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Genome-wide polygenic risk scores (PRS) for lifestyle disorders, like Type 2 Diabetes (T2D), are useful in identifying at-risk individuals early on in life, and to guide them towards healthier lifestyles. The current study was aimed at developing PRS for the Indian population using imputed genotype data from UK Biobank and testing the developed PRS on data from GenomegaDB of Indians living in India. 959 T2D cases and 2,818 controls were selected from Indian participants of UK Biobank to develop the PRS. Summary statistics available for South Asians, from the DIAMANTE consortium, were used to weigh genetic variants. LDpred2 algorithm was used to adjust the effect of linkage disequilibrium among the variants. The association of PRS with T2D, after adjusting for age, sex and top ten genetic principal components, was found to be very significant (AUC = 0.7953, OR = 2.9856 [95% CI: 2.7044–3.2961]). When participants were divided into four PRS quartile groups, the odds of developing T2D increased sequentially with the higher PRS groups. The highest PRS group (top 25%) showed 5.79 fold increased risk compared to the rest of the participants (75%). The PRS derived using the same set of variants was found to be significantly associated with T2D in the test dataset of 445 Indians (AUC = 0.7781, OR = 1.6656 [95%CI = 0.6127–4.5278]). Our study demonstrates a framework to derive Indian-specific PRS for T2D. The accuracy of the derived PRS shows it's potential to be used as a prognostic metric to stratify individuals, and to recommend personalized preventive strategies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Many Indians are at high risk of type 2 diabetes mellitus (T2DM). The blood glucose level can be improved through a healthy lifestyle (such as physical activity and a healthy diet). Yoga can help in T2DM prevention, being a culturally appropriate approach to improving lifestyle. We developed the Yoga Programme for T2DM Prevention (YOGA-DP), a 24-week structured lifestyle education and exercise (Yoga) program that included 27 group Yoga sessions and self-practice of Yoga at home. In this study, the feasibility of undertaking a definitive randomized controlled trial (RCT) was explored that will evaluate the intervention's effectiveness among high-risk individuals in India. Methods: A multicenter, two-arm, parallel-group, feasibility RCT was conducted in India. The outcome assessors and data analysts were blinded. Adults with a fasting blood glucose level of 100–125 mg/dL (i.e., at high risk of T2DM) were eligible. Participants were randomized centrally using a computer-generated randomization schedule. In the intervention group, participants received YOGA-DP. In the control group, participants received enhanced standard care. Results: In this feasibility trial, the recruitment of participants took 4 months (from May to September 2019). We screened 711 people and assessed 160 for eligibility. Sixty-five participants (33 in the intervention group and 32 in the control group) were randomized, and 57 (88%) participants were followed up for 6 months (32 in the intervention group and 25 in the control group). In the intervention group, the group Yoga sessions were continuously attended by 32 (97%) participants (median (interquartile range, IQR) number of sessions attended = 27 (3)). In the intervention group, Yoga was self-practiced at home by 30 (91%) participants (median (IQR) number of days per week and minutes per day self-practiced = 2 (2) and 35 (15), respectively). In the control group, one (3%) participant attended external Yoga sessions (on Pranayama) for 1 week during the feasibility trial period. There was no serious adverse event. Conclusions: The participant recruitment and follow-up and adherence to the intervention were promising in this feasibility study. In the control group, the potential contamination was low. Therefore, it should be feasible to undertake a definitive RCT in the future that will evaluate YOGA-DP's effectiveness among high-risk people in India. Feasibility Trial Registration: Clinical Trials Registry—India (CTRI) CTRI/2019/05/018893; registered on May 1, 2019. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes mellitus (T2DM) has affected many people worldwide. One population that is greatly affected by T2DM is the Asian Indian population. The relative effects of genetics and environment on the development of diabetes in adults are not completely understood. Objectives: We conducted an analysis to determine if location, through the environment and different diets, affects T2DM inheritance in Asian Indians. We hypothesised that the prevalence of T2DM depended on location. Materials and Methods: We analysed previously collected data on T2DM in the individual states of India and the U.S. and used this information to compare the prevalence of T2DM in Asian Indians living in these two countries. Results: A total of 1,117,465,226 individuals were surveyed in India. Of these, 108,295,674 individuals had T2DM. Similarly, of the 1,704,846 individuals in the US, 298,107 had T2DM. The prevalence of T2DM was 17.49% in Asian Indians living in the US compared to 9.69% for Indians living in India (P < 0.00001). In individuals with similar genetic backgrounds, environmental factors significantly influence the development of T2DM. