Dental caries and their relation to hba1c in adults with type 2 diabetes mellitus.

Diabetes mellitus with poor glycemic control is often associated with dental caries. We aim to assess the relationship between dental caries and HbA1c levels among adults with type 2 diabetes (T2D) in Chennai. A cutoff of HbA1c ≥7.0 to 7.9% (53-63 mmol/mol) was used to define Group 1 (n = 113) as moderately controlled and HbA1c ≥8.0% (64 mmol/mol) to define Group 2 (n = 228) as poorly controlled T2D. The absolute numbers of decayed, missing, and filled teeth were examined to calculate the decayed, missing and filled teeth index. Group 2 had a significantly higher percentage (48.2%) of decayed teeth when compared to Group 1 (28.3%). Group 2 had a 2.65 times higher risk of decayed teeth when adjusted for mean carbohydrate consumption, sweets consumption, oral hygiene, and brushing habit. T2D with higher HbA1c levels is associated with an increased number of decayed teeth. Hence, there is a need for monitoring dental status in T2D as earlier treatment may prevent or delay decay teeth.

Impact of age at type 2 diabetes mellitus diagnosis on mortality and vascular complications: systematic review and meta-analyses.

AIMS/HYPOTHESIS: Few studies examine the association between age at diagnosis and subsequent complications from type 2 diabetes. This paper aims to summarise the risk of mortality, macrovascular complications and microvascular complications associated with age at diagnosis of type 2 diabetes. METHODS: Data were sourced from MEDLINE and All EBM (Evidence Based Medicine) databases from inception to July 2018. Observational studies, investigating the effect of age at diabetes diagnosis on macrovascular and microvascular diabetes complications in adults with type 2 diabetes were selected according to pre-specified criteria. Two investigators independently extracted data and evaluated all studies. If data were not reported in a comparable format, data were obtained from authors, presented as minimally adjusted ORs (and 95% CIs) per 1 year increase in age at diabetes diagnosis, adjusted for current age for each outcome of interest. The study protocol was recorded with PROSPERO International Prospective Register of Systematic Reviews (CRD42016043593). RESULTS: Data from 26 observational studies comprising 1,325,493 individuals from 30 countries were included. Random-effects meta-analyses with inverse variance weighting were used to obtain the pooled ORs. Age at diabetes diagnosis was inversely associated with risk of all-cause mortality and macrovascular and microvascular disease (all p < 0.001). Each 1 year increase in age at diabetes diagnosis was associated with a 4%, 3% and 5% decreased risk of all-cause mortality, macrovascular disease and microvascular disease, respectively, adjusted for current age. The effects were consistent for the individual components of the composite outcomes (all p < 0.001). CONCLUSIONS/INTERPRETATION: Younger, rather than older, age at diabetes diagnosis was associated with higher risk of mortality and vascular disease. Early and sustained interventions to delay type 2 diabetes onset and improve blood glucose levels and cardiovascular risk profiles of those already diagnosed are essential to reduce morbidity and mortality. Graphical abstract.

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.

Diabetic ketoacidosis at diagnosis among youth with type 1 and type 2 diabetes: Results from SEARCH (United States) and YDR (India) registries.

BACKGROUND: There is significant global variation in the prevalence of diabetic ketoacidosis (DKA) at diagnosis among youth with type 1 diabetes (T1D). However, data for youth with type 2 diabetes (T2D) are limited, even in developed countries. We compared the prevalence of DKA at diagnosis among individuals with T1D and T2D from the SEARCH for Diabetes in Youth (SEARCH) and the Registry of Youth Onset Diabetes in India (YDR) registries. METHODS: We harmonized the SEARCH and YDR registries to the structure and terminology in the Observational Medical Outcome Partnership Common Data Model. Data used were from youth with T1D and T2D diagnosed before 20 years and newly diagnosed between 2006 and 2012 in YDR and 2009 and 2012 in SEARCH. RESULTS: There were 5366 US youth (4078 with T1D, 1288 with T2D) and 2335 Indian youth (2108 with T1D, 227 with T2D). More than one third of T1D youth enrolled in SEARCH had DKA at diagnosis which was significantly higher than in YDR (35.3% vs 28.7%, P < .0001). The burden of DKA in youth with T1D was significantly higher among younger age groups; this relationship was similar across registries (P = .4). The prevalence of DKA among T2D in SEARCH and YDR were 5.5% and 6.6% respectively (P = .4). CONCLUSIONS: There is significant burden of DKA at diagnosis with T1D among youth from United States and India, especially among the younger age groups. The reasons for this high prevalence are largely unknown but are critical to developing interventions to prevent DKA at diagnosis.

