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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]

Background: Recent studies have shown a high prevalence of Type-2-diabetes (T2DM) (24%) and prediabetes (18.1%) in Kerala. There is no community based study from South Asia regarding the prevalence of type 2 diabetes and its precursors in the young adult population. This community based study was done to find the prevalence of type 2 diabetes and its precursors in South Indian adult youth (18-30 years age) of Thiruvananthapuram district. Research Design and Methods: Cross sectional design was used for this study. Multistage cluster sampling was used to enrol community dwelling youth of 18 to 30 years, residing in Thiruvananthapuram district. Six panchayath wards from rural and urban regions and 4 from coastal area were randomly selected as the primary sampling units. Trained staff nurses conducted the survey with the help of accredited-social-health-activists (ASHA). Socio-demographic data, anthropometry, clinical features of insulin resistance, and random capillary glucose (CG) and blood pressure were assessed and recorded. Oral Glucose tolerance test or HbA1c was done for participants with a CG =130 mg/dl for diagnosis of diabetes and prediabetes. Results: A total of 1031 participants were included from the rural (n = 394), coastal (n = 269) and urban (n = 368) areas. Prevalence of hyperglycaemia i.e., T2DM and pre-diabetes was 0.48% (n = 5) and 2.4% (n = 25) respectively. Family-history of T2DM was present in 35.1% subjects. Prevalence of overweight, obesity and abdominal-obesity was 28.2%, 16.1% and 28.4% respectively. Clinical-features of insulin resistance (CFIR) were present in 27.1% subjects (acanthosis [17.7%], skin tags [1.7%] and PCOS phenotype [10.7%]). Among various anthropometric measurements and their derivatives, CFIR correlated best (r = 0.24, P < 0.01) with the product of BMI and the sum of abdominal circumference and hip circumference (Trivandrum Medical College [TMC] -adiposity-index), which is a newly proposed parameter. Hyperglycaemia was more common in males, did not correlate with waist hip ratio, and correlated best again with TMC-adiposity-index ((r = 0.13, P < 0.01). Conclusions: The burden of insulin resistance in the young South Indian population, hitherto unknown in any community based study, has been studied for the first time. The prevalence of precursors of T2DM is high in this population. Early identification of 'at risk' individuals could provide a window of opportunity for preventing or delaying future diabetes and its long term complications. TMC adiposity index could become a valuable tool in the anthropometric assessment for predicting future T2DM. [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]

Background: Diabetic nephropathy is known to be a leading complication of diabetes mellitus, characterized by diverse aspects such as high urinary albumin level, elevated blood pressure, and genetic susceptibility leading to end-stage renal disease. The current study was carried out to investigate the association of eNOS and TGFβ1 gene polymorphisms in the progression of diabetic nephropathy among type 2 diabetic patients in the South Indian population. The eNOS and TGFβ1 genetic variants were genotyped in 280 T2DM patients, 140 with DN, 140 without DN, and 140 controls. Genotyping was performed using ARMS PCR and the genomic variants were confirmed by the Sanger sequencing method. Results: A significant (p < 0.05) association was observed in the genotypic frequencies of eNOS (G > T) polymorphism in the T2DM patients with diabetic nephropathy when compared to controls. The frequency of TT (heterozygous) genotype was observed to increase in patients with type 2 diabetes and DN when compared to the diabetic patients without DN and controls. This indicates that diabetic patients with TT genotype are at an increased risk to develop DN. However, TGFβ1 (G > C) polymorphism did not show any association in the allele and genotypic frequencies with DN when compared with T2DM and controls. Conclusion: The results of the study propose a strong influence of TT genotype of eNOS gene be significantly linked with diabetic nephropathy in T2DM patients. Whereas no association was examined concerning TGFβ1 gene polymorphism and DN. Nevertheless, large sample size studies are required to confirm the part of these genetic variants in the development of DN. [ABSTRACT FROM AUTHOR]

