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Background: National estimates of the prevalence of vision impairment and blindness in people with diabetes are required to inform resource allocation. People with diabetes are more susceptible to conditions such as diabetic retinopathy that can impair vision; however, these are often missed in national studies. This study aims to determine the prevalence and risk factors of vision impairment and blindness in people with diabetes in India., Methods: Data from the SMART-India study, a cross-sectional survey with national coverage of 42 147 Indian adults aged 40 years and older, collected using a complex sampling design, were used to obtain nationally representative estimates for the prevalence of vision impairment and blindness in people with diabetes in India. Vulnerable adults (primarily those who did not have capacity to provide consent); pregnant and breastfeeding women; anyone deemed too ill to be screened; those who did not provide consent; and people with type 1 diabetes, gestational diabetes, or secondary diabetes were excluded from the study. Vision impairment was defined as presenting visual acuity of 0·4 logMAR or higher and blindness as presenting a visual acuity of 1·0 logMAR or higher in the better-seeing eye. Demographic, anthropometric, and laboratory data along with geographic distribution were analysed in all participants with available data. Non-mydriatic retinal images were used to grade diabetic retinopathy, and risk factors were also assessed., Findings: A total of 7910 people with diabetes were included in the analysis, of whom 5689 had known diabetes and 2221 were undiagnosed. 4387 (55·5%) of 7909 participants with available sex data were female and 3522 (44·5%) participants were male. The estimated national prevalence of vision impairment was 21·1% (95% CI 15·7-27·7) and blindness 2·4% (1·7-3·4). A higher prevalence of any vision impairment (29·2% vs 19·6%; p=0·016) and blindness (6·7% vs 1·6%; p<0·0001) was observed in those with ungradable images. In known diabetes, diabetic retinopathy (adjusted odds ratio [aOR] 3·06 [95% CI 1·25-7·51]), vision-threatening diabetic retinopathy (aOR 7·21 [3·52-14·75]), and diabetic macular oedema (aOR 5·41 [2·20-13·33]) were associated with blindness in adjusted analysis. Common sociodemographic risk factors for vision impairment and blindness include older age, lower educational attainment, and unemployment., Interpretation: Based on the estimated 101 million people with diabetes in 2021 and the interpretation of the data from this study, approximately 21 million people with diabetes have vision impairment in India, of whom 2·4 million are blind. Higher prevalence is observed in those from lower socio-economic strata and policy makers should focus on these groups to reduce inequalities in health care., Funding: Global Challenge Research Fund of United Kingdom Research and Innovation through the Medical Research Council., Competing Interests: Declaration of interests No competing interests are declared for the submitted work. SS reports consultancy fees from AbbVie, Amgen, Apellis, Bayer, Biogen, Boehringer Ingelheim, Novartis, Eyebiotech, Eyepoint Phamaceuticals, Janssen Pharmaceuticals, Novo Nordisk, Optos, Ocular Therapeutix, Kriya Therapeutics, OcuTerra, Roche, Stealth Biotherapeutics, and Sanofi; travel fees from Bayer and Roche; lecture fees from Bayer and Boehringer Ingelheim; stock options from Eyebiotech; and is a member of the data monitoring committee and advisory committee of Bayer and Novo Nordisk, outside of the submitted work. ATP reports payment for a trial design lecture from Bayer and for membership of a trial data monitoring committee from Roche, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aims: To examine associations between perceived stress and cardiometabolic risk factors in South Asians with prediabetes and assess whether a diabetes prevention program mitigates the impact of stress on cardiometabolic health., Methods: We conducted a secondary analysis of the Diabetes Community Lifestyle Improvement Program, a lifestyle modification trial for diabetes prevention in India (n = 564). Indicators for cardiometabolic health (weight, waist circumference, blood pressure, glucose, HbA1c, and lipids) were measured at each visit while perceived stress was assessed via questionnaire at baseline. Multivariable linear regression assessed associations between stress and cardiometabolic parameters at baseline and 3-year follow up., Results: At baseline, perceived stress was associated with higher weight (b=0.16; 95% CI: 0.04, 0.29) and waist circumference (b=0.11; 95% CI: 0.01, 0.21) but lower 30-minute postload glucose (b=-0.44; 95% CI: -0.76, -0.14) and LDL cholesterol (b=-0.40; 95% CI: -0.76, -0.03). Over the study period, perceived stress was associated with weight gain (b=0.20; 95% CI: 0.07, 0.33) and increased waist circumference (b=0.14; 95% CI: 0.04, 0.24). Additionally, higher perceived stress was associated with lower HDL cholesterol among the control arm (p interaction = 0.02)., Conclusions: Baseline stress was associated with negative cardiometabolic risk factor outcomes over time in those with prediabetes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: Retention of participants is a challenge in community-based longitudinal cohort studies. We aim to evaluate the factors associated with loss to follow-up and estimate attrition bias., Methods: Data are from an ongoing cohort study, Center for cArdiometabolic Risk Reduction in South Asia (CARRS) in India (Delhi and Chennai). Multinomial logistic regression analysis was used to identify sociodemographic factors associated with partial (at least one follow-up) or no follow-up (loss to follow-up). We also examined the impact of participant attrition on the magnitude of observed associations using relative ORs (RORs) of hypertension and diabetes (prevalent cases) with baseline sociodemographic factors., Results: There were 12 270 CARRS cohort members enrolled in Chennai and Delhi at baseline in 2010, and subsequently six follow-ups were conducted between 2011 and 2022. The median follow-up time was 9.5 years (IQR: 9.3-9.8) and 1048 deaths occurred. Approximately 3.1% of participants had no follow-up after the baseline visit. Younger (relative risk ratio (RRR): 1.14; 1.04 to 1.24), unmarried participants (RRR: 1.75; 1.45 to 2.11) and those with low household assets (RRR: 1.63; 1.44 to 1.85) had higher odds of being lost to follow-up. The RORs of sociodemographic factors with diabetes and hypertension did not statistically differ between baseline and sixth follow-up, suggesting minimal potential for bias in inference at follow-up., Conclusion: In this representative cohort of urban Indians, we found low attrition and minimal bias due to the loss to follow-up. Our cohort's inconsistent participation bias shows our retention strategies like open communication, providing health profiles, etc have potential benefits., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To identify the genetic etiology of neonatal diabetes in an infant and to elucidate the molecular mechanism of the identified mutation underlying the pathogenesis., Methods: Genetic analysis was carried out by sequencing of known etiological genes associated with NDM. Molecular characterization was performed by constructing a identified mutation in NKX2-2 gene and  functional aspects was tested using transactivation, protein expression, DNA binding, nuclear localization assays. Structural analysis was performed by modeling the NKX2-2 protein structure., Results: A novel homozygous frameshift mutation  c.772delC, p.Q258SFs*59 in the NKX2-2 gene was identified in a patient with neonatal diabetes. Functional studies revealed that this mutation resulted in an elongated protein sequence, affecting DNA binding activity and transcriptional function. Structural analysis suggested alterations in the protein's tertiary structure, likely contributing to its dysfunction., Conclusion: This study presents the first report of a stop-loss mutation in the NKX2-2 gene associated with NDM. Our findings emphasize the importance of functional and structural characterization to understand the biological consequences of such mutations. This comprehensive analysis provides insights into the molecular mechanisms underlying NDM and its clinical phenotype, which may aid in better diagnosis and management of patients with similar variants in the future., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Aims: To estimate the prevalence of undiagnosed diabetes and suboptimally controlled diabetes and the associated risk factors by community screening in India., Methods: In this multi-centre, cross-sectional study, house-to-house screening was conducted in people aged ≥40 years in urban and rural areas across 10 states and one union territory in India between November 2018 and March 2020. Participants underwent anthropometry, clinical and biochemical assessments. Capillary random blood glucose and point-of-care glycated haemoglobin (HbA 1c ) were used to diagnose diabetes. The prevalence of undiagnosed diabetes and suboptimal control (HbA 1c ≥53 mmol/mol [≥7%]) among those with known diabetes was assessed., Results: Among the 42,146 participants screened (22,150 urban, 19,996 rural), 5689 had known diabetes. The age-standardised prevalence of known diabetes was 13.1% (95% CI 12.8-13.4); 17.2% in urban areas and 9.4% in rural areas. The age-standardised prevalence of undiagnosed diabetes was 6.0% (95% CI 5.7-6.2); similar in both urban and rural areas with the highest proportions seen in the East (8.0%) and South (7.8%) regions. When we consider all people with diabetes in the population, 22.8% of individuals in urban areas and 36.7% in rural areas had undiagnosed diabetes. Almost 75% of the individuals with known diabetes had suboptimal glycaemic control., Conclusions: High prevalence of undiagnosed diabetes and suboptimally controlled diabetes emphasises the urgent need to identify and optimally treat people with diabetes to reduce the burden of diabetes., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Non-communicable disease (NCD) rates are rapidly increasing in India with wide regional variations. We aimed to quantify the prevalence of metabolic NCDs in India and analyse interstate and inter-regional variations., Methods: The Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study, a cross-sectional population-based survey, assessed a representative sample of individuals aged 20 years and older drawn from urban and rural areas of 31 states, union territories, and the National Capital Territory of India. We conducted the survey in multiple phases with a stratified multistage sampling design, using three-level stratification based on geography, population size, and socioeconomic status of each state. Diabetes and prediabetes were diagnosed using the WHO criteria, hypertension using the Eighth Joint National Committee guidelines, obesity (generalised and abdominal) using the WHO Asia Pacific guidelines, and dyslipidaemia using the National Cholesterol Education Program-Adult Treatment Panel III guidelines., Findings: A total of 113 043 individuals (79 506 from rural areas and 33 537 from urban areas) participated in the ICMR-INDIAB study between Oct 18, 2008 and Dec 17, 2020. The overall weighted prevalence of diabetes was 11·4% (95% CI 10·2-12·5; 10 151 of 107 119 individuals), prediabetes 15·3% (13·9-16·6; 15 496 of 107 119 individuals), hypertension 35·5% (33·8-37·3; 35 172 of 111 439 individuals), generalised obesity 28·6% (26·9-30·3; 29 861 of 110 368 individuals), abdominal obesity 39·5% (37·7-41·4; 40 121 of 108 665 individuals), and dyslipidaemia 81·2% (77·9-84·5; 14 895 of 18 492 of 25 647). All metabolic NCDs except prediabetes were more frequent in urban than rural areas. In many states with a lower human development index, the ratio of diabetes to prediabetes was less than 1., Interpretation: The prevalence of diabetes and other metabolic NCDs in India is considerably higher than previously estimated. While the diabetes epidemic is stabilising in the more developed states of the country, it is still increasing in most other states. Thus, there are serious implications for the nation, warranting urgent state-specific policies and interventions to arrest the rapidly rising epidemic of metabolic NCDs in India., Funding: Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare, Government of India., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Concordance in chronic disease status has been observed within couples. In urban India and Pakistan, little is known about couple concordance in diabetes, hypertension, and dyslipidaemia and associated socioeconomic characteristics and modifiable risk factors., Methods: We analysed cross-sectional data from 2548 couples from the Centre for cArdio-metabolic Risk Reduction in South Asia cohort in Chennai, Delhi and Karachi. We estimated couple concordance in presence of ≥1 of diabetes, hypertension and dyslipidaemia (positive concordance: both spouses (W+H+); negative concordance: neither spouse (W-H-); discordant wife: only wife (W+H-); or discordant husband: only husband (W-H+)). We assessed associations of five socioeconomic and household characteristics, and six modifiable risk factors with couple concordance using multinomial logistic regression models with couples as the unit of analysis (reference: W-H-)., Results: Of the couples, 59.4% (95% CI 57.4% to 61.3%) were concordant in chronic conditions (W+H+: 29.2% (95% CI 27.4% to 31.0%); W-H-: 30.2% (95% CI 28.4%- to 32.0%)); and 40.6% (95% CI 38.7% to 42.6%) discordant (W+H-: 13.1% (95% CI 11.8% to 14.4%); W-H+: 27.6% (95% CI 25.9% to 29.4%)). Compared with couples with no conditions (W-H-), couples had higher relative odds of both having at least one condition if they had higher versus lower levels of: income (OR 2.03 (95% CI 1.47 to 2.80)), wealth (OR 2.66 (95% CI 1.98 to 3.58)) and education (wives' education: OR 1.92 (95% CI 1.29 to 2.86); husbands' education: OR 2.98 (95% CI 1.92 to 4.66)) or weight status (overweight or obesity in both spouses ORs 7.17 (95% CI 4.99 to 10.30))., Conclusions: Positive couple concordance in major chronic conditions is high in urban India and Pakistan, especially among couples with relatively higher socioeconomic position. This suggests that prevention and management focusing on couples at high risk for concordant chronic conditions may be effective and more so in higher socioeconomic groups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background & Objectives: Screening of individuals for early detection and identification of undiagnosed diabetes can help in reducing the burden of diabetic complications. This study aimed to evaluate the performance of Madras Diabetes Research Foundation (MDRF)-Indian Diabetes Risk Score (IDRS) to screen for undiagnosed type 2 diabetes in a large representative population in India., Methods: Data were acquired from the Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study, a large national survey that included both urban and rural populations from 30 states/union territories in India. Stratified multistage design was followed to obtain a sample of 113,043 individuals (94.2% response rate). MDRF-IDRS used four simple parameters, viz. age, waist circumference, family history of diabetes and physical activity to detect undiagnosed diabetes. Receiver operating characteristic (ROC) with area under the curve (AUC) was used to assess the performance of MDRF-IDRS., Results: We identified that 32.4, 52.7 and 14.9 per cent of the general population were under high-, moderate- and low-risk category of diabetes. Among the newly diagnosed individuals with diabetes [diagnosed by oral glucose tolerance test (OGTT)], 60.2, 35.9 and 3.9 per cent were identified under high-, moderate- and low-risk categories of IDRS. The ROC-AUC for the identification of diabetes was 0.697 (95% confidence interval: 0.684-0.709) for urban population and 0.694 (0.684-0.704) for rural, as well as 0.693 (0.682-0.705) for males and 0.707 (0.697-0.718) for females. MDRF-IDRS performed well when the population were sub-categorized by state or by regions., Interpretation & Conclusions: Performance of MDRF-IDRS is evaluated across the nation and is found to be suitable for easy and effective screening of diabetes in Asian Indians.

