Methods and participant characteristics in the Cancer Risk in Vegetarians Consortium: a cross-sectional analysis across 11 prospective studies.

BACKGROUND: The associations of vegetarian diets with risks for site-specific cancers have not been estimated reliably due to the low number of vegetarians in previous studies. Therefore, the Cancer Risk in Vegetarians Consortium was established. The aim is to describe and compare the baseline characteristics between non-vegetarian and vegetarian diet groups and between the collaborating studies. METHODS: We harmonised individual-level data from 11 prospective cohort studies from Western Europe, North America, South Asia and East Asia. Comparisons of food intakes, sociodemographic and lifestyle factors were made between diet groups and between cohorts using descriptive statistics. RESULTS: 2.3 million participants were included; 66% women and 34% men, with mean ages at recruitment of 57 (SD: 7.8) and 57 (8.6) years, respectively. There were 2.1 million meat eaters, 60,903 poultry eaters, 44,780 pescatarians, 81,165 vegetarians, and 14,167 vegans. Food intake differences between the diet groups varied across the cohorts; for example, fruit and vegetable intakes were generally higher in vegetarians than in meat eaters in all the cohorts except in China. BMI was generally lower in vegetarians, particularly vegans, except for the cohorts in India and China. In general, but with some exceptions, vegetarians were also more likely to be highly educated and physically active and less likely to smoke. In the available resurveys, stability of diet groups was high in all the cohorts except in China. CONCLUSIONS: Food intakes and lifestyle factors of both non-vegetarians and vegetarians varied markedly across the individual cohorts, which may be due to differences in both culture and socioeconomic status, as well as differences in questionnaire design. Therefore, care is needed in the interpretation of the impacts of vegetarian diets on cancer risk.

Regional and socio-demographic variation in laboratory-based predictions of 10-year cardiovascular disease risk among adults in north and south India.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in India. There is no laboratory-based CVD risk data among Indians from different regions and backgrounds. This study estimated laboratory-based 10-year CVD risk across different population sub-groups. METHODS: Data from UDAY derived from cross-sectional surveys of rural and urban populations of northern (Haryana) and southern (Andhra Pradesh) India were analysed. World Health Organization/International Society of Hypertension laboratory-based equations calculated 10-year CVD risk among participants without CVD history. Wilcoxon rank sum test analyzed average CVD risk across subgroups. Chi-square test compared population proportions in different CVD risk categories. Regression analysis assessed the association between CVD risk and participant characteristics. RESULTS: The mean (SD) age of the participants (n = 8448) was 53.2 (9.2) years. Males in Haryana had increased CVD risk compared to those in Andhra Pradesh (p < 0.01). In both states, female gender was shown to have a protective effect on CVD risk (p < 0.01). Age correlated with increased risk (p < 0.01). Education level did not affect CVD risk however employment status may have. Hypertension, diabetes, hyperlipidemia, smoking, and insufficient exercise were associated with increased CVD risk (p < 0.01). Residence (urban versus rural) and wealth index did not largely affect CVD risk. CONCLUSION: Minor differences exist in the distribution of laboratory-based CVD risk across Indian population cohorts. CVD risk was similar in urban wealthy participants and rural poor and working-class communities in northern and southern India. Public health efforts need to target all major segments of the Indian population to curb the CVD epidemic.

Effect of Yoga-Based Cardiac Rehabilitation Program on Endothelial Function, Oxidative Stress, and Inflammatory Markers in Acute Myocardial Infarction: A Randomized Controlled Trial.

