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)

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

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

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

Emerging therapies to treat frailty syndrome in the elderly

Frailty syndrome (FS) has become increasingly recognized as a major predictor of co-morbidities and mortality in older individuals. Interventions with the potential to benefit frail elders include nutritional supplementation (vitamins D, carotenoids, creatine, dehydroepiandrosterone (DHEA), and beta-hydroxy-beta-methylbutyrate) and exercise modalities (tai chi and cobblestone walking). While these have not been explicitly tested for their impact on FS, vitamin D supplementation appears to offer significant promise in enhancing long-term health of the elderly. Exercise modalities such as tai chi and cobblestone walking, because of probable low risk and ease of participation, may also confer benefit. Additional studies are needed to investigate interventions that directly prevent, delay, and/or ameliorate frailty. Successful therapies may well involve multi-component approaches utilizing a combination of medication, nutritional supplementation, and exercise

Suitable Use of Injectable Agents to Overcome Hypoglycemia Risk, Barriers, and Clinical Inertia in Community-Dwelling Older Adults with Type 2 Diabetes Mellitus

The management of type 2 diabetes mellitus in older adults requires a comprehensive understanding of the relationship between the disease (medical) and the functional, psychological/cognitive, and social geriatric domains, to individualize both glycemic targets and therapeutic approaches. Prevention of hypoglycemia is a major priority that should be addressed as soon as its presence or risk is detected, adjusting the target and therapeutics accordingly. Nonetheless, treatment intensification should not be neglected when applicable, consistent with recommendations from organizations such as the American Geriatrics Society and the American Diabetes Association, to reduce not only long-term macrovascular and microvascular complications (individualization), but also short-term complications from hyperglycemia (polyuria, volume depletion, urinary incontinence). Such complications can negatively impact the physical and cognitive function of older adults, worsen their quality of life, and additionally affect their families and society. We emphasize individualization, utilizing the multiple classes of antihyperglycemic agents available. Metformin remains as first-line therapy, and additional agents offer advantages and disadvantages that ought to be considered when developing a patient-centric plan of care. For selected cases, injectable therapies such as long-acting basal insulin analogs and glucagon-like peptide-1 receptor agonists can offer advantages to counter hypoglycemia risk, patient-related barriers, and clinical inertia. Furthermore, some injectable agents could potentially simplify regimens while providing safe and effective glycemic control. In this review, we discuss the use of injectable therapies for selected community-dwelling older adults, barriers to transition to injectable therapy, and measures aimed at removing these barriers and assisting physicians and their teams to transition older patients to injectable therapies when appropriate

Long-Term Effects of Cataract Surgery on Tear Film Parameters

Purpose. To examine the differences in tear film parameters more than 3 months postsurgery in eyes with cataract surgery (surgical eyes) versus eyes without cataract surgery (nonsurgical eyes).Methods. 29 patients were seen at the Miami Veterans Affairs Medical Center (VAMC) who had cataract surgery by phacoemulsification in one eye more than 3 months prior to the study date and had no history of surgical intervention in their fellow eye. Tear film parameters were measured in both eyes and compared using McNemar tests for dichotomous variables and paired and single samplet-tests for continuous variables.Results. Mean patient age was 73 (standard deviation (SD): 11); 26 patients (90%) identified themselves as White and 7 (24%) as Hispanic. The mean number of days between surgery and this study was 952 (SD: 1109). There were no statistical differences between the surgical eye and the nonsurgical eye with respect to any of the measured tear film parameters. Confidence intervals around these differences were narrow enough to exclude a substantial effect of cataract surgery. The elapsed time between cataract surgery and measurement of the tear parameters did not appear to affect the difference in parameters between the two eyes.Conclusion. We found that eyes that had cataract surgery more than 3 months prior to testing had no differences in their tear film parameters compared to eyes without a history of surgery