To study the association and possible predictive role of visfatin, resistin, fetuin-A and chemerin with incident type 2 diabetes (T2DM) among Asian Indians with prediabetes. Their association with insulin resistance, β-cell function, glycaemia and anthropometry were also studied. This is a nested case–control study of a large 2-year prospective prevention trial in persons at high risk of developing T2DM. Baseline HbA1c values between 6.0% (42 mmol/mol) and 6.2% (44 mmol/mol) were chosen for this analysis (n = 144). At follow-up, persons with incident T2DM (HbA1c ≥ 6.5%, 48 mmol/mol) were grouped as cases (n = 72) and those reverted to normoglycaemia, (HbA1c < 5.7% (39 mmol/mol) as controls (n = 72). Insulin resistance showed the strongest association with incident T2DM ((Odds Ratio (OR): 23.22 [95%CI 6.36–84.77]; p < 0.0001). Baseline visfatin (OR: 6.56 [95%CI 2.21–19.5]; p < 0.001) and fetuin-A (OR: 1.01 [95%CI (1.01–1.04)]; p < 0.0001) independently contributed to the conversion of prediabetes to T2DM. The contribution was significantly higher when their elevated levels coexisted (OR: 12.63 [95%CI 3.57–44.63]; p < 0.0001). The area under the curve was 0.77 ± SE 0.4 (95%CI 0.69–0.85) and 0.80 ± SE 0.04 (95%CI 0.73–0.88) for visfatin (median 17.7 ng/ml, sensitivity and specificity: 75%, p < 0.0001) and fetuin-A (mean 236.2 µg/ml, sensitivity: 71%, specificity: 75%, p < 0.0001) respectively. Higher baseline visfatin and fetuin-A concentrations are strongly associated with incident T2DM and are predictive of future diabetes. [ABSTRACT FROM AUTHOR]

Background and aims: The purpose of the study is to assess the concentrations of spexin (SPX) and other specific biochemical parameters, subsequently spexin (SPX) gene polymorphisms among south Indian healthy controls and in T2DM and T2DM +HTN patient's blood samples, which were selected according to certain inclusion and exclusion criteria. Material and method: Named and kit methods are used for the evaluation of spexin, biochemical parameters, and for spexin (SPX) gene polymorphism. Results: In this prospective study, spexin concentration is a negatively associated biomarker, and elevated levels of glucose, insulin resistance, liver enzymes, and inflammation are independently associated with assessing the diabetic and arterial hypertension disease states. The SPX gene sequencing illustrates exon mutation in the 6th position and no polymorphism is detected in the 2nd, 3rd, 4th, and 5th exons. Whereas intronic mutations are observed in the 3rd and 5th positions. Furthermore, heterogeneous mutations are observed in the 8th and 13th samples. Samples 10 and 14 showed homozygous of -42G>A mutation in exon 6. Samples 11, 12, 18, 19, 21, and 22 showed a heterozygous mutation (-42G>R) in the intron that is present 5' to the exon 6. There is a deletion mutation in the acceptor site of the intron present 5' to the exon 4. Conclusion: This is the first study reporting an association between spexin gene polymorphisms and the levels of spexin peptides. [ABSTRACT FROM AUTHOR]

Background and aims: Diabetes mellitus is a systemic disease associated with periodontal diseases. Research conducted over more than a decade proves a bidirectional relationship between diabetes and periodontal disease. This study compares the periodontal status, dental caries and salivary pH in diabetics with non-diabetics. Materials and methods: About 100 subjects participated in the study. 50 subjects each were included in group I (control group), group II (test group). Periodontal status (assessed by Russel's index), salivary pH, dental caries of all patients were evaluated. Statistical analysis was done using a student t-test. Results: The mean periodontal status in group I was 0.32, whereas 3.78 in group II. There was a statistically significant increase in Russel's index in group II. The mean salivary pH in group I was 7.42, in group II it was 6.44 indicating a statistically significant decrease in salivary pH in the diabetic group. The mean DMFT index in group I was 1.68 whereas in group II it was 7.06. This shows a statistically significant increase in DMFT score in the test group. Conclusion: Diabetic patients seem to have poor periodontal status, reduced salivary pH, increased dental caries than controls. This strengthens the hypothesis that hyperglycemia worsens oral health of diabetic individuals. [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]

