Evaluation of Madras Diabetes Research Foundation-Indian Diabetes Risk Score in detecting undiagnosed diabetes in the Indian population: Results from the Indian Council of Medical Research-INdia DIABetes population-based study (INDIAB-15).

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.

Clinical profile and incidence of microvascular complications of childhood and adolescent onset type 1 and type 2 diabetes seen at a tertiary diabetes center in India.

AIM: To study the clinical characteristics and incidence of microvascular complications among childhood and adolescent onset type 1 (T1DM) and type 2 diabetes (T2DM) seen at a tertiary care diabetes center in India. METHODS: From our electronic medical records, we retrieved clinical and biochemical details of 4555 individuals with childhood and adolescent onset diabetes (diagnosed below the age of 20 years) seen between 1992 and 2017. T1DM was diagnosed if there was history of ketoacidosis or fasting C-peptide <0.3 PMol/mL and stimulated C-peptide <0.6 PMol/mL or if insulin treatment was required from the time of diagnosis. T2DM was diagnosed based on absence of ketosis, or fasting C-peptide ≥0.6 PMol/mL and stimulated >1.0 PMoL/mL, or response to oral hypoglycemic agents for more than 2 years. We calculated the incidence rates of retinopathy (presence of at least one definite microaneurysm by retinal photography), nephropathy (urinary albumin excretion ≥30 µg/mg of creatinine) and neuropathy (vibration perception threshold ≥20 V) per 1000 person-years of follow up. RESULTS: Among the 4555 individuals with childhood and adolescent-onset diabetes, 71.4% had T1DM, 19.5% T2DM and 9.1% other forms of diabetes. Age at first visit and duration of diabetes were significantly higher in T2DM when compared to T1DM. The age adjusted incidence of retinopathy was 52.9/1000 person years (Confidence Intervals [CI]: 42.9-62.8) in T1DM and 49.8/1000 person years (CI 30.8-68.8) in T2DM; nephropathy, 6.2 (CI 3.3-9.0) and 13.8 (CI 5.6-22.0); and neuropathy, 8.8(CI 3.6-14.0) and 24.0 (CI 9.8-38.2) in T1DM and T2DM, respectively. CONCLUSION: The incidence of microvascular complications is high among childhood and adolescent-onset T1DM and T2DM and these calls for more aggressive control of diabetes.

Prevalence of vitamin D deficiency in urban south Indians with different grades of glucose tolerance.

The present study assessed the prevalence of vitamin D deficiency in an urban south Indian population in individuals with different grades of glucose tolerance. A total of 1500 individuals (900 normal glucose tolerance (NGT), 300 prediabetes and 300 with type 2 diabetes mellitus (T2DM)) who were not on vitamin D supplementation were randomly selected from the Chennai Urban Rural Epidemiological Study follow-up study. Anthropometric, clinical examination and biochemical investigations (25-hydroxyvitamin D (25(OH)D), insulin, glycated Hb (HbA1c) and serum lipids) were measured. Vitamin D deficiency was defined as serum 25(OH)D < 20·0 ng/ml, insufficiency as 20-29·9 ng/ml and sufficiency as ≥30 ng/ml. Of the 1500 individuals studied, 45 % were males and the mean age was 46 (sd 12) years. Vitamin D levels lowered with increasing degrees of glucose tolerance (NGT: 21 (sd 11); prediabetes: 19 (sd 10); T2DM: 18 (sd 11) ng/ml, P < 0·001). The overall prevalence of vitamin D deficiency was 55 % and was significantly higher among individuals with T2DM (63 %) followed by prediabetes (58 %) and NGT (51 %) (Pfor trend < 0·001). Women had 1·6 times the risk of vitamin D deficiency compared with men (unadjusted OR 1·6 (95 % CI 1·3, 2·0) and adjusted OR 1·6 (95 % CI 1·2, 1·9)). However, there was no increasing trend observed with increasing age. The prevalence of abdominal obesity (66 v. 49 %), generalised obesity (80 v. 64 %), the metabolic syndrome (45 v. 37 %) and insulin resistance (38 v. 27 %) was significantly higher in those with vitamin D deficiency compared with those without. This study shows that vitamin D deficiency is highly prevalent in this urban south Indian population and was higher among individuals with T2DM and prediabetes compared with those with NGT.

