Epigenome-wide meta-analysis of BMI in nine cohorts: Examining the utility of epigenetically predicted BMI.

This study sought to examine the association between DNA methylation and body mass index (BMI) and the potential of BMI-associated cytosine-phosphate-guanine (CpG) sites to provide information about metabolic health. We pooled summary statistics from six trans-ethnic epigenome-wide association studies (EWASs) of BMI representing nine cohorts (n = 17,034), replicated these findings in the Women's Health Initiative (WHI, n = 4,822), and developed an epigenetic prediction score of BMI. In the pooled EWASs, 1,265 CpG sites were associated with BMI (p < 1E-7) and 1,238 replicated in the WHI (FDR < 0.05). We performed several stratified analyses to examine whether these associations differed between individuals of European and African descent, as defined by self-reported race/ethnicity. We found that five CpG sites had a significant interaction with BMI by race/ethnicity. To examine the utility of the significant CpG sites in predicting BMI, we used elastic net regression to predict log-normalized BMI in the WHI (80% training/20% testing). This model found that 397 sites could explain 32% of the variance in BMI in the WHI test set. Individuals whose methylome-predicted BMI overestimated their BMI (high epigenetic BMI) had significantly higher glucose and triglycerides and lower HDL cholesterol and LDL cholesterol compared to accurately predicted BMI. Individuals whose methylome-predicted BMI underestimated their BMI (low epigenetic BMI) had significantly higher HDL cholesterol and lower glucose and triglycerides. This study confirmed 553 and identified 685 CpG sites associated with BMI. Participants with high epigenetic BMI had poorer metabolic health, suggesting that the overestimation may be driven in part by cardiometabolic derangements characteristic of metabolic syndrome.

Effect of a multicomponent quality improvement strategy on sustained achievement of diabetes care goals and macrovascular and microvascular complications in South Asia at 6.5 years follow-up: Post hoc analyses of the CARRS randomized clinical trial.

BACKGROUND: Diabetes control is poor globally and leads to burdensome microvascular and macrovascular complications. We aimed to assess post hoc between-group differences in sustained risk factor control and macrovascular and microvascular endpoints at 6.5 years in the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomized trial. METHODS AND FINDINGS: This parallel group individual randomized clinical trial was performed at 10 outpatient diabetes clinics in India and Pakistan from January 2011 through September 2019. A total of 1,146 patients with poorly controlled type 2 diabetes (HbA1c ≥8% and systolic BP ≥140 mm Hg and/or LDL-cholesterol ≥130 mg/dL) were randomized to a multicomponent quality improvement (QI) strategy (trained nonphysician care coordinator to facilitate care for patients and clinical decision support system for physicians) or usual care. At 2.5 years, compared to usual care, those receiving the QI strategy were significantly more likely to achieve multiple risk factor control. Six clinics continued, while 4 clinics discontinued implementing the QI strategy for an additional 4-year follow-up (overall median 6.5 years follow-up). In this post hoc analysis, using intention-to-treat, we examined between-group differences in multiple risk factor control (HbA1c <7% plus BP <130/80 mm Hg and/or LDL-cholesterol <100 mg/dL) and first macrovascular endpoints (nonfatal myocardial infarction, nonfatal stroke, death, revascularization [angioplasty or coronary artery bypass graft]), which were co-primary outcomes. We also examined secondary outcomes, namely, single risk factor control, first microvascular endpoints (retinopathy, nephropathy, neuropathy), and composite first macrovascular plus microvascular events (which also included amputation and all-cause mortality) by treatment group and whether QI strategy implementation was continued over 6.5 years. At 6.5 years, assessment data were available for 854 participants (74.5%; n = 417 [intervention]; n = 437 [usual care]). In terms of sociodemographic and clinical characteristics, participants in the intervention and usual care groups were similar and participants at sites that continued were no different to participants at sites that discontinued intervention implementation. Patients in the intervention arm were more likely to exhibit sustained multiple risk factor control than usual care (relative risk: 1.77; 95% confidence interval [CI], 1.45, 2.16), p < 0.001. Cumulatively, there were 233 (40.5%) first microvascular and macrovascular events in intervention and 274 (48.0%) in usual care patients (absolute risk reduction: 7.5% [95% CI: -13.2, -1.7], p = 0.01; hazard ratio [HR] = 0.72 [95% CI: 0.61, 0.86]), p < 0.001. Patients in the intervention arm experienced lower incidence of first microvascular endpoints (HR = 0.68 [95% CI: 0.56, 0.83), p < 0.001, but there was no evidence of between-group differences in first macrovascular events. Beneficial effects on microvascular and composite vascular outcomes were observed in sites that continued, but not sites that discontinued the intervention. CONCLUSIONS: In urban South Asian clinics, a multicomponent QI strategy led to sustained multiple risk factor control and between-group differences in microvascular, but not macrovascular, endpoints. Between-group reductions in vascular outcomes at 6.5 years were observed only at sites that continued the QI intervention, suggesting that practice change needs to be maintained for better population health of people with diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01212328.