Context: Multiple observational studies have reported an inverse relationship between 25-hydroxyvitamin D concentrations (25(OH)D) and type 2 diabetes (T2D). However, the results of short- and long-term interventional trials concerning the relationship between 25(OH)D and T2D risk have been inconsistent.Objectives and Methods: To evaluate the causal role of reduced blood 25(OH)D in T2D, here we have performed a bidirectional Mendelian randomization study using 59,890 individuals (5,862 T2D cases and 54,028 controls) from European and Asian Indian ancestries. We used six known SNPs, including three T2D SNPs and three vitamin D pathway SNPs, as a genetic instrument to evaluate the causality and direction of the association between T2D and circulating 25(OH)D concentration.Results: Results of the combined meta-analysis of eight participating studies showed that a composite score of three T2D SNPs would significantly increase T2D risk by an odds ratio (OR) of 1.24, p = 1.82 × 10-32; Z score 11.86, which, however, had no significant association with 25(OH)D status (Beta -0.02nmol/L ± SE 0.01nmol/L; p = 0.83; Z score -0.21). Likewise, the genetically instrumented composite score of 25(OH)D lowering alleles significantly decreased 25(OH)D concentrations (-2.1nmol/L ± SE 0.1nmol/L, p = 7.92 × 10-78; Z score -18.68) but was not associated with increased risk for T2D (OR 1.00, p = 0.12; Z score 1.54). However, using 25(OH)D synthesis SNP (DHCR7; rs12785878) as an individual genetic instrument, a per allele reduction of 25(OH)D concentration (-4.2nmol/L ± SE 0.3nmol/L) was predicted to increase T2D risk by 5%, p = 0.004; Z score 2.84. This effect, however, was not seen in other 25(OH)D SNPs (GC rs2282679, CYP2R1 rs12794714) when used as an individual instrument.Conclusion: Our new data on this bidirectional Mendelian randomization study suggests that genetically instrumented T2D risk does not cause changes in 25(OH)D levels. However, genetically regulated 25(OH)D deficiency due to vitamin D synthesis gene (DHCR7) may influence the risk of T2D. [ABSTRACT FROM AUTHOR]

Background and Aims: Inflammatory processes provoke the synthesis of various acute-phase proteins like C-reactive protein (CRP) in the liver and orchestrate a predominant role in the development of insulin resistance. Against this backdrop, the present study was undertaken to evaluate the association of inflammatory markers, glycated hemoglobin, and circulating lipids with microvascular complications in type 2 DM patients. Material and Methods: Prospective hospital-based longitudinal study was conducted with 384 patients to complete the study. The metabolic profiles were measured at baseline, 3rd month (review I), 6th month (review II), and at 12th month (review III). Lipid profiles were measured at baseline. CRP was measured at baseline, 6th month and at 12th month. Results: The recruited patients were followed for three reviews. Blood sugar level, HbA1c, and CRP were significantly decreased when compared to baseline. In this study baseline, CRP showed a positive correlation with baseline sugar levels, LDL, total cholesterol, renal parameters except for VLDL and a strong negative correlation with baseline HDL and ankle-brachial index but no significant correlation was observed with cardiac autonomic neuropathy and vibration perception threshold. Conclusion: This study concluded that due to effective pharmacotherapy the CRP level and the metabolic profiles were reduced after 12 months of follow-up. [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]

