Search

Objective: To describe the natural history of diabetes in Indians., Research Design and Methods: Data are from participants older than 20 years in the Centre for Cardiometabolic Risk Reduction in South Asia longitudinal study. Glycemic states were defined per American Diabetes Association criteria. Markov models were used to estimate annual transition probabilities and sojourn time through states., Results: Among 2,714 diabetes-free participants, 641 had isolated impaired fasting glucose (iIFG), and 341 had impaired glucose tolerance (IGT). The annual transition to diabetes for those with IGT was 13.9% (95% CI 12.0, 15.9) versus 8.6% (7.3, 9.8) for iIFG. In the normoglycemia ↔ iIFG → diabetes model, mean sojourn time in normoglycemia was 40.3 (34.6, 48.2) years, and sojourn time in iIFG was 9.7 (8.4, 11.4) years. For the normoglycemia ↔ IGT → diabetes model, mean sojourn time in normoglycemia was 34.5 (29.5, 40.8) years, and sojourn time in IGT was 6.1 (5.3, 7.1) years., Conclusions: Individuals reside in normoglycemia for 35-40 years; however, progression from prediabetes to diabetes is rapid., (© 2024 by the American Diabetes Association.)

Background: The association between the glycaemic index and the glycaemic load with type 2 diabetes incidence is controversial. We aimed to evaluate this association in an international cohort with diverse glycaemic index and glycaemic load diets., Methods: The PURE study is a prospective cohort study of 127 594 adults aged 35-70 years from 20 high-income, middle-income, and low-income countries. Diet was assessed at baseline using country-specific validated food frequency questionnaires. The glycaemic index and the glycaemic load were estimated on the basis of the intake of seven categories of carbohydrate-containing foods. Participants were categorised into quintiles of glycaemic index and glycaemic load. The primary outcome was incident type 2 diabetes. Multivariable Cox Frailty models with random intercepts for study centre were used to calculate hazard ratios (HRs)., Findings: During a median follow-up of 11·8 years (IQR 9·0-13·0), 7326 (5·7%) incident cases of type 2 diabetes occurred. In multivariable adjusted analyses, a diet with a higher glycaemic index was significantly associated with a higher risk of diabetes (quintile 5 vs quintile 1; HR 1·15 [95% CI 1·03-1·29]). Participants in the highest quintile of the glycaemic load had a higher risk of incident type 2 diabetes compared with those in the lowest quintile (HR 1·21, 95% CI 1·06-1·37). The glycaemic index was more strongly associated with diabetes among individuals with a higher BMI (quintile 5 vs quintile 1; HR 1·23 [95% CI 1·08-1·41]) than those with a lower BMI (quintile 5 vs quintile 1; 1·10 [0·87-1·39]; p interaction=0·030)., Interpretation: Diets with a high glycaemic index and a high glycaemic load were associated with a higher risk of incident type 2 diabetes in a multinational cohort spanning five continents. Our findings suggest that consuming low glycaemic index and low glycaemic load diets might prevent the development of type 2 diabetes., Funding: Full funding sources are listed at the end of the Article., Competing Interests: Declaration of interests VMi reports a research grant from the Canadian Institutes of Health Research during the conduct of the study. DAJ reports research grants from the Soy Nutrition Institute and the Canadian Institutes of Health Research; in-kind supplies for trials as a research support from the Almond Board of California, Walnut Council of California, the Peanut Institute, Barilla, Unilever, Unico, Primo, Loblaw Companies, Quaker (Pepsico), Pristine Gourmet, Bunge, Kellogg Canada, and WhiteWave Foods; payment or honoraria for lectures or presentations from Nutritional Fundamentals for Health–Nutramedica, Saint Barnabas Medical Center Rutgers New Jersey Medical School, The University of Chicago, 2020 China Glycemic Index International Conference, Atlantic Pain Conference, Academy of Life Long Learning; and travel support from NUTS 2022 and the 40th International Symposium on Diabetes and Nutrition. DAJ is a co-chair of the International Carbohydrate Quality Consortium and has been invited by the International Diabetes Federation to join the committee on diabetes treatment and to take the lead in writing the dietary guidelines for the treatment of diabetes. His wife, Alexandra L Jenkins, is a director and partner of INQUIS Clinical Research for the Food Industry; his two daughters, Wendy Jenkins and Amy Jenkins, have published a vegetarian book that promotes the use of the foods described here (Jenkins WM, Jenkins AE, Jenkins AL, Brydson C. The portfolio diet for cardiovascular disease risk reduction. London: Elsevier, 2019); and his sister, Caroline Brydson, received funding through a grant from the St Michael's Hospital Foundation to develop a cookbook for one of his studies. AR reports funding from the Swedish state, the Swedish Research Council, and the Swedish Heart and Lung Foundation. AA reports consulting fees from NovoNordisk; payment or Honoria for lectures or presentations from NovoNordisk Scientific Board; support for attending meetings or travel to the European Society Cardiology Meeting from NovoNordisk; and participation on data safety monitoring board or advisory board for OPTIMAL-Stroke, OPTIMAL-Diabetes, and IMPACT-BP. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: A significant proportion of diabetic kidney disease (DKD) experience a rapid decline in eGFR, leading to end-stage kidney disease (ESKD) within months. This single-centered retrospective cohort study aimed to assess the prevalence, clinical profile, and predictors for rapid progression in type 2 diabetes mellitus (T2DM) patients with DKD., Method: Three hundred fifty-nine T2DM patients with DKD between January 2018 and 2022 were included and those with superimposed non-diabetic kidney disease, chronic kidney disease 5, and < 6 months follow-up were excluded. They were classified as rapid and non-rapid progressors based on the annual eGFR decline of > 5 ml/min/1.73 m 2 /year. The primary outcome analyzed was the progression to ESKD. The secondary outcomes were the onset of microvascular and macrovascular complications and predictors for rapid progression as well as ESKD., Results: In a median follow-up of 3.5 years, 61.3% were rapid progressors (mean eGFR decline of 15.4 ml/1.73m 2 /year) and 38.7% were non-rapid progressors (mean eGFR decline 1.8 ml/1.73m 2 /year. Among rapid progressors, 61.4% reached ESKD. Severe proteinuria, the presence of retinopathy, and acute kidney injury (AKI) episodes were strong predictors of rapid progression. Cardiovascular disease and diabetic retinopathy (microvascular complications) were significantly higher among rapid progressors and had a mortality rate of 7.2%., Conclusion: The majority of type 2 DKD patients were rapid progressors and two-thirds of them developed ESKD. The prevalence of hypertension, cardiovascular disease, diabetic retinopathy, AKI episodes, and mortality was higher in rapid progressors. Severe proteinuria and diabetic retinopathy were found to be strong predictors for rapid eGFR decline and its progression to ESKD., (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Aim: We aimed to determine the performance of European prediction models in an Indian population to classify type 1 diabetes(T1D) and type 2 diabetes(T2D)., Methods: We assessed discrimination and calibration of published models of diabetes classification, using retrospective data from electronic medical records of 83309 participants aged 18-50 years living in India. Diabetes type was defined based on C-peptide measurement and early insulin requirement. Models assessed combinations of clinical measurements: age at diagnosis, body mass index(mean = 26.6 kg/m 2 ), sex(male = 64.9 %), Glutamic acid decarboxylase(GAD) antibody, serum cholesterol, serum triglycerides, and high-density lipoprotein(HDL) cholesterol., Results: 67955 participants met inclusion criteria, of whom 0.8 % had T1D, which was markedly lower than model development cohorts. Model discrimination for clinical features was broadly similar in our Indian cohort compared to the European cohort: area under the receiver operating characteristic curve(AUC ROC) was 0.90 vs. 0.90 respectively, but was lower in the subset of young participants with measured GAD antibodies(n = 2404): and an AUC ROC of 0.87 when clinical features, sex, lipids and GAD antibodies were combined. All models substantially overestimated the likelihood of T1D, reflecting the lower prevalence of T1D in the Indian population. However, good model performance was achieved after recalibration by updating the model intercept and slope., Conclusion: Models for diabetes classification maintain the discrimination of T1D and T2D in this Indian population, where T2D is far more common, but require recalibration to obtain appropriate model probabilities. External validation and recalibration are needed before these tools can be used in non-European populations., 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 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). All rights reserved.)

Many individuals with intermediate hyperglycaemia (IH), including impaired fasting glycaemia (IFG) and impaired glucose tolerance (IGT), as presently defined, will progress to type 2 diabetes (T2D). There is confirmatory evidence that T2D can be prevented by lifestyle modification and/or medications, in people with IGT diagnosed by 2-h plasma glucose (PG) during a 75-gram oral glucose tolerance test (OGTT). Over the last 40 years, a wealth of epidemiological data has confirmed the superior value of 1-h plasma glucose (PG) over fasting PG (FPG), glycated haemoglobin (HbA 1c ) and 2-h PG in populations of different ethnicity, sex and age in predicting diabetes and associated complications including death. Given the relentlessly rising prevalence of diabetes, a more sensitive, practical method is needed to detect people with IH and T2D for early prevention or treatment in the often lengthy trajectory to T2D and its complications. The International Diabetes Federation (IDF) Position Statement reviews findings that the 1-h post-load PG ≥ 155 mg/dL (8.6 mmol/L) in people with normal glucose tolerance (NGT) during an OGTT is highly predictive for detecting progression to T2D, micro- and macrovascular complications, obstructive sleep apnoea, cystic fibrosis-related diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, and mortality in individuals with risk factors. The 1-h PG of 209 mg/dL (11.6 mmol/L) is also diagnostic of T2D. Importantly, the 1-h PG cut points for diagnosing IH and T2D can be detected earlier than the recommended 2-h PG thresholds. Taken together, the 1-h PG provides an opportunity to avoid misclassification of glycaemic status if FPG or HbA 1c alone are used. The 1-h PG also allows early detection of high-risk people for intervention to prevent progression to T2D which will benefit the sizeable and growing population of individuals at increased risk of T2D. Using a 1-h OGTT, subsequent to screening with a non-laboratory diabetes risk tool, and intervening early will favourably impact the global diabetes epidemic. Health services should consider developing a policy for screening for IH based on local human and technical resources. People with a 1-h PG ≥ 155 mg/dL (8.6 mmol/L) are considered to have IH and should be prescribed lifestyle intervention and referred to a diabetes prevention program. People with a 1-h PG ≥ 209 mg/dL (11.6 mmol/L) are considered to have T2D and should have a repeat test to confirm the diagnosis of T2D and then referred for further evaluation and treatment. The substantive data presented in the Position Statement provides strong evidence for redefining current diagnostic criteria for IH and T2D by adding the 1-h PG., 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., (Published by Elsevier B.V.)