Aims: The aim of this study was to evaluate the effects of yoga-based cardiac rehabilitation (Yoga-CaRe) on the endothelial system, oxidative stress, and inflammatory markers in patients with acute myocardial infarction (MI). Methods: A sub-study was conducted in two clinical sites of the Yoga-CaRe trial (a multicenter randomized controlled trial). Participants with acute MI were randomized and allocated to either the Yoga-CaRe program (13 sessions with encouragement to home practice) or enhanced standard care (three educational sessions). Endothelial function, oxidative stress, and inflammatory biomarkers were assessed using biomarkers such as asymmetric dimethylarginine (ADMA), endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), E-selectin, P-selectin, vascular cell adhesion molecule (VCAM), intercellular cell-adhesion molecule-1, total nitric oxide concentration (NOx), oxidized low-density lipoprotein (Oxd-LDL), superoxide dismutase, total antioxidant capacity (TAOC), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) at baseline and 12 weeks. Laboratory and statistical analysis were done by staff blinded to group allocation. Results: Eighty-two patients (of the 110 patients recruited) completed the study. The mean age was 53.1 ± 10.6 and 51.9 ± 10.7 years in enhanced standard care and Yoga-CaRe group, respectively. At 12 weeks, Yoga-CaRe significantly reduced ADMA, ET-1, and ICMA-1 than the enhanced standard care group. Although E-selectin and VCAM at 12 weeks were reduced in both groups, enhanced standard care had a significantly higher reduction than the Yoga-CaRe group. Among markers of oxidative stress, TAOC increased in the Yoga-CaRe group. We found no difference in eNOS, NOx, P-selectin, TNFα, CRP, and Oxd-LDL between the two groups. Conclusion: Yoga-CaRe improved the endothelial function (through a reduction in ET-1 and modulating adhesion molecules) and enhanced antioxidant capacity.

Development of a risk prediction model for postpartum onset of type 2 diabetes mellitus, following gestational diabetes; the lifestyle InterVention in gestational diabetes (LIVING) study.

AIMS: This study aimed to develop a prediction model for identifying a woman with gestational diabetes mellitus (GDM) at high risk of type 2 diabetes (T2DM) post-birth. METHODS: Utilising data from 1299 women in the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, two models were developed: one for pregnancy and another for postpartum. Key predictors included glucose test results, medical history, and biometric indicators. RESULTS: Of the initial cohort, 124 women developed T2DM within three years. The study identified seven predictors for the antenatal T2DM risk prediction model and four for the postnatal one. The models demonstrated good to excellent predictive ability, with Area under the ROC Curve (AUC) values of 0.76 (95% CI: 0.72 to 0.80) and 0.85 (95% CI: 0.81 to 0.88) for the antenatal and postnatal models, respectively. Both models underwent rigorous validation, showing minimal optimism in predictive capability. Antenatal model, considering the Youden index optimal cut-off point of 0.096, sensitivity, specificity, and accuracy were measured as 70.97%, 70.81%, and 70.82%, respectively. For the postnatal model, considering the cut-off point 0.086, sensitivity, specificity, and accuracy were measured as 81.40%, 75.60%, and 76.10%, respectively. CONCLUSIONS: These models are effective for predicting T2DM risk in women with GDM, although external validation is recommended before widespread application.

Potential Mediating Role of Iron Biomarkers in the Association of Sex With Glucose, Insulin, and Type 2 Diabetes.

Context: Sex-specific prevalence and incidence of type 2 diabetes (T2D) have been reported, but the underlying mechanisms are uncertain. Objective: In this study, we aimed to investigate whether iron biomarkers mediate the association between biological sex and glucose metabolism and the incidence of T2D. Methods: We used data from the general population enrolled in the prospective Prevention of REnal and Vascular ENd-stage Disease study in Groningen, The Netherlands. We measured ferritin, transferrin saturation (TSAT), hepcidin, soluble transferrin receptor (sTfR), fasting plasma glucose (FPG), fasting plasma insulin (FPI) levels, and incidence of T2D. We used multivariable regression and mediation analyses to investigate our hypothesis. All iron biomarkers, FPG, and FPI were log-transformed. Results: The mean (SD) age of the 5312 (51.3% female) individuals was 52.2 (11.6) years. Compared with males, females had lower FPG (ß = -.01; 95% CI -0.02, -0.01) and FPI (ß = -.03; 95% CI -0.05, -0.02) levels. Ferritin, hepcidin, and sTfR showed potential mediating effects on the association between sex and FPG, 21%, 5%, and 7.1%, respectively. Furthermore, these variables mediated 48.6%, 5.7%, and 3.1% of the association between sex and FPI, respectively. Alternatively, TSAT had a suppressive mediating role in the association of sex with FPG and FPI. The incidence of T2D was lower in females than in males (hazard ratio 0.58; 95% CI 0.44, 0.77), with 19.2% of this difference being mediated by ferritin. Conclusion: Iron biomarkers may partially mediate the association between sex and glucose homeostasis. Future studies addressing the causality of our findings are needed.

Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular disease.

Fixed-dose combination (FDC) therapy, also known as polypill therapy, targets risk factors for atherosclerotic cardiovascular disease (ASCVD) and has been proposed as a strategy to reduce global ASCVD burden. Here we conducted a systematic search for relevant studies from 2016-2022 to assess the effects of FDC therapy for prevention of ASCVD. The studies selected include randomized trials evaluating FDC therapy with at least one blood pressure-lowering drug and one lipid-lowering drug. The study data were independently extracted, the quality of evidence was appraised by multiple reviewers and effect estimates were pooled using a fixed-effect meta-analysis when statistical heterogeneity was low to moderate. The main outcomes of the analysis were all-cause mortality, fatal and nonfatal ASCVD events, adverse events, systolic blood pressure, low-density lipoprotein cholesterol and adherence. Among 26 trials (n = 27,317 participants, 43.2% female and mean age range 52.9-76.0), FDC therapy was associated with lower low-density lipoprotein cholesterol and systolic blood pressure, with higher rates of adherence and adverse events in both primary and mixed secondary prevention populations. For studies with a mostly primary prevention population, FDC therapy was associated with lower risk of all-cause mortality by 11% (5.6% versus 6.3%; relative risk (risk ratio) of 0.89; 95% confidence interval 0.78 to 1.00; I2 = 0%; four trials and 16,278 participants) and risk of fatal and nonfatal ASCVD events by 29% (6.1% versus 8.4%; relative risk (risk ratio) of 0.71; 95% confidence interval 0.63 to 0.79; I2 = 0%; five trials and 15,503 participants). One adequately powered trial in an exclusively secondary prevention population showed that FDC therapy reduced the risk of major adverse cardiovascular events by 24%. These findings support adoption and implementation of polypills to lower risk for all-cause mortality and ASCVD.

Association of pro-inflammatory cytokines, adipokines and hepatokine with incident diabetes in India: a nested case-control study within CARRS cohort.

AIMS: To study the association of pro-inflammatory markers with incident diabetes in India. METHODS: We did a nested case-control study within the CARRS (Centre for Ardiometabolic Risk Reduction in South Asia) cohort. Of the 5739 diabetes-free individuals at the baseline, 216 participants with incident diabetes and 432 age-, gender- and city-matched controls at 2-year follow-up were included. We measured high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 ( MCP-1), adiponectin, leptin and fetuin-A in the stored baseline blood samples. We did multivariate conditional logistic regression to estimate association of inflammatory markers (as quartiles) and incident diabetes. Covariates were baseline fasting plasma glucose (FPG) and lipids, body mass index (BMI), family history of diabetes, smoking and alcohol use. RESULTS: Baseline hsCRP and TNF-α were higher, and IL-6 and adiponectin were lower among cases vs. controls. In multivariate conditional logistic regression models, only quartile-3 (odds ratio [OR]: 2.96 [95% CI:1.39, 6.30]) and quartile-4 (OR: 2.58 [95% CI: 1.15, 5.79]) of TNF-α and quartile-4 of MCP-1 (OR: 2.55 [95% CI: 1.06, 6.16]) were positively associated with diabetes after adjusting for baseline FPG and BMI. These associations did not remain after adjusting for family history. High level (quartile-4) of IL-6 was negatively associated with diabetes after adjusting for all factors (OR: 0.18 [95% CI: 0.06, 0.55]). CONCLUSIONS: Higher TNF-α and MCP-1 levels and lower IL-6 were associated with higher risk of developing diabetes. Better understanding and potential methods of addressing these biomarkers, especially in relation to family history, are needed to address diabetes in South Asians.

The path to universal health coverage in five African and Asian countries: examining the association between insurance status and health-care use.