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Although not definitive, there is small increased risk of acute pancreatitis with the use of dipeptidyl peptidase 4 inhibitors (DPP4i). Hence, there is an interest in the elevation of pancreatic enzymes among type 2 diabetes mellitus (T2DM) patients using DPP4i. However, the studies regarding their association are limited and provide conflicting results. Moreover, there are no such studies among South Indian T2DM patients. Hence, we evaluated the prevalence of hyperamylasemia among South Indian T2DM patients and its association with DPP4i use. Methods: This cross-sectional study was conducted at a tertiary health care center from South India. Adult T2DM patients on stable doses of antidiabetic medications for at least previous 3 months were included in the study. Patients with other types of diabetes mellitus, gall stones, diabetic ketoacidosis, acute illness, chronic kidney disease and untreated hypothyroidism were excluded from the study. All participants were evaluated with glycemic parameters, serum creatinine and serum amylase. Hyperamylasemia was defined as serum amylase ≥220 U/L. Results: A total of 200 participants were included in the study among whom 93 patients were not on DPP4i whereas 107 were on DPP4i including 41 (38.32%) each on teneligliptin and sitagliptin. Baseline characteristics including glycemic measures were comparable between DPP4i users and nonusers. A total of 14 patients (7%) had hyperamylasemia but the prevalence of hyperamylasemia did not differ between DPP4i users and nonuser (6/107 vs. 8/93, P = 0.42). Conclusions: Asymptomatic hyperamylasemia is not uncommon in South Indian T2DM patients but is not associated with the use of DPP4i. [ABSTRACT FROM AUTHOR]

In recent years, numerous studies have explored the quality of life (QoL) in those with diabetes mellitus. The aim of this scoping review was to explore the current state of knowledge on QoL and its various associated factors among people with diabetes in India. Three databases were searched (PubMed, Scopus, and Medline) and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A total of 41 articles were included in the review. The included studies were largely conducted in the Southern states and mainly investigated individuals with type 2 diabetes. The World Health Organization Quality of Life (WHOQOL-BREF) and Short Form Health Survey (SF-36) were the instruments used most often. In general, the studies showed that people with diabetes had poorer QoL than those without diabetes, and women with diabetes reported poorer QoL than men, consistent with findings across the world. However, the studies had significant methodological flaws which limit the validity and generalizability of the findings. Therefore, there is an urgent need to conduct high-quality QoL studies which are representative of all states of India as well as different types of diabetes in India in order to address this gap in the evidence. [ABSTRACT FROM AUTHOR]

Background: Plasma omentin levels have been shown to be associated with circulating adiponectin concentrations and cardiometabolic disease-related outcomes. In this study, we aim to examine the association of omentin gene polymorphism with serum adiponectin levels and cardiometabolic health status using a genetic approach, and investigate whether these associations are modified by lifestyle factors. Methods: The study included 945 normal glucose tolerant and 941 unrelated individuals with type 2 diabetes randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Study participants were classified into cardiometabolically healthy and unhealthy, where cardiometabolically healthy were those without hypertension, diabetes, and dyslipidemia. Fasting serum adiponectin levels were measured by radioimmunoassay. The omentin A326T (rs2274907) single nucleotide polymorphism (SNP) was screened by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Results: The 'A' allele of the omentin SNP was significantly associated with lower adiponectin concentrations after adjusting for age, sex, body mass index (BMI), waist circumference (WC) and cardiometabolic health status (p = 1.90 x 10−47). There was also a significant association between circulating adiponectin concentrations and cardiometabolic health status after adjusting for age, sex, BMI, WC and Omentin SNP (p = 7.47x10-10). However, after adjusting for age, sex, BMI, WC and adiponectin levels, the association of 'A' allele with cardiometabolic health status disappeared (p = 0.79) suggesting that adiponectin serves as a mediator of the association between omentin SNP and cardiometabolic health status. There were no significant interactions between the SNP and dietary factors on adiponectin levels and cardiometabolic health status (p>0.25, for all comparisons). Conclusions: Our findings show that adiponectin might function as a mechanistic link between omentin SNP and increased risk of cardiometabolic diseases independent of common and central obesity in Asian Indians. Before strategies to promote adiponectin modulation could be implemented, further studies are required to confirm the molecular mechanisms involved in this triangular relationship between omentin gene, adiponectin and cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1007/s13300-023-01395-4. B Correction to: Diabetes Ther b https://doi.org/10.1007/s13300-023-01395-4 The "YOGA-DP Study Team" has been added to the author group in the article PDF. [Extracted from the article]