Diabetic kidney disease (DKD) is the most devastating complication of diabetes mellitus. Identification of patients at the early stages of progression may reduce the disease burden. The limitation of conventional markers such as serum creatinine and proteinuria intensify the need for novel biomarkers. The traditional paradigm of DKD pathogenesis has expanded to the activation of the immune system and inflammatory pathways. Monocyte chemo-attractant protein-1 (MCP-1) is extensively studied, as a key inflammatory mediator that modulates the development of DKD. Recent evidence supports the diagnostic role of MCP-1 in patients with or without proteinuria in DKD, as well as a significant role in the early prediction and risk stratification of DKD. In this review, we will summarize and update present evidence for MCP-1 for diagnostic ability and predicting the progression of DKD., (Copyright © 2023 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Background: Obesity, prediabetes, and type 2 diabetes mellitus (T2DM) pose a triple burden in India. Almost two-thirds of people with diabetes (PWD) in India are found to have suboptimal glycemic, blood pressure, and lipid control. Medical nutrition therapy (MNT) in diabetes has emphasized on the amount and type of carbohydrates for years. However, protein, an important macronutrient in diabetes management, needs to be focused upon, especially in India, where the consumption is found to be lower than the recommendations provided by most guidelines., Aim: An expert committee attempted to review the role of dietary protein in the management of T2DM, arrive at a consensus on the significance of increasing dietary protein for various benefits, and offer practical guidance on ways to improve protein intake among Indians., Methodology: A total of 10 endocrinologists and diabetologists, one nephrologist, and three registered dietitians representing four zones of India formed the expert committee. An in-depth review of literature in the Indian context was carried out, and the draft document was shared with the expert committee, and their views were incorporated into the same. The expert committee then assembled virtually to deliberate on various aspects of the role of protein in T2DM management. The experts from various specialties gave their valuable inputs and suggestions from their extensive personal clinical experience and research work, which helped to reach a consensus on the role and significance of protein in the management of T2DM and its complications in India., Results: There is abundant evidence that MNT is essential for the prevention and management of T2DM and its complications. Experts agreed that increasing protein intake offers myriad health benefits, namely reducing glycemic variability, improving glycemic control, increasing insulin sensitivity, improvement in lipid profile and immunity, and helping in weight management and preservation of muscle mass in PWD. The expert committee suggested aiming for an increase in protein intake by at least 5-10% of the current intake in lieu of carbohydrates in PWD. Experts also highlighted the need for more data quantifying the unmet protein needs in the Indian PWD, especially among vegetarians. Randomized controlled trials to study the effect of protein in diabetes complications such as cardiovascular disease (CVD) and diabetic kidney disease (DKD) and comorbid conditions such as sarcopenia among the Indian population are also warranted., Conclusion: Increasing protein quantity and quality in the diets of Indian PWD could significantly contribute to positive health outcomes. Increased protein intake, preferably through dietary sources to meet the requirements and, when required using diabetes-specific protein supplements (DSPS), is recommended in the prevention and control of T2DM., (© Journal of the Association of Physicians of India 2023.)

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been used for almost a decade and have proven to be effective not only in managing Type 2 diabetes (T2D), but their cardio and renal protective features make them very useful in managing patients with risk of multiple comorbidities. This systematic review was undertaken by the authors because there is no evidence currently available in India that has studied the suitability of SGLT2i as a first-line agent in patients newly diagnosed with T2D in India., Materials and Methods: First, literature was searched to identify features that are considered important when deciding on a first-line agent for managing T2D. A total of 5 broad topics were identified-glycemic control, extra glycemic effects, antihyperglycemic combination therapy, safety, and cost-effectiveness. These domains had further subheadings, and a total of 16 domains were identified. Metformin is the drug of choice as a first-line agent in such situations and has been considered the gold standard for evaluating the effects of SGLT2i across these domains. A systematic literature review on each domain was conducted to compare SGLT2i with the gold standard in Indian patients newly diagnosed with T2D. Evidence was graded (levels of evidence (LoE)-A, B, and C), and recommendations (class of recommendation (CoR)-I, II, and III) were classified by the expert group as defined in the methodology., Results: According to the systematic reviews conducted, 11 domains had Level A evidence, 2 domains (impact on lipids and gut microbiome) had Level B, and 3 domains had Level C (β-cell function, renal protection, and glycemic variability) evidence. Based on evidence and expert opinion, the authors recommend SGLT2i as a first-line agent for managing newly diagnosed patients with T2D with a Class I recommendation for 13 domains and Class II for the remaining 3 (impact on lipids, gut microbiome, and β-cell function). Although a poorer level of evidence (Level C) was available for the glycemic variability domain, the authors still reported this as Class I recommendations according to their expert opinion and consensus., Conclusion: This article advocates adopting SGLT2 inhibitors as the primary treatment choice for treating patients with newly diagnosed T2D in India., (© Journal of the Association of Physicians of India 2023.)

Objective: To examine whether the effect of conventional lifestyle interventions on type 2 diabetes incidence differs by glucose-defined prediabetes phenotype., Research Design and Methods: We searched multiple databases until 1 April 2023 for randomized controlled trials that recruited people with isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), and impaired fasting glucose plus impaired glucose tolerance (IFG+IGT). Individual participant data were pooled from relevant trials and analyzed through random-effects models with use of the within-trial interactions approach., Results: Four trials with 2,794 participants (mean age 53.0 years, 60.7% men) were included: 1,240 (44.4%), 796 (28.5%), and 758 (27.1%) had i-IFG, i-IGT, and IFG+IGT, respectively. After a median of 2.5 years, the pooled hazard ratio for diabetes incidence in i-IFG was 0.97 (95% CI 0.66, 1.44), i-IGT 0.65 (0.44, 0.96), and IFG+IGT 0.51 (0.38, 0.68; Pinteraction = 0.01)., Conclusions: Conventional lifestyle interventions reduced diabetes incidence in people with IGT (with or without IFG) but not in those with i-IFG., (© 2023 by the American Diabetes Association.)

Competing Interests: I declare no competing interests.

Introduction: Exposure to fine particulate matter has been associated with several cardiovascular and cardiometabolic diseases. However, such evidence mostly originates from low-pollution settings or cross-sectional studies, thus necessitating evidence from regions with high air pollution levels, such as India, where the burden of non-communicable diseases is high., Research Design and Methods: We studied the associations between ambient PM 2.5 levels and fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and incident type 2 diabetes mellitus (T2DM) among 12 064 participants in an adult cohort from urban Chennai and Delhi, India. A meta-analytic approach was used to combine estimates, obtained from mixed-effects models and proportional hazards models, from the two cities., Results: We observed that 10 μg/m 3 differences in monthly average exposure to PM 2.5 was associated with a 0.40 mg/dL increase in FPG (95% CI 0.22 to 0.58) and 0.021 unit increase in HbA1c (95% CI 0.009 to 0.032). Further, 10 μg/m 3 differences in annual average PM 2.5 was associated with 1.22 (95% CI 1.09 to 1.36) times increased risk of incident T2DM, with non-linear exposure response., Conclusions: We observed evidence of temporal association between PM 2.5 exposure, and higher FPG and incident T2DM in two urban environments in India, thus highlighting the potential for population-based mitigation policies to reduce the growing burden of diabetes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Diabetic retinopathy (DR) is a major sight-threatening microvascular complication in individuals with diabetes. Systemic inflammation combined with oxidative stress is thought to capture most of the complexities involved in the pathology of diabetic retinopathy. A high level of neutrophil-lymphocyte ratio (NLR) is an indicator of abnormal immune system activity. Current estimates of the association of NLR with diabetes and its complications are almost entirely derived from cross-sectional studies, suggesting that the nature of the reported association may be more diagnostic than prognostic. Therefore, in the present study, we examined the utility of NLR as a biomarker to predict the incidence of DR in the Scottish population., Methods: The incidence of DR was defined as the time to the first diagnosis of R1 or above grade in the Scottish retinopathy grading scheme from type 2 diabetes diagnosis. The effect of NLR and its interactions were explored using a competing risks survival model adjusting for other risk factors and accounting for deaths. The Fine and Gray subdistribution hazard model (FGR) was used to predict the effect of NLR on the incidence of DR., Results: We analysed data from 23,531 individuals with complete covariate information. At 10 years, 8416 (35.8%) had developed DR and 2989 (12.7%) were lost to competing events (death) without developing DR and 12,126 individuals did not have DR. The median (interquartile range) level of NLR was 2.04 (1.5 to 2.7). The optimal NLR cut-off value to predict retinopathy incidence was 3.04. After accounting for competing risks at 10 years, the cumulative incidence of DR and deaths without DR were 50.7% and 21.9%, respectively. NLR was associated with incident DR in both Cause-specific hazard (CSH = 1.63; 95% CI: 1.28-2.07) and FGR models the subdistribution hazard (sHR = 2.24; 95% CI: 1.70-2.94). Both age and HbA 1c were found to modulate the association between NLR and the risk of DR., Conclusions: The current study suggests that NLR has a promising potential to predict DR incidence in the Scottish population, especially in individuals less than 65 years and in those with well-controlled glycaemic status., (© 2023. The Author(s).)

