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.

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.

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.

Frequency of iron deficiency anemia in type 2 diabetes - Insights from tertiary diabetes care centres across India.

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.

Development and validation of predictive risk models for sight threatening diabetic retinopathy in patients with type 2 diabetes to be applied as triage tools in resource limited settings.

Background: Delayed diagnosis and treatment of sight threatening diabetic retinopathy (STDR) is a common cause of visual impairment in people with Type 2 diabetes. Therefore, systematic regular retinal screening is recommended, but global coverage of such services is challenging. We aimed to develop and validate predictive models for STDR to identify 'at-risk' population for retinal screening. Methods: Models were developed using datasets obtained from general practices in inner London, United Kingdom (UK) on adults with type 2 Diabetes during the period 2007-2017. Three models were developed using Cox regression and model performance was assessed using C statistic, calibration slope and observed to expected ratio measures. Models were externally validated in cohorts from Wales, UK and India. Findings: A total of 40,334 people were included in the model development phase of which 1427 (3·54%) people developed STDR. Age, gender, diabetes duration, antidiabetic medication history, glycated haemoglobin (HbA1c), and history of retinopathy were included as predictors in the Model 1, Model 2 excluded retinopathy status, and Model 3 further excluded HbA1c. All three models attained strong discrimination performance in the model development dataset with C statistics ranging from 0·778 to 0·832, and in the external validation datasets (C statistic 0·685 - 0·823) with calibration slopes closer to 1 following re-calibration of the baseline survival. Interpretation: We have developed new risk prediction equations to identify those at risk of STDR in people with type 2 diabetes in any resource-setting so that they can be screened and treated early. Future testing, and piloting is required before implementation. Funding: This study was funded by the GCRF UKRI (MR/P207881/1) and supported by the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology.

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.

Frequency and association of self-reported oral cancer among individuals with type 2 diabetes at a tertiary care diabetes centre in South India - A retrospective study.

AIM: To assess the frequency of self-reported oral cancer and associated factors among individuals with type 2 diabetes (T2D) at a tertiary care diabetes centre in South India. METHODS: Individuals with T2D who reported that they had oral cancer were included from the Diabetes Electronic Medical Records (DEMR) database. To assess the association of oral cancer with T2D, a retrospective nested case-control study design was adopted. Individuals with T2D and oral cancer diagnosed after the diagnosis of T2D (n = 78) were considered 'cases', while T2D without oral cancer were considered 'controls' (312) [in a ratio of 1:4 for cases and controls]. The cases and controls were matched for age, gender and duration of diabetes. Logistic regression was used to model predictors of oral cancer in T2D patients. RESULTS: Oral cancer was reported in 78 out of 379,138 (0.02%) individuals with T2D registered at the centre. Logistic regression analysis showed that a HbA1c value ≥ 9% had a significant association with oral cancer with an odds ratio of 2.3 (95% CI: 1.2-4.6) after adjusting for confounding factors. Among individuals with T2D, higher frequency of oral cancer prevalence and risk was observed among those who used any form of tobacco (32.6%, OR = 2.52, 95% CI: 1.5-4.3), consumed alcohol (29.2%, OR = 2.01, 95% CI: 1.2-3.3), and those with hypertension (23.9%, OR = 2.05, 95% CI: 1.2-3.6) and hypertriglyceridemia (24.7%, OR = 1.66, 95% CI: 1.01-2.7). Significant independent predictors of oral cancer among T2D were tobacco use (OR = 2.06, 95% CI: 1.1-4.00), high HbA1c (OR = 1.3, 95% CI: 1.03-1.5), hypertension (OR = 2.3, 95% CI: 1.3-4.2) and insulin use (OR = 1.8, 95% CI: 1.03-3.2). CONCLUSIONS: Regular dental check-ups as part of the follow-up for individuals with T2D will identify and diagnose oral cancer earlier. Further research is required to assess the physiological and biological mechanisms leading to oral cancer in individuals with T2D.

Prescribing Patterns and Response to Antihyperglycemic Agents Among Novel Clusters of Type 2 Diabetes in Asian Indians.

