Alain G. Bertoni

Benefits of Modest Weight Loss in Improving Cardiovascular Risk Factors in Overweight and Obese Individuals With Type 2 Diabetes

OBJECTIVE Overweight and obese individuals are encouraged to lose 5–10% of their body weight to improve cardiovascular disease (CVD) risk, but data supporting this recommendation are limited, particularly for individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted an observational analysis of participants in the Look AHEAD (Action For Health in Diabetes) study (n = 5,145, 40.5% male, 37% from ethnic/racial minorities) and examined the association between the magnitude of weight loss and changes in CVD risk factors at 1 year and the odds of meeting predefined criteria for clinically significant improvements in risk factors in individuals with type 2 diabetes. RESULTS The magnitude of weight loss at 1 year was strongly (P < 0.0001) associated with improvements in glycemia, blood pressure, tryiglycerides, and HDL cholesterol but not with LDL cholesterol (P = 0.79). Compared with weight-stable participants, those who lost 5 to <10% ([means ± SD] 7.25 ± 2.1 kg) of their body weight had increased odds of achieving a 0.5% point reduction in HbA1c (odds ratio 3.52 [95% CI 2.81–4.40]), a 5-mmHg decrease in diastolic blood pressure (1.48 [1.20–1.82]), a 5-mmHg decrease in systolic blood pressure (1.56 [1.27–1.91]), a 5 mg/dL increase in HDL cholesterol (1.69 [1.37–2.07]), and a 40 mg/dL decrease in triglycerides (2.20 [1.71–2.83]). The odds of clinically significant improvements in most risk factors were even greater in those who lost 10–15% of their body weight. CONCLUSIONS Modest weight losses of 5 to <10% were associated with significant improvements in CVD risk factors at 1 year, but larger weight losses had greater benefits.

Examining a Bidirectional Association Between Depressive Symptoms and Diabetes

CONTEXT Depressive symptoms are associated with development of type 2 diabetes, but it is unclear whether type 2 diabetes is a risk factor for elevated depressive symptoms. OBJECTIVE To examine the bidirectional association between depressive symptoms and type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of US men and women aged 45 to 84 years enrolled in 2000-2002 and followed up until 2004-2005. MAIN OUTCOME MEASURES Elevated depressive symptoms defined by Center for Epidemiologic Studies Depression Scale (CES-D) score of 16 or higher, use of antidepressant medications, or both. The CES-D score was also modeled continuously. Participants were categorized as normal fasting glucose (< 100 mg/dL), impaired fasting glucose (100-125 mg/dL), or type 2 diabetes (> or = 126 mg/dL or receiving treatment). Analysis 1 included 5201 participants without type 2 diabetes at baseline and estimated the relative hazard of incident type 2 diabetes over 3.2 years for those with and without depressive symptoms. Analysis 2 included 4847 participants without depressive symptoms at baseline and calculated the relative odds of developing depressive symptoms over 3.1 years for those with and without type 2 diabetes. RESULTS In analysis 1, the incidence rate of type 2 diabetes was 22.0 and 16.6 per 1000 person-years for those with and without elevated depressive symptoms, respectively. The risk of incident type 2 diabetes was 1.10 times higher for each 5-unit increment in CES-D score (95% confidence interval [CI], 1.02-1.19) after adjustment for demographic factors and body mass index. This association persisted following adjustment for metabolic, inflammatory, socioeconomic, or lifestyle factors, although it was no longer statistically significant following adjustment for the latter (relative hazard, 1.08; 95% CI, 0.99-1.19). In analysis 2, the incidence rates of elevated depressive symptoms per 1000-person years were 36.8 for participants with normal fasting glucose; 27.9 for impaired fasting glucose; 31.2 for untreated type 2 diabetes, and 61.9 for treated type 2 diabetes. Compared with normal fasting glucose, the demographic-adjusted odds ratios of developing elevated depressive symptoms were 0.79 (95% CI, 0.63-0.99) for impaired fasting glucose, 0.75 (95% CI, 0.44-1.27) for untreated type 2 diabetes, and 1.54 (95% CI, 1.13-2.09) for treated type 2 diabetes. None of these associations with incident depressive symptoms were materially altered with adjustment for body mass index, socioeconomic and lifestyle factors, and comorbidities. Findings in both analyses were comparable across ethnic groups. CONCLUSIONS A modest association of baseline depressive symptoms with incident type 2 diabetes existed that was partially explained by lifestyle factors. Impaired fasting glucose and untreated type 2 diabetes were inversely associated with incident depressive symptoms, whereas treated type 2 diabetes showed a positive association with depressive symptoms. These associations were not substantively affected by adjustment for potential confounding or mediating factors.