Wide-field imaging with smartphone based fundus camera: grading of severity of diabetic retinopathy and locating peripheral lesions in diabetic retinopathy.

AIM: To assess the performance of smartphone based wide-field retinal imaging (WFI) versus ultra-wide-field imaging (UWFI) for assessment of sight-threatening diabetic retinopathy (STDR) as well as locating predominantly peripheral lesions (PPL) of DR. METHODS: Individuals with type 2 diabetes with varying grades of DR underwent nonmydriatic UWFI with Daytona Plus camera followed by mydriatic WFI with smartphone-based Vistaro camera at a tertiary care diabetes centre in South India in 2021-22. Grading of DR as well as identification of PPL (DR lesions beyond the posterior pole) in the retinal images of both cameras was performed by senior retina specialists. STDR was defined by the presence of severe non-proliferative DR, proliferative DR or diabetic macular oedema (DME). The sensitivity and specificity of smartphone based WFI for detection of PPL and STDR was assessed. Agreement between the graders for both cameras was compared. RESULTS: Retinal imaging was carried out in 318 eyes of 160 individuals (mean age 54.7 ± 9 years; mean duration of diabetes 16.6 ± 7.9 years). The sensitivity and specificity for detection of STDR by Vistaro camera was 92.7% (95% CI 80.1-98.5) and 96.6% (95% CI 91.5-99.1) respectively and 95.1% (95% CI 83.5-99.4) and 95.7% (95% CI 90.3-98.6) by Daytona Plus respectively. PPL were detected in 89 (27.9%) eyes by WFI by Vistaro camera and in 160 (50.3%) eyes by UWFI. However, this did not translate to any significant difference in the grading of STDR between the two imaging systems. In both devices, PPL were most common in supero-temporal quadrant (34%). The prevalence of PPL increased with increasing severity of DR with both cameras (p < 0.001). The kappa comparison between the 2 graders for varying grades of severity of DR was 0.802 (p < 0.001) for Vistaro and 0.753 (p < 0.001) for Daytona Plus camera. CONCLUSION: Mydriatic smartphone-based widefield imaging has high sensitivity and specificity for detecting STDR and can be used to screen for peripheral retinal lesions beyond the posterior pole in individuals with diabetes.

Sex-Based Differences in Clinical Profile and Complications among Individuals with Type 2 Diabetes Seen at a Private Tertiary Diabetes Care Centre in India.

This study aimed to compare the clinical and biochemical profiles as well as the complications in males and females with type 2 diabetes (T2DM) presenting to a private tertiary diabetes care centre in India. This is a retrospective study, conducted between 1 January 2017 and 31 December 2019, and included 72,980 individuals with T2DM, aged ≥ 18 years (age and sex-matched-males-36,490; females-36,490). Anthropometric measurements, blood pressure, fasting plasma glucose (FPG), post-prandial plasma glucose (PPPG), glycated haemoglobin (HbA1c), lipids, urea, and creatinine were measured. Retinopathy was screened using retinal photography, neuropathy using biothesiometry, nephropathy measuring urinary albumin excretion, peripheral vascular disease (PVD) using Doppler, and coronary artery disease (CAD) based on the history of myocardial infarction and/or drug treatment for CAD and/or electrocardiographic changes. Obesity (73.6% vs. 59.0%) rates were significantly higher in females compared to males. FPG, PPPG, and HbA1c were higher among younger age groups among both sexes, with males having higher values compared to females. However, after the age of 44 years, control of diabetes was worse among females. In addition, only 18.8% of the females achieved glycemic control (HbA1c < 7%) compared to 19.9% in males (p < 0.001). Males had higher prevalence of neuropathy (42.9% vs. 36.9%), retinopathy (36.0% vs. 26.3%), and nephropathy (25.0% vs. 23.3%) compared to females. Males had 1.8- and 1.6-times higher risk of developing CAD and retinopathy compared to females. Hypothyroidism (12.5% vs. 3.5%) and cancers (1.3% vs. 0.6%) were significantly higher in females compared to males. In this large sample of T2DM seen at a chain of private tertiary diabetes centres, females had higher prevalence of metabolic risk factors and poorer diabetes control compared to males, emphasizing the need for better control of diabetes in females. However, males had higher prevalence of neuropathy, retinopathy, nephropathy, and CAD compared to females.

