Metabolic syndrome components and their response to lifestyle and metformin interventions are associated with differences in diabetes risk in persons with impaired glucose tolerance

AIMS: To determine the association of metabolic syndrome (MetS) and its components with diabetes risk in participants with impaired glucose tolerance (IGT), and whether intervention-related changes in MetS lead to differences in diabetes incidence. METHODS: We used the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) revised MetS definition at baseline and intervention-related changes of its components to predict incident diabetes using Cox models in 3234 Diabetes Prevention Program (DPP) participants with IGT over an average follow-up of 3.2 years. RESULTS: In an intention-to-treat analysis, the demographic-adjusted hazard ratios (95% confidence interval) for diabetes in those with MetS (vs. no MetS) at baseline were 1.7 (1.3-2.3), 1.7 (1.2-2.3) and 2.0 (1.3-3.0) for placebo, metformin and lifestyle groups, respectively. Higher levels of fasting plasma glucose and triglycerides at baseline were independently associated with increased risk of diabetes. Greater waist circumference (WC) was associated with higher risk in placebo and lifestyle groups, but not in the metformin group. In a multivariate model, favourable changes in WC (placebo and lifestyle) and high-density lipoprotein cholesterol (placebo and metformin) contributed to reduced diabetes risk. CONCLUSIONS: MetS and some of its components are associated with increased diabetes incidence in persons with IGT in a manner that differed according to DPP intervention. After hyperglycaemia, the most predictive factors for diabetes were baseline hypertriglyceridaemia and both baseline and lifestyle-associated changes in WC. Targeting these cardiometabolic risk factors may help to assess the benefits of interventions that reduce diabetes incidence

Prevalence of the Metabolic Syndrome Among U.S. Workers

This is the final version of the article. Available from American Diabetes Association via the DOI in this record.OBJECTIVE: Differences in the prevalence of cardiovascular disease (CVD) and its risk factors among occupational groups have been found in several studies. Certain types of workers (such as shift workers) may have a greater risk for metabolic syndrome, a precursor of CVD. The objective of this study was to assess the differences in prevalence and risk of metabolic syndrome among occupational groups using nationally representative data of U.S. workers. RESEARCH DESIGN AND METHODS: Data from 8,457 employed participants (representing 131 million U.S. adults) of the 1999-2004 National Health and Nutrition Examination Survey were used. Unadjusted and age-adjusted prevalence and simple and multiple logistic regression analyses were conducted, adjusting for several potential confounders (BMI, alcohol drinking, smoking, physical activity, and sociodemographic characteristics) and survey design. RESULTS: Of the workers, 20% met the criteria for the metabolic syndrome, with "miscellaneous food preparation and food service workers" and "farm operators, managers, and supervisors" having the greatest age-adjusted prevalence (29.6-31.1%) and "writers, artists, entertainers, and athletes," and "engineers, architects, scientists" the lowest (8.5-9.2%). In logistic regression analyses "transportation/material moving" workers had significantly greater odds of meeting the criteria for metabolic syndrome relative to "executive, administrative, managerial" professionals (odds ratio 1.70 [95% CI 1.49-2.52]). CONCLUSIONS: There is variability in the prevalence of metabolic syndrome by occupational status, with "transportation/material moving" workers at greatest risk for metabolic syndrome. Workplace health promotion programs addressing risk factors for metabolic syndrome that target workers in occupations with the greatest odds may be an efficient way to reach at-risk populations.This research was supported in part by the National Institute on Occupational Safety and Health (grant R01-0H-03915)

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: A comparative risk assessment

Background: High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods: We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates. Findings: In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1-11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6-7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation: The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases. Funding: UK Medical Research Council, US National Institutes of Health. © 2014 Elsevier Ltd

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Dyslipidemia and subclinical inflammation in subjects with the metabolic syndrome