Association between Dietary Practices and Growth Trajectories in Preschool Children.

OBJECTIVES: To estimate the association of dietary practices with early life weight among children born in 2001 in the U.S. METHODS: The Early Childhood Longitudinal Study (ECLS-B) is a population-based cohort followed from 9 months to Kindergarten entry (n~5000). We employed an auto-regressive cross-lagged model to assess the impacts of dietary practices on weight stability over time. We calculated age- and sex-standardized BMI z-scores using WHO growth curves. RESULTS: BMI z-scores had a stable increase over time. Later age of solid food introduction was associated with lower BMI z-score at age 2y [-0.03(-0.05,-0.004)]; having dinners more times per week with family at age 2y was associated with higher BMI z-score at 4y [0.03(0.01,0.05)]. These changes, of <0.05 BMI z-score, are small. Children with higher birthweight were introduced to solid foods at younger ages [-0.39 months(-0.45,-0.32)] and were breast fed longer [0.13 months(0.04,0.22)]. For girls, having dinner at a regular time at ages 2y and 4y was associated with lower BMI at ages 4y and 5y. CONCLUSIONS: Dietary practices in early childhood affect weight trajectories. However, these effects are small and are largely overshadowed by prior weight. Children's weight in infancy is associated with subsequent dietary practices but also small effects.

Rationale, Design and Baseline Characteristics of a Randomized Controlled Trial of a Cardiovascular Quality Improvement Strategy in India: The C-QIP Trial.

BACKGROUND: Quality of chronic care for cardiovascular disease (CVD) remains suboptimal worldwide. The Collaborative Quality ImProvement (C-QIP) trial aims to develop and test the feasibility and clinical effect of a multicomponent strategy among patients with prevalent CVD in India. METHODS: The C-QIP is a clinic-based, open randomized trial of a multicomponent intervention vs usual care that was locally developed and adapted for use in Indian settings through rigorous formative research guided by Consolidated Framework for Implementation Research (CFIR). The C-QIP intervention consisted of 5 components: 1) electronic health records and decision support system for clinicians, 2) trained nonphysician health workers (NPHW), 3) text-message based lifestyle reminders, 4) patient education materials, 5) quarterly audit and feedback reports. Patients with CVD (ischemic heart disease, ischemic stroke, or heart failure) attending outpatient CVD clinics were recruited from September 2022 to September 2023 and were randomized to the intervention or usual care arm for at least 12 months follow-up. The co-primary outcomes are implementation feasibility, fidelity (ie, dose delivered and dose received), acceptability, adoption and appropriateness, measured at multiple levels: patient, provider and clinic site-level, The secondary outcomes include prescription of guideline directed medical therapy (GDMT) (provider-level), and adherence to prescribed therapy, change in mean blood pressure (BP) and LDL-cholesterol between the intervention and control groups (patient-level). In addition, a trial-based process and economic evaluations will be performed using standard guidelines. RESULTS: We recruited 410 socio-demographically diverse patients with CVD from 4 hospitals in India. Mean (SD) age was 57.5 (11.7) years, and 73.0% were males. Self-reported history of hypertension (48.5%) and diabetes (41.5%) was common. At baseline, mean (SD) BP was 127.9 (18.2) /76.2 (11.6) mm Hg, mean (SD) LDLc: 80.3 (37.3) mg/dl and mean (SD) HbA1c: 6.8% (1.6%). At baseline, the GDMT varied from 62.4% for patients with ischemic heart disease, 48.6% for ischemic stroke and 36.1% for heart failure. CONCLUSION: This study will establish the feasibility of delivering contextually relevant, and evidence-based C-QIP strategy and assess whether it is acceptable to the target populations. The study results will inform a larger scale confirmatory trial of a comprehensive CVD care model in low-resource settings. TRIAL REGISTRATION: Clinical Trials Registry India: CTRI/2022/04/041847; Clinicaltrials.gov number: NCT05196659.

Test and Treat for Prediabetes: A Review of the Health Effects of Prediabetes and the Role of Screening and Prevention.