Aim: To study the association between cystatin C and sight-threatening diabetic retinopathy (STDR) in Asian Indians with type 2 diabetes (T2DM)., Methods: In a cross-sectional study carried out at two tertiary centres in India in 2022, individuals with T2DM underwent clinical and ophthalmic assessments and estimation of serum cystatin C. Grading of DR was done by retina specialists. STDR was defined by the presence of severe non-proliferative DR (NPDR), proliferative DR (PDR) and/or diabetic macular edema. Receiver operating characteristic (ROC) curves were used to identify cystatin C cut-off value for detecting STDR., Results: Among 420 individuals with T2DM (mean age 56 ± 9 years; mean duration of diabetes 14.5 ± 7.9 years), 121 (24.1 %) had No-DR, 119 (28.3 %) had No-STDR and 200 (49.6 %) had STDR. Mean cystatin C level was significantly higher in individuals with STDR compared to those with no-STDR and No-DR (1.34 vs 1.06 vs 0.93 mg/L, p < 0.001). Cystatin C cut-off value ≥1.11 mg/L had a C statistic of 0.944 (95 % CI: 0.909-0.968, p < 0.001), 96.8 % sensitivity and 78.2 % specificity for detection of STDR., Conclusion: Elevated serum cystatin C was strongly associated with STDR and could possibly be used as a biomarker for screening for sight-threatening diabetic retinopathy., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Maturity Onset Diabetes of the Young (MODY) is a form of monogenic diabetes caused by mutations in single genes, affecting adolescents or young adults. MODY is frequently misdiagnosed as type 1 diabetes (T1). Though several studies from India have reported on the genetic aspects of MODY, the clinical profile, complications and treatments given have not been reported so far, nor compared with T1D and type 2 diabetes (T2D)., Aim: To determine the prevalence, clinical features, and complications of common forms of genetically proven MODY seen at a tertiary diabetes centre in South India and compare them with matched individuals with T1D and T2D., Methods: Five hundred and thirty individuals identified as 'possible MODY' based on clinical criteria, underwent genetic testing for MODY. Diagnosis of MODY was confirmed based on pathogenic or likely pathogenic variants found using Genome Aggregation Database (gnomAD) and American College of Medical Genetics (ACMG) criteria. The clinical profile of MODY was compared with individuals with type 1 (T1D) and type 2 (T2D) diabetes, matched for duration of diabetes. Retinopathy was diagnosed by retinal photography; nephropathy by urinary albumin excretion > 30 µg/mg of creatinine and neuropathy by vibration perception threshold > 20 v on biothesiometry., Results: Fifty-eight patients were confirmed to have MODY (10.9%). HNF1A-MODY (n = 25) was the most common subtype followed by HNF4A-MODY (n = 11), ABCC8-MODY (n = 11), GCK-MODY (n = 6) and HNF1B-MODY (n = 5). For comparison of clinical profile, only the three 'actionable' subtypes - defined as those who may respond to sulphonylureas, namely, HNF1A, HNF4A and ABCC8-MODY, were included. Age at onset of diabetes was lower among HNF4A-MODY and HNF1A-MODY than ABCC8-MODY, T1D and T2D. Prevalence of retinopathy and nephropathy was higher among the three MODY subtypes taken together (n = 47) as compared to T1D (n = 86) and T2D (n = 86)., Conclusion: This is one of the first reports of MODY subtypes from India based on ACMG and gnomAD criteria. The high prevalence of retinopathy and nephropathy in MODY points to the need for earlier diagnosis and better control of diabetes in individuals with MODY., Competing Interests: Declaration of Competing Interest M/s Serdia Pharmaceuticals and M/s Servier are manufacturers of Gliclazide used in treatment of MODY., (Copyright © 2023 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Objective: South Asians are diagnosed with type 2 diabetes (T2D) more than a decade earlier in life than seen in European populations. We hypothesized that studying the genomics of age of diagnosis in these populations may give insight into the earlier age diagnosis of T2D among individuals of South Asian descent., Research Design and Methods: We conducted a meta-analysis of genome-wide association studies (GWAS) of age at diagnosis of T2D in 34,001 individuals from four independent cohorts of European and South Asian Indians., Results: We identified two signals near the TCF7L2 and CDKAL1 genes associated with age at the onset of T2D. The strongest genome-wide significant variants at chromosome 10q25.3 in TCF7L2 (rs7903146; P = 2.4 × 10-12, β = -0.436; SE 0.02) and chromosome 6p22.3 in CDKAL1 (rs9368219; P = 2.29 × 10-8; β = -0.053; SE 0.01) were directionally consistent across ethnic groups and present at similar frequencies; however, both loci harbored additional independent signals that were only present in the South Indian cohorts. A genome-wide signal was also obtained at chromosome 10q26.12 in WDR11 (rs3011366; P = 3.255 × 10-8; β = 1.44; SE 0.25), specifically in the South Indian cohorts. Heritability estimates for the age at diagnosis were much stronger in South Indians than Europeans, and a polygenic risk score constructed based on South Indian GWAS explained ∼2% trait variance., Conclusions: Our findings provide a better understanding of ethnic differences in the age at diagnosis and indicate the potential importance of ethnic differences in the genetic architecture underpinning T2D., (© 2023 by the American Diabetes Association.)

Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes which is detected by genetic testing. We looked at clinical and biochemcial variables that could help detect possible MODY among Asian Indians with youth-onset diabetes. From the diabetes electronic medical records of a diabetes care centre in Chennai in southern India, demographic, anthropometric, and biochemical details of 34 genetically confirmed MODY participants were extracted. They were compared with patients with type 1 diabetes (T1D) (n = 1011) and type 2 diabetes (T2D) (n = 1605), diagnosed below 30 years of age. Clinical and biochemical variables including body mass index (BMI), glycated hemoglobin, HDL cholesterol, and C-peptide (fasting and stimulated) were analyzed to determine whether cut points could be derived to identify individuals who could be sent for genetic testing to diagnose or rule out MODY in this ethnic group. The age at diagnosis was higher for T2D (26.5 ± 4.0 years) compared to T1D (18.2 ± 6.1 years) and MODY (17.8 ± 6.0 years). Individuals with MODY had BMI, glycated hemoglobin, total cholesterol, triglycerides, HDL cholesterol, and C-peptide levels which were intermediate between T1D and T2D. The identified probable parameters and their cut points to identify cases for MODY genetic screening were BMI 21.2-22.7 kg/m 2 , glycated hemoglobin 7.2-10%, HDL cholesterol 43-45 mg/dl, fasting C -peptide, 1.2-2.1 ng/ml and stimulated C-peptide, 2.1-4.5 ng/ml. Asian Indians with MODY have clinical features that are intermediate between T1D and T2D and selected biochemical parameters, especially stimulated C peptide cut points were the most useful to diagnose MODY., (© 2023. The Author(s).)