Background: National and subnational estimates of the prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy (VTDR) are needed to inform the stepwise implementation of systematic retinal screening for people with diabetes in India to decrease the rate of blindness. We aimed to assess these national and subnational estimates and to stratify the prevalence of diabetic retinopathy and VTDR on the basis of people with known versus undiagnosed diabetes, urban versus rural residence, and epidemiological transition level (ETL) and Socio-demographic Index (SDI) categories of states., Methods: We did a multicentre cross-sectional screening study for diabetic retinopathy using a complex cluster sampling design in people aged 40 years or older in ten Indian states and one union territory between Dec 20, 2018, and March 20, 2020. We did non-mydriatic retinal screening and assessed risk factor burden for people with diabetes. We estimated nationally weighted prevalence of diabetic retinopathy and VTDR for individuals with known and undiagnosed diabetes by urban versus rural residence, and by state categorisation by ETL and SDI. We also assessed adjusted risk factors., Findings: From 42 146 participants screened, 7910 (18·8%) were identified to have diabetes. Of these, 6133 (77·5%; 4350 with known diabetes and 1783 with undiagnosed diabetes) had gradable retinal images. 3411 (56%) participants were women and 2722 (44%) were men, and the median age was 56 years (IQR 49-65). The estimated national prevalence was 12·5% (95% CI 11·0-14·2) for diabetic retinopathy and 4·0% (3·4-4·8) for VTDR, with no significant differences between urban and rural residence for diabetic retinopathy. Compared with individuals with undiagnosed diabetes, we observed a higher prevalence of diabetic retinopathy (15·5% [13·4-17·8] vs 8·0% [6·3-10·1]) and VTDR (5·3% [4·5-6·3] vs 2·4% [1·6-3·6]) in individuals with known diabetes. The prevalence was significantly lower in low ETL-SDI states compared with high and middle ETL-SDI states for diabetic retinopathy (by 7·0%, 1·9-12·2, p=0·024) and VTDR (by 4·8%, 3·0-6·6, p<0·0001). Hyperglycaemia was the strongest modifiable risk factor., Interpretation: We estimate that, in absolute numbers, approximately 3 million people aged 40 years or older have VTDR in India, with a higher prevalence in those with known diabetes residing in high and middle ETI-SDI states., Funding: UKRI Global Challenge Research Fund., Competing Interests: Declaration of interests SS reports consultancy and payments for lectures from Bayer, Boehringer Ingelheim, Novartis, Oxurion, Roche, Allergan, and Apellis, outside the submitted work. ATP reports payment for a trial design lecture from Bayer and for membership of a trial data monitoring committee from Roche, outside the submitted work. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The prevalence of prediabetes, a forerunner of diabetes is very high, and its conversion to diabetes is also more rapid among Asian Indians. Prediabetes also predisposes to the development of macrovascular and to a lesser extent of microvascular complications of diabetes. In a large community-based epidemiological study, the Indian Council of Medical Research-India Diabetes (ICMR-INDIAB), data reported an overall prevalence of prediabetes of 10.3%, derived from 15 Indian states. This shows that the diabetes epidemic is far from over as many of them may soon convert to diabetes. Prediabetes, however, should not be considered a path to diabetes rather it should be a window of opportunity for the prevention of diabetes. This early screening, detection, and treatment of prediabetes should be made a national priority. Several countries have introduced lifestyle programs to prevent diabetes and, when indicated, pharmacological intervention with metformin as well. This consensus statement outlines the approaches to screening and lifestyle and pharmacological management of prediabetes in Asian Indians., (© Journal of the Association of Physicians of India 2011.)