The term prediabetes describes blood glucose levels above the normal range but below the threshold to diagnose type 2 diabetes. Several population health initiatives encourage a test and treat approach for prediabetes. In this approach, screening and identification of individuals with prediabetes should be followed by prompt referral to structured lifestyle modification programs or pharmacologic interventions that have been shown to prevent or delay the progression to type 2 diabetes in clinical trials. Here we provide a critical review of evidence for this test and treat approach by examining health outcomes associated with prediabetes and the availability and effectiveness of lifestyle modification approaches that target prediabetes. We also describe current limitations to the reach and uptake of evidence-based treatment options for prediabetes. Finally, we highlight lessons learned from identifying and labeling other preconditions to consider challenges and opportunities that may arise with increasing awareness of prediabetes as part of routine preventive care.

Association between low cognitive performance and diabetes-related health indicators across racial and ethnic groups in adults with diabetes.

AIM: To examine the associations between low cognitive performance (LCP) and diabetes-related health indicators (including body mass index [BMI], HbA1c, systolic blood pressure [SBP], low-density lipoprotein [LDL] and self-reported poor physical health) and whether these associations vary across racial/ethnic subgroups. METHODS: We identified adults aged 60 years or older with self-reported diabetes from the 2011-2014 National Health and Nutrition Examination Survey. Individuals with cognitive test scores in the lowest quartile were defined as having LCP. We used regression models to measure the associations of LCP with diabetes-related biometrics (BMI, HbA1c, SBP and LDL); and self-reported poor physical health. Moreover, we explored potential variations in these associations across racial/ethnic subgroups. RESULTS: Of 873 (261 with LCP) adults with diabetes, LCP was associated with higher HbA1c, SBP and LDL (adjusted difference: 0.41%, 5.01 mmHg and 5.08 mg/dL, respectively; P < .05), and greater odds of reporting poor physical health (adjusted odds ratio: 1.59, P < .05). The association between LCP and HbA1c was consistent across racial/ethnic groups, and notably pronounced in Hispanic and Other. BMI worsened with LCP, except for non-Hispanic Black. Excluding the Other group, elevated SBP was observed in people with LCP, with Hispanic showing the most significant association. LDL levels were elevated with LCP for Hispanic and Other. Physical health worsened with LCP for both non-Hispanic Black and Hispanic. CONCLUSIONS: We quantified the association between LCP and diabetes-related health indicators. These associations were more pronounced in Hispanic and Other racial/ethnic groups.

Renal function as an effect modifier of intensive glucose control in delaying cognitive function decline among individuals with type 2 diabetes: A revisit to the ACCORD MIND trial.

AIM: Dysglycaemia accelerates cognitive decline. Intensive glucose control may help delay or prevent cognitive function decline (CFD). We aimed to determine how patient characteristics influence the effect of intensive glucose control [glycated haemoglobin (HbA1c) <6.0%] on delaying CFD in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this post-hoc analysis of 2977 type 2 diabetes participants from the ACCORD MIND trial, we applied the causal forest and causal tree algorithms to identify the effect modifier of intensive glucose control in delaying CFD from 68 variables (demographics, disease history, medications, vitals and baseline biomarkers). The exposure was intensive versus standard glucose control (HbA1c <6.0% vs. 7.0%-7.9%). The main outcome was cognitive function changes from baseline to the 40th month follow-up, which were evaluated using the digit symbol substitution test, Rey auditory verbal learning test, mini-mental state examination and Stroop test. We used Cohen's d, a measure of standardized difference, to quantify the effect size of intensive glucose control on delaying CFD. RESULTS: Among all the baseline characteristics, renal function was the most significant effect modifier. Participants with urinary albumin levels <0.4 mg/dl [absolute function change (AFC): 0.51 in mini-mental state examination, 95% confidence interval (CI): 0.04, 0.98, Cohen's d: 0.25] had slower CFD with intensive glucose control. Patients with preserved renal function (estimated glomerular filtration rate between 60 and 90 ml/min/1.73 m2) were associated with small benefits (AFC: 1.28 in Stroop, 95% CI: 0.28, 2.27, Cohen's d: 0.12) when undergoing intensive glucose control. Conversely, participants with an estimated glomerular filtration rate <60 ml/min/1.73 m2 (AFC: -0.57 in the Rey auditory verbal learning test, 95% CI: -1.09, -0.05, Cohen's d: -0.30) exhibited faster CFD when undergoing intensive glucose control. Participants who were <60 years old showed a significant benefit from intensive glucose control in delaying CFD (AFC: 1.08 in the digit symbol substitution test, 95% CI: 0.06, 2.10, Cohen's d: 0.13). All p < .05. CONCLUSIONS: Our findings linked renal function with the benefits of intensive glucose control in delaying CFD, informing personalized HbA1c goals for those with diabetes and at risk of CFD.

Cardiometabolic Risk in Asian Americans by Social Determinants of Health: Serial Cross-sectional Analyses of the NHIS, 1999-2003 to 2014-2018.