Introduction: Women with family history of diabetes (FHD) are at significantly increased risk of developing gestational diabetes mellitus which may eventually lead to type 2 diabetes mellitus (T2DM) in later life. Objective: This study investigates the role of FHD on metabolic markers and gene polymorphisms and hence on T2DM susceptibility in nondiabetic pregnant women and the subsequent risks in their newborns. Materials and Methods: The present study was conducted on 200 healthy (nondiabetic and normotensive) adult Asian Indian women, including 100 with and 100 without FHD, living in and around Kolkata, India. During the gestational period, they were studied twice and followed up till delivery. During delivery, both mothers' venous blood and cord blood were collected to estimate serum CRP, glucose, and lipid profiles of the respective mothers and their newborns. Genotyping of PPARγ and TCF7L2 polymorphisms was done from these blood samples. Results: A comparison of the metabolic variables among the subjects with and without FHD revealed significant differences among them. We also found close relationship between mothers and their newborn babies in terms of both PPARγ (rs1801282) C/G and TCF7L2 (rs7903146) C/T polymorphisms. More specifically, genotyping results for mothers with FHD and their newborn babies showed high concordance in inheritance of alleles: (i) for PPARγ via the risk allele G (74.0%) which is carried over to the newborn babies (64.5%) and (ii) for TCF7L2 via the risk allele T (73.0%) which is carried over to the newborn babies (68.5%). Conclusion: This study leads to the conclusion that Asian Indian women population based in Kolkata, India, are ethnically and genetically predisposed to the risk factors of diabetes through FHD, which is reflected in their gestational phase, and it has a significant implication on their birth outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Women with family history of diabetes (FHD) are at significantly increased risk of developing gestational diabetes mellitus which may eventually lead to type 2 diabetes mellitus (T2DM) in later life. Objective: This study investigates the role of FHD on metabolic markers and gene polymorphisms and hence on T2DM susceptibility in nondiabetic pregnant women and the subsequent risks in their newborns. Materials and Methods: The present study was conducted on 200 healthy (nondiabetic and normotensive) adult Asian Indian women, including 100 with and 100 without FHD, living in and around Kolkata, India. During the gestational period, they were studied twice and followed up till delivery. During delivery, both mothers' venous blood and cord blood were collected to estimate serum CRP, glucose, and lipid profiles of the respective mothers and their newborns. Genotyping of PPARγ and TCF7L2 polymorphisms was done from these blood samples. Results: A comparison of the metabolic variables among the subjects with and without FHD revealed significant differences among them. We also found close relationship between mothers and their newborn babies in terms of both PPARγ (rs1801282) C/G and TCF7L2 (rs7903146) C/T polymorphisms. More specifically, genotyping results for mothers with FHD and their newborn babies showed high concordance in inheritance of alleles: (i) for PPARγ via the risk allele G (74.0%) which is carried over to the newborn babies (64.5%) and (ii) for TCF7L2 via the risk allele T (73.0%) which is carried over to the newborn babies (68.5%). Conclusion: This study leads to the conclusion that Asian Indian women population based in Kolkata, India, are ethnically and genetically predisposed to the risk factors of diabetes through FHD, which is reflected in their gestational phase, and it has a significant implication on their birth outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Variability in the levels of these trace elements may reflect altered insulin metabolism and poor glycaemic control in the background of elevated oxidative stress. Mineral metabolism is another entity that may be disrupted by diabetes mellitus. Conversely, there are studies implicating early imbalances of trace elements in upsetting glucose homeostasis and insulin metabolism. Aim: To estimate and compare serum zinc, copper and magnesium in Type 2 Diabetes Mellitus (DM) patients with non diabetic controls and to correlate the serum zinc, copper and magnesium with Glycated Haemoglobin levels in Type 2 DM. Materials and Methods: This cross-sectional study was conducted at the Sapthagiri Institute of Medical Sciences and Research Center, Bengaluru, Karnataka, India. The study included 30 Type 2 DM patients and 30 healthy, age and gender matched controls without Type 2 DM. Their serum levels of zinc, copper and magnesium were measured and compared. Statistical Package for the Social Sciences (SPSS) version 16 software was used to perform the statistical analysis. The data obtained was subjected to descriptive statistical analysis. Results: Mean±SD of serum zinc in Type 2 DM and controls was 93.44±46.99 μg/dL and 121.74±37.15 μg/dL, respectively. Serum zinc was significantly decreased in Type 2 DM. However, there was no significant alteration with respect to serum copper and magnesium. Pearson’s correlation analysis showed that the association between HbA1c with zinc (r=0.069, p=0.718), copper (r= -0.094, p=0.622) and magnesium (r=0.116, p=0.543) was random. Conclusion: Zinc deficiency noticed in Type 2 DM patients may be due to increased excretion in urine. Zinc oral preparations are cheap and easily available. Considering these, it can be further explored if micronutrient supplementation would help to improve the glycaemic variability in Type 2 DM. [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]

