Association of family history of cardiometabolic diseases (CMDs) and individual health behaviours: Analysis of CARRS study from South Asia.

OBJECTIVES: Family history is considered as an important predictor of cardiovascular diseases (CVDs) and diabetes. Available research findings suggest that family history of chronic diseases is associated with perceived risk of disease and adoption of healthy behaviours. We examined the association between family history of cardio-metabolic diseases (CMDs) and healthy behaviours among adults without self-reported CMDs. METHODS: Cross-sectional data of 12,484 adults, without self-reported CMDs, from the baseline survey of Centre for cArdiometabolic Risk Reduction in South-Asia (CARRS) cohort study were analysed. RESULTS: Family history was positively associated with non-smoking and high fruits & vegetables consumption in the age group of 45-64 years and moderate to high physical activity in the age group ≥65 years after adjusting for sex, education, wealth index, city and body mass index. CONCLUSIONS: Understanding perceived risks and cultural or psychological factors related to family history through ethnographic studies may deepen understanding of these associations.

Blood-derived miRNA levels are not correlated with metabolic or anthropometric parameters in obese pre-diabetic subjects but with systemic inflammation.

As blood-derived miRNAs (c-miRNAs) are modulated by exercise and nutrition, we postulated that they might be used to monitor the effects of a lifestyle intervention (LI) to prevent diabetes development. To challenge this hypothesis, obese Asian Indian pre-diabetic patients were submitted to diet modifications and physical activity for 4 months (LI group) and compared to a control group which was given recommendations only. We have considered 2 periods of time to analyze the data, i.e.; a first one to study the response to the intervention (4 months), and a second one post-intervention (8 months). At basal, 4 months and 8 months post-intervention the levels of 17 c-miRNAs were quantified, selected either for their relevance to the pathology or because they are known to be modulated by physical activity or diet. Their variations were correlated with variations of 25 metabolic and anthropometric parameters and cytokines. As expected, fasting-glycaemia, insulin-sensitivity, levels of exercise- and obesity-induced cytokines were ameliorated after 4 months. In addition, the levels of 4 miRNAs (i.e.; miR-128-3p, miR-374a-5p, miR-221-3p, and miR-133a-3p) were changed only in the LI group and were correlated with metabolic improvement (insulin sensitivity, cytokine levels, waist circumference and systolic blood pressure). However, 8 months post-intervention almost all ameliorated metabolic parameters declined indicating that the volunteers did not continue the protocol on their own. Surprisingly, the LI positive effects on c-miRNA levels were still detected, and were even more pronounced 8 months post-intervention. In parallel, MCP-1, involved in tissue infiltration by immune cells, and Il-6, adiponectin and irisin, which have anti-inflammatory effects, continued to be significantly and positively modified, 8 months post-intervention. These data demonstrated for the first time, that c-miRNA correlations with metabolic parameters and insulin sensitivity are in fact only indirect and likely associated with the level systemic inflammation. More generally speaking, this important result explains the high variability between the previous studies designed to identify specific c-miRNAs associated with the severity of insulin-resistance. The results of all these studies should take into account the level of inflammation of the patients. In addition, this finding could also explain why, whatever the pathology considered (i.e.; cancers, diabetes, neurodegenerative disorders, inflammatory diseases) the same subset of miRNAs is always found altered in the blood of patients vs healthy subjects, as these pathologies are all associated with the development of inflammation.

Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes.

BACKGROUND: Body mass index (BMI), a well-known risk factor for poor cardiovascular outcomes, is associated with differential DNA methylation (DNAm). Similarly, metabolic health has also been associated with changes in DNAm. It is unclear how overall metabolic health outside of BMI may modify the relationship between BMI and methylation profiles, and what consequences this may have on downstream cardiovascular disease. The purpose of this study was to identify cytosine-phosphate-guanine (CpG) sites at which the association between BMI and DNAm could be modified by overall metabolic health. RESULTS: The discovery study population was derived from three Women's Health Initiative (WHI) ancillary studies (n = 3977) and two Atherosclerosis Risk in Communities (ARIC) ancillary studies (n = 3520). Findings were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 1200). Generalized linear models regressed methylation ß values on the interaction between BMI and metabolic health Z score (BMI × MHZ) adjusted for BMI, MHZ, cell composition, chip number and location, study characteristics, top three ancestry principal components, smoking, age, ethnicity (WHI), and sex (ARIC). Among the 429,566 sites examined, differential associations between BMI × MHZ and DNAm were identified at 22 CpG sites (FDR q < 0.05), with one site replicated in MESA (cg18989722, in the TRAPPC9 gene). Three of the 22 sites were associated with incident coronary heart disease (CHD) in WHI. For each 0.01 unit increase in DNAm ß value, the risk of incident CHD increased by 9% in one site and decreased by 6-10% in two sites over 25 years. CONCLUSIONS: Differential associations between DNAm and BMI by MHZ were identified at 22 sites, one of which was validated (cg18989722) and three of which were predictive of incident CHD. These sites are located in several genes related to NF-kappa-B signaling, suggesting a potential role for inflammation between DNA methylation and BMI-associated metabolic health.