BACKGROUND: Diabetes and hypertension are common in Asian Americans and vary by subgroup. There may be further variation by social determinants of health (SDOHs), but few studies have examined this previously. OBJECTIVE: To examine the associations of SDOHs and diabetes and hypertension within and across Asian subgroups in the USA DESIGN: Series cross-sectional analyses SETTING: National Health Interview Surveys (NHIS) from 1999 to 2018 PARTICIPANTS: Asian-American adults (Chinese, Filipino, Asian Indian, and Other Asian [Korean, Vietnamese, Japanese, and other]) MEASUREMENTS: Self-reported diabetes and hypertension prevalence in pooled 5-year increments over 1999-2018 and multivariable regression models to assess the adjusted prevalence of diabetes or hypertension by poverty, marital status, education, and years in the USA, adjusting for age, sex, BMI, and health insurance status RESULTS: From 1999-2003 to 2014-2018, the age- and sex-adjusted prevalence of diabetes increased for Other Asians (absolute change: 4.6%) but not for other subgroups; age- and sex-adjusted hypertension prevalence significantly increased for Asian Indians and Other Asians (absolute change: 5-7.5%). For Filipinos, high school education or less was associated with an increase in diabetes prevalence over time (difference from 1999-2003 to 2014-2018: +6.0 (95% CI: 2.0-10.0)), while for Asian Indians, college education or higher was associated with an increase in diabetes prevalence for the same period (difference: +2.7 (95% CI: 0.01-5.4). Differences over the 2 time periods (1999-2003 and 2014-2018) show that Filipino and Other Asians, who lived in the USA for ≥10 years, increased in diabetes prevalence. Similar variations in associations of SDOHs by Asian subgroup were seen for hypertension. LIMITATIONS: Self-reported primary outcomes and multi-year data were pooled due to small sample sizes. CONCLUSIONS: The influence of SDOHs on cardiometabolic risk is not uniform among Asian Americans, implying tailored strategies may be needed for different population subgroups. PRIMARY FUNDING SOURCE: NIH.

Long-term Effects of a Collaborative Care Model on Metabolic Outcomes and Depressive Symptoms: 36-Month Outcomes from the INDEPENDENT Intervention.

BACKGROUND: Collaborative care (CC) is a multicomponent team-based approach to providing mental health care with systematic integration into outpatient medical settings. The 12-month INDEPENDENT CC intervention improved joint disease control measures in patients with both depression and diabetes at 12 and 24 months following randomization. OBJECTIVE: This study investigated the durability of intervention effects on patient outcomes at 36 months following randomization. PARTICIPANTS: Adult patients with poorly controlled T2D and depression in India randomized to CC or usual care. DESIGN: Post hoc analyses of between-group differences in patient outcomes at 36 months post-randomization (N = 331) and maintenance of outcomes from 12 to 36 months (N = 314). MAIN MEASURES: We evaluated combined risk factor improvement since baseline, defined as ≥ 50.0% reduction in Symptom Checklist Depression Scale (SCL-20) scores along with reduction of at least 0.5 percentage point hemoglobin A1C, 5 mmHg systolic blood pressure, or 10 mg/dL low-density lipoprotein cholesterol. Improvements in single risk factors were also examined. KEY RESULTS: There were no between-group differences in improvements since baseline in multiple or single risk factors at 36 months. Patients in the CC group with improved outcomes at 12 months were more likely to maintain a ≥ 50.0% reduction since baseline in SCL-20 scores (CC [54.9%] vs. UC [40.9%]; RR: 1.27 [95% CI: 1.04, 1.56]) and 0.5 percentage point reduction since baseline in hemoglobin A1C (CC [31.9%] vs. UC [19.5%]; RR: 1.64 [95% CI: 1.11, 2.41]) at 36 months. CONCLUSIONS: While improvements since baseline in patient outcomes did not differ between the collaborative care and usual care groups at 36 months, patients who received CC were more likely to maintain improvements in depressive symptoms and glucose levels at 36 months if they had achieved these improvements at the end of active intervention. TRIAL REGISTRATION NUMBER: NCT02022111.

Cost-effectiveness of a multicomponent quality improvement care model for diabetes in South Asia: The CARRS randomized clinical trial.