Aim: To examine the incidence of cardiovascular disease (CVD), of death, and the comparative effects of 12 common modifiable risk factors for both outcomes in South Asia., Methods and Results: Prospective study of 33 583 individuals 35-70 years of age from India, Bangladesh, or Pakistan. Mean follow-up period was 11 years. Age and sex adjusted incidence of a CVD event and mortality rates were calculated for the overall cohort, by urban or rural location, by sex, and by country. For each outcome, mutually adjusted population attributable fractions (PAFs) were calculated in 32 611 individuals without prior CVD to compare risks associated with four metabolic risk factors (hypertension, diabetes, abdominal obesity, high non-HDL cholesterol), four behavioural risk factors (tobacco use, alcohol use, diet quality, physical activity), education, household air pollution, strength, and depression. Hazard ratios were calculated using Cox regression models, and average PAFs were calculated for each risk factor or groups of risk factors. Cardiovascular disease was the most common cause of death (35.5%) in South Asia. Rural areas had a higher incidence of CVD (5.41 vs. 4.73 per 1000 person-years) and a higher mortality rate (10.27 vs. 6.56 per 1000 person-years) compared with urban areas. Males had a higher incidence of CVD (6.42 vs. 3.91 per 1000 person-years) and a higher mortality rate (10.66 vs. 6.85 per 1000 person-years) compared with females. Between countries, CVD incidence was highest in Bangladesh, while the mortality rate was highest in Pakistan. The modifiable risk factors studied contributed to approximately 64% of the PAF for CVD and 69% of the PAF for death. Largest PAFs for CVD were attributable to hypertension (13.1%), high non-HDL cholesterol (11.1%), diabetes (8.9%), low education (7.7%), abdominal obesity (6.9%), and household air pollution (6.1%). Largest PAFs for death were attributable to low education (18.9%), low strength (14.6%), poor diet (6.4%), diabetes (5.8%), tobacco use (5.8%), and hypertension (5.5%)., Conclusion: In South Asia, both CVD and deaths are highest in rural areas and among men. Reducing CVD and premature mortality in the region will require investment in policies that target a broad range of health determinants., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Non-nutritive sweeteners (NNSs) are used to substitute sugar in the diet and are approved by the regulatory bodies in many countries, including the Food and Agriculture Organization (FAO)/the World Health Organization (WHO). Non-nutritive sweeteners are here to stay, as it is an effective strategy to reduce sugar and caloric intake which is a public health priority today. It is a tool to increase dietary compliance in the management of obesity and diabetes and is a partner for fitness seekers. However, the debate on its safety and efficacy continues, including several myths associated with its usage. This review has evaluated the scientific literature in-depth and concludes that NNSs are safe to use within an acceptable daily intake (ADI). Non-nutritive sweeteners are beneficial for their intended use, including weight management and diabetes control when consumed as a part of a dietary management program. The current data do not provide sufficient evidence that NNSs can affect the gut microbiome, and more research, particularly at relevant doses, is required. We also need more randomized control trials (RCTs) among the Indian population on the impact of sugar reduction with NNSs and its health benefits to strengthen the evidence for its use in medical nutrition management and preventive health, helping the individual make an informed choice., (© Journal of the Association of Physicians of India 2011.)

Objectives: This study evaluated the perception and practices of health care providers (physicians, diabetologists, and endocrinologists) regarding the treatment of hypertension in patients with diabetes in India., Methods: Health care providers throughout India who treated patients with diabetes and hypertension were invited to participate in an online survey and periodic 21 virtual meetings. They were questioned about their perception and practices in managing these patients, and strategies to improve blood pressure (BP)., Results: The online survey was completed by 2,513 health care providers, and 344 participated in virtual meetings. More than 50% reported that 31-50% of their patients with diabetes also had hypertension. Home BP monitoring was recommended by 88%, and lifestyle modifications were consistently recommended. Choice of antihypertensive treatment varied based on comorbidities, and a renin-angiotensin system blocker plus a calcium channel blocker (CCB) was the most common combination for dual antihypertensive therapy. Suggested strategies to improve BP control included patient awareness/education, lifestyle modifications, better follow-up/monitoring, and optimization of therapy., Conclusion: Indian health care providers were aware of clinical recommendations and practices regarding treatment of patients with diabetes and hypertension, and generally make clinical decisions consistent with current guidelines. Optimization of care for these patients is essential to reduce cardiovascular disease risk and improve patient outcomes., (© Journal of the Association of Physicians of India 2011.)

Background: There is little information on comprehensive diabetes care comprising glycaemic, lipid, and blood pressure control in India; therefore, we aimed to assess the achievement of treatment targets among adults with self-reported diabetes., Methods: The Indian Council of Medical Research (ICMR)-India Diabetes (INDIAB) study is a cross-sectional, population-based survey of adults aged 20 years or older in all 30 states and union territories of India. We used a stratified multistage sampling design, sampling states in a phased manner, and selected villages in rural areas and census enumeration blocks in urban areas. We used a three-level stratification method on the basis of geography, population size, and socioeconomic status for each state. For the outcome assessment, good glycaemic control was defined as HbA 1c of less than 7·0% (A), blood pressure control was defined as less than 140/90 mm Hg (B), and the LDL cholesterol target was defined as less than 100 mg/dL (C). ABC control was defined as the proportion of individuals meeting glycaemic, blood pressure, and LDL cholesterol targets together. We also performed multiple logistic regression to assess the factors influencing achievement of diabetes treatment targets., Findings: Between Oct 18, 2008, and Dec 17, 2020, 113 043 individuals (33 537 from urban areas and 79 506 from rural areas) participated in the ICMR-INDIAB study. For this analysis, 5789 adults (2633 in urban areas and 3156 in rural areas) with self-reported diabetes were included in the study population. The median age was 56·1 years (IQR 55·7-56·5). Overall, 1748 (weighted proportion 36·3%, 95% CI 34·7-37·9) of 4834 people with diabetes achieved good glycaemic control, 2819 (weighted proportion 48·8%, 47·2-50·3) of 5698 achieved blood pressure control, and 2043 (weighted proportion 41·5%, 39·9-43·1) of 4886 achieved good LDL cholesterol control. Only 419 (weighted proportion 7·7%) of 5297 individuals with self-reported diabetes achieved all three ABC targets, with significant heterogeneity between regions and states. Higher education, male sex, rural residence, and shorter duration of diabetes (<10 years) were associated with better achievement of combined ABC targets. Only 951 (weighted proportion 16·7%) of the study population and 227 (weighted proportion 36·9%) of those on insulin reported using self-monitoring of blood glucose., Interpretation: Achievement of treatment targets and adoption of healthy behaviours remains suboptimal in India. Our results can help governments to adopt policies that prioritise improvement of diabetes care delivery and surveillance in India., Funding: Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Callus formation in the diabetic foot increases the risk of ulcer onset. It is standard procedure to remove these dead tissue layers to reduce rising pressures. In a surgical procedure known as scalpel debridement, or chiropody the callus tissue is removed up to the epidermal layer. Factors may influence the outcome of this surgical process such as clinician inexperience. In an effort to standardize the debridement process, tissue oxygenation (TO) measurements are obtained before and after to study the effect of debridement on callus tissue., Methods: Fifteen debridement cases were analyzed using near infrared (NIR) imaging to study changes in TO. The NIR-based device used in this study estimates effective changes in TO in terms of oxy-, deoxy-, total hemoglobin, and oxygen saturation. Weber contrasts between callus tissue and the surrounding normal tissue were compared following debridement for all TO parameters. In a secondary analysis, callus tissue was segmented into quadrants and a percent of significance (in terms of total TO change) was calculated using a t -test., Results: Results show majority of cases displayed greater than 80% as the significant change in TO following debridement, except in cases with the presence of blood clot (a common precursor for ulceration). In cases where incomplete debridement was suspected, a significant change in TO was still observed., Conclusions: With extensive systematic studies in the future, NIR imaging technique to measure changes in TO may be implemented as a low-cost hand-held imaging device useful for objectively assessing the effectiveness of the scalpel debridement process.