Role of cystatin C in the detection of sight-threatening diabetic retinopathy in Asian Indians with type 2 diabetes.

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.

Clinical and biochemical profile of childhood-adolescent-onset type 1 diabetes and adult-onset type 1 diabetes among 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.

Identification of appropriate biochemical parameters and cut points to detect Maturity Onset Diabetes of Young (MODY) in Asian Indians in a clinic setting.

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/m2, 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.

Prevalence, clinical features and complications of common forms of Maturity Onset Diabetes of the Young (MODY) seen at a tertiary diabetes centre in south India.

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.

Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17).

BACKGROUND: Non-communicable disease (NCD) rates are rapidly increasing in India with wide regional variations. We aimed to quantify the prevalence of metabolic NCDs in India and analyse interstate and inter-regional variations. METHODS: The Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study, a cross-sectional population-based survey, assessed a representative sample of individuals aged 20 years and older drawn from urban and rural areas of 31 states, union territories, and the National Capital Territory of India. We conducted the survey in multiple phases with a stratified multistage sampling design, using three-level stratification based on geography, population size, and socioeconomic status of each state. Diabetes and prediabetes were diagnosed using the WHO criteria, hypertension using the Eighth Joint National Committee guidelines, obesity (generalised and abdominal) using the WHO Asia Pacific guidelines, and dyslipidaemia using the National Cholesterol Education Program-Adult Treatment Panel III guidelines. FINDINGS: A total of 113 043 individuals (79 506 from rural areas and 33 537 from urban areas) participated in the ICMR-INDIAB study between Oct 18, 2008 and Dec 17, 2020. The overall weighted prevalence of diabetes was 11·4% (95% CI 10·2-12·5; 10 151 of 107 119 individuals), prediabetes 15·3% (13·9-16·6; 15 496 of 107 119 individuals), hypertension 35·5% (33·8-37·3; 35 172 of 111 439 individuals), generalised obesity 28·6% (26·9-30·3; 29 861 of 110 368 individuals), abdominal obesity 39·5% (37·7-41·4; 40 121 of 108 665 individuals), and dyslipidaemia 81·2% (77·9-84·5; 14 895 of 18 492 of 25 647). All metabolic NCDs except prediabetes were more frequent in urban than rural areas. In many states with a lower human development index, the ratio of diabetes to prediabetes was less than 1. INTERPRETATION: The prevalence of diabetes and other metabolic NCDs in India is considerably higher than previously estimated. While the diabetes epidemic is stabilising in the more developed states of the country, it is still increasing in most other states. Thus, there are serious implications for the nation, warranting urgent state-specific policies and interventions to arrest the rapidly rising epidemic of metabolic NCDs in India. FUNDING: Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare, Government of India.

Tele-Ophthalmology Versus Face-to-Face Retinal Consultation for Assessment of Diabetic Retinopathy in Diabetes Care Centers in India: A Multicenter Cross-Sectional Study.

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.

Prevalence and risk factors for diabetic retinopathy in prediabetes in Asian Indians.

AIM: To assess the prevalence of diabetic retinopathy (DR) and associated risk factors in Asian Indians with prediabetes. METHODS: In a cross-sectional study conducted at two tertiary care diabetes centres in Chennai, India, clinical and biochemical assessment and nonmydriatic ultra-wide field fundus photography was performed in individuals with prediabetes (impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) based on oral glucose tolerance test (OGTT) and/or glycated hemoglobin (HbA1c) between 5.7% and 6.4% in 2019. The retinal photographs were graded by certified ophthalmologists. Systemic risk factors associated with DR in prediabetes were assessed. RESULTS: The mean age of the 192 individuals with prediabetes was 48 ± 13 years (55.2% were males). DR was present in 12 (6.3%) individuals of which nine (4.7%) had mild non-proliferative DR (NPDR) and three (1.6%) had moderate NPDR. None had severe sight-threatening DR. The Poisson multiple regression analysis showed that after adjusting for other systemic covariates, HbA1c values ≥ 6% (6-6.4%) was associated with 2 times higher relative risk of DR (Risk ratio 1.95 (95% CI 1.07-3.545, p = 0.028) in comparison to HbA1c < 6%). CONCLUSION: DR was present in about 6% of the Asian Indians with prediabetes. Higher HbA1c values among individuals with prediabetes was associated with twice the relative risk for DR. Robust control of HbA1c should be encouraged even before the diagnosis of diabetes is established.