OBJECTIVES: To assess the cost-effectiveness of a multicomponent strategy versus usual care in people with type 2 diabetes in South Asia. DESIGN: Economic evaluation from healthcare system and societal perspectives. SETTING: Ten diverse urban clinics in India and Pakistan. PARTICIPANTS: 1146 people with type 2 diabetes (575 in the intervention group and 571 in the usual care group) with mean age of 54.2 years, median diabetes duration: 7 years and mean HbA1c: 9.9% (85 mmol/mol) at baseline. INTERVENTION: Multicomponent strategy comprising decision-supported electronic health records and non-physician care coordinator. Control group received usual care. OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs) per unit achievement in multiple risk factor control (HbA1c <7% (53 mmol/mol) and SBP <130/80 mmHg or LDLc <2.58 mmol/L (100 mg/dL)), ICERs per unit reduction in HbA1c, 5-mmHg unit reductions in systolic BP, 10-unit reductions in LDLc (mg/dl) (considered as clinically relevant) and ICER per quality-adjusted life years (QALYs) gained. ICERs were reported in 2020 purchasing power parity-adjusted international dollars (INT$). The probability of ICERs being cost-effective was considered depending on the willingness to pay (WTP) values as a share of GDP per capita for India (Int$ 7041.4) and Pakistan (Int$ 4847.6). RESULTS: Compared to usual care, the annual incremental costs per person for intervention group were Int$ 1061.9 from a health system perspective and Int$ 1093.6 from a societal perspective. The ICER was Int$ 10,874.6 per increase in multiple risk factor control, $2588.1 per one percentage point reduction in the HbA1c, and $1744.6 per 5 unit reduction in SBP (mmHg), and $1271 per 10 unit reduction in LDLc (mg/dl). The ICER per QALY gained was $33,399.6 from a societal perspective. CONCLUSIONS: In a trial setting in South Asia, a multicomponent strategy for diabetes care resulted in better multiple risk factor control at higher costs and may be cost-effective depending on the willingness to pay threshold with substantial uncertainty around cost-effectiveness for QALYs gained in the short term (2.5 years). Future research needs to confirm the long-term cost-effectiveness of intensive multifactorial intervention for diabetes care in diverse healthcare settings in LMICs.

Knowledge Gaps, Challenges, and Opportunities in Health and Prevention Research for Asian Americans, Native Hawaiians, and Pacific Islanders: A Report From the 2021 National Institutes of Health Workshop.

Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S. population, and AsA have had the fastest growth rate since 2010. Yet the National Institutes of Health (NIH) has invested only 0.17% of its budget on AsA and NHPI research between 1992 and 2018. More than 40 ethnic subgroups are included within AsA and NHPI (with no majority subpopulation), which are highly diverse culturally, demographically, linguistically, and socioeconomically. However, data for these groups are often aggregated, masking critical health disparities and their drivers. To address these issues, in March 2021, the National Heart, Lung, and Blood Institute, in partnership with 8 other NIH institutes, convened a multidisciplinary workshop to review current research, knowledge gaps, opportunities, barriers, and approaches for prevention research for AsA and NHPI populations. The workshop covered 5 domains: 1) sociocultural, environmental, psychological health, and lifestyle dimensions; 2) metabolic disorders; 3) cardiovascular and lung diseases; 4) cancer; and 5) cognitive function and healthy aging. Two recurring themes emerged: Very limited data on the epidemiology, risk factors, and outcomes for most conditions are available, and most existing data are not disaggregated by subgroup, masking variation in risk factors, disease occurrence, and trajectories. Leveraging the vast phenotypic differences among AsA and NHPI groups was identified as a key opportunity to yield novel clues into etiologic and prognostic factors to inform prevention efforts and intervention strategies. Promising approaches for future research include developing collaborations with community partners, investing in infrastructure support for cohort studies, enhancing existing data sources to enable data disaggregation, and incorporating novel technology for objective measurement. Research on AsA and NHPI subgroups is urgently needed to eliminate disparities and promote health equity in these populations.

Body Mass Index Trajectories From Childhood to Adulthood and Age at Onset of Overweight and Obesity: The Influence of Parents' Weight Status.

We investigated the influence of parents' weight status on their children's growth trajectories and its association with age at onset of overweight and obesity. We used 16,396 height and weight records from 3,284 youths from the Panel Study of Income Dynamics, followed across childhood into adulthood (United States, 1997-2017). Across age groups, we modeled body mass index trajectories (ages 5-32 years) according to parents' weight status, using mixed-effect models to estimate age at onset of overweight and obesity and proportion with obesity from childhood to adulthood. There were large differences in growth patterns according to parents' weight status: Children of parents with obesity had, on average, overweight at age 6 (95% confidence interval (CI): 5, 7) and steep growth trajectories until age 12; children of normal-weight parents had slower increases in body mass index, reaching overweight on average at age 25 (95% CI: 24, 27). By age 30, 30% (95% CI: 28, 31) of youths had obesity. Differences in early-life growth persisted into adulthood: 48% (95% CI: 45, 52) of adult children of parents with obesity had obesity versus 16% (95% CI: 14, 19) of those of normal-weight parents. Trajectories to unhealthy weight were heavily influenced by parents' weight status, especially before age 12, children of parents with obesity having overweight 19 earlier in life than children of normal-weight parents.