Despite major efforts to achieve universal health coverage (UHC), progress has lagged in many African and Asian countries. A key strategy pursued by many countries is the use of health insurance to increase access and affordability. However, evidence on insurance coverage and on the association between insurance and UHC is mixed. We analysed nationally representative cross-sectional data collected between 2022 and 2023 in Ethiopia, Kenya, South Africa, India, and Laos. We described public and private insurance coverage by sociodemographic factors and used logistic regression to examine the associations between insurance status and seven health-care use outcomes. Health insurance coverage ranged from 25% in India to 100% in Laos. The share of private insurance ranged from 1% in Ethiopia to 13% in South Africa. Relative to the population with private insurance, the uninsured population had reduced odds of health-care use (adjusted odds ratio 0·68, 95% CI 0·50-0·94), cardiovascular examinations (0·63, 0·47-0·85), eye and dental examinations (0·54, 0·42-0·70), and ability to get or afford care (0·64, 0·48-0·86); private insurance was not associated with unmet need, mental health care, and cancer screening. Relative to private insurance, public insurance was associated with reduced odds of health-care use (0·60, 0·43-0·82), mental health care (0·50, 0·31-0·80), cardiovascular examinations (0·62, 0·46-0·84), and eye and dental examinations (0·50, 0·38-0·65). Results were highly heterogeneous across countries. Public health insurance appears to be only weakly associated with access to health services in the countries studied. Further research is needed to improve understanding of these associations and to identify the most effective financing strategies to achieve UHC.

Standardized treatment protocols for hypertension: global availability, characteristics, and alignment with the hypertension guideline recommendations.

BACKGROUND: Hypertension control is suboptimal globally. Implementing evidence-based, simple, standardized treatment protocols (STPs) has been instrumental in effectively and efficiently improving treatment and control of hypertension. We aimed to identify, characterize, and critically appraise hypertension STPs. METHODS: We defined STP as a series of steps for the pharmacological treatment of primary hypertension, with information on target population, BP threshold for treatment initiation, target BP, specific drugs/classes/doses, and follow-up frequency. STPs for adult patients were identified from the websites of relevant health organizations, Google search, and through expert consultations (until July 2023). STPs for secondary, gestational, or malignant hypertension or those that were templates/samples were excluded. Included STPs were critically appraised using HEARTS in the Americas Checklist for hypertension management in primary care and compared with the 2021 WHO hypertension management guideline recommendations. RESULTS: Fifty STPs were identified. All STPs had a stepwise treatment approach, involved guideline-recommended first-line drugs, and 98% consisted of at least four steps. Majority (54%) recommended monotherapy with calcium channel blockers as first-line treatment. Only 44% STPs recommended treatment initiation with combination therapy, and 16% recommended single-pill combinations. Most (62%) had dose-intensification as the second step. Most (74%) STPs did not provide complete dosing information. Only one STP mentioned a target time for achieving BP control. On average, STPs scored a performance of 68% on the HEARTS Checklist. CONCLUSION: Several STPs are available globally; however, most of them have enormous scope for improvement through interventions aimed at alignment with the latest evidence-based guidelines and multistakeholder engagement.

Changing socioeconomic and geographic gradients in cardiovascular disease risk factors among Indians aged 15-49 years - evidence from nationally representative household surveys.