Clinical Profile of Long-Term Survivors and Nonsurvivors with Type 1 Diabetes in India.

Objective: To compare the clinical profile of long-term survivors and nonsurvivors with type 1 diabetes (T1D) in India. Research Design and Methods: This is a retrospective study of 76 individuals with T1D who had survived for at least 40 years ("survivors") and 51 individuals with T1D who had died with shorter duration of diabetes ("non-survivors"), from diabetes clinics in different cities of India. Prevalence of complications in both groups and causes of death of the nonsurvivors were analyzed. Retinopathy was diagnosed by retinal photography; chronic kidney disease (CKD) by urinary albumin excretion (micro-or macroalbuminuria) and estimated glomerular filtration rate; peripheral vascular disease (PVD) by doppler measurement of ankle-brachial pressure index; coronary artery disease (CAD) based on history of myocardial infarction or coronary revascularization, and neuropathy by biothesiometry. Results: Mean glycated hemoglobin (8.4% ± 1.5% vs. 10.7% ± 2.2%, P < 0.001), serum low-density lipoprotein cholesterol (91 ± 29 mg/dL vs. 107 ± 22 mg/dL, P = 0.004), and systolic blood pressure (135 ± 16 mmHg vs. 153 ± 37 mmHg, P = 0.003) were lower, and high-density lipoprotein cholesterol (51 ± 11 mg/dL vs. 43 ± 15 mg/dL, P = 0.002) higher, among survivors compared to nonsurvivors. Diabetic retinopathy, CKD, neuropathy, PVD, and CAD were more frequent among nonsurvivors. CAD [25.5%] and renal failure [23.5%] were the most frequent causes of death. Conclusions: In this first report of long-term survivors with T1D from India, we report that survivors had better glycemic and blood pressure control, more favorable lipid profiles and lower prevalence of complications compared to nonsurvivors. However, there could be other protective factors as well, which merit further studies.

Variations in glycated haemoglobin with age among individuals with normal glucose tolerance: Implications for diagnosis and treatment-Results from the ICMR-INDIAB population-based study (INDIAB-12).

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

Achievement of guideline recommended diabetes treatment targets and health habits in people with self-reported diabetes in India (ICMR-INDIAB-13): a national cross-sectional study.

BACKGROUND: There is little information on comprehensive diabetes care comprising glycaemic, lipid, and blood pressure control in India; therefore, we aimed to assess the achievement of treatment targets among adults with self-reported diabetes. METHODS: The Indian Council of Medical Research (ICMR)-India Diabetes (INDIAB) study is a cross-sectional, population-based survey of adults aged 20 years or older in all 30 states and union territories of India. We used a stratified multistage sampling design, sampling states in a phased manner, and selected villages in rural areas and census enumeration blocks in urban areas. We used a three-level stratification method on the basis of geography, population size, and socioeconomic status for each state. For the outcome assessment, good glycaemic control was defined as HbA1c of less than 7·0% (A), blood pressure control was defined as less than 140/90 mm Hg (B), and the LDL cholesterol target was defined as less than 100 mg/dL (C). ABC control was defined as the proportion of individuals meeting glycaemic, blood pressure, and LDL cholesterol targets together. We also performed multiple logistic regression to assess the factors influencing achievement of diabetes treatment targets. FINDINGS: Between Oct 18, 2008, and Dec 17, 2020, 113 043 individuals (33 537 from urban areas and 79 506 from rural areas) participated in the ICMR-INDIAB study. For this analysis, 5789 adults (2633 in urban areas and 3156 in rural areas) with self-reported diabetes were included in the study population. The median age was 56·1 years (IQR 55·7-56·5). Overall, 1748 (weighted proportion 36·3%, 95% CI 34·7-37·9) of 4834 people with diabetes achieved good glycaemic control, 2819 (weighted proportion 48·8%, 47·2-50·3) of 5698 achieved blood pressure control, and 2043 (weighted proportion 41·5%, 39·9-43·1) of 4886 achieved good LDL cholesterol control. Only 419 (weighted proportion 7·7%) of 5297 individuals with self-reported diabetes achieved all three ABC targets, with significant heterogeneity between regions and states. Higher education, male sex, rural residence, and shorter duration of diabetes (<10 years) were associated with better achievement of combined ABC targets. Only 951 (weighted proportion 16·7%) of the study population and 227 (weighted proportion 36·9%) of those on insulin reported using self-monitoring of blood glucose. INTERPRETATION: Achievement of treatment targets and adoption of healthy behaviours remains suboptimal in India. Our results can help governments to adopt policies that prioritise improvement of diabetes care delivery and surveillance in India. FUNDING: Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare.