Aim: To assess the prescribing patterns and response to different classes of antihyperglycemic agents in novel clusters of type 2 diabetes (T2D) described in India. Materials and Methods: We attempted to replicate the earlier described clusters of T2D, in 32,867 individuals with new-onset T2D (within 2 years of diagnosis) registered between October 2013 and December 2020 at 15 diabetes clinics located across India, by means of k-means clustering utilizing 6 clinically relevant variables. Individuals who had follow-up glycated hemoglobin (HbA1c) up to 2 years were included for the drug response analysis (n = 13,247). Results: Among the 32,867 participants included in the study, 20,779 (63.2%) were males. The average age at diagnosis was 45 years and mean HbA1c at baseline was 8.9%. The same four clusters described in India earlier were replicated. Forty percent of the study participants belonged to the mild age-related diabetes cluster, followed by insulin-resistant obese diabetes (27%), severe insulin-deficient diabetes (21%), and combined insulin-resistant and insulin-deficient diabetes (12%) clusters. The most frequently used antihyperglycemic agents were sulfonylureas, metformin, and dipeptidyl peptidase-4 inhibitors apart from insulin. While there were significant differences in HbA1c reduction between drugs across clusters, these were largely driven by differences in the baseline (pretreatment) HbA1c. Conclusions: In this new cohort, we were able to reliably replicate the four subtypes of T2D earlier described in Asian Indians. Prescribing patterns show limited usage of newer antihyperglycemic agents across all clusters. Randomized clinical trials are required to establish differential drug responses between clusters.

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.

Retrospective analysis (2009-2017) of factors associated with progression and regression of non-alcoholic fatty liver disease (Hepatic steatosis) in patients with type 2 diabetes seen at a tertiary diabetes centre in Southern India.

AIM: To identify the profiles and factors associated with progression/regression of ultrasound-derived hepatic steatosis with type 2 diabetes mellitus seen at a tertiary diabetes center in southern India. METHODS: Participants were individuals with type 2 diabetes mellitus with at least two consecutive ultrasound measurements available. Hepatic steatosis was assessed using high-resolution B-mode ultrasonography. Admittedly ultrasonography has lower sensitivity and specificity, however, it is the only modality available in a routine clinical setting to screen for hepatic steatosis. Progression or regression of hepatic steatosis was assessed after a mean follow-up of 3.0 ± 2.1 years and correlated with clinical and biochemical parameters. RESULTS: A total of 1835 participants with type 2 diabetes mellitus were studied, of whom 88.6% had some form of hepatic steatosis at baseline which included mild steatosis (grade 1) in 982 (53.5%), moderate steatosis (grade 2) in 628 (34.2%) and severe steatosis (grade 3) in 15 (0.8%). Hepatic steatosis progression, regression or no change in grade of hepatic steatosis were seen in 21.5%, 26.6% and 51.9% of participants. Increase in body weight, body mass index, glycated haemoglobin, serum triglycerides and gamma glutamyl transferase were the factors associated with progression of hepatic steatosis, whereas regression showed reduction in body weight, body mass index, fasting plasma glucose and glycated haemoglobin. CONCLUSION: Among South Indian type 2 diabetes patients with hepatic steatosis, severity of steatosis progressed in 1/3rd while it regressed in 1/4th. These retrospective data need proper ascertainment in controlled studies.

Profiles of Intraday Glucose in Type 2 Diabetes and Their Association with Complications: An Analysis of Continuous Glucose Monitoring Data.