Higher rates of diabetic ketoacidosis and admission to the paediatric intensive care unit among newly diagnosed children with type 1 diabetes in Kuwait during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic might have a multifaceted effect on children with type 1 diabetes (T1D), either directly through infection itself or indirectly due to measures implemented by health authorities to control the pandemic. OBJECTIVE: To compare data on children newly diagnosed with T1D in Kuwait during the COVID-19 pandemic to the pre-pandemic period. RESEARCH DESIGN AND METHODS: We analysed data on children aged 12 years or less registered in the Childhood-Onset Diabetes electronic Registry (CODeR) in Kuwait. Data were incidence rate (IR), diabetic ketoacidosis (DKA), and its severity and admission to the paediatric intensive care unit (PICU). RESULTS: The IR of T1D was 40.2 per 100,000 (95% CI; 36.0-44.8) during the COVID-19 pandemic period and was not statistically different from pre-pandemic. A higher proportion of incident T1D cases presented with DKA and were admitted to the PICU during the pandemic (52.2% vs. 37.8%: p Ë‚ 0.001, 19.8% vs. 10.9%; p = 0.002, respectively). The COVID-19 pandemic was positively associated with presentation of DKA and admission to PICU (AOR = 1.73; 95% CI, 1.13-2.65; p = 0.012, AOR = 2.04; 95% CI, 1.13-3.67; p = 0.018, respectively). Children of families with a positive history for diabetes were less likely to present with DKA and get admitted to the PICU during the COVID-19 pandemic (AOR = 0.38; 95% CI, 0.20-0.74; p = 0.004, AOR = 0.22; 95% CI, 0.08-0.61; p = 0.004, respectively). CONCLUSION: High rates of DKA at presentation and admission to PICU in incident T1D cases during the COVID-19 pandemic warrant further studies and effective mitigation efforts through increasing awareness, early detection, and timely intervention.

Obesity-associated metabolites in relation to type 2 diabetes risk: A prospective nested case-control study of the CARRS cohort.

AIMS: To determine whether obesity-associated metabolites are associated with type 2 diabetes (T2DM) risk among South Asians. MATERIALS AND METHODS: Serum-based nuclear magnetic resonance imaging metabolomics data were generated from two South Asian population-based prospective cohorts from Karachi, Pakistan: CARRS1 (N = 4017) and CARRS2 (N = 4802). Participants in both cohorts were followed up for 5 years and incident T2DM was ascertained. A nested case-control study approach was developed to select participants from CARRS1 (Ncases  = 197 and Ncontrols  = 195) and CARRS2 (Ncases  = 194 and Ncontrols  = 200), respectively. First, we investigated the association of 224 metabolites with general obesity based on body mass index and with central obesity based on waist-hip ratio, and then the top obesity-associated metabolites were studied in relation to incident T2DM. RESULTS: In a combined sample of the CARRS1 and CARRS2 cohorts, out of 224 metabolites, 12 were associated with general obesity and, of these, one was associated with incident T2DM. Fifteen out of 224 metabolites were associated with central obesity and, of these, 10 were associated with incident T2DM. The higher level of total cholesterol in high-density lipoprotein (HDL) was associated with reduced T2DM risk (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.53, 0.86; P = 1.2 × 10-3 ), while higher cholesterol esters in large very-low-density lipoprotein (VLDL) particles were associated with increased T2DM risk (OR 1.90, 95% CI 1.40, 2.58; P = 3.5 × 10-5 ). CONCLUSION: Total cholesterol in HDL and cholesterol esters in large VLDL particles may be an important biomarker in the identification of early development of obesity-associated T2DM risk among South Asian adults.

Improving care for hypertension and diabetes in india by addition of clinical decision support system and task shifting in the national NCD program: I-TREC model of care.

BACKGROUND: The growing burden of hypertension and diabetes is one of the major public health challenges being faced by the health system in India. Clinical Decision Support Systems (CDSS) that assist with tailoring evidence-based management approaches combined with task-shifting from more specialized to less specialized providers may together enhance the impact of a program. We sought to integrate a technology "CDSS" and a strategy "Task-shifting" within the Government of India's (GoI) Non-Communicable Diseases (NCD) System under the Comprehensive Primary Health Care (CPHC) initiative to enhance the program's impact to address the growing burden of hypertension and diabetes in India. METHODS: We developed a model of care "I-TREC" entirely calibrated for implementation within the current health system across all facility types (Primary Health Centre, Community Health Centre, and District Hospital) in a block in Shaheed Bhagat Singh (SBS) Nagar district of Punjab, India. We undertook an academic-community partnership to incorporate the combination of a CDSS with task-shifting into the GoI CPHC-NCD system, a platform that assists healthcare providers to record patient information for routine NCD care. Academic partners developed clinical algorithms, a revised clinic workflow, and provider training modules with iterative collaboration and consultation with government and technology partners to incorporate CDSS within the existing system. DISCUSSION: The CDSS-enabled GoI CPHC-NCD system provides evidence-based recommendations for hypertension and diabetes; threshold-based prompts to assure referral mechanism across health facilities; integrated patient database, and care coordination through workflow management and dashboard alerts. To enable efficient implementation, modifications were made in the patient workflow and the fulcrum of the use of technology shifted from physician to nurse. CONCLUSION: Designed to be applicable nationwide, the I-TREC model of care is being piloted in a block in the state of Punjab, India. Learnings from I-TREC will provide a roadmap to other public health experts to integrate and adapt their interventions at the national level. TRIAL REGISTRATION: CTRI/2020/01/022723.