Association of an Intensive Lifestyle Intervention With Remission of Type 2 Diabetes

CONTEXT The frequency of remission of type 2 diabetes achievable with lifestyle intervention is unclear. OBJECTIVE To examine the association of a long-term intensive weight-loss intervention with the frequency of remission from type 2 diabetes to prediabetes or normoglycemia. DESIGN, SETTING, AND PARTICIPANTS Ancillary observational analysis of a 4-year randomized controlled trial (baseline visit, August 2001-April 2004; last follow-up, April 2008) comparing an intensive lifestyle intervention (ILI) with a diabetes support and education control condition (DSE) among 4503 US adults with body mass index of 25 or higher and type 2 diabetes. INTERVENTIONS Participants were randomly assigned to receive the ILI, which included weekly group and individual counseling in the first 6 months followed by 3 sessions per month for the second 6 months and twice-monthly contact and regular refresher group series and campaigns in years 2 to 4 (n=2241) or the DSE, which was an offer of 3 group sessions per year on diet, physical activity, and social support (n=2262). MAIN OUTCOME MEASURES Partial or complete remission of diabetes, defined as transition from meeting diabetes criteria to a prediabetes or nondiabetic level of glycemia (fasting plasma glucose <126 mg/dL and hemoglobin A1c <6.5% with no antihyperglycemic medication). RESULTS Intensive lifestyle intervention participants lost significantly more weight than DSE participants at year 1 (net difference, -7.9%; 95% CI, -8.3% to -7.6%) and at year 4 (-3.9%; 95% CI, -4.4% to -3.5%) and had greater fitness increases at year 1 (net difference, 15.4%; 95% CI, 13.7%-17.0%) and at year 4 (6.4%; 95% CI, 4.7%-8.1%) (P < .001 for each). The ILI group was significantly more likely to experience any remission (partial or complete), with prevalences of 11.5% (95% CI, 10.1%-12.8%) during the first year and 7.3% (95% CI, 6.2%-8.4%) at year 4, compared with 2.0% for the DSE group at both time points (95% CIs, 1.4%-2.6% at year 1 and 1.5%-2.7% at year 4) (P < .001 for each). Among ILI participants, 9.2% (95% CI, 7.9%-10.4%), 6.4% (95% CI, 5.3%-7.4%), and 3.5% (95% CI, 2.7%-4.3%) had continuous, sustained remission for at least 2, at least 3, and 4 years, respectively, compared with less than 2% of DSE participants (1.7% [95% CI, 1.2%-2.3%] for at least 2 years; 1.3% [95% CI, 0.8%-1.7%] for at least 3 years; and 0.5% [95% CI, 0.2%-0.8%] for 4 years). CONCLUSIONS In these exploratory analyses of overweight adults, an intensive lifestyle intervention was associated with a greater likelihood of partial remission of type 2 diabetes compared with diabetes support and education. However, the absolute remission rates were modest. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00017953.

Exercise Training for Type 2 Diabetes Mellitus Impact on Cardiovascular Risk: A Scientific Statement From the American Heart Association

1. Introduction …3244 2. Beneficial Effects of Exercise in T2DM…3245 3. Cardiac Risks of Exercise Training in T2DM…3249 4. Noncardiac Risks of Exercise Training in T2DM…3251 5. Exercise Training Guidelines…3252 6. Approaches to Adherence…3254 7. Special/Minority Groups…3255 8. Conclusions…3256 9. References…3257 The increasing prevalence of overweight and obesity has led to an unprecedented epidemic of type 2 diabetes mellitus (T2DM)1–4 and is likely to be followed by an epidemic of patients with complications of T2DM.5 Given the observed increases in the prevalence of T2DM in adults over the past few decades in developed countries,1,2,6 population-based efforts to reduce the cardiovascular complications of T2DM are as critical as the measures to prevent the problem.4,7 T2DM is the sixth-leading cause of death,8 with most deaths attributed to cardiovascular disease (CVD; nearly 70%) and with ischemic heart disease being responsible for nearly 50% of these deaths.9 The economic cost of T2DM has been estimated to be

Novel metabolic risk factors for incident heart failure and their relationship with obesity: the MESA (Multi-Ethnic Study of Atherosclerosis) study.