Epigenome-wide association study of diet quality in the Women's Health Initiative and TwinsUK cohort.

BACKGROUND: Diet quality is a risk factor for chronic disease and mortality. Differential DNA methylation across the epigenome has been associated with chronic disease risk. Whether diet quality is associated with differential methylation is unknown. This study assessed whether diet quality was associated with differential DNA methylation measured across 445 548 loci in the Women's Health Initiative (WHI) and the TwinsUK cohort. DESIGN: The discovery cohort consisted of 4355 women from the WHI. The replication cohort consisted of 571 mono- and dizygotic twins from the TwinsUK cohort. DNA methylation was measured in whole blood using the Illumina Infinium HumanMethylation450 Beadchip. Diet quality was assessed using the Alternative Healthy Eating Index 2010 (AHEI-2010). A meta-analysis, stratified by study cohort, was performed using generalized linear models that regressed methylation on AHEI-2010, adjusting for cell composition, chip number and location, study characteristics, principal components of genetic relatedness, age, smoking status, race/ethnicity and body mass index (BMI). Statistical significance was defined as a false discovery rate < 0.05. Significant sites were tested for replication in the TwinsUK cohort, with significant replication defined by P < 0.05 and a consistent direction. RESULTS: Diet quality was significantly associated with differential DNA methylation at 428 cytosine-phosphate-guanine (CpG) sites in the discovery cohort. A total of 24 CpG sites were consistent with replication in the TwinsUK cohort, more than would be expected by chance (P = 2.7x10-4), with one site replicated in both the blood and adipose tissue (cg16379999 located in the body of SEL1L). CONCLUSIONS: Diet quality was associated with methylation at 24 CpG sites, several of which have been associated with adiposity, inflammation and dysglycaemia. These findings may provide insight into pathways through which diet influences chronic disease.

Cost-effectiveness of a Stepwise Approach vs Standard Care for Diabetes Prevention in India.

Importance: A stepwise approach that includes screening and lifestyle modification followed by the addition of metformin for individuals with high risk of diabetes is recommended to delay progression to diabetes; however, there is scant evidence regarding whether this approach is cost-effective. Objective: To estimate the cost-effectiveness of a stepwise approach in the Diabetes Community Lifestyle Improvement Program. Design, Setting, and Participants: This economic evaluation study included 578 adults with impaired glucose tolerance, impaired fasting glucose, or both. Participants were enrolled in the Diabetes Community Lifestyle Improvement Program, a randomized clinical trial with 3-year follow-up conducted at a diabetes care and research center in Chennai, India. Interventions: The intervention group underwent a 6-month lifestyle modification curriculum plus stepwise addition of metformin; the control group received standard lifestyle advice. Main Outcomes and Measures: Cost, health benefits, and incremental cost-effectiveness ratios (ICERs) were estimated from multipayer (including direct medical costs) and societal (including direct medical and nonmedical costs) perspectives. Costs and ICERs were reported in 2019 Indian rupees (INR) and purchasing power parity-adjusted international dollars (INT $). Results: The mean (SD) age of the 578 participants was 44.4 (9.3) years, and 364 (63.2%) were men. Mean (SD) body mass index was 27.9 (3.7), and the mean (SD) glycated hemoglobin level was 6.0% (0.5). Implementing lifestyle modification and metformin was associated with INR 10 549 (95% CI, INR 10 134-10 964) (INT $803 [95% CI, INT $771-834]) higher direct costs; INR 5194 (95% CI, INR 3187-INR 7201) (INT $395; 95% CI, INT $65-147) higher direct nonmedical costs, an absolute diabetes risk reduction of 10.2% (95% CI, 1.9% to 18.5%), and an incremental gain of 0.099 (95% CI, 0.018 to 0.179) quality-adjusted life-years per participant. From a multipayer perspective (including screening costs), mean ICERs were INR 1912 (INT $145) per 1 percentage point diabetes risk reduction, INR 191 090 (INT $14 539) per diabetes case prevented and/or delayed, and INR 196 960 (INT $14 986) per quality-adjusted life-year gained. In the scenario of a 50% increase or decrease in screening and intervention costs, the mean ICERs varied from INR 855 (INT $65) to INR 2968 (INT $226) per 1 percentage point diabetes risk reduction, from INR 85 495 (INT $6505) to INR 296 681 (INT $22 574) per diabetes case prevented, and from INR 88 121 (INT $6705) to INR 305 798 (INT $23 267) per quality-adjusted life-year gained. Conclusions and Relevance: The findings of this study suggest that a stepwise approach for diabetes prevention is likely to be cost-effective, even if screening costs for identifying high-risk individuals are added.