Glucose monitoring has evolved from self-monitoring of blood glucose to glycated hemoglobin, and the latest continuous glucose monitoring (CGM). A key challenge to adoption of CGM for management of diabetes in Asia is the lack of regional CGM recommendations. Hence, thirteen diabetes-specialists from eight Asia-Pacific (APAC) countries/regions convened to formulate evidence-based, APAC-specific CGM recommendations for individuals with diabetes. We defined CGM metrics/targets and developed 13 guiding-statements on use of CGM in: (1) people with diabetes on intensive insulin therapy, and (2) people with type 2 diabetes on basal insulin with/without glucose lowering drugs. Continual use of CGM is recommended in individuals with diabetes on intensive insulin therapy and suboptimal glycemic control, or at high risk of problematic hypoglycemia. Continual/intermittent CGM may also be considered in individuals with type 2 diabetes on basal insulin regimen and with suboptimal glycemic control. In this paper, we provided guidance for optimizing CGM in special populations/situations, including elderly, pregnancy, Ramadan-fasting, newly diagnosed type 1 diabetes, and comorbid renal disease. Statements on remote CGM, and stepwise interpretation of CGM data were also developed. Two Delphi surveys were conducted to rate the agreement on statements. The current APAC-specific CGM recommendations provide useful guidance for optimizing use of CGM in the region., 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 © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Diabetes Technology Society assembled a panel of clinician experts in diabetology, cardiology, clinical chemistry, nephrology, and primary care to review the current evidence on biomarker screening of people with diabetes (PWD) for heart failure (HF), who are, by definition, at risk for HF (Stage A HF). This consensus report reviews features of HF in PWD from the perspectives of 1) epidemiology, 2) classification of stages, 3) pathophysiology, 4) biomarkers for diagnosing, 5) biomarker assays, 6) diagnostic accuracy of biomarkers, 7) benefits of biomarker screening, 8) consensus recommendations for biomarker screening, 9) stratification of Stage B HF, 10) echocardiographic screening, 11) management of Stage A and Stage B HF, and 12) future directions. The Diabetes Technology Society panel recommends 1) biomarker screening with one of two circulating natriuretic peptides (B-type natriuretic peptide or N-terminal prohormone of B-type natriuretic peptide), 2) beginning screening five years following diagnosis of type 1 diabetes (T1D) and at the diagnosis of type 2 diabetes (T2D), 3) beginning routine screening no earlier than at age 30 years for T1D (irrespective of age of diagnosis) and at any age for T2D, 4) screening annually, and 5) testing any time of day. The panel also recommends that an abnormal biomarker test defines asymptomatic preclinical HF (Stage B HF). This diagnosis requires follow-up using transthoracic echocardiography for classification into one of four subcategories of Stage B HF, corresponding to risk of progression to symptomatic clinical HF (Stage C HF). These recommendations will allow identification and management of Stage A and Stage B HF in PWD to prevent progression to Stage C HF or advanced HF (Stage D HF)., Competing Interests: Declaration of Competing Interests APandey has received research support from the National Institute on Aging GEMSSTAR Grant (1R03AG067960-01), and the National Institute on Minority Health and Disparities (R01MD017529). APandey has received grant funding from Applied Therapeutics and Gilead Sciences; has received honoraria outside of the present study as an advisor/consultant for Tricog Health Inc., Lilly USA, Rivus, Cytokinetics, Pieces Technologies, and Roche Diagnostics, and has received nonfinancial support from Pfizer and Merck. APandey is also a consultant for Palomarin Inc. with stock compensation. CMR has received funding from AstraZeneca, Dexcom Inc., Fresenius, Nutricia, and Recor. VNS' employer, University of Colorado, receives research support from Sanofi, NovoNordisk, Insulet, Dexcom, Tandem Diabetes Care, JDRF and NIH, and received honorarium from Dexcom, Insulet, NovoNordisk, Medscape, Lifescan and Tandem Diabetes Care for speaking or advisory role. ABG has received honoraria for lectures/ advisory boards from Abbott, AstraZeneca, Boehirnger Ingelheim, Roche Diagnostics, and Vifor. JB is a consultant for Abbott, Adrenomed, Amgen, Applied Therapeutics, American Regent, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharma, Impulse Dynamics, Innolife, Janssen, LivaNova, Medtronic, Merck, Novartis, NovoNordisk, Occlutech, Relypsa, Roche, Sequana, and Vifor. RMB has received research support, has acted as a consultant, or has been on the scientific advisory board for Abbott Diabetes Care, Ascensia, Bigfoot Biomedical, Inc., CeQur, DexCom, Eli Lilly, Hygieia, Insulet, Medtronic, Novo Nordisk, Onduo, Roche Diabetes Care, Sanofi, United Healthcare, Vertex Pharmaceuticals and Zealand Pharma. RMB's employer, non-profit HealthPartners Institute, contracts for his services for which he receives no personal income. SJG has received research support from the Duke University Department of Medicine Chair's Research Award, American Heart Association (#929502), Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards for Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim/Lilly, Cytokinetics, Roche Diagnostics, scPharmaceuticals, and Sanofi; has received speaker fees from Boehringer Ingelheim and Cytokinetics; and serves as a consultant for Amgen, Bayer, Bristol Myers Squibb, Corteria Pharmaceuticals, CSL Vifor, Merck, PharmaIN, Roche Diagnostics, Sanofi, Tricog Health, and Urovant Pharmaceuticals. MNK is a consultant or on the advisory board for Alnylam, Amgen, Applied Therapeutics, Astra Zeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Pfizer, Sanofi, Vifor Pharma, and Youngene. MNK received other research support from Astra Zeneca. MNK received honorariums from Astra Zeneca, Boehringer Ingelheim, and Novo Nordisk. LAL has received research funding from, has provided CME on behalf of and/or has acted as an advisor to Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion, HLS, Kowa, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi and Servier and is on a DSMB for Applied Therapeutics. BM was speaker honorarium and member of advisory board of Astra Zeneca, Boehringer Ingelheim, Novo Nordisk. CM serves or has served on the advisory panel for Novo Nordisk, Sanofi, Merck Sharp and Dohme Ltd., Eli Lilly and Company, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Imcyse, Insulet, Zealand Pharma, Avotres, Mannkind, Sandoz and Vertex. Financial compensation for these activities has been received by KU Leuven; KU Leuven has received research support for CM from Medtronic, Imcyse, Novo Nordisk, Sanofi and ActoBio Therapeutics; CM serves or has served on the speakers bureau for Novo Nordisk, Sanofi, Eli Lilly and Company, Boehringer Ingelheim, Astra Zeneca and Novartis. Financial compensation for these activities has been received by KU Leuven. TWM provides research support and speaking support for Abbott Diabetes Care, Dexcom, Medtronic, Novo Nordisk, Lilly Diabetes, and Sanofi; research support for Insulet Corporation and Novo Nordisk; and is on the advisory panel for Dexcom and Medscape. All funds from all activities are managed by his employer, non-profit HealthPartners Institute dba International Diabetes Center and TWM receives no personal income from these activities. VM has acted as consultant and speaker, received research or educational grants from Sanofi, Novo Nordisk, MSD, Eli Lilly, Novartis, Boehringer Ingelheim, Lifescan J & J, Roche Diagnostics, Abbott, USV, Dr. Reddy’s Laboratories, Sun Pharma and from several Indian pharmaceutical companies. KVP has served as a consultant to Novo Nordisk. APeters received research support from Abbott, Dexcom, and Insulet; was on the advisory board for Zealand, Vertez, and Medscape; and has stock options in Omada/Teladoc. YS was on the advisory board for Roche Diagnostics and Abbott Diagnostics and was a a speaker for Roche Diagnostics. YS has a patent: 20210401347. JJS is faculty at Lifescan Diabetes Institute. GU has received research grant support from Dexcom and Abbott. GU's employer, Emory University, has received funding from Bayer. DCK is a consultant for EOFlow, Integrity, Lifecare, Rockley Photonics, and Thirdwayv. AMY, JH, DK, RP-B, LB, YMB, GAF, GG, ER, GMCR, DBS, KW, EEW, and AHBW have nothing relevant to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: HNF1A is an essential component of the transcription factor network that controls pancreatic β-cell differentiation, maintenance, and glucose stimulated insulin secretion (GSIS). A continuum of protein malfunction is caused by variations in the HNF1A gene, from severe loss-of-function (LOF) variants that cause the highly penetrant Maturity Onset Diabetes of the Young (MODY) to milder LOF variants that are far less penetrant but impart a population-wide risk of type 2 diabetes that is up to five times higher. Before classifying and reporting the discovered variations as relevant in clinical diagnosis, a critical review is required. Functional investigations offer substantial support for classifying a variant as pathogenic, or otherwise as advised by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) ACMG/AMP criteria for variant interpretation., Objective: To determine the molecular basis for the variations in the HNF1A gene found in patients with monogenic diabetes in India., Methods: We performed functional protein analyses such as transactivation, protein expression, DNA binding, nuclear localization, and glucose stimulated insulin secretion (GSIS) assay, along with structural prediction analysis for 14 HNF1A variants found in 20 patients with monogenic diabetes., Results: Of the 14 variants, 4 (28.6%) were interpreted as pathogenic, 6 (42.8%) as likely pathogenic, 3 (21.4%) as variants of uncertain significance, and 1 (7.14%) as benign. Patients harboring the pathogenic/likely pathogenic variants were able to successfully switch from insulin to sulfonylureas (SU) making these variants clinically actionable., Conclusion: Our findings are the first to show the need of using additive scores during molecular characterization for accurate pathogenicity evaluations of HNF1A variants in precision medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kavitha, Ranganathan, Gopi, Vetrivel, Hemavathy, Mohan and Radha.)

Objectives: To suggest how continuous glucose monitoring (CGM) may be used intermittently in individuals with type 2 diabetes (T2D)., Materials and Methods: The use of CGM is largely in those with type 1 diabetes (T1D), in whom it makes sense to use CGM continuously as CGM provides a valuable tool to not only adjust their insulin doses but also to match it with their diet, physical activity, and other lifestyle modifications. In the case of T2D, however, especially for those not on insulin, the use of CGM may not be needed on a continuous basis. The use of CGM on an intermittent basis is rarely discussed in the literature. This article tries to provide clinical situations where CGM can be used intermittently., Results: Intermittent use of CGM defined as the "use of CGM once in 2 or 3 months or a fixed frequency," and may be useful in several situations in those with T2D. We suggest the following indications for the intermittent use of CGM in T2D-newly diagnosed patients where treatment is being started, uncontrolled diabetes where treatment is being altered, starting intensive lifestyle modification, during infections, during preoperative control, in children and adolescents with T2D, as a motivational tool to improve behavioral modification, after metabolic surgery, and in patients on steroids, apart from other indications., Conclusion: Intermittent use of CGM in T2D can be useful in special situations and can also be cost saving particularly in resource-constrained regions of the world., (© Journal of the Association of Physicians of India 2011.)

Purpose: The study was conducted to compare the compliance to intravitreal injection treatment and follow-up in patients with center-involving diabetic macular edema (CI-DME) and treatment outcomes between a tertiary eye care facility and a tertiary diabetes care center., Methods: A retrospective review was conducted on treatment naïve DME patients who had received intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in 2019. Participants were people with type 2 diabetes who were under regular care at the eye care center or the diabetes care center in Chennai. The outcome measures were noted at months 1, 2, 3, 6, and 12., Results: A review of 136 patients treated for CI-DME (72 from the eye care center and 64 from a diabetes care center) was carried out. The severity of diabetic retinopathy (DR) was similar in both centers. There was no statistically significant (P > 0.05) difference in the choice of initial intravitreal drug in the two centers. At 12-month follow-up, only 29.16% came for a follow-up in the eye center vs. 76.56% in a diabetes care center (P = 0.000). The multivariate logistic regression showed increasing age was associated with non-compliance in both the groups (eye care center: odds ratio [OR] 0.91; 95% confidence interval [CI] 0.82-1.21; P = 0.044) and diabetes care center (OR 1.15; 95% CI 1.02-1.29; P = 0.020)., Conclusion: The follow-up rate between eye care and diabetic care center with DME showed a significant disparity. By providing comprehensive diabetes care for all complications under one roof, compliance with follow-up can be improved in people with DME., Competing Interests: None

Objectives: Our study aimed to systematically review the literature and synthesise findings on potential associations of built environment characteristics with type 2 diabetes (T2D) in Asia., Design: Systematic review of the literature., Data Sources: Online databases Medline, Embase and Global Health were used to identify peer-reviewed journal articles published from inception to 23 January 2023., Eligibility Criteria: Eligible studies included cohort, cross-sectional and case-control studies that explored associations of built environment characteristics with T2D among adults 18 years and older in Asia., Data Extraction and Synthesis: Covidence online was used to remove duplicates and perform title, abstract and full-text screening. Data extraction was carried out by two independent reviewers using the OVID database and data were imported into MS Excel. Out of 5208 identified studies, 28 studies were included in this systematic review. Due to heterogeneity in study design, built environment and outcome definitions, a semiqualitative analysis was conducted, which synthesised results using weighted z-scores., Results: Five broad categories of built environment characteristics were associated with T2D in Asia. These included urban green space, walkability, food environment, availability and accessibility of services such as recreational and healthcare facilities and air pollution. We found very strong evidence of a positive association of particulate matter (PM 2.5 , PM 10 ), nitrogen dioxide and sulfur dioxide (p<0.001) with T2D risk., Conclusion: Several built environment attributes were significantly related to T2D in Asia. When compared with Western countries, very few studies have been conducted in Asia. Further research is, therefore, warranted to establish the importance of the built environment on T2D. Such evidence is essential for public health and planning policies to (re)design neighbourhoods and help improve public health across Asian countries., Prospero Registration Number: CRD42020214852., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

The prevalence of diabetes is increasing at an alarming rate globally, particularly in India. In the urban areas, the prevalence of diabetes among adults aged ≥20 y, which was around 2% in the early 1970's, has increased by >20% in 50 y. The rapid nutrition transition due to high economic growth rates increased urbanization and globalization has resulted in higher intakes of processed refined grain staples, mainly white rice in Southern and Eastern India and refined wheat in Northern and Western India. This coupled with inadequate quantity and quality of protein; unhealthy fats; lower intake of vegetables, fruits, and fiber; and a sedentary lifestyle are the main drivers of the diabetes epidemic in India. This review attempts to discuss both the quality and quantity of Indian diets with specific reference to macronutrients. This review also outlines some of the strategies that can be employed to slow down the diabetes epidemic in this region. We believe that the lessons learned from India would be applicable to other developing nations as well, particularly to the South East Asian region., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Competing Interests: JT declares shares in OrionPharma, Aktivolabs, and Digostics outside of the submitted work. All other authors declare no competing interests.