Aims: To identify profiles of type 2 diabetes from continuous glucose monitoring (CGM) data using ambulatory glucose profile (AGP) indicators and examine the association with prevalent complications. Methods: Two weeks of CGM data, collected between 2015 and 2019, from 5901 adult type 2 diabetes patients were retrieved from a clinical database in Chennai, India. Non-negative matrix factorization was used to identify profiles as per AGP indicators. The association of profiles with existing complications was examined using multinomial and logistic regressions adjusted for glycated hemoglobin (HbA1c; %), sex, age at onset, and duration of diabetes. Results: Three profiles of glycemic variability (GV) were identified based on CGM data-Profile 1 ["TIR Profile"] (n = 2271), Profile 2 ["Hypo"] (n = 1471), and Profile 3 ["Hyper"] (n = 2159). Compared with time in range (TIR) profile, those belonging to Hyper had higher mean fasting plasma glucose (202.9 vs. 167.1, mg/dL), 2-h postprandial plasma glucose (302.1 vs. 255.6, mg/dL), and HbA1c (9.7 vs. 8.6; %). Both "Hypo profile" and "Hyper profile" had higher odds of nonproliferative diabetic retinopathy ("Hypo": 1.44, 1.20-1.73; "Hyper": 1.33, 1.11-1.58), macroalbuminuria ("Hypo": 1.58, 1.25-1.98; "Hyper": 1.37, 1.10-1.71), and diabetic kidney disease (DKD; "Hypo": 1.65, 1.18-2.31; "Hyper": 1.88, 1.37-2.58), compared with "TIR profile." Those in "Hypo profile" (vs. "TIR profile") had higher odds of proliferative diabetic retinopathy (PDR; 2.84, 1.65-2.88). Conclusions: We have identified three profiles of GV from CGM data. While both "Hypo profile" and "Hyper profile" had higher odds of prevalent DKD compared with "TIR profile," "Hypo profile" had higher odds of PDR. Our study emphasizes the clinical importance of recognizing and treating hypoglycemia (which is often unrecognized without CGM) in patients with type 2 Diabetes Mellitus.

Novel subgroups of type 2 diabetes and their association with microvascular outcomes in an Asian Indian population: a data-driven cluster analysis: the INSPIRED study.

INTRODUCTION: Type 2 diabetes is characterized by considerable heterogeneity in its etiopathogenesis and clinical presentation. We aimed to identify clusters of type 2 diabetes in Asian Indians and to look at the clinical implications and outcomes of this clustering. RESEARCH DESIGN AND METHODS: From a network of 50 diabetes centers across nine states of India, we selected 19 084 individuals with type 2 diabetes (aged 10-97 years) with diabetes duration of less than 5 years at the time of first clinic visit and performed k-means clustering using the following variables: age at diagnosis, body mass index, waist circumference, glycated hemoglobin, serum triglycerides, serum high-density lipoprotein cholesterol and C peptide (fasting and stimulated). This was then validated in a national epidemiological data set of representative individuals from 15 states across India. RESULTS: We identified four clusters of patients, differing in phenotypic characteristics as well as disease outcomes: cluster 1 (Severe Insulin Deficient Diabetes, SIDD), cluster 2 (Insulin Resistant Obese Diabetes, IROD), cluster 3 (Combined Insulin Resistant and Deficient Diabetes, CIRDD) and cluster 4 (Mild Age-Related Diabetes, MARD). While SIDD and MARD are similar to clusters reported in other populations, IROD and CIRDD are novel clusters. Cox proportional hazards showed that SIDD had the highest hazards for developing retinopathy, followed by CIRDD, while CIRDD had the highest hazards for kidney disease. CONCLUSIONS: Compared with previously reported clustering, we show two novel subgroups of type 2 diabetes in the Asian Indian population with important implications for prognosis and management. The coexistence of insulin deficiency and insulin resistance seems to be peculiar to the Asian Indian population and is associated with an increased risk of microvascular complications.

Acceptability and Utilization of Newer Technologies and Effects on Glycemic Control in Type 2 Diabetes: Lessons Learned from Lockdown.