Aim: To report on glycated haemoglobin (HbA1c) values among individuals with normal glucose tolerance (NGT) at different age groups, using data acquired from a large national survey in India., Materials and Methods: Data on glycaemic parameters at different age groups were obtained from the Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study, in adults aged ≥ 20 years representing all parts of India. Age-wise distribution of HbA1c was assessed among individuals with NGT (n = 14,222) confirmed by an oral glucose tolerance test using the World Health Organization (WHO) criteria. Results were validated in another large epidemiological study (n = 1077) conducted in Chennai, India., Results: Among NGT individuals, HbA1c increased gradually with age from 5.16 ± 0.71% (33 mmol/mol) in the age group of 20-29 years to 5.49 ± 0.69% (37 mmol/mol) in those aged 70 + years. In the validation study, conducted in another study population, HbA1c was 5.35 ± 0.43% (35 mmol/mol) in age group of 20-29 years and 5.74 ± 0.50% (39 mmol/mol) in those aged 70 and above. In the INDIAB study, for every decadal increase in age, there is a 0.08% increase in HbA1c and this increase was more significant in females (females: 0.10% vs. males: 0.06%) and in urban (urban: 0.10% vs. rural: 0.08%) population., Conclusions: HbA1c levels increase steadily with age. This suggests that age-specific cutoffs be used while utilizing HbA1c to diagnose diabetes and prediabetes, so as to minimize the risk of overdiagnosis and unnecessary initiation of treatment in elderly people who could have physiological increase in HbA1c levels., (© 2021. Springer-Verlag Italia S.r.l., part of Springer Nature.)

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., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

Background and Aim: Neonatal diabetes mellitus (NDM) is a rare monogenic disorder of pancreatic beta cell mass and/or function. In the present study we aimed to evaluate the INS gene mutations in a cohort of children with Permanent Neonatal Diabetes Mellitus (PNDM) and to explore the clinical and genetic characteristics of PNDM caused by INS mutations., Methods: Direct sequencing of all exons of INS genes was carried out in 189 children with PNDM. Clinical and biochemical data were collected and correlated. The pathogenicity of mutations was determined based on the American College of Medical Genetics and Genomics and Association of Medical Pathology guidelines., Results: Two novel mutations (His34Pro, Leu35Met) in a compound heterozygous state and seven known mutations (Gly32Ser, Phe48Cys, Arg89Cys, Cys96Tyr, Ser98Ile, Try108Asp and Cys109Phe) in the INS gene were identified in 8 patients out of the total of 189 PNDM children studied. Four mutations were involved in defects with disulphide bond formation and hence were in crucial regions of the gene. All the mutations were de novo in origin., Conclusions: This is the first comprehensive study from India to investigate the insulin gene mutations in PNDM and to show that INS gene mutations also contribute to the causation of PNDM., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: To assess the effect of migration (rural-to-urban and vice versa) on prevalence of diabetes and metabolic disorders in Asian Indians participating in the Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study., Materials and Methods: The ICMR-INDIAB study is a national study on diabetes and associated cardiometabolic disorders in individuals aged ≥20 years from 28 states and 2 union territories of India. Individuals who moved to a different place from their place of birth and had resided in the new location for at least one year were considered as migrants. Anthropometric measurements, blood pressure estimation and a capillary oral glucose tolerance test were performed., Results: Of the 113,043 participants, 66.4% were non-migrant rural dwellers, 19.4% non-migrant urban dwellers, 8.4% rural-urban migrants, 3.8% multiple migrants and 2.0% urban-rural migrants. Weighted prevalence of diabetes was highest in rural-urban migrants followed by urban dwellers, urban-rural migrants and rural dwellers [14.7%, 13.2%, 12.7% and 7.7% respectively (p < 0.001)]. Rural-urban migrants had highest prevalence of abdominal obesity (50.5%) compared to the other three groups. The risk for diabetes was 1.9 times higher in rural-urban migrants than among rural dwellers. Five risk factors [hypertension, abdominal and generalized obesity, physical inactivity and low fruit and vegetable intake] together explained 69.8% (partial population attributable risk) of diabetes among rural-urban migrants and 66.4% among non-migrant urban dwellers., Conclusions: Rural-to-urban migration is associated with increased risk of developing diabetes and other cardiometabolic abnormalities. Adoption of healthier lifestyle patterns among migrants could help prevent/delay onset of these abnormalities in this population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The increased burden of diabetes in India has resulted in an increase in the complications of diabetes including sight-threatening diabetic retinopathy (DR). Visual impairment and blindness due to DR can be prevented by early detection and management of sight-threatening DR. Life-long evaluation by repetitive retinal screening of people with diabetes is an essential strategy as DR has an asymptomatic presentation. Fundus examination by trained ophthalmologists and fundus photography are established modes of screening. Various modes of opportunistic screening have been followed in India. Hospital-based screening (diabetes care/eye care) and community-based screening are the common modes. Tele-ophthalmology programs based on retinal imaging, remote interpretation, and grading of DR by trained graders/ophthalmologists have facilitated greater coverage of DR screening and enabled timely referral of those with sight-threatening DR. DR screening programs use nonmydriatic or mydriatic fundus cameras for retinal photography. Hand-held/smartphone-based fundus cameras that are portable, less expensive, and easy to use in remote places are gaining popularity. Good retinal image quality and accurate diagnosis play an important role in reducing unnecessary referrals. Recent advances like nonmydriatic ultrawide field fundus photography can be used for DR screening, though likely to be more expensive. The advent of artificial intelligence and deep learning has raised the possibility of automated detection of DR. Efforts to increase the awareness regarding DR is essential to ensure compliance to regular follow-up. Cost-effective sustainable models will ensure systematic nation-wide DR screening in the country., Competing Interests: None

The ORNATE India project is an interdisciplinary, multifaceted United Kingdom (UK)-India collaborative study aimed to build research capacity and capability in India and the UK to tackle the burden of diabetes-related visual impairment. For 51 months (October 2017-December 2021), this project built collaboration between six institutions in the UK and seven in India, including the Government of Kerala. Diabetic retinopathy (DR) screening models were evaluated in the public system in Kerala. An epidemiological study of diabetes and its complications was conducted through 20 centers across India covering 10 states and one union territory. The statistical analysis is not yet complete. In the UK, risk models for diabetes and its complications and artificial intelligence-aided tools are being developed. These were complemented by joint studies on various aspects of diabetes between collaborators in the UK and India. This interdisciplinary team enabled increased capability in several workstreams, resulting in an increased number of publications, development of cost-effective risk models, algorithms for risk-based screening, and policy for state-wide implementation of sustainable DR screening and treatment programs in primary care in Kerala. The increase in research capacity included multiple disciplines from field workers, administrators, project managers, project leads, screeners, graders, optometrists, nurses, general practitioners, and research associates in various disciplines. Cross-fertilization of these disciplines enabled the development of several collaborations external to this project. This collaborative project has made a significant impact on research capacity development in both India and the UK., Competing Interests: None