Background: Cardiovascular diseases (CVDs) are the leading cause of death in most low- and middle-income countries (LMICs). CVDs and their metabolic risk factors have historically been concentrated among urban residents with higher socioeconomic status (SES) in LMICs such as India. However, as India develops, it is unclear whether these socioeconomic and geographic gradients will persist or change. Understanding these social dynamics in CVD risk is essential for mitigating the rising burden of CVDs and to reach those with the greatest needs. Methods: Using nationally representative data with biomarker measurements from the fourth (2015-16) and fifth (2019-21) Indian National Family and Health Surveys, we investigated trends in the prevalence of four CVD risk factors: smoking (self-reported), unhealthy weight (BMI ≥25 kgm2), diabetes (random plasma glucose concentration ≥200 mg/dL or self-reported diabetes), and hypertension (one of: average systolic blood pressure ≥140 mmHg, average diastolic blood pressure ≥90 mmHg, self-reported past diagnosis, or self-reported current antihypertensive medication use) among adults aged 15-49 years. We first described changes at the national level and then trends stratified by place of residence (urban versus rural), geographic region (northern, northeastern, central, eastern, western, southern), regional level of development (Empowered Action Group member state or not), and two measures of socioeconomic status: level of education (no education, primary incomplete, primary complete, secondary incomplete, secondary complete, higher) and wealth (quintiles). Findings: Unhealthy weight increased among all social and geographic groups but both the absolute and the relative changes were substantially higher among people with low SES (as measured by education or wealth) and in rural areas. For diabetes and hypertension, the prevalence increased for those from disadvantaged groups while staying constant or even decreasing among the wealthier and more educated. In contrast, smoking consumption declined for all social and geographic groups. Interpretation: In 2015-16, CVD risk factors were higher among more advantaged subpopulations in India. However, between 2015-16 and 2019-21, the prevalence of these risk factors grew more rapidly for less wealthy and less educated subpopulations and those living in rural areas. These trends have resulted in CVD risk becoming far more widespread throughout the population; CVD can no longer be characterized as a wealthy urban phenomenon. Funding: This work was supported by the Alexander von Humboldt Foundation (grant received by NS); the Stanford Diabetes Research Center [grant received by PG] and the Chan Zuckerberg Biohub [grant received by PG].

Corrigendum: Impact of a tobacco sales ban on the frequency of tobacco consumption in India during the COVID-19 pandemic.

[This corrects the article DOI: 10.18332/tid/161855.].

Impact of a tobacco sales ban on the frequency of tobacco consumption in India during the COVID-19 pandemic.

INTRODUCTION: Measures to address the COVID-19 pandemic in India included a ban on the sale and use of tobacco products during 2020 when stay at home guidance (lockdown) was in place. In this study we examined the extent of reduction in frequency of tobacco consumption across all products. METHODS: Telephone survey was conducted between July and August 2020 across an existing cohort of tobacco users (n=801) residing in Delhi (55.4%) and Chennai (44.6%), India. The participants were recruited irrespective of their gender and use of any kind of tobacco product(s). The survey questionnaire was based on the STOP (Studying Tobacco users Of Pakistan) survey and adapted to the context of smoking and smokeless tobacco use in India. RESULTS: Cigarette consumption declined from a median value of 5.0 (IQR: 2-10) sticks in the pre-lockdown period to 2.0 (IQR: 0.4-5) sticks during the lockdown period. Reductions were reported in the daily use of bidis, from 8 (IQR: 4-12) sticks to 5 (IQR: 2-10) sticks and for smokeless tobacco users from 3.5 (IQR: 2-5) packs to 2 (IQR: 1-4) packs during the lockdown. Furthermore, the number of daily cigarette smokers in our cohort decreased from 32.6% (n=261) in the pre-lockdown period to 27.5% (n=220) during lockdown and smokeless tobacco users decreased from 35.8% (n=287) in pre-lockdown period to 30.3% (n=243) during the lockdown period. CONCLUSIONS: The decrease in tobacco use can be attributed to various societal and environmental factors. However, the pandemic-linked lockdown provided an opportune condition to reduce the use of tobacco products, which could be due to restricted access and increase in health awareness during the COVID-19 lockdown.

Linking population-based cohorts with cancer registries in LMIC: a case study and lessons learnt in India.