Aim: To evaluate the effects of a prolonged lockdown due to Coronavirus (COVID-19) on the adoption of newer technologies and changes in glycemic control on patients with type 2 diabetes (T2D) in India. Methods: The study population included a random list of 3000 individuals with T2D derived from 30,748 individuals who had visited a large tertiary diabetes center during the past year. The survey was carried out through a telephonic interview. A structured questionnaire was used to collect information on changes in lifestyle, access and challenges to diabetes care and use of technologies such as telemedicine facilities and use of self-monitoring of blood glucose (SMBG), etc. Results: Of the 2510 individuals successfully interviewed (83.7% response rate), 382 (15.2%) reported having attempted to consult their health care providers during the lockdown, of whom only 30.6% utilized the telemedicine facility. However, 96 (82%) of those who utilized the telemedicine facility (n = 117) were happy with their experience and 68 (58.1%) were willing to continue to use the facility in the future. Only 11.4% of participants utilized online support for management of diabetes. Use of SMBG increased significantly from 15.5% to 51.3% during the lockdown. There was an improvement in glycemic control during the lockdown (HbA1c:before vs. during lockdown: 8.2% ± 1.9% vs. 7.7% ± 1.7%, P < 0.001) in a nonrandomly selected subset of subjects (n = 205). Conclusions: Acceptance of telemedicine facilities remains suboptimal in this Asian Indian population, in spite of high levels of satisfaction among those who utilized it. The COVID-19 pandemic and the subsequent lockdown have not adversely affected metabolic control in our patients, and indeed there appears to be an improvement in HbA1c levels. Greater accessibility and acceptance of technology could help individuals with diabetes to maintain better contact with their physicians and ensure better metabolic control in the future.

A Multicenter Real-Life Study on the Effect of Flash Glucose Monitoring on Glycemic Control in Patients with Type 1 and Type 2 Diabetes.

AIM: To assess the efficacy of ambulatory glucose profiling (AGP) generated by FreeStyle LibrePro™ flash glucose monitoring (FCGM) on glycemic control in patients with uncontrolled type 1 diabetes (T1D) and type 2 diabetes (T2D). METHODS: Clinical and biochemical data were obtained from 5072 patients with diabetes who had an A1c ≥7% (2536 who had been initiated on FCGM-based AGP between March 2015 and October 2016 [cases] and 2536 age-, gender-, A1c-, site- and time-matched controls who were not initiated on AGP) across seven diabetes clinics in India. Anthropometric and clinical measurements were obtained through standardized techniques. Fasting and postprandial plasma glucose and glycated hemoglobin(A1c) were estimated before and after initiation of AGP. RESULTS: Overall, there was a significant decrease in A1c both in cases and controls; however, the magnitude of reduction was higher among cases (1% vs.0.7%; P < 0.001).The overall reduction in A1c among cases was higher in T2D (9.2% to 8.3%) compared with T1D (9.6% to 9.4%); however, the absolute difference in A1c reduction between cases and controls was higher among T1D (0.5% vs. 0.2%) patients. The reduction in glycemic parameters was irrespective of age or gender (P for trend <0.001) across all study sites. The greatest reductions in A1c were noted within 6 months of AGP initiation. Multiple logistic regression showed that those who did not use AGP had a 1.42 higher risk (95% CI: 1.24-1.64) of not achieving even 0.1% reduction in A1c compared with those who were initiated on AGP even after adjusting for age, gender, body-mass index, systolic blood pressure, time to follow-up A1c, and medication use. CONCLUSIONS: This study shows that FCGM-based AGP with FreeStyle LibrePro is associated with significant reductions in A1c levels in both T1D and T2D. In addition, improvement in A1c levels was maintained across all age groups and in patients enrolled at different diabetes clinics in India.

Younger-onset versus older-onset type 2 diabetes: Clinical profile and complications.