Background: The cardiovascular complications associated with type 2 diabetes mellitus could be attributed to changes in myocardial mitochondrial metabolism. Though it is a known fact that permeabilized cardiac muscle fibers and isolated mitochondria are metabolically compromised in the Caucasian population, studies of Asian Indian myocardial mitochondrial function are lacking. Thus, the objective of the present study is to analyze if there is altered cardiac mitochondrial substrate utilization in diabetic Asian Indians. Methods: Mitochondrial substrate utilization was measured using high‐resolution respirometry in isolated mitochondria prepared from right atrial appendage tissues of diabetic and nondiabetic subjects undergoing coronary artery bypass graft surgery. Western blotting and densitometric analysis were also done to compare the levels of proteins involved in fatty acid metabolism and regulation. Results: The mitochondrial oxygen consumption rate for fatty acid substrate was shown to be decreased in diabetic subjects compared to nondiabetic subjects along with an unvaried mitochondrial DNA copy number and uniform levels of electron transport chain complex proteins and proteins involved in fatty acid metabolism and regulation. Decreased glutamate but unchanged pyruvate‐mediated state 3 respiration were also observed in diabetic subjects. Conclusion: The current study reports deranged cardiac mitochondrial fatty acid‐mediated complex I respiration in type 2 diabetic Asian Indians with comparable levels of regulators of fatty acid oxidation to that of nondiabetic myocardium. Altered glutamate‐mediated mitochondrial respiration also points toward possible alterations in mitochondrial complex I activity. When compared with previous reports on other ethnic populations, the current study suggests that Asian Indian population too have altered cardiac mitochondrial substrate utilization. [ABSTRACT FROM AUTHOR]

Introduction: We present a new diabetes risk score developed and validated in a multi-ethnic population in Guyana, South America. Measurement of in-country diabetes prevalence is a vital epidemiologic tool to combat the pandemic. It is believed that for every person diagnosed with type 2 diabetes there is another undiagnosed. The International Diabetes Federation (IDF) recommends a two-step detection programme using a risk score questionnaire to identify high-risk individuals followed by glycaemic measure. Methods: Data on 798 persons from the 2016 STEPwise Approach to Chronic Disease Risk Factor Surveillance (STEPS) were used to correlate responses to 36 questions with glycated haemoglobin (HbA1C) and fasting plasma glucose (FPG) results. Bootstrapping was used to internally validate the derived seven-variable model. This model with the addition of family history questions was tested in a convenience sample of 659 Guyanese adults and externally validated in a cohort of another 528. Results: An 8-item Guyana Diabetes Risk Score (GDRS) was derived. The final model performed with an area under the curve (AUC) of 0.812 Conclusions: The validated eight-item Guyana Diabetes Risk Score will be extremely useful in identifying individuals at high risk of having diabetes in Caribbean, Black or East Indian populations. [ABSTRACT FROM AUTHOR]

Aim: Microtubule actin cross-linking factor 1 (MACF1) has been identified as a type 2 diabetes (T2D) candidate gene, and variant rs2296172 of the gene was found associated with T2D in multiple populations. However, it has never been explored in Mizo population. The aim of the present study was to replicate the association of variant rs2296172 of MACF1 gene with T2D in Mizo population of Northeast India. Methodology: The variation was genotyped using TaqMan allele discrimination assay in 755 individuals (425 cases and 330 healthy controls), belonging to the Mizo population. Results: The variant rs2296172 MACF1 was found to be significantly associated with T2D (p value = 0.001) in Mizo population group with an observed odds ratio of 1.8 [1.3–2.8] at 95% CI after correction with age, gender and BMI. Conclusion: This study is the first replication report from Northeast India, showing variant rs2296172 of MACF1 gene associated with T2D in Mizo population. This independent study highlights MACF1 as a candidate gene for T2D in Asian Indian populations, suggesting it is critical to evaluate the variant rs2296172 in other distinct endogamous Indian population cohorts. [ABSTRACT FROM AUTHOR]