Random plasma glucose predicts the diagnosis of diabetes.

AIMS/HYPOTHESIS: Early recognition of those at high risk for diabetes as well as diabetes itself can permit preventive management, but many Americans with diabetes are undiagnosed. We sought to determine whether routinely available outpatient random plasma glucose (RPG) would be useful to facilitate the diagnosis of diabetes. METHODS: Retrospective cohort study of 942,446 U.S. Veterans without diagnosed diabetes, ≥3 RPG in a baseline year, and ≥1 primary care visit/year during 5-year follow-up. The primary outcome was incident diabetes (defined by diagnostic codes and outpatient prescription of a diabetes drug). RESULTS: Over 5 years, 94,599 were diagnosed with diabetes [DIAB] while 847,847 were not [NONDIAB]. Baseline demographics of DIAB and NONDIAB were clinically similar, except DIAB had higher BMI (32 vs. 28 kg/m2) and RPG (150 vs. 107 mg/dl), and were more likely to have Black race (18% vs. 15%), all p<0.001. ROC area for prediction of DIAB diagnosis within 1 year by demographic factors was 0.701, and 0.708 with addition of SBP, non-HDL cholesterol, and smoking. These were significantly less than that for prediction by baseline RPG alone (≥2 RPGs at/above a given level, ROC 0.878, p<0.001), which improved slightly when other factors were added (ROC 0.900, p<0.001). Having ≥2 RPGs ≥115 mg/dl had specificity 77% and sensitivity 87%, and ≥2 RPGs ≥130 mg/dl had specificity 93% and sensitivity 59%. For predicting diagnosis within 3 and 5 years by RPG alone, ROC was reduced but remained substantial (ROC 0.839 and 0.803, respectively). CONCLUSIONS: RPG levels below the diabetes "diagnostic" range (≥200 mg/dl) provide good discrimination for follow-up diagnosis. Use of such levels-obtained opportunistically, during outpatient visits-could signal the need for further testing, allow preventive intervention in high risk individuals before onset of disease, and lead to earlier identification of diabetes.

Multimorbidity of four cardiometabolic and chronic pulmonary disease groups: prevalence and attributable fraction in US adults, 2007-2012.

BACKGROUND: Cardiometabolic and chronic pulmonary diseases may be associated with modifiable risk factors that can be targeted to prevent multimorbidity. OBJECTIVES: (i) Estimate the prevalence of multimorbidity across four cardiometabolic and chronic pulmonary disease groups; (ii) compare the prevalence of multimorbidity to that of one disease and no disease; and (iii) quantify population attributable fractions (PAFs) for modifiable risk factors of multimorbidity. DESIGN: Data from adults aged 18-79 years who participated in the US National Health and Nutrition Examination Survey 2007-2012 were examined. Multimorbidity was defined as ≥2 co-occurring diseases across four common cardiometabolic and chronic pulmonary disease groups. Multivariate-adjusted PAFs for poverty, obesity, smoking, hypertension, and low high-density lipoprotein (HDL) cholesterol were estimated. RESULTS: Among 16,676 adults, the age-standardized prevalence of multimorbidity was 9.3%. The occurrence of multimorbidity was greater with age, from 1.5% to 5.9%, 15.0% and 34.8% for adults aged 18-39, 40-54, 55-64 and 65-79 years, respectively. Multimorbidity was greatest among the poorest versus non-poorest adults and among blacks versus other races/ethnicities. Multimorbidity was also greater in adults with obesity, hypertension, and low HDL cholesterol. Risk factors with greatest PAFs were hypertension (38.8%; 95% confidence interval [CI] 29.4-47.4) and obesity (19.3%; 95% CI 10.2-28.2). CONCLUSIONS: In the USA, 9.3% of adults have multimorbidity across four chronic disease groups, with a disproportionate burden among older, black, and poor adults. Our results suggest that targeting two intermediate modifiable risk factors, hypertension and obesity, might help to reduce the prevalence of multimorbidity in US adults.