OBJECTIVES: In resource-constrained settings, cancer epidemiology research typically relies on self-reported diagnoses. To test a more systematic alternative approach, we assessed the feasibility of linking a cohort with a cancer registry. SETTING: Data linkage was performed between a population-based cohort in Chennai, India, with a local population-based cancer registry. PARTICIPANTS: Data set of Centre for Cardiometabolic Risk Reduction in South-Asia (CARRS) cohort participants (N=11 772) from Chennai was linked with the cancer registry data set for the period 1982-2015 (N=140 986). METHODS AND OUTCOME MEASURES: Match*Pro, a probabilistic record linkage software, was used for computerised linkages followed by manual review of high scoring records. The variables used for linkage included participant name, gender, age, address, Postal Index Number and father's and spouse's name. Registry records between 2010 and 2015 and between 1982 and 2015, respectively, represented incident and all (both incident and prevalent) cases. The extent of agreement between self-reports and registry-based ascertainment was expressed as the proportion of cases found in both data sets among cases identified independently in each source. RESULTS: There were 52 self-reported cancer cases among 11 772 cohort participants, but 5 cases were misreported. Of the remaining 47 eligible self-reported cases (incident and prevalent), 37 (79%) were confirmed by registry linkage. Among 29 self-reported incident cancers, 25 (86%) were found in the registry. Registry linkage also identified 24 previously not reported cancers; 12 of those were incident cases. The likelihood of linkage was higher in more recent years (2014-2015). CONCLUSIONS: Although linkage variables in this study had limited discriminatory power in the absence of a unique identifier, an appreciable proportion of self-reported cases were confirmed in the registry via linkages. More importantly, the linkages also identified many previously unreported cases. These findings offer new insights that can inform future cancer surveillance and research in low-income and middle-income countries.

Collaborative Quality Improvement Strategy in Secondary Prevention of Cardiovascular Disease in India: Findings from a Multi-Stakeholder, Qualitative Study using Consolidated Framework for Implementation Research (CFIR).

Background: Cardiovascular disease (CVD) is highly prevalent in India, and little is known about the perception of patients and providers about a package of collaborative quality improvement (C-QIP) strategies consisting of provider-focused electronic health records-decision support system (EHR-DSS), non-physician health workers (NPHW), and patient-facing text messages to enhance the CVD care. Objective: To explore the barriers and enablers of the C-QIP strategy from the perspective of providers, health administrators, patients, and care givers in India. Methods: We conducted a qualitative study using the consolidated framework for implementation research (CFIR) to understand the challenges and facilitators of implementing C-QIP strategy to enhance CVD care in the Indian context. A diverse sample of 38 physicians, 14 non-physician health workers (nurses, pharmacists), 4 health administrators, and 16 patients and their caregivers participated in semi-structured interviews. All interviews were audio-recorded, transcribed, translated, anonymised, and coded using MAXQDA software. We used the framework method and CFIR domains to analyze the qualitative data. Results: Barriers perceived from providers' and health administrators' perspectives in providing quality CVD care were high patient volume, physician burnout, lack of robust communication or referral system, paucity of electronic health records, lack of patient counsellors, polypharmacy, poor patient adherence to medications, and lack of financial incentives. Low health literacy, high cost of treatment, misinformation bias, and difficulty in maintaining lifestyle changes were barriers from patients' perspectives. The CFIR identified key enablers for the implementation of C-QIP such as standardized treatment protocol, reduced medication errors, improved physician-patient relationships, and enhanced patient self-care through trained and supported NPHW. Barriers included: heterogenous healthcare settings, diverse patient groups and comorbidities, associated costs of care and interoperability, confidentiality, and data privacy issues around the use of EHR-DSS. Conclusion: Strategies to enhance CVD care must be low-cost, culturally acceptable, and integrated into existing care pathways.

Anxiety and depression among adult tobacco users during the COVID-19 restrictions in India.

Background: The world witnessed a highly contagious and deadly disease, COVID-19, toward the end of 2019. India is one of the worst affected countries. We aimed to assess anxiety and depression levels among adult tobacco users and people who recently quit tobacco during COVID-19 lockdown in India. Materials and methods: The study was conducted across two Indian cities, Delhi and Chennai (July-August, 2020) among adult tobacco users (n = 801). Telephonic interviews were conducted using validated mental health tools (Patient Health Questionnaire-PHQ-9 and Generalized Anxiety Disorder-GAD-7) to assess the anxiety and depression levels of the participants. Descriptive analysis and multiple logistic regression were used to study the prevalence and correlates of depression and anxiety. Results: We found that 20.6% of tobacco users had depression symptoms (3.9% moderate to severe); 20.7% had anxiety symptoms (3.8% moderate to severe). Risk factors associated with depression and anxiety included food, housing, and financial insecurity. Conclusion: During COVID-19 lockdown, mental health of tobacco users (primarily women) was associated with food, housing and financial insecurity. The Indian Government rightly initiated several health, social and economic measures to shield the most vulnerable from COVID-19, including a ban on the sale of tobacco products. It is also necessary to prioritize universal health coverage, expanded social security net, tobacco cessation and mental health services to such vulnerable populations during pandemic situations.