T2D is a complex disease with poorly understood mechanisms. In Asian Indians, it is associated with "thin fat" phenotype which resembles with partial lipodystrophy. We hypothesized that disturbed expression of lipodystrophy genes might play a role in T2D pathogenesis. Therefore, we attempted to establish a link between these two diseases by studying the overlap between the network of lipodystrophy genes and the differentially expressed genes (DEGs) in the peripheral subcutaneous adipose tissue of Asian Indians diabetics. We found that 16, out of 138 lipodystrophy genes were differentially regulated in diabetics and around 18% overlap between their network and the DEGs; the expression level of lipodystrophy genes showed an association with disease-related intermediate phenotypic traits among diabetics but not in the control group. We also attempted to individualize the diabetic patients based on ±2 fold altered expression of lipodystrophy genes as compared to their average expression in the control group. In conclusion, significant overlap exists between some of the lipodystrophy genes and their network with DEGs in the peripheral adipose tissue in diabetics. They possibly play a role in the pathogenesis of diabetes and individualization of diabetics is possible based on their altered expression in their peripheral adipose tissue. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a complex disease with an elusive link between its molecular aetiology and clinical presentation. Although, the role of visceral adipose tissue in insulin-resistance and T2D is known, limited information is available on the role of peripheral-subcutaneous adipose tissue especially in Asian Indians. In this microarray-based study of diabetic and normal glucose tolerant Asian Indians, we generated the transcriptome of their thigh adipose tissue and analyzed differentially expressed genes (DEGs) using weighted gene co-expression network analysis; further we identified perturbed pathways implicated by these DEGs in relevant co-expression modules. We also attempted to link these pathways with known aspects of T2D pathophysiology in terms of their association with some of their intermediate traits, namely; adipocyte size, HOMA-B, HOMA-R, Hb1Ac, insulin, glucose-level, TNF-α, IL-6, VLDLs, LDLs, HDLs, and NEFAs. It was observed that several modules of co-expressed genes show an association with diabetes and some of its intermediate phenotypic traits mentioned above. Therefore, these findings suggest a role of peripheral subcutaneous adipose tissue in the pathophsiology of T2D in Asian Indians. Additionally, our study indicated that the peripheral subcutaneous adipose tissue in diabetics shows pathologic changes characterized by adipocyte hypertrophy and up-regulation of inflammation-related pathways. [ABSTRACT FROM AUTHOR]

Background & objectives: Diabetes genomics research has illuminated single nucleotide polymorphism (SNP) in several genes including, fat mass and obesity associated (FTO) (rs9939609 and rs9926289), potassium voltage-gated channel subfamily J member 11 (rs5219), SLC30A 8 (rs13266634) and peroxisome proliferator-activated receptor gamma 2 (rs1805192). The present study was conducted to investigate the involvement of these polymorphisms in conferring susceptibility to type 2 diabetes (T2D) in the North East Indian population, and also to establish their association with anthropometric parameters. Methods: DNA was extracted from blood samples of 155 patients with T2D and 100 controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. To confirm the association between the inheritance of SNP and T2D development, logistic regression analysis was performed. Results: For the rs9939609 variant (FTO), the dominant model AA/(AT+TT) revealed significant association with T2D [odds ratio (OR)=2.03, P=0.021], but was non-significant post correction for multiple testing (P=0.002). For the rs13266634 variant (SLC30A 8), there was considerable but non-significant difference in the distribution pattern of genotypic polymorphisms between the patients and the controls (P=0.004). Significant association was observed in case of the recessive model (CC+CT)/TT (OR=4.56 P=0.001), after adjusting for age, gender and body mass index. In addition, a significant association (P=0.001) of low-density lipoprotein (mg/dl) could be established with the FTO (rs9926289) polymorphism assuming dominant model. Interpretation & conclusions: The current study demonstrated a modest but significant effect of SLC30A8 (rs13266634) polymorphisms on T2D predisposition. Considering the burgeoning prevalence of T2D in the Indian population, the contribution of these genetic variants studied, to the ever-increasing number of T2D cases, appears to be relatively low. This study may serve as a foundation for performing future genome-wide association studies (GWAS) involving larger populations. [ABSTRACT FROM AUTHOR]

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).