Reduced Cardiovascular Disease Incidence With a National Lifestyle Change Program.

INTRODUCTION: Lifestyle change programs implemented within healthcare systems could reach many Americans, but their impact on cardiovascular disease (CVD) remains unclear. The MOVE! program is the largest lifestyle change program implemented in a healthcare setting in the U.S. This study aimed to determine whether MOVE! participation was associated with reduced CVD incidence. METHODS: This retrospective cohort study, analyzed in 2013-2015, used national Veterans Health Administration databases to identify MOVE! participants and eligible non-participants for comparison (2005-2012). Patients eligible for MOVE!-obese or overweight with a weight-related health condition, and no baseline CVD-were examined (N=1,463,003). Of these, 169,248 (12%) were MOVE! PARTICIPANTS: Patients were 92% male, 76% white, with mean age 52 years and BMI of 32. The main outcome was incidence of CVD (ICD-9 and procedure codes for coronary artery disease, cerebrovascular disease, peripheral vascular disease, and heart failure). RESULTS: Adjusting for age, race, sex, BMI, statin use, and baseline comorbidities, over a mean 4.9 years of follow-up, MOVE! participation was associated with lower incidence of total CVD (hazard ratio [HR]=0.83, 95% CI=0.80, 0.86); coronary artery disease (HR=0.81, 95% CI=0.77, 0.86); cerebrovascular disease (HR=0.87, 95% CI=0.82, 0.92); peripheral vascular disease (HR=0.89, 95% CI=0.83, 0.94); and heart failure (HR=0.78, 95% CI=0.74, 0.83). The association between MOVE! participation and CVD incidence remained significant when examined across categories of race/ethnicity, BMI, diabetes, hypertension, smoking status, and statin use. CONCLUSIONS: Although participation was limited, MOVE! was associated with reduced CVD incidence in a nationwide healthcare setting.

The Stepwise Approach to Diabetes Prevention: Results From the D-CLIP Randomized Controlled Trial.

OBJECTIVE: This study tests the effectiveness of expert guidelines for diabetes prevention: lifestyle intervention with addition of metformin, when required, among people with prediabetes. RESEARCH DESIGN AND METHODS: The Diabetes Community Lifestyle Improvement Program (D-CLIP) is a randomized, controlled, translation trial of 578 overweight/obese Asian Indian adults with isolated impaired glucose tolerance (iIGT), isolated impaired fasting glucose (iIFG), or IFG+IGT in Chennai, India. Eligible individuals were identified through community-based recruitment and randomized to standard lifestyle advice (control) or a 6-month, culturally tailored, U.S. Diabetes Prevention Program-based lifestyle curriculum plus stepwise addition of metformin (500 mg, twice daily) for participants at highest risk of conversion to diabetes at ≥4 months of follow-up. The primary outcome, diabetes incidence, was assessed biannually and compared across study arms using an intention-to-treat analysis. RESULTS: During 3 years of follow-up, 34.9% of control and 25.7% of intervention participants developed diabetes (P = 0.014); the relative risk reduction (RRR) was 32% (95% CI 7-50), and the number needed to treat to prevent one case of diabetes was 9.8. The RRR varied by prediabetes type (IFG+IGT, 36%; iIGT, 31%; iIFG, 12%; P = 0.77) and was stronger in participants 50 years or older, male, or obese. Most participants (72.0%) required metformin in addition to lifestyle, although there was variability by prediabetes type (iIFG, 76.5%; IFG+IGT, 83.0%; iIGT, 51.3%). CONCLUSIONS: Stepwise diabetes prevention in people with prediabetes can effectively reduce diabetes incidence by a third in community settings; however, people with iIFG may require different interventions.