Cardiovascular Health in India - a Report Card from Three Urban and Rural Surveys of 22,144 Adults.

Background: Markers of ideal cardiovascular health (CVH) predict cardiovascular events. We estimated the prevalence of ideal CVH markers in two levels of cities and villages in India. Methods: We did pooled analysis of individual-level data from three cross sectional surveys of adults ≥ 30 years over 2010-14 (CARRS: Centre for cArdiometabolic Risk Reduction in South Asia; UDAY and Solan Surveillance Study) representing metropolitan cities; smaller cities and rural areas in diverse locations of India. We defined ideal CVH using modified American Heart Association recommendations: not smoking, ≥ 5 servings of fruits and vegetables (F&V), high physical activity (PA), body mass index (BMI) <25 Kg/m2, blood pressure (BP) <120/80 mm Hg, fasting plasma glucose (FPG) <100 mg/dl, and total cholesterol (TC) <200 mg/dL. We estimated (1) age-and sex-standardized prevalence of ideal CVH and (2) prevalence of good (≥6 markers), moderate (4-5), and poor CVH (≤3) adjusted for age, sex, education, and stratified by setting and asset tertiles. Results: Of the total 22,144 participants, the prevalence of ideal CVH markers were: not smoking (76.7% [95% CI 76.1, 77.2]), consumed ≥5 F&V (4.2% [3.9, 4.5]), high PA (67.5% [66.8, 68.2]), optimum BMI (59.6% [58.9, 60.3]), ideal BP (34.5% [33.9, 35.2]), FPG (65.8% [65.1, 66.5]) and TC (65.4% [64.7, 66.1]). The mean number of ideal CVH metrics was 3.7(95% CI: 3.7, 3.8). Adjusted prevalence of good, moderate, and poor CVH, varied across settings: metropolitan (3.9%, 41.0%, and 55.1%), smaller cities (7.8%, 49.2%, and 43%), and rural (10.4%, 60.9%, and 28.7%) and across asset tertiles: Low (11.0%, 55.9%, 33.1%), Middle (6.3%, 52.2%, 41.5%), and High (5.0%, 46.4%, 48.7%), respectively. Conclusion: Achievement of ideal CVH varied, with higher prevalence in rural and lower asset tertiles. Multi-sectoral and targeted policy and program actions are needed to improve CVH in diverse contexts in India.

Effects of a Lifestyle Intervention to Prevent Deterioration in Glycemic Status Among South Asian Women With Recent Gestational Diabetes: A Randomized Clinical Trial.