Clinical profile at diagnosis with youth-onset type 1 and type 2 diabetes in two pediatric diabetes registries: SEARCH (United States) and YDR (India).

BACKGROUND: Over the last decades, diabetes in youth has increased in both India and the United States, along with the burden of long-term complications and healthcare costs. However, there are limited standardized population-based data in contemporary youth cohorts for comparison of clinical and demographic characteristics of diabetes for both type 1 (T1D) and type 2 (T2D). METHODS: In partnership, we harmonized demographic and clinical data from the SEARCH for Diabetes in Youth (SEARCH) registry in the United States and the Registry of People with Diabetes with Youth Age at Onset (YDR) in India to the structure and terminology of the Observational Medical Outcomes Partnership Common Data Model. Data were from youth with T1D and T2D, aged <20 years and newly diagnosed between 2006 and 2010. We compared key characteristics across registries using χ2 tests and t-tests. RESULTS: In total, there were 9650 youth with T1D and 2406 youth with T2D from 2006 to 2012. SEARCH youth were diagnosed at younger ages than YDR youth for T1D and T2D (10.0 vs 10.5 years, P < .001 and 14.7 vs 16.1 years, P < .001, respectively). For T2D, SEARCH had a higher proportion of females and significantly lower proportion of youth of high socioeconomic status compared to YDR. For T1D and T2D, SEARCH youth had higher BMI, lower blood pressure, and lower A1c compared to YDR youth. CONCLUSIONS: These data offer insights into the demographic and clinical characteristics of diabetes in youth across the two countries. Further research is needed to better understand why these differences exist.

Treatment regimens and glycosylated hemoglobin levels in youth with Type 1 and Type 2 diabetes: Data from SEARCH (United States) and YDR (India) registries.

OBJECTIVE: To compare treatment regimens and glycosylated hemoglobin (A1c) levels in Type 1 (T1D) and Type 2 diabetes (T2D) using diabetes registries from two countries-U.S. SEARCH for Diabetes in Youth (SEARCH) and Indian Registry of youth onset diabetes in India (YDR). METHODS: The SEARCH and YDR data were harmonized to the structure and terminology in the Observational Medical Outcomes Partnership Common Data Model. Data used were from T1D and T2D youth diagnosed <20 years between 2006-2012 for YDR, and 2006, 2008, and 2012 for SEARCH. We compared treatment regimens and A1c levels across the two registries. RESULTS: There were 4003 T1D (SEARCH = 1899; YDR = 2104) and 611 T2D (SEARCH = 384; YDR = 227) youth. The mean A1c was higher in YDR compared to SEARCH (T1D:11.0% ± 2.9% vs 7.8% ± 1.7%, P < .001; T2D:9.9% ± 2.8% vs 7.2% ± 2.1%, P < .001). Among T1D youth in SEARCH, 65.1% were on a basal/bolus regimen, whereas in YDR, 52.8% were on once/twice daily insulin regimen. Pumps were used by 16.2% of SEARCH and 1.5% of YDR youth with T1D. Among T2D youth, in SEARCH and YDR, a majority were on metformin only (43.0% vs 30.0%), followed by insulin + any oral hypoglycemic agents (26.3% vs 13.7%) and insulin only (12.8% vs 18.9%), respectively. CONCLUSION: We found significant differences between SEARCH and YDR in treatment patterns in T1D and T2D. A1c levels were higher in YDR than SEARCH youth, for both T1D and T2D, irrespective of the regimens used. Efforts to achieve better glycemic control for youth are urgently needed to reduce the risk of long-term complications.