Purpose: There is an exponential rise in the prevalence of diabetes mellitus (DM) in India. Ideally all people with DM should be periodically screening for diabetic retinopathy (DR) but is not practical with current infrastructure. An alternate strategy is to identify high-risk individuals with vision-threatening diabetic retinopathy (VTDR) for priority screening and treatment., Methods: We reanalyzed four population-based studies, conducted in South India between 2001 and 2010, and reclassified individuals above 40 years into known and newly diagnosed diabetes. Multiple regression analysis was done to identify risk factors in people with known and new DM., Results: The prevalence of DR in 44,599 subjects aged ≥40 years was 14.8% (18.4 and 4.7% in known and new DM, respectively), and the prevalence of VTDR was 5.1%. Higher risk factors of VTDR were older age >50 years, diabetes duration >5 years, and systolic blood pressure >140 mm Hg. Targeted screening of people with diabetes using high-risk criteria obtained from this study was able to detect 93.5% of all individuals with VTDR., Conclusion: In a limited resource country like India, a high-risk group-based targeted screening of individuals with DM could be prioritized while continuing the current opportunistic screening till India adopts universal screening of all people with DM., Competing Interests: None

Artificial intelligence (AI) has evolved over the last few years; its use in DR screening has been demonstrated in multiple evidences across the globe. However, there are concerns right from the data acquisition, bias in data, difficulty in comparing between different algorithm, challenges in machine learning, its application in different group of population, and human barrier to AI adoption in health care. There are also legal and ethical concerns related to AI. The tension between risks and concerns on one hand versus potential and opportunity on the other have driven a need for authorities to implement policies for AI in DR screening to address these issues. The policy makers should support and facilitate research and development of AI in healthcare, but at the same time, it has to be ensured that the use of AI in healthcare aligns with recognized standards of safety, efficacy, and equity. It is essential to ensure that algorithms, datasets, and decisions are auditable and when applied to medical care (such as screening, diagnosis, or treatment) are clinically validated and explainable. Policy frameworks should require design of AI systems in health care that are informed by real-world workflow and human-centric design. Lastly, it should be ensured that healthcare AI solutions align with all relevant ethical obligations, from design to development to use and to be delivered properly in the real world., Competing Interests: None

Objective: One-hour plasma glucose (1-h PG) during the oral glucose tolerance test (OGTT) is an accurate predictor of type 2 diabetes. We performed a meta-analysis to determine the optimum cutoff of 1-h PG for detection of type 2 diabetes using 2-h PG as the gold standard., Research Design and Methods: We included 15 studies with 35,551 participants from multiple ethnic groups (53.8% Caucasian) and 2,705 newly detected cases of diabetes based on 2-h PG during OGTT. We excluded cases identified only by elevated fasting plasma glucose and/or HbA 1c . We determined the optimal 1-h PG threshold and its accuracy at this cutoff for detection of diabetes (2-h PG ≥11.1 mmol/L) using a mixed linear effects regression model with different weights to sensitivity/specificity (2/3, 1/2, and 1/3)., Results: Three cutoffs of 1-h PG, at 10.6 mmol/L, 11.6 mmol/L, and 12.5 mmol/L, had sensitivities of 0.95, 0.92, and 0.87 and specificities of 0.86, 0.91, and 0.94 at weights 2/3, 1/2, and 1/3, respectively. The cutoff of 11.6 mmol/L (95% CI 10.6, 12.6) had a sensitivity of 0.92 (0.87, 0.95), specificity of 0.91 (0.88, 0.93), area under the curve 0.939 (95% confidence region for sensitivity at a given specificity: 0.904, 0.946), and a positive predictive value of 45%., Conclusions: The 1-h PG of ≥11.6 mmol/L during OGTT has a good sensitivity and specificity for detecting type 2 diabetes. Prescreening with a diabetes-specific risk calculator to identify high-risk individuals is suggested to decrease the proportion of false-positive cases. Studies including other ethnic groups and assessing complication risk are warranted., (© 2021 by the American Diabetes Association.)

Introduction: South Asians (SA) and Pima Indians have high prevalence of diabetes but differ markedly in body size. We hypothesize that young SA will have higher diabetes incidence than Pima Indians at comparable body mass index (BMI) levels., Research Design and Methods: We used prospective cohort data to estimate age-specific, sex, and BMI-specific diabetes incidence in SA aged 20-44 years living in India and Pakistan from the Center for Cardiometabolic Risk Reduction in South Asia Study (n=6676), and compared with Pima Indians, from Pima Indian Study (n=1852)., Results: At baseline, SA were considerably less obese than Pima Indians (BMI (kg/m 2 ): 24.4 vs 33.8; waist circumference (cm): 82.5 vs 107.0). Age-standardized diabetes incidence (cases/1000 person-years, 95% CI) was lower in SA than in Pima Indians (men: 14.2, 12.2-16.2 vs 37.3, 31.8-42.8; women: 14.8, 13.0-16.5 vs 46.1, 41.2-51.1). Risk of incident diabetes among 20-24-year-old Pima men and women was six times (relative risk (RR), 95% CI: 6.04, 3.30 to 12.0) and seven times (RR, 95% CI: 7.64, 3.73 to 18.2) higher as compared with SA men and women, respectively. In those with BMI <25 kg/m 2 , however, the risk of diabetes was over five times in SA men than in Pima Indian men. Among those with BMI ≥30 kg/m 2 , diabetes incidence in SA men was nearly as high as in Pima men. SA and Pima Indians had similar magnitude of association between age, sex, BMI, and insulin secretion with diabetes. The effect of family history was larger in SA, whereas that of insulin resistance was larger in Pima Indians CONCLUSIONS: In the background of relatively low insulin resistance, higher diabetes incidence in SA is driven by poor insulin secretion in SA men. The findings call for research to improve insulin secretion in early natural history of diabetes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Introduction: We compared diabetes incidence in South Asians aged ≥45 years in urban India (Chennai and Delhi) and Pakistan (Karachi), two low-income and middle-income countries undergoing rapid transition, with blacks and whites in the US, a high-income country., Research Design and Methods: We computed age-specific, sex-specific and body mass index (BMI)-specific diabetes incidence from the prospective Center for Cardiometabolic Risk Reduction in South Asia Study (n=3136) and the Atherosclerosis Risk in Communities Study (blacks, n=3059; whites, n=9924). We assessed factors associated with incident diabetes using Cox proportional hazards regression., Results: South Asians have lower BMI and waist circumference than blacks and whites (median BMI, kg/m 2 : 24.9 vs 28.2 vs 26.0; median waist circumference, cm 87.5 vs 96.0 vs 95.0). South Asians were less insulin resistant than blacks and whites (age-BMI-adjusted homeostatic model assessment of insulin resistance, µIU/mL/mmol/L: 2.30 vs 3.45 vs 2.59), and more insulin deficient than blacks but not whites (age-BMI-adjusted homeostasis model assessment of β-cell dysfunction, µIU/mL/mmol/L: 103.7 vs 140.6 vs 103.9). Age-standardized diabetes incidence (cases/1000 person-years (95% CI)) in South Asian men was similar to black men and 1.6 times higher (1.37 to 1.92) than white men (26.0 (22.2 to 29.8) vs 26.2 (22.7 to 29.7) vs 16.1 (14.8 to 17.4)). In South Asian women, incidence was slightly higher than black women and 3 times (2.61 to 3.66) the rate in white women (31.9 (27.5 to 36.2) vs 28.6 (25.7 to 31.6) vs 11.3 (10.2 to 12.3)). In normal weight (BMI <25 kg/m 2 ), diabetes incidence adjusted for age was 2.9 times higher (2.09 to 4.28) in South Asian men, and 5.3 times (3.64 to 7.54) in South Asian women than in white women., Conclusions: South Asian adults have lower BMI and are less insulin resistant than US blacks and whites, but have higher diabetes incidence than US whites, especially in subgroups without obesity. Factors other than insulin resistance (ie, insulin secretion) may play an important role in the natural history of diabetes in South Asians., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There are very few reports pertaining to Indian patients with neonatal diabetes mellitus (NDM). Activating or gain of function mutations of K ATP channel genes namely KCNJ11 and ABCC8 are most predominant cause of permanent neonatal diabetes mellitus (PNDM)., Objectives: To identify the genotype-phenotype correlation of K ATP channel gene defects in a large series of (n = 181) Indian PNDM patients., Methods: Direct sequencing of all exons of KCNJ11 and ABCC8 genes in all 181 patients with PNDM were performed. Clinical and biochemical data were collected., Results: We have identified the molecular basis of K ATP -NDM in 39 out of 181 patients (22%). Of these, 20 had KCNJ11 mutations and 19 had ABCC8 mutations, thus comprising 51% of KCNJ11 and 49% of ABCC8. There were four novel mutations (D1128Tfs*16, Y1287C, S1422T, and H1537R) in ABCC8 gene. Three patients with KCNJ11 mutations had developmental delay with DEND syndrome. In patients with ABCC8 mutations developmental delay was seen in seven out of 19 (36.8%). Of this, three patients (15.7%) had DEND phenotype and four (21%) had iDEND. Of the 39 patients, 33 (84%) patients were shifted to sulfonylurea therapy (glibenclamide). Of this, 19(57.5%) patients harbored KCNJ11 mutations and 14(42.1%) ABCC8 mutations., Conclusions: This is the first largest study in NDM patients in India demonstrating the importance of K ATP channel gene mutation screening in PNDM and efficacy of glibenclamide for Indian patients with K ATP -PNDM. The success rate of transfer is more in patients with KCNJ11 mutations compared with those with ABCC8 mutations., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: The aim of this study was to identify factors that influence patients' motivation and ability to self-manage their diabetes and depressive symptoms., Methods: From 2016 to 17, in-depth interviews were conducted with 62 patients receiving the INDEPENDENT care model across two clinics in India. Using a realist evaluation approach, a hypothesized program theory for patient activation was tested and refined., Findings: The refined theory demonstrates that motivation, education, and engagement cumulatively contribute to patient activation., Conclusion: The results indicate that positive and sustained patient-provider relationships drive patient motivation and enhance implementation of the care model., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The increasing prevalence of diabetes, combined with a growing global shortage of health care professionals (HCP), necessitates the need to develop new approaches to diabetes care delivery to expand access to care, lessen the burden on people with diabetes, improve efficiencies, and reduce the unsustainable financial liability on health systems and payers. Use of digital diabetes technologies and telehealth protocols within a digital/virtual diabetes clinic has the potential to address these challenges. However, several issues must be resolved to move forward. In February 2020, organizers of the Advanced Technologies & Treatments for Diabetes Annual Conference convened an international panel of HCP, researchers, patient advocates, and industry representatives to review the status of digital diabetes technologies, characterize deficits in current technologies, and identify issues for consideration. Since that meeting, the importance of using telehealth and digital diabetes technologies has been demonstrated amid the global coronavirus disease (COVID-19) pandemic. This article summarizes the panel's discussion of the opportunities, obstacles, and requisites for advancing the use of these technologies as a standard of care for the management of diabetes.