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.

Aim: To compare the clinical and biochemical profile and prevalence of complications among childhood/adolescent-onset (CAO; onset of diabetes< 20 years of age) and adult-onset (AO; onset of diabetes- ≥ 20 years of age) type 1 diabetes (T1D), seen at a tertiary care diabetes center in south India., Method: Data of 5578 individuals with T1D, diagnosed based on a history of diabetic ketoacidosis or ketonuria, fasting C-peptide < 0.3 pmol/mL and stimulated C-peptide values < 0.6 pmol/mL, and requirement of insulin right from the time of diagnosis, presenting to our center between 1991 and 2021, were retrieved from our electronic medical records. Retinopathy was assessed by retinal photography, chronic kidney disease (CKD) by urinary albumin excretion ≥ 30 µg/mg of creatinine and/or eGFR < 60 mL/min, and neuropathy by vibration perception threshold >= 20v on biothesiometry., Results: Overall, 3559 (63.8%) of individuals with T1D, belonged to CAO group and 2019 (36.2%) to AO category. AO had higher prevalence of all microvascular complications compared to CAO at every diabetes duration interval, even after adjusting for A1c. Among the AO group, prevalence of retinopathy, CKD, and neuropathy was higher in the GAD negative group. Among CAO there were no differences between the GAD negative and GAD positive groups with respect to prevalence of complications of diabetes., Conclusion: AO with T1D had higher prevalence of microvascular complications compared to CAO. Among AO, GAD negative individuals had higher percentage of retinopathy and CKD compared to GAD positive group., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

The global burden of diabetic kidney disease (DKD) is escalating, and it remains as a predominant cause of the end-stage renal disease (ESRD). DKD is associated with increased cardiovascular disease and morbidity in all types of diabetes. Prediction of progression with albuminuria and eGFR is challenging in DKD, especially in non-proteinuric DKD patients. The pathogenesis of DKD is multifactorial characterized by injury to all components of the nephron, whereas albuminuria is an indicator of only glomerular injury. The limits in the diagnostic and prognostic value of urine albumin demonstrate the need for alternative and clinically significant early biomarkers, allowing more targeted and effective diabetic treatment, to reduce the burden of DKD and ESRD. Identification of biomarkers, based on multifactorial pathogenesis of DKD can be the crucial paradigm in the treatment algorithm of DKD patients. This review focuses on the potential biomarkers linked to DKD pathogenesis, particularly with the hope of broadening the diagnostic window to identify patients with different stages of DKD progression., (© 2022. The Author(s).)

The impact of global diabetes prevention efforts has been modest despite the promise of landmark diabetes prevention trials nearly twenty years ago. While national and regional initiatives show potential, challenges remain to adapt large-scale strategies in the real-world that fits individuals and their communities. Additionally, the sedentary lifestyle changes during the COVID-19 pandemic and guidelines that now call for earlier screening (e.g., US Preventative Task Force) will increase the pool of eligible adults worldwide. Thus, a more adaptable, person-centered approach that expands the current toolkit is urgently needed to innovate and revitalize our approach to diabetes prevention. This review identifies key priorities to optimize the population-level delivery of diabetes prevention based on a consensus-based evaluation of the current evidence among experts in global translational programs; key priorities identified include (1) participant eligibility, (2) intervention intensity, (3) delivery components, (4) behavioral economics, (5) technology, and (6) the role of pharmacotherapy. We offer a conceptual framework for a broader, person-centered approach to better address an individual's risk, readiness, barriers, and digital competency., 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., (Published by Elsevier B.V.)

Monogenic diabetes includes several clinical conditions generally characterized by early-onset diabetes, such as neonatal diabetes, maturity-onset diabetes of the young (MODY) and various diabetes-associated syndromes. However, patients with apparent type 2 diabetes mellitus may actually have monogenic diabetes. Indeed, the same monogenic diabetes gene can contribute to different forms of diabetes with early or late onset, depending on the functional impact of the variant, and the same pathogenic variant can produce variable diabetes phenotypes, even in the same family. Monogenic diabetes is mostly caused by impaired function or development of pancreatic islets, with defective insulin secretion in the absence of obesity. The most prevalent form of monogenic diabetes is MODY, which may account for 0.5-5% of patients diagnosed with non-autoimmune diabetes but is probably underdiagnosed owing to insufficient genetic testing. Most patients with neonatal diabetes or MODY have autosomal dominant diabetes. More than 40 subtypes of monogenic diabetes have been identified to date, the most prevalent being deficiencies of GCK and HNF1A. Precision medicine approaches (including specific treatments for hyperglycaemia, monitoring associated extra-pancreatic phenotypes and/or following up clinical trajectories, especially during pregnancy) are available for some forms of monogenic diabetes (including GCK- and HNF1A-diabetes) and increase patients' quality of life. Next-generation sequencing has made genetic diagnosis affordable, enabling effective genomic medicine in monogenic diabetes., (© 2023. Crown.)

In 2021 an estimated 74 million individuals had diabetes in India, almost all type 2 diabetes. More than half of patients with diabetes are estimated to be undiagnosed and more 90% have dyslipidemia that is associated with accelerated development of atherosclerotic cardiovascular disease (ASCVD). Patients of Indian descent with diabetes have multiple features that distinguish them from patients with diabetes in Western populations. These include characteristics such as earlier age of onset, higher frequency of features of the metabolic syndrome, more prevalent risk factors for ASCVD, and more aggressive course of ASCVD complications. In light of the unique features of diabetes and diabetic dyslipidemia in individuals of Indian descent, the Lipid Association of India developed this expert consensus statement to provide guidance for management of diabetic dyslipidemia in this very high risk population. The recommendations contained herein are the outgrowth of a series of 165 webinars conducted by the Lipid Association of India across the country from May 2020 to July 2021, involving 155 experts in endocrinology and cardiology and an additional 2880 physicians., Competing Interests: Conflict of interest Raman Puri: Boehringer Ingelheim, Novartis Vimal Mehta: Institutional research grants from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, LIB Therapeutics, Novo Nordisk, Torrent P Barton Duell: Advisory activities: Akcea/Ionis, Esperion, Novo Nordisk, Regeneron, Kaneka. Institutional grants: Regeneron, Regenxbio, Retrophin/Travere V Mohan: Research or educational grants from Abbott, AstraZeneca, Boehringer Ingelheim, Dr. Reddy's Lab, Johnson and Johnson, Lifescan, MSD, Novartis, Novo Nordisk, Roche Diabetes Care India Private Ltd, Sanofi-Aventis, USV, other Indian pharmaceutical companies S. S. Iyengar: Dr. Reddy's Lab, Amgen, Emcure, Glenmark, Boehringer Ingelheim, Pfizer, Novartis Vinod Mittal: Boehringer Ingelheim, USV, Cipla, Intas, Emcure, MacLeods S N Narasingan: USV, Novo Nordisk, Eris, Glenmark, Torrent, Boehringer Ingelheim J.B. Chemicals and Pharmaceuticals Nathan D. Wong: Amgen, Amarin, Novartis, Esperion SK Wangnoo: Sanofi- Aventis, Nova Nordisk, Boehringer Ingelheim, Astra Zeneca The other authors report no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Background and Aim: Basal insulin combined oral therapy consisting of insulin and oral anti-diabetic drugs (OADs) is recommended for type 2 diabetes uncontrolled on OADs. There is a lack of clear evidence and recommendations on the combined use of basal insulin analogues to more than one OADs (glimepiride plus metformin) in effective control of glycemic parameters and its safety in terms of reduced hypoglycemic events, weight gain and cardiovascular risk. In this context, a group of clinical experts discussed the utility of basal insulin combined oral therapy with metformin and glimepiride in the current era., Methods: The clinical experts discussed and provided their inputs virtually. The expert panel included clinical experts comprising endocrinologists and diabetologists from India and Nepal., Results: The panel thoroughly reviewed existing literature on the subject and proposed clinical evidence and practice-based guidelines., Conclusion: These current clinical practice guidelines highlight the efficacy and safety of basal insulin combination therapy with various available basal insulins including neutral protamine hagedorn, detemir, glargine and degludec in addition to metformin and glimepiride therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To assess the cost-effectiveness of collaborative versus usual care in adults with poorly controlled type 2 diabetes and depression in India., Research Design and Methods: We performed a within-trial cost-effectiveness analysis of a 24-month parallel, open-label, pragmatic randomized clinical trial at four urban clinics in India from multipayer and societal perspectives. The trial randomly assigned 404 patients with poorly controlled type 2 diabetes (HbA1c ≥8.0%, systolic blood pressure ≥140 mmHg, or LDL cholesterol ≥130 mg/dL) and depressive symptoms (9-item Patient Health Questionnaire score ≥10) to collaborative care (support from nonphysician care coordinators, electronic registers, and specialist-supported case review) for 12 months, followed by 12 months of usual care or 24 months of usual care. We calculated incremental cost-effectiveness ratios (ICERs) in Indian rupees (INR) and international dollars (Int'l-$) and the probability of cost-effectiveness using quality-adjusted life-years (QALYs) and depression-free days (DFDs)., Results: From a multipayer perspective, collaborative care costed an additional INR309,558 (Int'l-$15,344) per QALY and an additional INR290.2 (Int'l-$14.4) per DFD gained compared with usual care. The probability of cost-effectiveness was 56.4% using a willingness to pay of INR336,000 (Int'l-$16,654) per QALY (approximately three times per-capita gross domestic product). The willingness to pay per DFD to achieve a probability of cost-effectiveness >95% was INR401.6 (Int'l-$19.9). From a societal perspective, cost-effectiveness was marginally lower. In sensitivity analyses, integrating collaborative care in clinical workflows reduced incremental costs by ∼47% (ICER 162,689 per QALY, cost-effectiveness probability 89.4%), but cost-effectiveness decreased when adjusting for baseline values., Conclusions: Collaborative care for patients with type 2 diabetes and depression in urban India can be cost-effective, especially when integrated in clinical workflows. Long-term cost-effectiveness might be more favorable. Scalability across lower- and middle-income country settings depends on heterogeneous contextual factors., (© 2022 by the American Diabetes Association.)