AIMS: To compare the clinical profile and complications between younger and older onset type 2 diabetes (T2DM) patients at a tertiary care diabetes center in south India. METHODS: We compared individuals with T2DM detected at age ≤25years (n=267) and at age≥50years (n=267), matched for gender and duration of diabetes. We reviewed electronic patient charts and extracted data on biochemical parameters (plasma glucose, serum lipids and glycated hemoglobin). We estimated prevalence of complications (retinopathy, nephropathy, neuropathy, and peripheral vascular disease). We examined odds of having each complication, after adjusting for clinical differences between younger- and older-onset T2DM. RESULTS: Individuals with younger-onset T2DM had significantly greater glycated hemoglobin (8.7 vs. 7.5%), serum cholesterol (160 vs. 148mg/dl), serum triglycerides (147 vs. 128mg/dl), LDL cholesterol (92 vs. 82mg/dl) and lower HDL cholesterol levels (39 vs. 42mg/dl). However, waist circumference (90.4 vs. 92.6cm) and systolic blood pressure (125 vs. 133mmHg) were significantly higher in older onset T2DM. Prevalence of retinopathy (47.6 vs. 31.0%) was higher in younger onset T2DM while neuropathy (41.8 vs. 9.2%) and peripheral vascular disease (6.2 vs. 1.2%) were higher in older onset T2DM. In multiple logistic regression analysis, after adjusting for glycated hemoglobin, hypertension, and hypercholesterolemia, younger onset T2DM had a higher odds of developing retinopathy [Odds Ratio: 2.19; Confidence Intervals: 1.42-3.38] when compared to older onset T2DM. CONCLUSIONS: Younger onset T2DM patients have worse glycemic and lipid control, and higher prevalence of retinopathy compared to older onset T2DM patients. This underscores the need for more aggressive metabolic control in young-onset T2DM.

Metabolic profile of normal glucose-tolerant subjects with elevated 1-h plasma glucose values.

AIM: The aim of this study was to compare the metabolic profiles of subjects with normal glucose tolerance (NGT) with and without elevated 1-h postglucose (1HrPG) values during an oral glucose tolerance test (OGTT). METHODOLOGY: The study group comprised 996 subjects without known diabetes seen at tertiary diabetes center between 2010 and 2014. NGT was defined as fasting plasma glucose <100 mg/dl (5.5 mmol/L) and 2-h plasma glucose <140 mg/dl (7.8 mmol/L) after an 82.5 g oral glucose (equivalent to 75 g of anhydrous glucose) OGTT. Anthropometric measurements and biochemical investigations were done using standardized methods. The prevalence rate of generalized and central obesity, hypertension, dyslipidemia, and metabolic syndrome (MS) was determined among the NGT subjects stratified based on their 1HrPG values as <143 mg/dl, ≥143-<155 mg/dl, and ≥155 mg/dl, after adjusting for age, sex, body mass index (BMI), waist circumference, alcohol consumption, smoking, and family history of diabetes. RESULTS: The mean age of the 996 NGT subjects was 48 ± 12 years and 53.5% were male. The mean glycated hemoglobin for subjects with 1HrPG <143 mg/dl was 5.5%, for those with 1HrPG ≥143-<155 mg/dl, 5.6% and for those with 1HrPG ≥155 mg/dl, 5.7%. NGT subjects with 1HrPG ≥143-<155 mg/dl and ≥155 mg/dl had significantly higher BMI, waist circumference, systolic and diastolic blood pressure, triglyceride, total cholesterol/high-density lipoprotein (HDL) ratio, triglyceride/HDL ratio, leukocyte count, and gamma glutamyl aminotransferase (P < 0.05) compared to subjects with 1HrPG <143 mg/dl. The odds ratio for MS for subjects with 1HrPG ≥143 mg/dl was 1.84 times higher compared to subjects with 1HrPG <143 mg/dl taken as the reference. CONCLUSION: NGT subjects with elevated 1HrPG values have a worse metabolic profile than those with normal 1HrPG during an OGTT.

Current practices in the diagnosis and management of gestational diabetes mellitus in India (WINGS-5).

AIM: To obtain information on existing practices in the diagnosis and management of gestational diabetes mellitus (GDM) among physicians/diabetologists/endocrinologists and obstetricians/gynecologists (OB/GYNs) in India. METHODS: Details regarding diagnostic criteria used, screening methods, management strategies, and the postpartum follow-up of GDM were obtained from physicians/diabetologists/endocrinologists and OB/GYNs across 24 states of India using online/in-person surveys using a structured questionnaire. RESULTS: A total of 3841 doctors participated in the survey of whom 68.6% worked in private clinics. Majority of OB/GYNs (84.9%) preferred universal screening for GDM, and screening in the first trimester was performed by 67% of them. Among the OB/GYNs, 600 (36.7%) reported using the nonfasting 2 h criteria for diagnosing GDM whereas 560 (29.4%) of the diabetologists/endocrinologists reported using the same. However, further questioning on the type of blood sample collected and the glucose load used revealed that, in reality, only 208 (12.7%) and 72 (3.8%), respectively, used these criteria properly. The survey also revealed that the International Association of Diabetes and Pregnancy Study Groups criteria was followed properly by 299 (18.3%) of OB/GYNs and 376 (19.7%) of physicians/diabetologists/endocrinologists. Postpartum oral glucose tolerance testing was advised by 56% of diabetologists and 71.6% of OB/GYNs. CONCLUSION: More than half of the physicians/diabetologists/endocrinologists and OB/GYNs in India do not follow any of the recommended guidelines for the diagnosis of GDM. This emphasizes the need for increased awareness about screening and diagnosis of GDM both among physicians/diabetologists/endocrinologists and OB/GYNs in India.