Introduction: The COVID-19 pandemic resulted in a national lockdown in India from midnight on 25 March 2020, with conditional relaxation by phases and zones from 20 April. We evaluated the impact of the lockdown in terms of healthcare provisions, physical health, mental health and social well-being within a multicentre cross-sectional study in India., Methods: The SMART India study is an ongoing house-to-house survey conducted across 20 regions including 11 states and 1 union territory in India to study diabetes and its complications in the community. During the lockdown, we developed an online questionnaire and delivered it in English and seven popular Indian languages (Hindi, Tamil, Marathi, Telegu, Kannada, Bengali, Malayalam) to random samples of SMART-India participants in two rounds from 5 May 2020 to 24 May 2020. We used multivariable logistic regression to evaluate the overall impact on health and healthcare provision in phases 3 and 4 of lockdown in red and non-red zones and their interactions., Results: A total of 2003 participants completed this multicentre survey. The bivariate relationships between the outcomes and lockdown showed significant negative associations. In the multivariable analyses, the interactions between the red zones and lockdown showed that all five dimensions of healthcare provision were negatively affected (non-affordability: OR 1.917 (95% CI 1.126 to 3.264), non-accessibility: OR 2.458 (95% CI 1.549 to 3.902), inadequacy: OR 3.015 (95% CI 1.616 to 5.625), inappropriateness: OR 2.225 (95% CI 1.200 to 4.126) and discontinuity of care: OR 6.756 (95% CI 3.79 to 12.042)) and associated depression and social loneliness., Conclusion: The impact of COVID-19 pandemic and lockdown on health and healthcare was negative. The exaggeration of income inequality during lockdown can be expected to extend the negative impacts beyond the lockdown., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Prior to the discovery of insulins, diabetes was managed predominantly by dietary interventions. Discovery of insulin and its first human trial highlighted the need for higher purity insulin thereby steering the subsequent journey of insulin development. Considering the limitations of the early preparations like short duration of action and need for several injections per day, attempts at protracting the duration of insulin action were made. This led to the development of intermediate-acting Neutral Protamine Hagedorn (NPH) and the Lente family of insulins. This review provides insights into the discovery of insulins and the shortcomings of early protracted release preparations, which in turn, gave impetus to the search for a 'true' basal insulin, which could mimic the endogenous human basal insulin secretion., (© Journal of the Association of Physicians of India 2011.)

Objective: We aimed to compare cardiovascular (CV) events, all-cause mortality, and CV mortality rates among adults with and without diabetes in countries with differing levels of income., Research Design and Methods: The Prospective Urban Rural Epidemiology (PURE) study enrolled 143,567 adults aged 35-70 years from 4 high-income countries (HIC), 12 middle-income countries (MIC), and 5 low-income countries (LIC). The mean follow-up was 9.0 ± 3.0 years., Results: Among those with diabetes, CVD rates (LIC 10.3, MIC 9.2, HIC 8.3 per 1,000 person-years, P < 0.001), all-cause mortality (LIC 13.8, MIC 7.2, HIC 4.2 per 1,000 person-years, P < 0.001), and CV mortality (LIC 5.7, MIC 2.2, HIC 1.0 per 1,000 person-years, P < 0.001) were considerably higher in LIC compared with MIC and HIC. Within LIC, mortality was higher in those in the lowest tertile of wealth index (low 14.7%, middle 10.8%, and high 6.5%). In contrast to HIC and MIC, the increased CV mortality in those with diabetes in LIC remained unchanged even after adjustment for behavioral risk factors and treatments (hazard ratio [95% CI] 1.89 [1.58-2.27] to 1.78 [1.36-2.34])., Conclusions: CVD rates, all-cause mortality, and CV mortality were markedly higher among those with diabetes in LIC compared with MIC and HIC with mortality risk remaining unchanged even after adjustment for risk factors and treatments. There is an urgent need to improve access to care to those with diabetes in LIC to reduce the excess mortality rates, particularly among those in the poorer strata of society., (© 2020 by the American Diabetes Association.)