Background: The triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance, an important pathway in the development of type 2 diabetes and cardiovascular diseases. However, the association of the TyG index with cardiovascular diseases and mortality has mainly been investigated in Asia, with few data available from other regions of the world. We assessed the association of insulin resistance (as determined by the TyG index) with mortality and cardiovascular diseases in individuals from five continents at different levels of economic development, living in urban or rural areas. We also examined whether the associations differed according to the country's economical development., Methods: We used the TyG index as a surrogate measure for insulin resistance. Fasting triglycerides and fasting plasma glucose were measured at the baseline visit in 141 243 individuals aged 35-70 years from 22 countries in the Prospective Urban Rural Epidemiology (PURE) study. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] x fasting plasma glucose [mg/dL]/2). We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random effects to test the associations between the TyG index and risk of cardiovascular diseases and mortality. The primary outcome of this analysis was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, and non-fatal myocardial infarction, or stroke). Secondary outcomes were non-cardiovascular mortality, cardiovascular mortality, all myocardial infarctions, stroke, and incident diabetes. We also did subgroup analyses to examine the magnitude of associations between insulin resistance (ie, the TyG index) and outcome events according to the income level of the countries., Findings: During a median follow-up of 13·2 years (IQR 11·9-14·6), we recorded 6345 composite cardiovascular diseases events, 2030 cardiovascular deaths, 3038 cases of myocardial infarction, 3291 cases of stroke, and 5191 incident cases of type 2 diabetes. After adjusting for all other variables, the risk of developing cardiovascular diseases increased across tertiles of the baseline TyG index. Compared with the lowest tertile of the TyG index, the highest tertile (tertile 3) was associated with a greater incidence of the composite outcome (HR 1·21; 95% CI 1·13-1·30), myocardial infarction (1·24; 1·12-1·38), stroke (1·16; 1·05-1·28), and incident type 2 diabetes (1·99; 1·82-2·16). No significant association of the TyG index was seen with non-cardiovascular mortality. In low-income countries (LICs) and middle-income countries (MICs), the highest tertile of the TyG index was associated with increased hazards for the composite outcome (LICs: HR 1·31; 95% CI 1·12-1·54; MICs: 1·20; 1·11-1·31; p interaction =0·01), cardiovascular mortality (LICs: 1·44; 1·15-1·80; p interaction =0·01), myocardial infarction (LICs: 1·29; 1·06-1·56; MICs: 1·26; 1·10-1·45; p interaction =0·08), stroke (LICs: 1·35; 1·02-1·78; MICs: 1·17; 1·05-1·30; p interaction =0·19), and incident diabetes (LICs: 1·64; 1·38-1·94; MICs: 2·68; 2·40-2·99; p interaction <0·0001). In contrast, in high-income countries, higher TyG index tertiles were only associated with an increased hazard of incident diabetes (2·95; 2·25-3·87; p interaction <0·0001), but not of cardiovascular diseases or mortality., Interpretation: The TyG index is significantly associated with future cardiovascular mortality, myocardial infarction, stroke, and type 2 diabetes, suggesting that insulin resistance plays a promoting role in the pathogenesis of cardiovascular and metabolic diseases. Potentially, the association between the TyG index and the higher risk of cardiovascular diseases and type 2 diabetes in LICs and MICs might be explained by an increased vulnerability of these populations to the presence of insulin resistance., Funding: Full funding sources are listed at the end of the paper (see Acknowledgments)., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The burden of Gestational Diabetes Mellitus (GDM) is very high in south Asia (SA) and southeast Asia (SEA). Thus, there is a need to understand the prevalence and risk factors for developing prediabetes and type 2 diabetes mellitus (T2DM) postpartum, in this high-risk population., Aim: To conduct a systematic review and meta-analysis to estimate the prevalence of prediabetes and T2DM among the women with history of GDM in SA and SEA., Methods: A comprehensive literature search was performed in the following databases: Medline, EMBASE, Web of Knowledge and CINHAL till December 2021. Studies that had reported greater than six weeks of postpartum follow-up were included. The pooled prevalence of diabetes and prediabetes were estimated by random effects meta-analysis model and I2 statistic was used to assess heterogeneity., Results: Meta-analysis of 13 studies revealed that the prevalence of prediabetes and T2DM in post-GDM women were 25.9% (95%CI 18.94 to 33.51) and 29.9% (95%CI 17.02 to 44.57) respectively. Women with history of GDM from SA and SEA seem to have higher risk of developing T2DM than women without GDM (RR 13.2, 95%CI 9.52 to 18.29, p<0.001). The subgroup analysis showed a rise in the prevalence of T2DM with increasing duration of follow-up., Conclusion: The conversion to T2DM and prediabetes is very high among women with history of GDM in SA and SEA. This highlights the need for follow-up of GDM women for early identification of dysglycemia and to plan interventions to prevent/delay the progression to T2DM., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Shivashri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Aim: The interplay between cardiovascular disease (CVD), chronic kidney disease (CKD) and type 2 diabetes (T2D) is well established. We aim at providing an evidence-based expert opinion regarding the prevention and treatment of both heart failure (HF) and renal complications in people with T2D., Method: ology: The consensus recommendations were developed by subject experts in endocrinology, cardiology, and nephrology. The criteria for consensus were set to statements with ≥80% of agreement among clinicians specialized in endocrinology, cardiology, and nephrology. Key expert opinions were formulated based on scientific evidence and clinical judgment., Results: Assessing the risk factors of CVD or CKD in people with diabetes and taking measures to prevent HF or kidney disease are essential. Known CVD or CKD among people with diabetes confers a very high risk for recurrent CVD. Metformin plus lifestyle modification should be the first-line therapy (unless contraindicated) for the management of T2D. Glucagon-like peptide 1 (GLP-1) agonists can be preferred in people with atherosclerotic cardiovascular disease (ASCVD) or with high-risk indicators, along with sodium-glucose cotransporter-2 inhibitors (SGLT2i), whereas SGLT2i are the first choice in HF and CKD. The GLP-1 agonists can be used in people with CKD if SGLT2i are not tolerated., Conclusion: Current evidence suggests SGLT2i as preferred agents among people with T2D and HF, and for those with T2D and ASCVD. SGLT2i and GLP-1RA also lower CV outcomes in those with diabetes and ASCVD, and the treatment choice should depend on the patient profile., Competing Interests: Declaration of competing interest Dr. V. Mohan has served as a consultant and speaker and received research or educational grants from Astra Zeneca, Novo Nordisk, MSD, Novartis, Boehringer Ingelheim, USV, Dr. Reddy's Laboratories, Eli Lilly, Lifescan J & J, Sanofi-Aventis, Roche Diagnostics, Abbott, and several Indian pharmaceutical companies.Dr. A.K. Singh has no conflicts of interest to declare. Dr. A.H. Zargar was a speaker/advisor for Boehringer Ingelheim, AstraZeneca, and Johnson and Johnson and has received honoraria for his professional services. Dr. Alan Almeida has served as a consultant and speaker for Abbott, AstraZeneca, Bayer, and Dr. Reddy's Laboratories and has received honoraria for the same. Dr. A.K. Bhalla has been a speaker/advisor for Dr. Reddy ’s, Zydus, La Renon Healthcare, Fresenius Kabi, Boehringer Ingelheim, AstraZeneca, Novartis, Pfizer, Abbott, Bayer, Boston Scientific, GE, and Siemens and has received honoraria for his professional services from them. He has been part of trials sponsored by Zydus, Baxter, Siemens, GE, Abbott, AstraZeneca, and PPD as a principal investigator (PI).Dr. J.C. Mohan has been a speaker/advisor for Johnson and Johnson, Boehringer Ingelheim, AstraZeneca, Novartis, Pfizer, Abbott, Bayer, Boston Scientific, GE, Siemens, Toshiba Health Systems and has received honoraria for his professional services from them. He has been part of the ATTR-ACT trial of Pfizer as a PI.Dr. Jamshed Dalal has received speaker honoraria from Astra Zeneca Pharma India Limited and Boehringer Ingelheim, India. Dr. Manisha Sahay has received speaker honoraria from AstraZeneca and Johnson and Johnson. Dr. P.P. Mohanan has received an honorarium from AstraZeneca for academic purposes. Dr. Sanjay Maitra has been a speaker/advisor for Johnson and Johnson, Boehringer Ingelheim, and AstraZeneca, Dr. Sujoy Ghosh has served as a consultant and speaker and received research or educational grants from Astra Zeneca, Novo Nordisk, MSD, Novartis, Boehringer Ingelheim, Glenmark, USV, Dr. Reddy's Laboratories, Eli Lilly, Lifescan J & J, Sanofi-Aventis, Roche Diagnostics, Abbott, and several Indian pharmaceutical companies. Dr. Tarun Jeloka has been a speaker/advisor for AstraZeneca and Zydus and has received honoraria for his professional services from them. Dr. Upendra Kaul has been a speaker/advisor for Boehringer Ingelheim, AstraZeneca, Novartis, Pfizer, Abbott, Bayer, Medtronic, Boston Scientific, and GE and has received honoraria for his professional services from them. He has been associated with PARAGON-HF, EMPEROR-Reduced, and EMPEROR-Preserved trials as a PI. Dr. Vinay Sakhuja has no conflicts of interest to declare. Dr. M.K. Das has no conflicts of interest to declare., (Copyright © 2022. Published by Elsevier Ltd.)