ß-Cell Function and Insulin Sensitivity in Normal Glucose-Tolerant Subjects Stratified by 1-Hour Plasma Glucose Values.

AIM: This study was designed to assess ß-cell function and insulin sensitivity indices among normal glucose tolerance (NGT) subjects stratified by 1-h plasma glucose (1hPG) values during an oral glucose tolerance test (OGTT). MATERIALS AND METHODS: One hundred sixty-six NGT subjects underwent a five-point OGTT, and glucose and insulin levels were estimated. We calculated the following indices: (a) ß-cell function (homeostasis assessment model-ß-cell function [HOMA-ß] and Insulinogenic Index [IGI]) and (b) insulin sensitivity (homeostasis assessment model-insulin resistance [HOMA-IR], Matsuda Index, and Insulin Sensitivity Index [ISI]). RESULTS: NGT subgroups with elevated 1hPG values (i.e., 1hPG ≥143 to <155 mg/dL and 1hPG ≥155 mg/dL) did not differ from those with 1hPG <143 mg/dL by HOMA-ß (P = 0.236) but had significantly lower IGIs (367 ± 239 vs. 257 ± 243 vs. 246 ± 239; P = 0.019). With respect to ISIs, HOMA-IR was not significantly different among the groups (P = 0.103). However, the Matsuda Index (11.2 ± 5.0 vs. 7.4 ± 4.8 vs. 5.5 ± 4.9; P < 0.001) and ISI (0.015 ± 0.010 vs. 0.012 ± 0.006 vs. 0.011 ± 0.011; P = 0.028) were significantly lower in subjects with elevated 1hPG values. CONCLUSIONS: NGT subjects with elevated 1hPG levels have alterations in ß-cell function and insulin sensitivity compared with those with normal 1hPG levels.

Prevalence and clinical profile of metabolic syndrome among type 1 diabetes mellitus patients in southern India.

AIM: To assess the prevalence of metabolic syndrome (MetS) among patients with type 1 diabetes mellitus(T1DM) and to look at prevalence of diabetes complications in T1DM with and without MetS. METHODS: We studied 451 T1DM patients attending a tertiary diabetes centre in Chennai, South India. T1DM was diagnosed based on absence of beta cell reserve and requirement of insulin from the time of diagnosis. Data on clinical and biochemical characteristics as well as complications details to study the prevalence were also extracted from electronic records. T1DM patients were divided into those with and without MetS[diagnosed according to the harmonizing the metabolic syndrome criteria(IDF/NHLBI/AHA/WHF/IAS/IASO)]. RESULTS: The overall prevalence of MetS among T1DM was 22.2%(100/451). Patients with MetS were older, had longer diabetes duration, acanthosis nigricans, and increased serum cholesterol. In the unadjusted logistic regression analysis, retinopathy, nephropathy and neuropathy were associated with MetS. However after adjustment for age, gender, diabetes duration, HbA1C and BMI significant association was seen only between MetS and retinopathy [odds ratio (OR) 2.82, 95% CI 1.18-6.74, p = 0.020] and nephropathy [OR 4.92, 95% CI 2.59-9.33, p < 0.001]. CONCLUSION: Prevalence of MetS is high among Asian Indian T1DM patients, and its presence is associated with increased risk of diabetic retinopathy and nephropathy.