COVID-19 and tobacco cessation: lessons from India.

OBJECTIVES: The Government of India prohibited the sale of tobacco products during the COVID-19 lockdown to prevent the spread of the SARS-CoV-2 virus. This study assessed the tobacco cessation behaviour and its predictors among adult tobacco users during the initial COVID-19 lockdown period in India. METHODS: A cross-sectional study was conducted with 801 adult tobacco users (both smoking and smokeless tobacco) in two urban metropolitan cities of India over a 2-month period (July to August 2020). The study assessed complete tobacco cessation and quit attempts during the lockdown period. Logistic and negative binomial regression models were used to study the correlates of tobacco cessation and quit attempts, respectively. RESULTS: In total, 90 (11.3%) tobacco users reported that they had quit using tobacco after the COVID-19 lockdown period. Overall, a median of two quit attempts (interquartile range 0-6) was made by tobacco users. Participants with good knowledge on the harmful effects of tobacco use and COVID-19 were significantly more likely to quit tobacco use (odds ratio [OR] 2.2; 95% confidence interval [CI] 1.2-4.0) and reported more quit attempts (incidence risk ratio 5.7; 95% CI 2.8-11.8) compared to those with poor knowledge. Participants who had access to tobacco products were less likely to quit tobacco use compared to those who had no access (OR 0.3; 95% CI 0.2-0.5]. CONCLUSIONS: Access restrictions and correct knowledge on the harmful effects of tobacco use and COVID-19 can play an important role in creating a conducive environment for tobacco cessation among users.

Lifetime risk of diabetes in metropolitan cities in India.

AIMS/HYPOTHESIS: We aimed to estimate the lifetime risk of diabetes and diabetes-free life expectancy in metropolitan cities in India among the population aged 20 years or more, and their variation by sex, age and BMI. METHODS: A Markov simulation model was adopted to estimate age-, sex- and BMI-specific lifetime risk of developing diabetes and diabetes-free life expectancy. The main data inputs used were as follows: age-, sex- and BMI-specific incidence rates of diabetes in urban India taken from the Centre for Cardiometabolic Risk Reduction in South Asia (2010-2018); age-, sex- and urban-specific rates of mortality from period lifetables reported by the Government of India (2014); and prevalence of diabetes from the Indian Council for Medical Research INdia DIABetes study (2008-2015). RESULTS: Lifetime risk (95% CI) of diabetes in 20-year-old men and women was 55.5 (51.6, 59.7)% and 64.6 (60.0, 69.5)%, respectively. Women generally had a higher lifetime risk across the lifespan. Remaining lifetime risk (95% CI) declined with age to 37.7 (30.1, 46.7)% at age 60 years among women and 27.5 (23.1, 32.4)% in men. Lifetime risk (95% CI) was highest among obese Indians: 86.0 (76.6, 91.5)% among 20-year-old women and 86.9 (75.4, 93.8)% among men. We identified considerably higher diabetes-free life expectancy at lower levels of BMI. CONCLUSIONS/INTERPRETATION: Lifetime risk of diabetes in metropolitan cities in India is alarming across the spectrum of weight and rises dramatically with higher BMI. Prevention of diabetes among metropolitan Indians of all ages is an urgent national priority, particularly given the rapid increase in urban obesogenic environments across the country. Graphical abstract.

Temporal changes in diabetes prevalence and achievement of care goals in urban South Asia from 2010 to 2016 - The Center for Cardio-metabolic Risk Reduction in South Asia Study.