Comparison of the incidence of diabetes in United States and Indian youth: An international harmonization of youth diabetes registries.

OBJECTIVE: Incidence of youth-onset diabetes in India has not been well described. Comparison of incidence, across diabetes registries, has the potential to inform hypotheses for risk factors. We sought to compare the incidence of diabetes in the U.S.-based registry of youth onset diabetes (SEARCH) to the Registry of Diabetes with Young Age at Onset (YDR-Chennai and New Delhi regions) in India. METHODS: We harmonized data from both SEARCH and YDR to the Observational Medical Outcomes Partnership (OMOP) Common Data Model. Data were from youth registered with incident diabetes (2006-2012). Denominators were from census and membership data. We calculated diabetes incidence by averaging the total cases across the entire follow-up period and dividing this by the estimated census population corresponding to the source population for case ascertainment. Incidence was calculated for each of the registries and compared by type and within age and sex categories using a 2-sided, skew-corrected inverted score test. RESULTS: Incidence of type 1 was higher in SEARCH (21.2 cases/100 000 [95% CI: 19.9, 22.5]) than YDR (4.9 cases/100 000 [95% CI: 4.3, 5.6]). Incidence of type 2 diabetes was also higher in SEARCH (5.9 cases/100 000 [95% CI: 5.3, 6.6] in SEARCH vs 0.5/cases/100 000 [95% CI: 0.3, 0.7] in YDR). The age distribution of incident type 1 diabetes cases was similar across registries, whereas type 2 diabetes incidence was higher at an earlier age in SEARCH. Sex differences existed in SEARCH only, with a higher rate of type 2 diabetes among females. CONCLUSION: The incidence of youth-onset type 1 and 2 diabetes was significantly different between registries. Additional data are needed to elucidate whether the differences observed represent diagnostic delay, differences in genetic susceptibility, or differences in distribution of risk factors.

Prepubertal Childhood Onset Type 2 Diabetes Mellitus: Four Case Reports.

BACKGROUND: The prevalence of childhood onset type 2 diabetes (T2D) is increasing, but prepubertal T2D is still unusual. METHODS: We report four cases of T2D with onset at or below 10 years of age registered at a tertiary diabetes centre in southern India.T2D was diagnosed based on the absence of ketosis, good beta cell reserve as shown by the C peptide assay, absence of GAD antibodies and pancreatic calculi, and response to oral hypoglycemic agents. RESULTS: All four patients were female, obese and had acanthosis nigricans. Polycystic ovarian syndrome and fatty liver were found in two cases. All were treated with metformin but two patients needed insulin additionally. Two had hypercholesterolemia and hypertension. One patient developed non-proliferative diabetic retinopathy on follow up. CONCLUSIONS: T2D is now beginning to be seen in the first decade of life. A proper clinical work up of children with diabetes will prevent misclassification as type 1 diabetes and help avoid unnecessary insulin therapy.

Increased serum levels of novel T cell cytokines IL-33, IL-9 and IL-17 in subjects with type-1 diabetes.

The role of adaptive immune cytokines in the pathogenesis of type-1 Diabetes Mellitus (T1DM) is well known. Even though reports on the serum levels of both Th-1 and Th-2 cytokines are available, those on newly described T cell cytokines such as IL-17, IL-33 and IL-9 in T1DM are scarce. We therefore measured the serum levels of both T cell polarizing (IL-33 and IL-12) and T cell effector (IFN-γ, IL-4, IL-10, IL-17 and IL-9) cytokines in T1DM subjects with and without microvascular (retinopathy and nephropathy) complications (MVC). All the tested cytokines were significantly elevated in T1DM subjects except for IFN-γ (which failed to attain statistical significance) with no significant difference between those with and without MVC. From the serum cytokine analysis, no apparent Th polarization could be determined for the T1DM subjects.