Metabolic syndrome (MS) is a cluster of risk factors for cardiovascular disease (CVD) and type 2 Diabetes (T2D) that has received increased attention from both epidemiologists and clinicians. However, there is scarcity of studies on how to identify subjects at high risk for the MS, and how to reduce and reverse its components (i.e. dyslipidemia, obesity, hyperglycemia, and hypertension) and associated risk factors such as high C-reactive protein (CRP) levels (i.e., subclinical inflammation).This dissertation focused on known metabolic and underlying factors associated with MS including, dyslipidemia (i.e. high triglycerides and low HDL-cholesterol), insulin resistance (IR), obesity, and inflammation. First, using a population-based approach, we examined the prevalence of the MS and its components in Zulia State, Venezuela, and established associated demographic and clinical risk factors for the MS. Then, using a high-risk population approach with patients that attended a screening program for glucose intolerance at the University of Miami, we evaluated the relationships among IR, apolipoprotein (apo) C-III levels, and dyslipidemia, as well as the association of CRP with the MS and its components.We found that approximately 1 in 3 patients meet the National Cholesterol Education Program/Adult Treatment Panel III diagnostic criteria for the MS in Zulia State, Venezuela with low HDL-cholesterol (65.3%), abdominal obesity (42.9%) and HTN (38.1%) as the most frequent MS components. MS prevalence increased with age, degree of obesity, family history of diabetes and hypertension, and sedentary lifestyle. We also found that MS was associated with high apo C-III (\u3e14 mg/dl) levels in Hispanics and white non-Hispanics, but not in African-Americans. Overall apo C-III was directly associated with hypertriglyceridemia and IR (high HOMAIR), while an inverse relationship with low-density lipoprotein (LDL) particle size was evident in all T2D subjects and only among normoglycemic subjects with MS. Finally, we found that elevated CRP levels are associated with the presence of abdominal obesity and IR but not with other MS components in this high-risk population for CVD and diabetes, suggesting a potential role of IR and obesity in the development of the subclinical inflammation associated with the MS

Cardiovascular disease in diabetes: prevention and intervention

A combination of preventive and intervention management strategies are needed to reduce the morbidity and mortality of cardiovascular disease (CVD) in diabetic patients. Fundamental to the preventive approach is the position that diabetes constitutes a coronary heart disease (CHD) risk equivalent and therefore requires aggressive screening and management of those cardiovascular risk factors known to contribute to CVD. These include hypercholesterolemia (raised LDL-cholesterol), atherogenic dyslipidemia, hypertension, cigarette smoking, hyperglycemia, and the procoagulant state. In addition because the genesis of CVD in diabetic subjects begins prior to diagnosis, individuals at increased risk for diabetes should be targeted for CVD risk factor screening and management according to standard recommendations. At the intervention level, it is recommended that diabetic individuals without known coronary heart disease and with two other CVD risk factors undergo stress testing. Finally, in the past 5 years significant advances have occurred in our understanding and management of acute myocardial infarction and of revascularization strategies, and these have now been shown to reduce the morbidity and mortality caused by established coronary heart disease in diabetic subjects

Exercise and Quality of Life

Exercise is a fundamental intervention for any patient with diabetes or at risk for it. Exercise not only contributes to the control of blood glucose but also reduces the risk of metabolic abnormalities and diabetes-related complications and comorbidities. Despite the growing prevalence of diabetes in the world, most people are not as physically active as guidelines and evidence recommend. In this chapter, we focus on the topic of exercise and quality of life, briefly addressing quality of life assessment in patients with diabetes. In addition, given the strong association of depression with diabetes and its impact on quality of life, we also cover the potential benefits of exercise interventions in the setting of diabetes and depression. While most studies show evidence of short- and long-term exercise interventions, there are still several areas that require further research. Moreover, the impact from exercise in older adults requires additional attention, given the aging of the population and because older people may have long-standing disease, with greater prevalence of its complications, as well as greater prevalence of multimorbidity, which will also impact their quality of life