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 study the frequency of iron deficiency anemia (IDA) in individuals with type 2 diabetes mellitus (T2DM) seen at tertiary diabetes care centres across India., Methods: This is a retrospective study (January 1, 2017-December 31, 2019), which included 1137 individuals with T2DM, aged ≥18 years, for whom data on glycemic, lipid and haematological parameters were available. Anthropometric measurements were done using standardized techniques. Biochemical investigations included fasting plasma glucose[FPG], post prandial plasma glucose, HbA1c, lipids and serum ferritin and iron wherever feasible., Results: Of the 1137 individuals included for the study, 117 (10.3%) were categorized as no 'iron deficiency' (ID) group [normal hemoglobin: male ≥13 g/dl, female ≥12 g/dl and normal serum ferritin ≥70 μg/L], 123 (10.8%) as ID group [normal hemoglobin and low serum ferritin <70 μg/L)], 447 (39.3%) as IDA group [low haemoglobin: male <13 g/dl, female <12 g/dl and low serum ferritin] and 450 (39.6%) as 'anemia of chronic disease' (ACD) group [low hemoglobin and normal serum ferritin]. The percentage of women having ID (57.7%) and IDA (65.3%) was significantly higher than their male counterparts. ID was most prevalent (61.7%) in the individuals with duration of diabetes <5 years whereas ACD was most prevalent (50.5%) in individuals with long standing diabetes (>10 years). Independent risk factors for IDA were female gender (OR 3.3,95% CI:1.75-6.23, p < 0.001), duration of diabetes (OR 1.05, 95% CI 1.01-1.11, p = 0.028) and FPG (OR 1.01, 95% CI 0.99-1.00, p = 0.018)., Conclusions: There is a need of identifying and monitoring iron status and anemia in patients with T2DM., Competing Interests: Declaration of competing interest The authors declare no competing interest associated with this manuscript., (Copyright © 2022 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Objective: Intake of white rice has been associated with elevated risk for type 2 diabetes (T2D), while studies on brown rice are conflicting. To inform dietary guidance, we synthesised the evidence on white rice and brown rice with T2D risk., Design: Systematic review and meta-analysis., Data Sources: PubMed, EMBASE and Cochrane databases were searched through November 2021., Eligibility Criteria: Prospective cohort studies of white and brown rice intake on T2D risk (≥1 year), and randomised controlled trials (RCTs) comparing brown rice with white rice on cardiometabolic risk factors (≥2 weeks)., Data Extraction and Synthesis: Data were extracted by the primary reviewer and two additional reviewers. Meta-analyses were conducted using random-effects models and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using the Newcastle Ottawa Scale for prospective cohort studies and the Cochrane Risk of Bias Tool for RCTs. Strength of the meta-evidence was assessed using NutriGrade., Results: Nineteen articles were included: 8 cohort studies providing 18 estimates (white rice: 15 estimates, 25 956 cases, n=5 77 426; brown rice: 3 estimates, 10 507 cases, n=1 97 228) and 11 RCTs (n=1034). In cohort studies, white rice was associated with higher risk of T2D (pooled RR, 1.16; 95% CI: 1.02 to 1.32) comparing extreme categories. At intakes above ~300 g/day, a dose-response was observed (each 158 g/day serving was associated with 13% (11%-15%) higher risk of T2D). Intake of brown rice was associated with lower risk of T2D (pooled RR, 0.89; 95% CI: 0.81 to 0.97) comparing extreme categories. Each 50 g/day serving of brown rice was associated with 13% (6%-20%) lower risk of T2D. Cohort studies were considered to be of good or fair quality. RCTs showed an increase in high-density lipoprotein-cholesterol (0.06 mmol/L; 0.00 to 0.11 mmol/L) in the brown compared with white rice group. No other significant differences in risk factors were observed. The majority of RCTs were found to have some concern for risk of bias. Overall strength of the meta-evidence was moderate for cohort studies and moderate and low for RCTs., Conclusion: Intake of white rice was associated with higher risk of T2D, while intake of brown rice was associated with lower risk. Findings from substitution trials on cardiometabolic risk factors were inconsistent., Prospero Registration Number: CRD42020158466., Competing Interests: Competing interests: DJAJ has received research grants from Loblaw Companies, the Almond Board of California, Soy Nutrition Institute (SNI) and the Canadian Institutes of Health Research (CIHR). He has received in-kind supplies for trials as a research support from the Almond board of California, Walnut Council of California, the Peanut Institute, Barilla, Unilever, Unico, Primo, Loblaw Companies, Quaker (Pepsico), Pristine Gourmet, Bunge Limited, Kellogg Canada, WhiteWave Foods. He has been on the speaker's panel, served on the scientific advisory board and/or received travel support and/or honoraria from Nutritional Fundamentals for Health (NFH)-Nutramedica, Saint Barnabas Medical Center, The University of Chicago, 2020 China Glycaemic Index (GI) International Conference, Atlantic Pain Conference, Academy of Life Long Learning, Loblaw Companies, Diet Quality Photo Navigation (DQPN), Better Therapeutics (FareWell), Verywell, True Health Initiative (THI), Heali AI Corp, Institute of Food Technologists (IFT), Soy Nutrition Institute (SNI), Herbalife Nutrition Institute (HNI), Herbalife International, Pacific Health Laboratories, Nutritional Fundamentals for Health (NFH), the Soy Foods Association of North America, the Nutrition Foundation of Italy (NFI), the Toronto Knowledge Translation Group (St. Michael's Hospital), the Canadian College of Naturopathic Medicine, The Hospital for Sick Children, the Canadian Nutrition Society (CNS) and the American Society of Nutrition (ASN). He is a member of the International Carbohydrate Quality Consortium (ICQC). His wife, Alexandra L Jenkins, is a director and partner of INQUIS Clinical Research for the Food Industry, his two daughters, Wendy Jenkins and Amy Jenkins, have published a vegetarian book that promotes the use of the low glycaemic index plant foods advocated here, The Portfolio Diet for Cardiovascular Risk Reduction (Academic Press/Elsevier 2020 ISBN:978-0-12-810510-8) and his sister, Caroline Brydson, received funding through a grant from the St. Michael's Hospital Foundation to develop a cookbook for one of his studies. He is also vegan. VSM and SV are involved in the production and distribution of brown rice. VSM has developed a healthier variety of white rice and is involved in studies on glycaemic index of various rice varieties. TK has received research support from the International Life Science Institute (ILSI), and the National Honey Board. VSM is a consultant for the Nutrition Guidance Expert Advisory Group for the WHO. SB is a scientific consultant for Layer IV for work that is unrelated to this manuscript. There are no other financial or personal conflicts of interest to disclose that are related to the contents of this manuscript. The funding sources had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report or in the decision to submit the article for publication. The authors are not affiliated with the funding institutions., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

There is conflicting evidence about the association between dairy products and cardiometabolic risk (CMR). We aimed to assess the association of total dairy intake with CMR factors and to investigate the association of unfermented and fermented dairy intake with CMR in Asian Indians who are known to have greater susceptibility to type 2 diabetes and cardiovascular diseases compared to white Europeans. The study comprised 1033 Asian Indian adults with normal glucose tolerance chosen from the Chennai Urban Rural Epidemiological Study (CURES). Dietary intake was assessed using a validated open-ended semi-quantitative food frequency questionnaire. Metabolic syndrome (MS) was diagnosed based on the new harmonising criteria using central obesity, dyslipidaemia [low high-density lipoprotein cholesterol (HDL) and increased serum triglycerides (TG)], hypertension and glucose intolerance. Increased consumption of dairy (≥5 cups per day of total, ≥4 cups per day of unfermented or ≥2 cups per day of fermented dairy) was associated with a lower risk of high fasting plasma glucose (FPG) [hazards ratio (HR), 95% confidence interval (CI): 0.68, 0.48−0.96 for total dairy; 0.57, 0.34−0.94 for unfermented dairy; and 0.64, 0.46−0.90 for fermented dairy; p < 0.05 for all] compared to a low dairy intake (≤1.4 cups per day of total dairy; ≤1 cup per day of unfermented dairy; and ≤0.1 cup per day of fermented dairy). A total dairy intake of ≥5 cups per day was also protective against high blood pressure (BP) (HR: 0.65, 95% CI: 0.43−0.99, p < 0.05), low HDL (HR: 0.63, 95% CI: 0.43−0.92, p < 0.05) and MS (HR: 0.71, 95% CI: 0.51−0.98, p < 0.05) compared to an intake of ≤1.4 cups per day. A high unfermented dairy intake (≥4 cups per day) was also associated with a lower risk of high body mass index (BMI) (HR: 0.52, 95% CI: 0.31−0.88, p < 0.05) compared to a low intake (≤1 cup per day), while a reduced risk of MS was observed with a fermented dairy intake of ≥2 cups per day (HR: 0.71, 95% CI: 0.51−0.98, p < 0.05) compared to an intake of ≤0.1 cup per day. In summary, increased consumption of dairy was associated with a lower risk of MS and components of CMR.