Future risk of diabetes among Indians with metabolic and phenotypic obesity: Results from the 10-year follow-up of the Chennai Urban Rural Epidemiology Study (CURES-158).

AIM: To investigate the risk of type 2 diabetes (T2DM) among the combinations of BMI categories and metabolic syndrome in Asian Indians. MATERIALS AND METHODS: Individuals from the Chennai Urban Rural Epidemiology Study cohort (n = 1,368), free of diabetes at baseline were stratified by BMI and metabolic health as metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically obese non-obese (MONO) and metabolically obese obese (MOO). Phenotypic obesity was defined as BMI ≥ 25 kg/m2 and metabolic obesity as presence of any two of the metabolic abnormalities: hyperglycemia, high blood pressure, high triglyceridemia or low HDL cholesterol. Hazard ratios for progression to diabetes were estimated using Cox proportional hazard regression. RESULTS: During median 9.1 years of follow-up, incident cases of diabetes were highest among MOO-45.1%, followed by MONO-41.3%, MHO-27.1% and MHNO-15.9%. Incidence rates of diabetes among MOO, MONO, MHO and MHNO were 57.8, 50.9, 30.4 and 18.1 per 1000 person years, respectively. Hazard ratio for diabetes development were 1.71 in MHO, 2.87 in MONO, and 3.39 in MOO compared with MHNO. CONCLUSIONS: Increased BMI and metabolic risk factor clustering independently contribute to the increased risk of T2DM in obese individuals. Screening for metabolic abnormalities should be performed routinely in clinic to identify high-risk individuals and institute appropriate preventive measures.

Comparison of Glycemic Excursion Using Flash Continuous Glucose Monitoring in Patients with Type 2 Diabetes Mellitus Before and After Treatment with Voglibose.

Purpose: To determine the effect of Voglibose add-on therapy on daily glycemic excursions (using FreeStyle® Libre Pro™, a Flash glucose monitoring system) in Indian patients with type 2 diabetes mellitus (T2DM) receiving a stable dose of metformin (Met) or metformin+sulfonylurea (Met+SU). Patients and Methods: T2DM patients with glycosylated hemoglobin (HbA1c) ≥7.0% and at least two postprandial excursions ≥140 mg/dL (within 2 h of meal) during the screening phase (visit 1/day -14 ± 2) were enrolled in this prospective, multicenter interventional study. The patients were randomized at visit 2 (day 0 ± 2) to receive Voglibose 0.2 or 0.3 mg tablets (BID/TID) as add-on therapy to Met and Met+SU. All the patients were followed at day 14 ± 2 (visit 3), month 3 ± 14 days (visit 4), 14 weeks (i.e., visit 4 + 14 days) ±2 days (visit 5), and month 6 ± 14 days (visit 6). Continuous glucose monitoring was performed to study glycemic excursions at visits 2, 3, and 5. The study outcomes were: change in average number of glycemic excursions per day, percent time spent in glucose fluctuations, mean Postprandial glucose (PPG), Fasting plasma glucose (FPG), day and night time mean glucose levels from baseline to day 14 and week 14; change in mean amplitude of glycemic excursion (MAGE) from baseline to 14 weeks; and mean HbA1c level at 3 and 6 months. Results: Out of 110 patients enrolled, 101 patients (91.8%) (Met+SU+Voglibose: 73 and Met+Voglibose: 28) completed the study. There was a significant decrease in average number of glycemic excursions per day from baseline to day 14 in the Met+Sul+Voglibose group and to week 14 in the Met+Voglibose group. There was also a significant reduction in percent time spent above target glucose range from baseline to day 14 in both treatment groups and to week 14 in the Met+SU+Voglibose group. A significant reduction in mean PPG area under the curve, day and night time mean glucose levels, and mean FPG levels from baseline to day 14 was reported in both treatment groups. A significant reduction in night time glucose, and average MAGE and HbA1c levels was reported from baseline to week 14 in the Met+Voglibose group and the Met+SU+Voglibose group, respectively. At 6 months, body weight, glucose levels, cholesterol, low-density lipoprotein-cholesterol, and HbA1c were significantly lower, especially in the Met+SU+Voglibose arm. Conclusion: Voglibose was useful in reducing glycemic variability and improving glycemic control in Asian Indian adults with T2DM. (CTRI/2018/04/013074).