RELATIONSHIP OF ADIPOKINES AND PROINFLAMMATORY CYTOKINES AMONG ASIAN INDIANS WITH OBESITY AND YOUTH ONSET TYPE 2 DIABETES.

OBJECTIVE: It is well known that inflammation is associated with diabetes, but it is unclear whether obesity mediates this association in individuals with youth-onset type 2 diabetes mellitus (T2DM-Y). METHODS: We recruited individuals with T2DM-Y (age at onset <25 years) and age-matched normal glucose tolerance (NGT) subjects. Participants were further classified using Asia-Pacific body mass index cut-points for obesity and categorized as: nonobese NGT (n = 100), Obese NGT (n = 50), nonobese T2DM-Y (n = 50), and obese T2DM-Y (n = 50). We compared adipokines (adiponectin and leptin) and proinflammatory cytokines (tumor necrosis factor alpha [TNF-α] and monocyte chemotactic protein-1 [MCP-1]) across groups. RESULTS: Compared to nonobese NGT, the other 3 groups (obese NGT, nonobese T2DM-Y, and obese T2DM-Y) were found to have lower adiponectin (7.7 vs. 5.7, 4.2, 3.8 µg/mL, P<.01), and higher leptin (3.6 vs. 5.4, 5.7, 7.9 µg/mL, P<.001) and MCP 1 (186 vs. 272, 340, 473 pg/mL, P<.001) respectively. However, TNF-α levels were higher only among nonobese T2DM-Y (112 pg/mL) and obese T2DM-Y (141 pg/mL, P<.01 for each). After adjusting for age, sex, waist, hypertension, homeostatic model assessment of insulin resistance (HOMA-IR), serum cholesterol, triglycerides, and family history of diabetes, adiponectin was associated with 33% and 41% lower odds of being nonobese T2DM and obese T2DM, respectively. However, adjusted for same factors, leptin, TNF-α, and MCP-1 were associated with markedly higher odds (5- to 14-fold) of nonobese and obese T2DM. CONCLUSION: In young Asian Indians, leptin and proinflammatory cytokines are positively, and adiponectin negatively, associated with both nonobese and obese T2DM-Y compared to nonobese NGT individuals.

Clinical profile of nonalcoholic Fatty liver disease among young patients with type 1 diabetes mellitus seen at a diabetes speciality center in India.

OBJECTIVE: To estimate the prevalence and clinical profile of nonalcoholic fatty liver disease (NAFLD) among young type 1 diabetes mellitus (T1DM) patients at a tertiary care diabetes center in India. METHODS: Electronic medical records of T1DM patients (age at first diagnosis of T1DM ≤25 years) registered between January 1992 and May 2013 who had undergone ultrasonography and denied history of any alcohol intake (n = 736) were reviewed. NAFLD was diagnosed if there was any degree of fatty liver. Retinopathy was initially assessed by direct and indirect ophthalmoscopy and later by retinal photography. Nephropathy was diagnosed if urine protein excretion was >500 mg/day, and neuropathy was diagnosed if a patient's vibration perception threshold on biothesiometry was ≥20 V. RESULTS: A total of 204/736 (27.7%) T1DM patients had NAFLD. Compared to T1DM subjects without NAFLD those with NAFLD had higher body mass index (BMI) (18.9 ± 4.2 vs. 20.2 ± 4.7 kg/m2, P<.001), waist circumference (67.9 ± 13.2 vs. 71.9 ± 13.3 cm, P<.05), systolic blood pressure (110 ± 15 vs. 116 ± 18 mm Hg, P<.001) and diastolic blood pressure (72 ± 9 vs. 74 ± 10 mm Hg, P<.05), while fasting blood glucose (201 ± 101 vs. 183 ± 101 mg/dL, P<.05) and alkaline phosphatase (419 [12.5] vs. 315 [15.8], P<.001) levels were lower in patients with T1DM with NAFLD. Multiple logistic regression analysis showed a significant association between NAFLD and retinopathy (odds ratio [OR]: 2.01, 95% confidence interval [CI]: 1.13-3.43; P = .017, after adjusting for sex, duration of diabetes, overweight/obesity, hypertension, fasting plasma glucose, nephropathy, and nephropathy (OR: 1.89, 95% CI: 1.02-3.50; P = .042), after adjusting for sex and fasting plasma glucose. CONCLUSIONS: This study suggests that NAFLD is also seen among T1DM patients and that it has an independent and significant association with retinopathy and nephropathy.