Association of persistent organic pollutants and non-persistent pesticides with diabetes and diabetes-related health outcomes in Asia: A systematic review.

BACKGROUND: Over half of the people with diabetes in the world live in Asia. Emerging scientific evidence suggests that diabetes is associated with environmental pollutants, exposures that are also abundant in Asia. OBJECTIVE: To systematically review the literature concerning the association of persistent organic pollutants (POPs) and non-persistent pesticides with diabetes and diabetes-related health outcomes in Asia. METHODS: PubMed and Embase were searched to identify studies published up to November 2014. A secondary reference review of all extracted articles and the National Toxicology Program Workshop on the association of POPs with diabetes was also conducted. A total of 19 articles met the inclusion criteria and were evaluated in this review. RESULTS: To date, the evidence relating POPs and non-persistent pesticides with diabetes in Asian populations is equivocal. Positive associations were reported between serum concentrations of polychlorinated dibenzodioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and several organochlorine pesticides (DDT, DDE, oxychlordane, trans-nonachlor, hexachlorobenzene, hexachlorocyclohexane) with diabetes. PCDD/Fs were also associated with blood glucose and insulin resistance, but not beta-cell function. There were substantial limitations of the literature including: most studies were cross-sectional, few studies addressed selection bias and confounding, and most effect estimates had exceptionally wide confidence intervals. Few studies evaluated the effects of organophosphates. CONCLUSIONS: Well-conducted research is urgently needed on these pervasive exposures to inform policies to mitigate the diabetes epidemic in Asia.

The role of lifestyle change for prevention of cardiovascular disease in diabetes.

The burden of cardiovascular disease (CVD) is disproportionately greater in those with diabetes than in the general population, including higher rates of hospitalization, stroke, myocardial infarction, and mortality. Health-promoting lifestyle factors reduce both diabetes and CVD in healthy individuals; however, the efficacy of these strategies for CVD reduction in people with preexisting diabetes is unclear. In this review, we describe the most recent evidence (2013-2014) surrounding the effects of lifestyle changes on CVD outcomes in those with diabetes, and we contextualize the evidence against a backdrop of earlier key findings. Two major randomized controlled trials were identified, providing opposing conclusions about the role of lifestyle factors on CVD events in those with diabetes. Other recent prospective observational analyses support associations of physical activity and reduced CVD risk in diabetes. Limitations across studies include the use of self-report for measurement of lifestyle or lifestyle change, the length of follow-up needed to measure CVD outcomes, and the role of participants' medications on associations of lifestyle factors and CVD outcomes. Equivocal findings from the two randomized controlled trials support the need for additional research to identify the specific lifestyle factors that reduce CVD mortality and macrovascular complications in populations with diabetes.

A systematic review of overweight, obesity, and type 2 diabetes among Asian American subgroups.

This systematic review synthesizes data published between 1988 and 2009 on mean BMI and prevalence of overweight, obesity, and type 2 diabetes among Asian subgroups in the U.S. We conducted systematic searches in Pub- Med for peer-reviewed, English-language citations that reported mean BMI and percent overweight, obesity, and diabetes among South Asians/Asian Indians, Chinese, Filipinos, Koreans, and Vietnamese. We identified 647 database citations and 23 additional citations from hand-searching. After screening titles, abstracts, and full-text publications, 97 citations remained. None were published between 1988 and 1992, 28 between 1993 and 2003, and 69 between 2004 and 2009. Publications were identified for the following Asian subgroups: South Asian (n=8), Asian Indian (n=20), Chinese (n=44), Filipino (n=22), Korean (n= 8), and Vietnamese (n=3). The observed sample sizes ranged from 32 to 4245 subjects with mean ages from 24 to 78 years. Among samples of men and women, the lowest reported mean BMI was in South Asians (22.1 kg/m(2)), and the highest was in Filipinos (26.8 kg/m(2)). Estimates for overweight (12.8-46.7%) and obesity (2.1-59.0%) were variable. Among men and women, the highest rate of diabetes was reported in Asian Indians with BMI ≥ 30 kg/m(2) (32.9%, age and sex standardized). This review suggests heterogeneity among U.S. Asian populations in cardiometabolic risk factors, yet comparisons are limited due to variability in study populations, methods, and definitions used in published reports. Future efforts should adopt standardized methods to understand overweight, obesity and diabetes in this growing U.S. ethnic population.