AIM: Achievement of treatment targets among individuals with diabetes remains suboptimal in many parts of the globe. We aimed to assess changes in diabetes prevalence and achievement of diabetes care goals in South Asia using two consecutive cross-sectional population-based surveys. METHODS: Two representative samples of South Asian adults were recruited using identical methods from Chennai, Delhi, and Karachi in 2010-11 (n = 16,288; response rate-94.7%) and 2015-16 (n = 14,587; response rate-94.0%) through the Center for Cardio-metabolic Risk Reduction in South Asia (CARRS) Study. Quality of care goals were defined as HbA1c <53 mmol/mol (7.0%), blood pressure (BP) control: <140/90 mmHg, lipid control: LDL cholesterol <2.56 mmol/l (100 mg/dl), and self-reported non-smoking. RESULTS: Weighted prevalence of self-reported diabetes increased by 9.0% [13% (95%CI: 13-14) to 15% (14-15)] while that of newly diagnosed diabetes decreased by 16% [6.1% (5.7-6.6) to 5.1% (4.6-5.6)]. There were improvements in achieving glycaemic (25% to 30%, p = 0.002) and lipid (34% to 45%, p < 0.001) goals, but no notable improvements in BP control or smoking status. The proportion of individuals with self-reported diabetes meeting more than one target also increased. CONCLUSIONS: Diabetes prevalence continues to grow among urban South Asians and large gaps still exist in the attainment of treatment targets. Concerted policy, systemic, clinical and individual efforts are needed to close these care gaps.

Postprandial glycemic response differed by early life nutritional exposure in a longitudinal cohort: a single- and multi-biomarker approach.

PURPOSE: Populations malnourished in early life are at increased risk for cardiometabolic diseases. We assessed if improved nutrition predicts cardiometabolic function, as assessed by postprandial biomarker responses. METHODS: Participants had been randomized at the village level to receive one of two nutritional supplements as children. At mean age 44 y (range 37-53 years), we obtained plasma samples before and 2 h after a mixed-component meal challenge. We assayed biomarkers including lipids, glycemic measurements, and inflammatory cytokines. We compared postprandial biomarker responses among those who received the improved nutrition intervention from conception through to their second birthday (the first 1000 days) to those with other exposure status, including those who received the improved nutrition intervention at other ages, and those who received the less nutritious supplement. RESULTS: Among 1027 participants (59.4% female), 22.9% were exposed to improved nutrition in the first 1000 days. Insulin increased the most in response to the meal challenge (over twofold), and non-esterified fatty acids decreased the most (by half). Glucose increased postprandial by 11.4% in the exposed group, compared with 15.7% in the other exposure group (p < 0.05), which remained significant after adjusting for confounders (- 4.7%; 95% confidence interval: - 9.3%, - 0.01%). Responses to the prandial challenges for the other biomarkers did not differ by intervention group (all p > 0.05). CONCLUSION: Early life exposure to improved nutrition was associated with a more favorable postprandial glucose response in this population. We did not observe a difference in overall cardiometabolic responses between the exposure groups.

Health, psychosocial, and economic impacts of the COVID-19 pandemic on people with chronic conditions in India: a mixed methods study.

BACKGROUND: People with chronic conditions are disproportionately prone to be affected by the COVID-19 pandemic but there are limited data documenting this. We aimed to assess the health, psychosocial and economic impacts of the COVID-19 pandemic on people with chronic conditions in India. METHODS: Between July 29, to September 12, 2020, we telephonically surveyed adults (n = 2335) with chronic conditions across four sites in India. Data on participants' demographic, socio-economic status, comorbidities, access to health care, treatment satisfaction, self-care behaviors, employment, and income were collected using pre-tested questionnaires. We performed multivariable logistic regression analysis to examine the factors associated with difficulty in accessing medicines and worsening of diabetes or hypertension symptoms. Further, a diverse sample of 40 participants completed qualitative interviews that focused on eliciting patient's experiences during the COVID-19 lockdowns and data analyzed using thematic analysis. RESULTS: One thousand seven hundred thirty-four individuals completed the survey (response rate = 74%). The mean (SD) age of respondents was 57.8 years (11.3) and 50% were men. During the COVID-19 lockdowns in India, 83% of participants reported difficulty in accessing healthcare, 17% faced difficulties in accessing medicines, 59% reported loss of income, 38% lost jobs, and 28% reduced fruit and vegetable consumption. In the final-adjusted regression model, rural residence (OR, 95%CI: 4.01,2.90-5.53), having diabetes (2.42, 1.81-3.25) and hypertension (1.70,1.27-2.27), and loss of income (2.30,1.62-3.26) were significantly associated with difficulty in accessing medicines. Further, difficulties in accessing medicines (3.67,2.52-5.35), and job loss (1.90,1.25-2.89) were associated with worsening of diabetes or hypertension symptoms. Qualitative data suggest most participants experienced psychosocial distress due to loss of job or income and had difficulties in accessing in-patient services. CONCLUSION: People with chronic conditions, particularly among poor, rural, and marginalized populations, have experienced difficulties in accessing healthcare and been severely affected both socially and financially by the COVID-19 pandemic.