Introduction: Type 2 diabetes is a heterogeneous disease and its categorization into different clusters has revealed distinct subgroups from all over the world including India but no such study has been done till date in north India. Aims and Objectives: To identify clusters intype 2 diabetes mellitus by k means clustering and to describe different characteristics of patients in each of the identified clusters. Methods: Optimal number of clusters i.e., the K value was decided by two step clustering and the subtypes of the clusters were obtained by K means clustering using SPSS version 29 software. Variables which were used for clustering were age atdiagnosis, BMI, HbA1c, HOMA islet and HOMA insulin resistance (based on fasting C-peptide levels) along with waist circumference which has important role in type 2 diabetes mellitus physiology in south east Asians. Results: Total number of participants were 520, out of which 47.7% were males and females were 52.3%. The optimal number of clusters i.e., K = 4 was determined based on silhouette width. Using this K value K means clustering was done which resulted in formation of clusters differing in phenotypic characters. Cluster 1 severe insulin deficient diabetes (SIDD), Cluster 2 Mild age-related diabetes (MARD), Cluster 3 severe insulin resistant diabetes (SIRD), Cluster 4 mild obesity related diabetes (MOD). Phenotypically these clusters were same as defined by Ahlqvist et al in Scandinavian population. When compared with these Swedish clusters, MOD cluster was most common in our study population (37.1% vs 21.6%). SIDD cluster was more common than in Swedish study (21.3% vs 17.5%). In Swedish study MARD cluster was most common (39.1%) where as in our study it constituted 24.2% of patients. Conclusion: This study suggests that clusters in type 2 diabetes can be replicated in different ethnicities and highlights importance of including waist circumference in clustering in Asian Indians. Further studies are needed to look at differences in treatment response when treatment targeting the basic pathophysiological mechanism in different clusters is given to the respective clusters. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic myonecrosis or muscle infarction is an unusual complication of Type 2 Diabetes, usually associated with longstanding disease. It commonly presents as an acute non-traumatic palpable swelling of the affected muscle with predilection for the quadriceps and thigh muscles, often accompanied by retinopathy and nephropathy. Methodology: A retrospective review of the medical records of patients admitted with diabetic myonecrosis under the Department of Endocrinology, Christian Medical College Vellore over a period of ten years(2006-2015) was done. Data pertaining to clinical, biochemical and radiological characteristics were obtained and treatment modalities and outcomes were recorded. Results and Analysis: A total of n = 4 patients with diabetic myonecrosis and completed clinical data were included in the study. In our present series, the mean age at presentation was 45.5 years (±7.3 years), the mean duration of the diabetes was 9.0 years (±2.5 years)with an equal distribution of male and female subjects. The mean HbA1c (9.5 ± 0.6%) was suggestive of poor glycemic control at presentation with all (100%) the patients in our series having concomitant one or more microvascular complications. While laboratory parameters of elevated CPK or LDH were mostly normal, the findings of T1 hyperintense and T2 hypointense heterogenous lower limb lesions were present in all the subjects (n = 4). Conservative management with bed rest, analgesics and good glycemic control were effective in good clinical improvement over a period of 1-2 months. Conclusions: Our series of diabetic myonecrosis in Indian patients with Type 2 diabetes mellitus, elucidates the varied clinical presentations, with MRI findings rather than laboratory markers being the mainstay of diagnosis. [ABSTRACT FROM AUTHOR]

The article discusses the challenges posed by the coronavirus disease 2019 (COVID-19) pandemic for developing countries like India as of October 2020. Topics covered include its increase of mortality risks on patients with diabetes mellitus (DM), and the latter's need for strict glycemic control to prevent complications. Also noted are the COVID-19 vulnerabilities of patients with hypertension (HTN), ischemic heart disease (IHD), and chronic obstructive pulmonary disease (COPD).