172 billion in 2007 in the United States alone3 (up from

Dyslipidemia Prevalence, Treatment, and Control in the Multi-Ethnic Study of Atherosclerosis (MESA) Gender, Ethnicity, and Coronary Artery Calcium

132 billion in 2002)10 and is likely to be greater when the other indirect costs of its associated complications are included.11 These complications are due to atherosclerotic vascular disease4 but also reflect a susceptibility of patients with T2DM to heart failure,12,13 perhaps mediated by direct effects on the myocardium.14,15 Pharmaceutical intervention for glycemic control has shown beneficial results for microvascular complications in patients with T2DM; however, whether this therapy has beneficial effects on macrovascular complications and …

Clinical ResearchHeart FailureNovel Metabolic Risk Factors for Incident Heart Failure and Their Relationship With Obesity: The MESA (Multi-Ethnic Study of Atherosclerosis) Study

OBJECTIVES The objectives of this study were to determine the associations of the metabolic syndrome, inflammatory markers, and insulin resistance with incident congestive heart failure (CHF), beyond established risk factors, and to examine whether these risk factors may provide the link between obesity and CHF. BACKGROUND Recently, increasing interest has emerged on the potential role of novel risk factors such as systemic inflammation, insulin resistance, and albuminuria in the pathophysiology of CHF and their relationship with obesity. METHODS The MESA (Multi-Ethnic Study of Atherosclerosis) study is a community-based multicenter cohort study of 6,814 participants (age 45 to 84 years, 3,601 women) of 4 ethnicities: Caucasians, African Americans, Hispanics, and Chinese Americans. Participants were recruited between 2000 and 2002 from 6 U.S. communities. Median follow-up time was 4 years. Participants with history of symptomatic cardiovascular disease were excluded. Cox proportional hazards models were used to analyze the associations of the metabolic syndrome, inflammatory markers, insulin resistance, and albuminuria with incident CHF, independent of established risk factors (age, gender, hypertension, diabetes mellitus, left ventricular hypertrophy, obesity, serum total cholesterol, and smoking), an interim myocardial infarction, and baseline magnetic resonance imaging parameters of left ventricular structure and function. RESULTS A total of 79 participants developed CHF during follow-up, and 26 participants (32.9%) had a myocardial infarction prior to CHF and 65% of the cases had CHF with preserved function (left ventricular ejection fraction >or=40%). In multivariable analyses, serum interleukin-6 (hazard ratio [HR] for 1 standard deviation 1.50, 95% confidence interval [CI] 1.10 to 2.03) or C-reactive protein (HR for 1 standard deviation 1.38; 95% CI 1.01 to 1.86) and macroalbuminuria (HR 4.31, 95% CI 1.58 to 11.76) were predictors of CHF, independent of obesity and the other established risk factors. Although obesity was significantly associated with incident CHF, this association was no longer significant after adding inflammatory markers (interleukin-6 or C-reactive protein) to the model. CONCLUSIONS Inflammatory markers and albuminuria are independent predictors of CHF. The association of obesity and CHF may be related to pathophysiologic pathways associated with inflammation.

Features of the Metabolic Syndrome and Diabetes Mellitus as Predictors of Aortic Valve Calcification in the Multi-Ethnic Study of Atherosclerosis

Background— To assess the implementation challenge facing the Third Report of the Adult Treatment Panel (ATP III) of the National Cholesterol Education Program, we determined the prevalence, treatment, and control of dyslipidemia, including ethnic and gender differences, in persons free of known clinical cardiovascular disease (CVD). In addition, this report provides information about the presence of coronary artery calcium (CAC) across groups defined by risk and recommendations for the use of lipid-lowering drugs. Methods and Results— The Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter cohort study of 6814 persons aged 45 to 84 years who were free of clinical CVD at baseline (2000–2002). Participants with complete fasting lipid profiles (n=6704) were evaluated for CVD risk and self-reported use of lipid-lowering therapy. CAC was assessed by CT. Drug treatment thresholds and goals were defined according to ATP III. Models were constructed to adjust for age, clinic site, risk factors, socioeconomic characteristics, and healthcare access variables with the use of Poisson regression. Overall, 29.3% (1964/6704) had dyslipidemia, among whom lipid-lowering drug therapy was reported by 54.0% (1060/1964). Control to ATP III goal was observed in 75.2% (797/1060) of participants with treated dyslipidemia and 40.6% (797/1964) of participants with dyslipidemia. Men were more likely than women to qualify for drug therapy and less likely to be treated and controlled. Relative to non-Hispanic whites, Chinese Americans were less likely to qualify for drug treatment, but no differences in treatment and control rates were observed. Black and Hispanic Americans had prevalence of dyslipidemia that was comparable to that of non-Hispanic whites but were less likely to be treated and controlled. Ethnic disparities were attenuated substantially by adjustment for healthcare access variables; however, the gender disparities persisted despite adjustment for risk factors, socioeconomic characteristics, and healthcare access variables. Control of dyslipidemia was achieved less commonly in the CVD high- and intermediate-risk groups than in the low-risk group. Among high-risk individuals, 19.7% of those who did not qualify for lipid-lowering drug treatment had CAC >400. The proportion of drug treatment–qualifying persons who were not treated differed by presence and severity of CAC, with 48.0%, 46.8%, and 39.6% of eligible persons with no CAC, with CAC >0 and <400, and with CAC >400 not receiving treatment, respectively (P for difference=0.04). Conclusions— Dyslipidemia is common among persons without CVD. The quality of care for dyslipidemia is suboptimal in general and variable by CVD risk group, ethnicity, and gender. The utility of incorporating CAC screening into the risk stratification and treatment process should be investigated in light of the substantial proportions of persons with CAC who are currently classified as not requiring treatment. Research and quality improvement programs are needed to optimize management of dyslipidemia.