Effect of internal migration on diabetes and metabolic abnormalities in India - The ICMR-INDIAB study.

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

Incidence of hypertension among Asian Indians: 10 year follow up of the Chennai Urban Rural Epidemiology Study (CURES-153).

AIMS: There are very few studies on incidence of hypertension from developing countries. We report on the incidence of hypertension and its risk factors in Chennai city in southern India. METHODS: Participants were 1691 individuals from the Chennai Urban Rural Epidemiology Study (CURES) cohorts who did not have hypertension (normotensive n = 878, prehypertension n = 813) at baseline and who were followed for a median of 9.0 years. During the follow-up, 41 with missing blood pressure values were excluded, leaving 1650 individuals for the present analysis. Incidence rates of hypertension and predictors of progression to prehypertension and/or hypertension were estimated using Cox proportional hazards model. RESULTS: During the follow-up period, 426 out of 1650 individuals developed hypertension, giving an overall incidence of hypertension of 28.7(95%CI 26.1-31.5) per 1000 person-years. Individuals with dysglycemia at baseline had higher incident rates of hypertension. Collectively, four modifiable risk factors [pre-hypertension, dysglycemia, central obesity and physical inactivity] accounted for 87.2% of the population attributable risk of incident hypertension. CONCLUSIONS: Higher body weight, BMI, age and dysglycemia were associated with an increased risk of incident hypertension. Prehypertension, dysglycemia, central obesity and physical inactivity accounted for 87% of incident hypertension.

Correlation between markers of renal function and sight-threatening diabetic retinopathy in type 2 diabetes: a longitudinal study in an Indian clinic population.

INTRODUCTION: Previous epidemiological studies have reported on the prevalence of diabetic kidney disease (DKD) and diabetic retinopathy (DR) from India. The aim of this study is to evaluate the effect of DKD on the development of new-onset DR and sight-threatening diabetic retinopathy (STDR) in Asian Indians with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: The study was done on anonymized electronic medical record data of people with T2D who had undergone screening for DR and renal work-up as part of routine follow-up at a tertiary care diabetes center in Chennai, South India. The baseline data retrieved included clinical and biochemical parameters including renal profiles (serum creatinine, estimated glomerular filtration rate (eGFR) and albuminuria). Grading of DR was performed using the modified Early Treatment Diabetic Retinopathy Study grading system. STDR was defined as the presence of proliferative diabetic retinopathy (PDR) and/or diabetic macular edema. DKD was defined by the presence of albuminuria (≥30 µg/mg) and/or reduction in eGFR (<60 mL/min/1.73 m2). Cox regression analysis was used to evaluate the hazard ratio (HR) for DR and STDR. RESULTS: Data of 19 909 individuals with T2D (mean age 59.6±10.2 years, mean duration of diabetes 11.1±12.1 years, 66.1% male) were analyzed. At baseline, DR was present in 7818 individuals (39.3%), of whom 2249 (11.3%) had STDR. During the mean follow-up period of 3.9±1.9 years, 2140 (17.7%) developed new-onset DR and 980 individuals with non-proliferative DR (NPDR) at baseline progressed to STDR. Higher serum creatinine (HR 1.5, 95% CI 1.3 to 1.7; p<0.0001), eGFR <30 mL/min/1.73 m2 (HR 4.9, 95% CI 2.9 to 8.2; p<0.0001) and presence of macroalbuminuria >300 µg/mg (HR 3.0, 95% CI 2.4 to 3.8; p<0.0001) at baseline were associated with increased risk of progression to STDR. CONCLUSIONS: DKD at baseline is a risk factor for progression to STDR. Physicians should promptly refer their patients with DKD to ophthalmologists for timely detection and management of STDR.