India leads the world with largest number of diabetic subjects earning the dubious distinction of being termed the "diabetes capital of the world". According to the Diabetes Atlas 2006 published by the International Diabetes Federation, the number of people with diabetes in India currently around 40.9 million is expected to rise to 69.9 million by 2025 unless urgent preventive steps are taken. The so called "Asian Indian Phenotype" refers to certain unique clinical and biochemical abnormalities in Indians which include increased insulin resistance, greater abdominal adiposity i.e., higher waist circumference despite lower body mass index, lower adiponectin and higher high sensitive C-reactive protein levels. This phenotype makes Asian Indians more prone to diabetes and premature coronary artery disease. At least a part of this is due to genetic factors. However, the primary driver of the epidemic of diabetes is the rapid epidemiological transition associated with changes in dietary patterns and decreased physical activity as evident from the higher prevalence of diabetes in the urban population. Even though the prevalence of microvascular complications of diabetes like retinopathy and nephropathy are comparatively lower in Indians, the prevalence of premature coronary artery disease is much higher in Indians compared to other ethnic groups. The most disturbing trend is the shift in age of onset of diabetes to a younger age in the recent years. This could have long lasting adverse effects on nation's health and economy. Early identification of at-risk individuals using simple screening tools like the Indian Diabetes Risk Score (IDRS) and appropriate lifestyle intervention would greatly help in preventing or postponing the onset of diabetes and thus reducing the burden on the community and the nation as a whole. [ABSTRACT FROM AUTHOR]

Background & objectives: With increasing number of people with diabetes worldwide, particularly in India, it is necessary to search for low cost screening methods. We compared the effectiveness and costs of screening for undiagnosed type 2 diabetes mellitus (T2DM), using oral glucose tolerance testing (OGTT) alone, or following a positive result from the Indian Diabetes Risk Score (IDRS) or following a positive result from genotyping of the TCF7L2 polymorphisms in Asian Indians. Methods: In subjects without known diabetes (n=961) recruited from the Chennai Urban Rural Epidemiology Study (CURES), OGTT, IDRS, and genotyping of rs12255372 (G/T) and rs7903146(C/T) of TCF7L2 polymorphisms were done. IDRS includes four parameters: age, abdominal obesity, family history of T2DM and physical activity. Results: OGTT identified 72 subjects with newly diagnosed diabetes (NDD), according to the World Health Organization criteria of fasting plasma glucose ≥ 126 mg/dl or a plasma glucose ≥ 200 mg/dl, 2 h after 75 g oral glucose load. IDRS screening (cut-off ≥ 60) yielded 413 positive subjects, which included 54 (75%) of the 72 NDD subjects identified by OGTT. Genotyping yielded 493 positive subjects which only included 36 (50%) of the 72 NDD subjects showing less discriminatory power. Screening with both SNPs missed 27 (37.5%) NDD subjects identified by IDRS. In contrast, IDRS missed only 9 (12.5%) of the NDD subjects identified by genotyping. Total screening cost for OGTT alone, or with IDRS were 384,400 and 182,810 respectively. Comparing OGTT alone to IDRS followed by OGTT, the incremental cost per additional NDD subject detected by doing OGTT on everyone was 11,199 (201,590 for detecting additional 18 NDD subjects). Interpretation & conclusions: For screening a population of subjects without diagnosed diabetes in India, a simple diabetes risk score is more effective and less expensive than genotyping or doing OGTT on the whole population. [ABSTRACT FROM AUTHOR]