Oral cancer and diabetes are highly prevalent among the Indian population and are part of the top four non-communicable diseases responsible for mortality and morbidity. Their numbers are so great that they pose a unique burden to the socioeconomic growth of the country. In recent years, there has been an increase in the number of studies examining the role of diabetes in oral cancer reporting co-existence of diabetes and cancer. There is also growing evidence of a higher risk for developing a number of cancers among individuals with diabetes, including pancreatic, liver, gynecologic, colorectal, oral and breast cancer, and consequently 'diabetic oncopathy' is emerging as one of the complications of diabetes. Diabetes may lead to the development of cancer through oxidative damage leading to accumulation of DNA mutations and/or through immune dysfunction, which predisposes to viral infection. Cancer and diabetes may co-occur due to shared risk factors such as increased insulin-like growth factor-1 and obesity, but there is no clear biologic link between the two disorders. This literature review aims to review the evidence showing the current burden of two non-communicable diseases, diabetes and oral cancer and their potential association, with particular reference to India., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The pathophysiology of type 2 diabetes differs markedly by ethnicity., Purpose: A systematic review and meta-analysis was conducted to assess the impact of ethnicity on the glucose-lowering efficacy of the newer oral agents, sodium-glucose cotransporter 2 inhibitors (SGLT-2i), glucagon-like peptide 1 receptor agonists (GLP-1RA), and dipeptidyl peptidase 4 inhibitors (DPP-4i), using evidence from randomized clinical trials (RCTs)., Data Sources: A literature search was conducted in PubMed of all randomized, placebo-controlled trials of DPP-4i, SGLT-2i, and GLP-1RA. The search strategy was developed based on Medical Subject Headings (MeSH) terms and keywords., Study Selection: A total of 64 studies that qualified for meta-analysis after full-text review based on predefined inclusion and exclusion criteria-RCTs with at least 50 patients in each arm, >70% of population from Asian or white group, duration ≥24 weeks, and publication up to March 2019-were selected for systematic review and meta-analysis., Data Extraction: Data extraction was done for aggregated study-level data by two independent researchers. Absolute changes in HbA 1c (%) from baseline to 24 weeks between the drug and placebo were considered as the primary end point of the study., Data Synthesis: Change in HbA 1c was evaluated by computing mean differences and 95% CIs between treatment and placebo arms., Limitations: The study is based on summarized data and could not be separated based on East Asians and South Asians., Conclusions: The glucose-lowering efficacy of SGLT-2i, and to a lesser extent DPP-4i, was greater in studies of predominantly Asian ethnicity compared with studies of predominantly white ethnicity. There was no difference seen by ethnicity for GLP-1RA., (© 2020 by the American Diabetes Association.)

Background: Diabetes mellitus (DM), has been associated with increased fracture risk. However, there are no data pertaining to the prevalence of fractures for patients with DM in India. The aim of this study was to determine the prevalence of fractures in Asian Indians with and without diabetes., Methods: The study used the data of Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study, a community- based cross sectional survey conceived with the aim of obtaining the prevalence rates of diabetes in India as a whole. A community-based sample of 57,117 individuals aged ≥20 years was obtained. Diabetes was diagnosed by oral glucose tolerance test using capillary blood (except in self-reported diabetes). Fractures were self-reported., Results: Fracture data were available in 54,093 subjects. Out of these, 1416 (2.6%) had fractures. Overall prevalence of diabetes and prediabetes was 7.1% and 10.5% respectively. Prevalence of fractures was significantly higher in diabetes group (4%) compared with non-diabetes group (2.5%). In multivariate logistic regression analysis, diabetes was associated with an increased risk (1) of any fracture (OR=1.28, 95% CI: 1.07-1.5) and (2) of low trauma fracture (hip and spine combined) (OR = 1.8, 95% CI:1.1-2.8). After gender stratification, diabetes was a risk factor for fracture only in women. Age (>40 years) in women, high waist circumference (>90 cm) in men, alcohol consumption and urban residence in both men and women were other significant contributors to fracture risk., Conclusion: Increased prevalence of self-reported fractures was seen in individuals with diabetes in this population-based study from India., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Aims: India has the second largest number of patients with diabetes, and research to contain it and limit its complications is needed., Methods: A literature search was done using Pubmed and Google Scholar search engines to prepare a narrative review on this topic., Results: India's contribution to research on diabetes remains inadequate, both quantitatively and qualitatively. Most of the work thus far has been done by a limited number of organisations and individuals, and has been confined to certain limited areas of interest. Nearly 40% of the publications on diabetes in India between 2000 and 2009 originated from just 20 institutions. Many important aspects of diabetes in India remain uninvestigated. In this review we make an attempt to evaluate the current status of diabetes research in India and to understand the hurdles dissuading a large proportion of healthcare professionals in India from embarking on a career in research. We also suggest solutions for overcoming these hurdles., Conclusions: Considering the major health and economic problems posed by the unrestrained diabetes epidemic in India, research in this area remains highly inadequate., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Purpose of Review: Fibrocalculous pancreatic diabetes (FCPD) is an uncommon form of diabetes occurring in underprivileged developing countries of the world. We attempt to review the latest evidence on epidemiology, secular trends, etiopathogenic mechanisms, and treatment modalities of FCPD with particular reference to studies from the past decade., Recent Findings: There has been little new data on FCPD over the past decade even from countries where it was considered to be prevalent. There appears to be a decline in prevalence of the condition of late. There is also some evidence to show that the condition develops due to as yet unknown environmental influences acting on a background of genetic susceptibility. FCPD is a severe form of diabetes and may be a premalignant condition. FCPD deserves more attention than it currently receives, because of its unique clinical features and management strategies, and its propensity to develop pancreatic adenocarcinoma.

Objective: Our aims were to assess the association of dairy intake with prevalence of metabolic syndrome (MetS) (cross-sectionally) and with incident hypertension and incident diabetes (prospectively) in a large multinational cohort study., Methods: The Prospective Urban Rural Epidemiology (PURE) study is a prospective epidemiological study of individuals aged 35 and 70 years from 21 countries on five continents, with a median follow-up of 9.1 years. In the cross-sectional analyses , we assessed the association of dairy intake with prevalent MetS and its components among individuals with information on the five MetS components (n=112 922). For the prospective analyses , we examined the association of dairy with incident hypertension (in 57 547 individuals free of hypertension) and diabetes (in 131 481 individuals free of diabetes)., Results: In cross-sectional analysis, higher intake of total dairy (at least two servings/day compared with zero intake; OR 0.76, 95% CI 0.71 to 0.80, p-trend<0.0001) was associated with a lower prevalence of MetS after multivariable adjustment. Higher intakes of whole fat dairy consumed alone (OR 0.72, 95% CI 0.66 to 0.78, p-trend<0.0001), or consumed jointly with low fat dairy (OR 0.89, 95% CI 0.80 to 0.98, p-trend=0.0005), were associated with a lower MetS prevalence. Low fat dairy consumed alone was not associated with MetS (OR 1.03, 95% CI 0.77 to 1.38, p-trend=0.13). In prospective analysis, 13 640 people with incident hypertension and 5351 people with incident diabetes were recorded. Higher intake of total dairy (at least two servings/day vs zero serving/day) was associated with a lower incidence of hypertension (HR 0.89, 95% CI 0.82 to 0.97, p-trend=0.02) and diabetes (HR 0.88, 95% CI 0.76 to 1.02, p-trend=0.01). Directionally similar associations were found for whole fat dairy versus each outcome., Conclusions: Higher intake of whole fat (but not low fat) dairy was associated with a lower prevalence of MetS and most of its component factors, and with a lower incidence of hypertension and diabetes. Our findings should be evaluated in large randomized trials of the effects of whole fat dairy on the risks of MetS, hypertension, and diabetes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims : In this study, we aimed to estimate cross-sectional associations of fish or shellfish consumption with diabetes and glycemia in three South Asian mega-cities. Methods : We analyzed baseline data from 2010-2011 of a cohort ( n = 16,287) representing the population ≥20 years old that was neither pregnant nor on bedrest from Karachi (unweighted n = 4017), Delhi (unweighted n = 5364), and Chennai (unweighted n = 6906). Diabetes was defined as self-reported physician-diagnosed diabetes, fasting plasma glucose ≥126 mg/dL (7.0 mmol/L), or glycated hemoglobin A1c (HbA1c) ≥6.5% (48 mmol/mol). We estimated adjusted and unadjusted odds ratios for diabetes using survey estimation logistic regression for each city, and differences in glucose and HbA1c using survey estimation linear regression for each city. Adjusted models controlled for age, gender, body mass index, waist-height ratio, sedentary lifestyle, educational attainment, tobacco use, an unhealthy diet index score, income, self-reported physician diagnosis of high blood pressure, and self-reported physician diagnosis of high cholesterol. Results : The prevalence of diabetes was 26.7% (95% confidence interval: 24.8, 28.6) in Chennai, 36.7% (32.9, 40.5) in Delhi, and 24.3% (22.0, 26.6) in Karachi. Fish and shellfish were consumed more frequently in Chennai than in the other two cities. In Chennai, the adjusted odds ratio for diabetes, comparing more than weekly vs. less than weekly fish consumption, was 0.81 (0.61, 1.08); in Delhi, it was 1.18 (0.87, 1.58), and, in Karachi, it was 1.30 (0.94, 1.80). In Chennai, the adjusted odds ratio of prevalent diabetes among persons consuming shellfish more than weekly versus less than weekly was 1.08 (95% CI: 0.90, 1.30); in Delhi, it was 1.35 (0.90, 2.01), and, in Karachi, it was 1.68 (0.98, 2.86). Conclusions : Both the direction and the magnitude of association between seafood consumption and glycemia may vary by city. Further investigation into specific locally consumed seafoods and their prospective associations with incident diabetes and related pathophysiology are warranted.

