factors. CONCLUSION: Cigarette smoking predicts incident type 2 diabetes, but smoking cessation leads to higher short-term risk. For smokers at risk for diabetes, smoking cessation should be coupled with strategies for diabetes prevention and early detection.

Colorectal cancer outcomes, recurrence, and complications in persons with and without diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Diabetes mellitus increases the risk of incident colorectal cancer, but it is less clear if pre-existing diabetes mellitus influences mortality outcomes, recurrence risk, and/or treatment-related complications in persons with colorectal cancer. METHODS: We performed a systematic review and meta-analysis comparing colorectal cancer mortality outcomes, cancer recurrence, and treatment-related complications in persons with and without diabetes mellitus. We searched MEDLINE and EMBASE through October 1, 2008, including hand-searching references of qualifying articles. We included studies in English that evaluated diabetes mellitus and cancer treatment outcomes, prognosis, and/or mortality. The initial search identified 8,208 titles, of which 15 articles met inclusion criteria. Each article was abstracted by one author using a standardized form and re-reviewed by another author for accuracy. Authors graded quality based on pre-determined criteria. RESULTS: We found significantly increased short-term perioperative mortality in persons with diabetes mellitus. In the meta-analysis of long-term mortality, persons with diabetes mellitus had a 32% increase in all-cause mortality compared to those without diabetes mellitus (95% CI: 1.24, 1.41). Although data on other outcomes are limited, available studies suggest that pre-existing diabetes mellitus predicts increased risk of some post-operative complications as well as 5-year cancer recurrence. In contrast, there is little evidence that diabetes confers increased risk for long-term cancer-specific mortality. CONCLUSIONS: Patients with colorectal cancer and pre-existing diabetes mellitus have an increased risk of short- and long-term mortality. Future research should determine whether improvements in prevention and treatment of diabetes mellitus will improve outcomes for colorectal cancer patients.