Lifestyle Change and Mobility in Obese Adults with Type 2 Diabetes

OBJECTIVES The objectives of this study were to determine the associations of the metabolic syndrome, inflammatory markers, and insulin resistance with incident congestive heart failure (CHF), beyond established risk factors, and to examine whether these risk factors may provide the link between obesity and CHF. BACKGROUND Recently, increasing interest has emerged on the potential role of novel risk factors such as systemic inflammation, insulin resistance, and albuminuria in the pathophysiology of CHF and their relationship with obesity. METHODS The MESA (Multi-Ethnic Study of Atherosclerosis) study is a community-based multicenter cohort study of 6,814 participants (age 45 to 84 years, 3,601 women) of 4 ethnicities: Caucasians, African Americans, Hispanics, and Chinese Americans. Participants were recruited between 2000 and 2002 from 6 U.S. communities. Median follow-up time was 4 years. Participants with history of symptomatic cardiovascular disease were excluded. Cox proportional hazards models were used to analyze the associations of the metabolic syndrome, inflammatory markers, insulin resistance, and albuminuria with incident CHF, independent of established risk factors (age, gender, hypertension, diabetes mellitus, left ventricular hypertrophy, obesity, serum total cholesterol, and smoking), an interim myocardial infarction, and baseline magnetic resonance imaging parameters of left ventricular structure and function. RESULTS A total of 79 participants developed CHF during follow-up, and 26 participants (32.9%) had a myocardial infarction prior to CHF and 65% of the cases had CHF with preserved function (left ventricular ejection fraction >or=40%). In multivariable analyses, serum interleukin-6 (hazard ratio [HR] for 1 standard deviation 1.50, 95% confidence interval [CI] 1.10 to 2.03) or C-reactive protein (HR for 1 standard deviation 1.38; 95% CI 1.01 to 1.86) and macroalbuminuria (HR 4.31, 95% CI 1.58 to 11.76) were predictors of CHF, independent of obesity and the other established risk factors. Although obesity was significantly associated with incident CHF, this association was no longer significant after adding inflammatory markers (interleukin-6 or C-reactive protein) to the model. CONCLUSIONS Inflammatory markers and albuminuria are independent predictors of CHF. The association of obesity and CHF may be related to pathophysiologic pathways associated with inflammation.

Dietary intake of saturated fat by food source and incident cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis

Background— Calcific aortic valve disease is common in the elderly, is correlated with common cardiovascular risk factors, and is associated with increased cardiovascular event risk; however, whether metabolic syndrome is associated with an increased prevalence of aortic valve calcium (AVC) is not known. Methods and Results— The prevalence of AVC, as assessed by computed tomography, was compared in 6780 Multi-Ethnic Study of Atherosclerosis (MESA) participants with metabolic syndrome (n=1550; National Cholesterol Education Program’s Adult Treatment Panel III [ATP III] criteria), diabetes mellitus (n=1016), or neither condition (n=4024). The prevalence of AVC for those with neither condition, metabolic syndrome, or diabetes mellitus was, respectively, 8%, 12%, and 17% in women (P<0.001) and 14%, 22%, and 24% in men (P<0.001). Compared with those with neither condition, the adjusted relative risks for the presence of AVC were 1.45 (95% CI 1.11 to 1.90) for metabolic syndrome and 2.12 (95% CI 1.54 to 2.92) for diabetes mellitus in women and 1.70 (95% CI 1.32 to 2.19) for metabolic syndrome and 1.73 (95% CI 1.33 to 2.25) for diabetes mellitus in men. There was a graded, linear relationship between AVC prevalence and the number of metabolic syndrome components in both women and men (both P<0.001). Similar results were obtained when the International Diabetes Federation metabolic syndrome definition was used. Conclusions— In the MESA cohort, the metabolic syndrome and diabetes mellitus are associated with increased risk of AVC, and AVC prevalence is increased with increasing number of metabolic syndrome components.