Background: Gain-of-function of ATP-sensitive K + (K ATP ) channels because of mutations in the genes encoding SUR1 (ABCC8) or Kir6.2 (KCNJ11) is a major cause of neonatal diabetes mellitus (NDM). Our aim is to determine molecular defects in K ATP channels caused by ABCC8 mutations in Asian Indian children with NDM by in vitro functional studies., Methods: Wild-type (WT; NM&#95;000352.4) or mutant sulfonylurea receptor 1 (SUR1) and Kir6.2 were co-expressed in COSm6 cells. Biogenesis efficiency and surface expression of mutant channels were assessed by immunoblotting and immunostaining. The response of mutant channels to cytoplasmic ATP and ADP was assessed by inside-out patch-clamp recordings. The response of mutant channels to known K ATP inhibitors in intact cells were determined by 86 Rb efflux assays., Results: Five SUR1 missense mutations, D212Y, P254S, R653Q, R992C, and Q1224H, were studied and showed increased activity in MgATP/MgADP. Two of the mutants, D212Y and P254S, also showed reduced response to ATP 4- inhibition, as well as markedly reduced surface expression. Moreover, all five mutants were inhibited by the K ATP channel inhibitors glibenclamide and carbamazepine., Conclusions: The study shows the mechanisms by which five SUR1 mutations identified in Asian Indian NDM patients affect K ATP channel function to cause the disease. The reduced ATP 4- sensitivity caused by the D212Y and P254S mutations in the L0 of SUR1 provides novel insight into the role of L0 in channel inhibition by ATP. The results also explain why sulfonylurea therapy is effective in two patients and inform how it should be effective for the other three patients., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Telemedicine is a promising strategy that utilizes telecommunication to provide health care in remote areas, facilitating beneficial interaction between the health care provider and people in rural areas and making affordable and accessible medical care available to remote, inaccessible areas of the world. This article provides an overview of some of the ways telemedicine is improving diabetes care outcomes at the community level. Telemedicine can play a number of roles in moving quality diabetes care forward. It is currently being used to create awareness among urban and rural population about the risk factors and prevention of diabetes; to facilitate patient monitoring; for remote diabetic retinopathy screening; and in diabetes prevention at the primary, secondary, and tertiary level. We also highlight the use of automated artificial intelligence software combined with telemedicine to conduct efficient real-time screening of complications such as diabetic retinopathy in remote areas where such facilities are currently unavailable.

Background: Understanding where adults with diabetes in India are lost in the diabetes care cascade is essential for the design of targeted health interventions and to monitor progress in health system performance for managing diabetes over time. This study aimed to determine (i) the proportion of adults with diabetes in India who have reached each step of the care cascade and (ii) the variation of these cascade indicators among states and socio-demographic groups., Methods: We used data from a population-based household survey carried out in 2015 and 2016 among women and men aged 15-49 years in all states of India. Diabetes was defined as a random blood glucose (RBG) ≥ 200 mg/dL or reporting to have diabetes. The care cascade-constructed among those with diabetes-consisted of the proportion who (i) reported having diabetes ("aware"), (ii) had sought treatment ("treated"), and (iii) had sought treatment and had a RBG < 200 mg/dL ("controlled"). The care cascade was disaggregated by state, rural-urban location, age, sex, household wealth quintile, education, and marital status., Results: This analysis included 729,829 participants. Among those with diabetes (19,453 participants), 52.5% (95% CI, 50.6-54.4%) were "aware", 40.5% (95% CI, 38.6-42.3%) "treated", and 24.8% (95% CI, 23.1-26.4%) "controlled". Living in a rural area, male sex, less household wealth, and lower education were associated with worse care cascade indicators. Adults with untreated diabetes constituted the highest percentage of the adult population (irrespective of diabetes status) aged 15 to 49 years in Goa (4.2%; 95% CI, 3.2-5.2%) and Tamil Nadu (3.8%; 95% CI, 3.4-4.1%). The highest absolute number of adults with untreated diabetes lived in Tamil Nadu (1,670,035; 95% CI, 1,519,130-1,812,278) and Uttar Pradesh (1,506,638; 95% CI, 1,419,466-1,589,832)., Conclusions: There are large losses to diabetes care at each step of the care cascade in India, with the greatest loss occurring at the awareness stage. While health system performance for managing diabetes varies greatly among India's states, improvements are particularly needed for rural areas, those with less household wealth and education, and men. Although such improvements will likely have the greatest benefits for population health in Goa and Tamil Nadu, large states with a low diabetes prevalence but a high absolute number of adults with untreated diabetes, such as Uttar Pradesh, should not be neglected.

Aims: Diabetes prevention interventions have been less successful in Asian Indians compared to other populations, which may be due in part to dietary differences. The objective of this study was to determine the impact of a diabetes prevention intervention on diet and risk of diabetes in Asian Indians at high risk., Methods: Data were included from the Diabetes Community Lifestyle Improvement Program (D-CLIP), a randomized control trial to prevent diabetes in overweight/obese Asian Indian adults (20-65 years) with prediabetes. Respondents received standard treatment (control; n = 283) or a 6-month intervention (n = 295) that included education and support to reduce intakes of fat and total calories (kilocalories; kcal). Diet was ascertained using a food frequency questionnaire, and incident diabetes was determined from annual 2-h plasma glucose post-oral glucose tolerance test or biannual fasting plasma glucose., Results: There were 485 (control 240; intervention 245) respondents with complete diet data at baseline. At 6 months, the intervention was associated with decreased intake of total energy (- 185.6 kcal/day; 95% CI - 353.6, - 17.5 kcal/day) and refined cereals (- 7.2 g/1000 kcal; 95% CI - 12.7, - 1.7 g/1000 kcal), and increased intakes of fruits and vegetables (33.4 g/1000 kcal; 95% CI 16.0, 50.8 g/1000 kcal). The intervention group was half (HR 0.49; 95% CI 0.25, 0.94) as likely to develop diabetes at 1 year, and the hazard was significantly attenuated (12.2%; P = 0.015) with adjustment for fruits and vegetable intake., Conclusion: The D-CLIP decreased the total energy intake and increased the intakes of fruits and vegetables, and reduced the 1-year incidence of diabetes by half., Trial Registration: Clinicaltrails.gov # NCT01283308.

The concept of precision medicine is becoming increasingly popular. The use of big data, genomics and other "omics" like metabolomics, proteomics and transcriptomics could make the dream of personalised medicine become a reality in the near future. As far as polygenic forms of diabetes like type 2 and type 1 diabetes are concerned, interesting leads are emerging, but precision diabetes is still in its infancy. However, with regard to monogenic forms of diabetes like maturity-onset diabetes of the young and neonatal diabetes mellitus, rapid strides have been made and precision diabetes has already become part of the clinical tools used at advanced diabetes centres. In patients with some monogenic form of diabetes, if the appropriate gene defects are identified, insulin injections can be stopped and be replaced by oral sulphonylurea drugs. In the coming years, rapid advances can be expected in the field of precision diabetes, thereby making the control of diabetes more effective and hopefully leading to prevention of its complications and improvement of the quality of life of people afflicted with diabetes., (© 2019 The Author(s) Published by S. Karger AG, Basel.)