Importance: Women with recent gestational diabetes (GDM) have increased risk of developing type 2 diabetes. Objective: To investigate whether a resource-appropriate and context-appropriate lifestyle intervention could prevent glycemic deterioration among women with recent GDM in South Asia. Design, Setting, and Participants: This randomized, participant-unblinded controlled trial investigated a 12-month lifestyle intervention vs usual care at 19 urban hospitals in India, Sri Lanka, and Bangladesh. Participants included women with recent diagnosis of GDM who did not have type 2 diabetes at an oral glucose tolerance test (OGTT) 3 to 18 months postpartum. They were enrolled from November 2017 to January 2020, and follow-up ended in January 2021. Data were analyzed from April to July 2021. Interventions: A 12-month lifestyle intervention focused on diet and physical activity involving group and individual sessions, as well as remote engagement, adapted to local context and resources. This was compared with usual care. Main Outcomes and Measures: The primary outcome was worsening category of glycemia based on OGTT using American Diabetes Association criteria: (1) normal glucose tolerance to prediabetes (ie, impaired fasting glucose or impaired glucose tolerance) or type 2 diabetes or (2) prediabetes to type 2 diabetes. The primary analysis consisted of a survival analysis of time to change in glycemic status at or prior to the final patient visit, which occurred at varying times after 12 months for each patient. Secondary outcomes included new-onset type 2 diabetes and change in body weight. Results: A total of 1823 women (baseline mean [SD] age, 30.9 [4.9] years and mean [SD] body mass index, 26.6 [4.6]) underwent OGTT at a median (IQR) 6.5 (4.8-8.2) months postpartum. After excluding 160 women (8.8%) with type 2 diabetes, 2 women (0.1%) who met other exclusion criteria, and 49 women (2.7%) who did not consent or were uncontactable, 1612 women were randomized. Subsequently, 11 randomized participants were identified as ineligible and excluded from the primary analysis, leaving 1601 women randomized (800 women randomized to the intervention group and 801 women randomized to usual care). These included 600 women (37.5%) with prediabetes and 1001 women (62.5%) with normoglycemia. Among participants randomized to the intervention, 644 women (80.5%) received all program content, although COVID-19 lockdowns impacted the delivery model (ie, among 644 participants who engaged in all group sessions, 476 women [73.9%] received some or all content through individual engagement, and 315 women [48.9%] received some or all content remotely). After a median (IQR) 14.1 (11.4-20.1) months of follow-up, 1308 participants (81.2%) had primary outcome data. The intervention, compared with usual care, did not reduce worsening glycemic status (204 women [25.5%] vs 217 women [27.1%]; hazard ratio, 0.92; [95% CI, 0.76-1.12]; P = .42) or improve any secondary outcome. Conclusions and Relevance: This study found that a large proportion of women in South Asian urban settings developed dysglycemia soon after a GDM-affected pregnancy and that a lifestyle intervention, modified owing to the COVID-19 pandemic, did not prevent subsequent glycemic deterioration. These findings suggest that alternate or additional approaches are needed, especially among high-risk individuals. Trial Registration: Clinical Trials Registry of India Identifier: CTRI/2017/06/008744; Sri Lanka Clinical Trials Registry Identifier: SLCTR/2017/001; and ClinicalTrials.gov Identifier: NCT03305939.

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.

Health System Performance for Multimorbid Cardiometabolic Disease in India: A Population-Based Cross-Sectional Study.

Background: The prevalence of multimorbidity in low- and middle-income countries (LMICs) is thought to be rising rapidly. Research on the state of healthcare for multimorbidity in LMICs is needed to provide an impetus for integration of care across conditions, a baseline to monitor progress, and information for targeting of interventions to those most in need. Focusing on multimorbid cardiometabolic disease in India, this study thus aimed to determine 1) the proportion of adults with co-morbid diabetes and hypertension who successfully completed each step of the chronic disease care continuum from diagnosis to control for both conditions, and 2) how having additional cardiovascular disease (CVD) risk factors is associated with health system performance along the care continuum for diabetes, hypertension, and co-morbid diabetes and hypertension. Methods: Using a nationally representative household survey carried out in 2015 and 2016 among women aged 15-49 years and men aged 15-54 years, we created a 'cascade of care' for diabetes, hypertension, and co-morbid diabetes and hypertension by determining the proportion of those with the condition who had been diagnosed, were on treatment, and achieved control. We used Poisson regression with a robust error structure to estimate how having additional cardiovascular disease (CVD) risk factors (diabetes, hypertension, current smoking, and obesity) was associated with reaching each cascade step for diabetes, hypertension, and co-morbid diabetes and hypertension. Findings: Seven hundred thirty-four thousand seven hundred ninety-four adults were included in the analysis. Among individuals with co-morbid diabetes and hypertension, 28·8% (95% CI, 26·7%-31·0%), 16·1% (95% CI, 14·4%-17·9%), and 3·7% (95% CI, 2·8%-4·9%) - with these proportions varying between states by a factor of 4·8, 7·9, and 56·8 - were aware, treated, and achieved control of both conditions, respectively. Men, adults with lower household wealth, and those living in rural areas were less likely to reach each cascade step. Having additional CVD risk factors generally did not increase the probability of reaching each cascade step for diabetes, hypertension, and co-morbid diabetes and hypertension, except that having concurrent diabetes increased the probability of successfully transitioning through the hypertension care cascade. Interpretation: While varying widely between states and population groups, health system performance for co-morbid diabetes and hypertension is generally low in India, and there appears to be little integration of care across CVD risk factors. Funding: European Research Council.