Epidemiological studies have shown an inverse correlation between the incidence of lymphatic filariasis (LF) and the incidence of allergies and autoimmunity. However, the interrelationship between LF and type-2 diabetes is not known and hence, a cross sectional study to assess the baseline prevalence and the correlates of sero-positivity of LF among diabetic subjects was carried out (n = 1416) as part of the CURES study. There was a significant decrease in the prevalence of LF among diabetic subjects (both newly diagnosed [5.7%] and those under treatment [4.3%]) compared to pre-diabetic subjects [9.1%] (p = 0.0095) and non-diabetic subjects [10.4%] (p = 0.0463). A significant decrease in filarial antigen load (p = 0.04) was also seen among diabetic subjects. Serum cytokine levels of the pro-inflammatory cytokines—IL-6 and GM-CSF—were significantly lower in diabetic subjects who were LF positive, compared to those who were LF negative. There were, however, no significant differences in the levels of anti-inflammatory cytokines—IL-10, IL-13 and TGF-β—between the two groups. Although a direct causal link has yet to be shown, there appears to be a striking inverse relationship between the prevalence of LF and diabetes, which is reflected by a diminished pro-inflammatory cytokine response in Asian Indians with diabetes and concomitant LF. Author Summary: Childhood helminth infections can reduce the risk and severity of allergies and autoimmune diseases, by means of immunomodulation, and a decrease in helminth infections could potentially account for the increased prevalence of these diseases in the western world (hygiene hypothesis). We hypothesized that the same immunomodulatory effect can have an impact on metabolic diseases like obesity, diabetes, hypertension and atherosclerosis, wherein inflammation plays a crucial role (extended hygiene hypothesis). To test this hypothesis, we examined the prevalence of lymphatic filariasis (LF) among diabetic, pre-diabetic and non-diabetic subjects who were part of the CURES (Chennai Urban Rural Epidemiology Study) study. In accordance with our hypothesis, we found reduced prevalence of LF among diabetic subjects compared to non-diabetic and pre-diabetic subjects. This was associated with decreased filarial antigen load and anti-filarial antibody levels. The association remained significant even after adjusting for socioeconomic status, age and gender. Interestingly, within the diabetic subjects, those who were filarial positive had reduced levels of pro-inflammatory markers (TNF-α, IL-6 and GM-CSF) compared to those who were filarial negative. In light of these findings, the decreasing incidence of filarial infection due to mass drug administration could potentially have an unexpected adverse impact on the prevalence of diabetes in India. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the prevalence of, and risk factors for, diabetic neuropathy among Asian Indian type 2 diabetic subjects. Subjects were recruited from CURES, a population-based study conducted on a representative population of Chennai city in south India. Of the 1529 known diabetic [KD] subjects, 1382 participated in the study [response rate: 90.4%]; in addition, 354 newly detected diabetic [NDD] subjects were also randomly selected. Neuropathy was diagnosed if the vibratory perception threshold of the right great toe measured by biothesiometry (Biomedical Instrument Co., Newbury, Ohio, USA) was ≥25. Of the total of 1736 individuals, biothesiometry studies were performed in 1632 subjects (94.0% response rate). The overall prevalence of neuropathy was 11% [age-standardized-5.8%], while it was 12.2% [age-standardized-6.5%] and 10% [age-standardized-5.2%] in male and female subjects respectively. The prevalence of neuropathy was significantly higher among KD subjects compared to NDD subjects [12.1% vs 6.8%, p=0.006]. It was also higher among subjects with diabetic retinopathy [26.9% vs 16.9%, p=0.001] and proteinuria [9.6% vs 5.3%, p=0.019] compared to those without. There was a linear increase in the prevalence of neuropathy with increasing age among both genders [p<0.0001]. The odds ratio (OR) for neuropathy in subjects having duration of diabetes >15 years was 5.51 [95% confidence interval (CI): 3.04-10.01, p<0.0001]. Multivariate logistic regression analysis showed age [OR: 1.16, 95% CI: 1.13-1.19, p<0.001], height [OR: 1.04, 95% CI: 1.01 -1.07, p=0.016] and fasting plasma glucose [OR: 1.00, 95% CI: 1.00 -1.01, p=0.001] to be significantly associated with neuropathy. Duration of diabetes showed an association with neuropathy but significance was lost when age was introduced into the model. This is the first population-based data on prevalence of diabetic neuropathy from India, which has the largest number of diabetic patients in the world. [ABSTRACT FROM AUTHOR]