Pan-leukocyte exhaustion is a physiological process associated with immune homeostasis. Too much of immune exhaustion can lead to immune impairment and increased susceptibility to infections and cancer; too little can lead to chronic inflammation. Since type-2 diabetes subjects have both impaired immunity and metainflammation, we looked at TLR induced pan-immune exhaustion and its regulation, in these subjects. TLR induced expression of PD-1 and CTLA-4 in T cells, B cells, monocytes and neutrophils, in whole blood cultures, were quantified by flowcytometry. Circulating levels and in vitro secretion of IFN-β and α-Defensin-1 (α-DEF-1) were quantified by ELISA. TLR induced expression of PU.1, IRF-3,-4 and -5 in whole blood cultures was quantified by qRT-PCR. Systemic lipid and protein peroxidation was quantified by spectrophotometry. TLR induced expression of PD-1 (in monocytes) and CTLA-4 expression (in B cells and neutrophils) were decreased in drug naive newly diagnosed diabetes patients. This was associated with decreased secretion and circulating levels of IFN-β and increased secretion and circulating levels of α-DEF-1 in these subjects. No major derangement in the transcriptional network was seen. Many of these defects were only partially rectified in those under treatment. Together, we hypothesize that the high defensin levels could inhibit TLR signalling leading to reduced IFN-β levels, which in turn could lead to reduced expression of PD-1 and CTLA-4 in the immune cells. This effect along with systemic redox stress could fuel metainflammation in type-2 diabetes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aim: To evaluate the effectiveness of tele-ophthalmology (TO) versus face-to-face screening for diabetic retinopathy (DR) in diabetes care centers (DCC) across India. Methods: This is an observational, multicenter, retrospective, cross-sectional study of DR screening in individuals with diabetes performed across 35 branches of a chain of DCC in 20 cities in India over 1 year. In 30 DCC, DR screening was performed by TO, where retinal images obtained using Fundus on Phone camera were uploaded through the telemedicine network for centralized DR grading by eight retina specialists. In five DCC, DR screening was performed by fundus examination (FE) by the same retina specialists. The rate of detection of sight-threatening DR (STDR) (defined as the presence of proliferative DR and/or diabetic macular edema) through the two modes was compared. Results: A total of 58,612 individuals were screened for DR from January 1, 2018 to December 31, 2018: 25,316 by TO and 33,296 by FE. The mean age and mean duration of diabetes of the individuals with diabetes screened by TO was 55.8 ± 11.2 years and 9.5 ± 7.3 years; and in individuals screened by FE, it was 57.5 ± 11.6 years and 11.5 ± 8.0 years respectively. The mean glycated hemoglobin was 8.8% ± 2.1% and 8.5% ± 1.9% in the two groups, respectively. Any DR was detected in 31.7% (95% confidence interval [CI]: 31.0-32.3) by tele-screening and in 38.5% (95% CI: 37.9-39.0) by FE, whereas STDR was detected in 7.3% (95% CI: 7.0-7.7) by TO and in 10.5% (95% CI: 10.2-10.9) by FE. Overall, 11.4% individuals with diabetes in the TO group, including 4.1% with ungradable images, were advised referral to retina specialists for further management. Conclusion: Screening for DR at DCC using TO is feasible and effective for STDR detection in India and may be adopted throughout India.

Type 2 diabetes (T2DM) is conventionally considered a progressive disorder, with most patients requiring increasingly intensive therapy to control hyperglycemia over time. Recently, there has been a major paradigm shift towards trying to reverse T2DM. Emerging evidence suggests that remission of T2DM is feasible in a subset of patients. Identification and careful selection of candidates for remission are crucial for the success of these programs. Among various dietary strategies, low-calorie diets (LCDs) and low-carbohydrate diets (LCBDs) have been demonstrated as being effective in facilitating remission of T2DM in a targeted population within a clinical setting. Remission with LCBDs may be maintained in the absence of weight loss, however, long-term evidence is limited and remission may not be maintained without long-term carbohydrate restriction, which poses major challenges. In very low-calorie diets (VLCDs), weight loss of 15 kg or greater and maintenance of weight loss is the main driver and predictor of remission. However, most individuals with T2DM were unable to maintain remission beyond 2 years, despite being on VLCDs. More data are required on the long-term sustainability of remission in an ethnically diverse population like Asian Indians with T2DM who have less obesity and hence less weight to lose. Moreover, "re-reversal" or "relapse" of diabetes can occur in a large percentage of individuals who discontinue the dietary restrictions. Hence, regular follow-up by a multi-disciplinary team to ensure sustainability of the lifestyle modification is crucial to the maintenance of remission of T2DM., (© Journal of the Association of Physicians of India 2011.)

Aims/hypothesis: South Asians in general, and Asian Indians in particular, have higher risk of type 2 diabetes compared with white Europeans, and a younger age of onset. The reasons for the younger age of onset in relation to obesity, beta cell function and insulin sensitivity are under-explored., Methods: Two cohorts of Asian Indians, the ICMR-INDIAB cohort (Indian Council of Medical Research-India Diabetes Study) and the DMDSC cohort (Dr Mohan's Diabetes Specialties Centre), and one of white Europeans, the ESDC (East Scotland Diabetes Cohort), were used. Using a cross-sectional design, we examined the comparative prevalence of healthy, overweight and obese participants with young-onset diabetes, classified according to their BMI. We explored the role of clinically measured beta cell function in diabetes onset in Asian Indians. Finally, the comparative distribution of a partitioned polygenic score (pPS) for risk of diabetes due to poor beta cell function was examined. Replication of the genetic findings was sought using data from the UK Biobank., Results: The prevalence of young-onset diabetes with normal BMI was 9.3% amongst white Europeans and 24-39% amongst Asian Indians. In Asian Indians with young-onset diabetes, after adjustment for family history of type 2 diabetes, sex, insulin sensitivity and HDL-cholesterol, stimulated C-peptide was 492 pmol/ml (IQR 353-616, p<0.0001) lower in lean compared with obese individuals. Asian Indians in our study, and South Asians from the UK Biobank, had a higher number of risk alleles than white Europeans. After weighting the pPS for beta cell function, Asian Indians have lower genetically determined beta cell function than white Europeans (p<0.0001). The pPS was associated with age of diagnosis in Asian Indians but not in white Europeans. The pPS explained 2% of the variation in clinically measured beta cell function, and 1.2%, 0.97%, and 0.36% of variance in age of diabetes amongst Asian Indians with normal BMI, or classified as overweight and obese BMI, respectively., Conclusions/interpretation: The prevalence of lean BMI in young-onset diabetes is over two times higher in Asian Indians compared with white Europeans. This phenotype of lean, young-onset diabetes appears driven in part by lower beta cell function. We demonstrate that Asian Indians with diabetes also have lower genetically determined beta cell function., (© 2022. The Author(s).)

Diabetic kidney disease (DKD) is the most common cause of renal failure and a major contributor to the socioeconomic burden in chronic kidney disease (CKD) patients worldwide. The pathogenesis of DKD involves all the structures in the nephron, and it is indicated by proteinuria, hypertension, and progressive decline in renal function, leading to substantial morbidity and mortality. Due to the limitations of currently available standard markers (albuminuria and glomerular filtration rate) in the diagnosis and clinical grading of DKD, it's time to have novel biomarkers for early detection, targeted and effective therapy to prevent the progression. Microparticles (MPs) are extracellular vesicles measuring 0.1-1 µm derived by cytoskeletal reorganization in the form of cytoplasmic blebs which alters the phospholipid cytochemistry of the cell membrane. They are shed during cell activation and apoptosis as well as plays an important role in cell-to-cell communication. Over the last few decades, both plasma and urinary MPs have been investigated, validated and the preliminary research looks promising. With alterations in their number and composition documented in clinical situations involving both Type1 and 2 diabetes mellitus, microparticles assay appears to be promising in early diagnosis and prognostication of DKD. We cover the basics of microparticles and their involvement in DKD in this review article., (Copyright © 2022. Published by Elsevier B.V.)

Aims: Despite their established benefits, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) remain underutilized for type 2 diabetes mellitus (T2DM) management, which indicates that subcutaneous injection is an unfavorable mode of delivery from the patient's perspective. This review summarizes existing challenges related to medication adherence and the use of antihyperglycemia injectables, revisits the established safety and efficacy of oral semaglutide, and explores its features and considerations for use among the Indian T2DM population., Methods: We performed a literature search using MEDLINE and the National Institutes of Health Clinical Trials Registry from July 1, 2016, to July 1, 2021, to identify publications on oral semaglutide approval, T2DM treatment guidelines, and clinical evidence for oral drug formulation., Results: Oral semaglutide is the first oral GLP-1 RA approved for T2DM patients based on phase 3, randomized PIONEER trials. The multitargeted action of this drug offers glycemic control, weight control, and cardiovascular, renal, and additional benefits, including patient convenience and enhanced medication adherence. In addition to achieving glycemic control, the cost of semaglutide is reported to be lower than other GLP-1 RA in the West, thus potentially mitigating the economic burden that appears to be high among the Indian population., Conclusions: Currently, there is no data available on oral semaglutide in Indian clinical settings. However, significant improvements in glycemic control, cardiac and renal benefits, as well as weight loss across clinical trials should encourage clinicians to prioritize oral semaglutide over other antidiabetic agents., Competing Interests: Declaration of competing interest VM acted as consultant and speaker, received research or educational grants from Novo Nordisk, Johnson & Johnson, USV Private Limited, Abbott, Biocon, Astra Zeneca, Boehringer Ingelheim, Dr. Reddy's Laboratories, LifeScan, Lilly, MSD, Novartis, Roche Diabetes Care India Pvt. Ltd, Sanofi-Aventis, and other Indian pharmaceutical companies. AGU, AKS, GB, and JK received honoraria from Novo Nordisk. SJ, AD, BS, and SG received speaker honoraria from Novo Nordisk for conducting medical education lectures. No potential conflict of interest was reported by SC and RR. Novo Nordisk neither influenced the content of this publication nor was it involved in the study design, data collection, analysis, interpretation, or review., (Copyright © 2022 Diabetes India. Published by Elsevier Ltd. All rights reserved.)