Performance of European prediction models for classification of type 1 and type 2 diabetes in Indians.

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/m2), 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.

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.

A Cross-Sectional Multicentre Study to Validate Insulin Sensitivity Index Cut-Offs for Detection of Metabolic Syndrome in Indian Adolescents with Type-1 Diabetes.

Background: A previous study compared insulin sensitivity indices for the detection of double diabetes (DD) in Indian adolescents with type-1 diabetes (T1D) and derived a cut-off to predict future risk for the development of metabolic syndrome (MS) in adolescents with T1D. We conducted the current study with the aim to validate these cut-offs for detecting DD among Indian subjects with T1D from various geographical locations. Methods: This multicentric cross-sectional study included 161 Indian adolescents with T1D. Demographic, anthropometric, clinical, and biochemical data were collected using standard protocols. Insulin sensitivity (IS) was calculated using various equations developed to determine insulin sensitivity in subjects with T1D. Metabolic syndrome was diagnosed using International Diabetes Federation (IDF) Consensus Definition 2017. Results: We report 4.3% prevalence of MS in Indian adolescents with T1D with an additional 29.8% of study participants at risk of development of MS. Low High density lipoprotein (HDL) (23.6%) was the commonest abnormal component of the MS definition. Insulin sensitivity calculated by an equation derived by the SEARCH group was the most appropriate index to identify MS and metabolic risk in Indian adolescents with T1D. The proposed cut-off of 5.48 had high specificity, positive predictive value, and negative predictive value in identifying the risk of the development of DD. Conclusions: Insulin sensitivity calculated by the equation proposed by the SEARCH group together with cut-offs derived in earlier study may be used effectively to identify risk of development of MS/DD in Indian adolescents with T1D from various geographical locations.

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.

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.

Clinical features, complications and treatment of rarer forms of maturity-onset diabetes of the young (MODY) - A review.

Maturity onset diabetes of the young (MODY) is the most common form of monogenic diabetes and is currently believed to have 14 subtypes. While much is known about the common subtypes of MODY (MODY-1, 2, 3 and 5) little is known about its rare subtypes (MODY4, 6-14). With the advent of next-generation sequencing (NGS) there are several reports of the rarer subtypes of MODY emerging from across the world. Therefore, a greater understanding on these rarer subtypes is needed. A search strategy was created, and common databases were searched, and 51 articles finally selected. INS-(MODY10) and ABCC8-(MODY12) mutations were reported in relatively large numbers compared to the other rare subtypes. The clinical characteristics of the rare MODY subtypes exhibited heterogeneity between families reported with the same mutation. Obesity and diabetic ketoacidosis (DKA) were also reported among rarer MODY subtypes which presents as a challenge as these are not part of the original description of MODY by Tattersal and Fajans. The treatment modalities of the rarer subtypes included oral drugs, predominantly sulfonylureas, insulin but also diet alone. Newer drugs like DPP-4 and SGLT2 inhibitors have also been tried as new modes of treatment. The microvascular and macrovascular complications among the patients with various MODY subtypes are less commonly reported. Recently, there is a view that not all the 14 forms of 'MODY' are true MODY and the very existence of some of these rarer subtypes as MODY has been questioned. This scoping review aims to report on the clinical characteristics, treatment and complications of the rarer MODY subtypes published in the literature.

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.

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.