Background and aim Insulin resistance plays a crucial role in the pathogenesis of type 2 diabetes and cardiovascular diseases. Recently, paraoxonase-1(PON1) is reported to have an ability to reduce insulin resistance by promoting glucose transporter-4 (GLUT-4) expression in vitro. Single nucleotide polymorphism (SNP) in PON1 is associated with variability in enzyme activity and concentration. Based on this we aimed to investigate the association of PON1 (Q192R and L55M) polymorphisms with the risk of developing insulin resistance in adult South Indian population. Methods Two hundred and eighty seven (287) Type 2 diabetes patients and 293 healthy controls were enrolled in this study. All the study subjects were genotyped for PON1 (Q192R and L55M) missense polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) method. Fasting serum insulin level was measured by ELISA. Results The distribution of QR/RR and LM/MM genotypes were significantly higher in type 2 diabetes patients compared with healthy controls. Moreover, the R and M alleles were significantly associated with type 2 diabetes with an Odds Ratio of 1.68 (P < 0.005) and 2.24 (P < 0.005) respectively. SNP 192 Q > R genotypes were found to be significantly associated with higher BMI, cholesterol, triglycerides, LDL, fasting serum insulin and HOMA-IR. Further, the mutant allele or genotypes of PON1 L55M were associated with higher BMI, triglycerides, VLDL, fasting serum insulin and HOMA-IR among adult type 2 diabetes patients. Conclusion PON1 (Q192R and L55M) polymorphisms may play a crucial role in pathogenesis and susceptibility of insulin resistance thus leads to the development of type 2 diabetes in South Indian population. [ABSTRACT FROM AUTHOR]

The aim of this study of Asian Indian migrants in New Zealand was to determine cut-off points for body mass index, waist circumference, waist-to-hip ratio, and waist-to-height ratio that best discriminate for increased risk of type 2 diabetes and cardiovascular disease. One hundred and seventy-five (90F, 85M) Asian Indian volunteers (aged >50 y) were recruited from urban Auckland, New Zealand. Body weight, height and waist and hip circumferences were measured using standard techniques. Waist-to-hip ratio, waist-to-height ratio and body mass index were derived. Total and percent body fat by dual energy X-ray absorptiometry, and fasting glucose, insulin and lipids were measured. Three measures of metabolic risk were determined: the homeostasis model assessment of insulin resistance, the McAuley score for insulin sensitivity and metabolic syndrome by International Diabetes Federation criteria. Body mass index, percent body fat and anthropometric measurements of central adiposity generally did not perform well as indicators of metabolic risk in this high risk population of Asian Indian migrants. Our data support the use of lower ethnic specific body mass index and waist circumference for Asian Indian women and men. The discriminatory power of waist-to-height ratio was similar to that of body mass index. Hence, waist-to-height ratio could be used as a simple screening tool. A recommendation, of a waist-to- height ratio of less than 0.5 that would underpin the simple public health message of "your waist circumference should be less than half your height." [ABSTRACT FROM AUTHOR]

Context: There is little data correlating dietary fibre (DF) intake and cardiovascular risk in Asian Indians with diabetes. Aim: To assess the DF intake and its association with lipid profile (total serum cholesterol and low density lipoprotein [LDL] - cholesterol levels) in urban Asian Indians with diabetes. Subjects and Methods: Dietary assessment using validated Food Frequency Questionnaire was conducted in 1191 free-living adults with known diabetes in the Chennai Urban Rural Epidemiology Study. Subjects taking medication for dyslipidemia, and those with cardiovascular disease and implausible energy intake (n = 262) were excluded, leaving 929 participants. Anthropometric and relevant biochemical parameters were measured using standardized techniques. Results: Diabetic individuals who consumed DF median intake of DF group. The risk of hypercholesterolemia (odds ratio [OR] =1.38 [95% confidence interval [CI]: 1.02-1.85], P = 0.04), and high LDL cholesterol (OR: 1.43 [95% CI: 1.06-1.94], P = 0.02) was higher among those whose DF intake was less than the median. Serum triglycerides and high density lipoprotein cholesterol were not associated with DF intake. The main sources of DF were vegetables and legumes. Conclusion: In urban Asian Indians with diabetes, lower DF intake is positively related to total cholesterol and LDL cholesterol levels. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to a study by R. M. Anjana and colleagues regarding predictors of diabetes and prediabetes progression among Asian Indians, which appeared within the issue.