Diabetes Mellitus In Indian Population Research Articles

A spectral domain optical coherence tomography (SD-OCT) study of intraretinal hyperreflective foci and its relationship with visual acuity and grades of retinopathy among patients of diabetes mellitus in Indian population

BackgroundHyperreflective foci (HRF) are biomarkers in detection of diabetic retinopathy (DR). Presence of HRF on spectral domain optical coherence tomography (SD-OCT) can give a correlation with visual acuity change and grades of DR. Purpose of this study is to determine the presence, location, and role of HRF in the retina of DM patients with and without retinopathy. MethodsA total of 192 eyes of patients suffering from type II DM were evaluated. Patients were divided into 2 groups, with Group A having diabetes without retinopathy (20 patients) and group B (76 patients) having diabetes and various grades of retinopathy. SD-OCT was performed in all patients, passing through the center of fovea. On OCT, presence and absence of HRF were noted. Characteristics of the hyper-reflective spots were evaluated: location, shape, size, back shadowing and association with central macular thickness (CMT), visual acuity, and grades of retinopathy. ResultsHRF were present in 169 eyes (88%) out of 192 eyes. The shape and location of HRF tend to change with disease progression. HRF were significantly associated with increasing grades of retinopathy (χ2 = 57.586, p < 0.01) Association of macular edema was significant with both retinopathy (χ2 = 8.895, p < 0.05) and HRF (χ2 = 34.720, p < 0.01). Association of best-corrected visual acuity with HRF (χ2 = 21.232, p < 0.01), macular edema (χ2 = 86.960, p < 0.01), and CMT (χ2 = 47.959, p< 0 .01) was significant. ConclusionHRF is a great indicator for early diagnosis of subclinical retinopathy and can be used to monitor the progression of disease and development of macular edema. Significant difference is present in HRF distribution and morphology.

Predictive value of adiposity index in identifying depression in individuals with type 2 diabetes mellitus in Indian population

Objectives: Type 2 diabetes mellitus (T2DM) patients are four times more prone to develop depression. Common subjective tool to evaluate depression is Patient Health Questionnaire-9 (PHQ-9). Depression in T2DM remains unaddressed because of lack of objective tools resulting in poor treatment compliance. Both obesity and metabolic disturbances could influence mental health status. Therefore, this study was designed to determine the better adiposity index to predict depression in T2DM. Materials and Methods: In this clinic-based cross-sectional study, 400 individuals (260 = T2DM and 140 = healthy) were recruited. Based on PHQ-9, T2DM patients were divided into T2DM + Dep (PHQ-9 ≤ 10) and T2DM-Dep (PHQ-9 &lt; 10). The relationship between the PHQ-9 score and adiposity indices was examined by Pearson’s/Spearman’s correlation. The receiver-operating characteristic curve analysis was used to identify the cutoff value. Statistical Analysis: Statistical analysis was performed using SPSS 22.0 version (IBM Corp., Armonk, New York, United States). Results: Female diabetic patients showed significant correlation only in lipid accumulation product index (LAPI) and visceral adiposity index (VAI) (r = 0.206 and r = 0.0.237, respectively), while male diabetic patients did not show any significant association. Interestingly, T2DM + Dep group showed significant association between LAPI (r = 0.248) with PHQ-9 score, while T2DM-Dep group did not show significant association. VAI had maximum area under the curve in T2DM patients (0.619, p = 0.002) as well as in female diabetic patients (0.684, p = 0.002). The cutoff value for identifying depression among diabetic individuals was 5.60, with 70.3% sensitivity and 48.2% specificity, while in diabetic females, it was 6.612, with 70% sensitivity and 61.4% specificity. Conclusions: VAI might be the best adiposity index to predict depression among diabetic individuals.

Exploring the rare variants associated with Type 2 Diabetes Mellitus in Indian population and its disease-drug association studies: an in-silico approach

The diversified eating habits and religious culture of Indian population may be one of the reasons they largely contribute to the global diabetes burden. In the present investigation, an in-silico approach was carried out to explore hub genes in the Indian population with Type 2 Diabetes Mellitus (T2DM) that are scantily reported in the GWAS catalogue and probable potential anti-diabetic drugs from plants. This computational approach unwrapped LEP (leptin) as the hub gene among 170 genes analyzed with 14 non-synonymous single nucleotide polymorphisms (nsSNPs) with MAF < 0.01. The mutation of the LEP gene leads to a decrease in leptin concentration, which increases the risk of obesity and T2DM. According to the DUET webserver, 11 of 14 mutations examined were found to destabilize the LEP protein. Among 14, four barely reported LEP variants rs781301976 (I45N), rs776443424 (S52F), rs200915360 (D76Y), and rs1191666811 (D162N) were unzipped to be associated with T2DM, which may be the probable potential drug targets. The virtual screening revealed Vescalagin as having the highest binding energy among 336 natural compounds. Molecular docking of Vescalagin depicted higher binding energy (-9.0 kcal/mol) against mutated LEP [rs200915360 (D76Y)] compared to wild (-8.9 kcal/mol) and LEP-Metformin complexes. The trajectory analysis of MD simulations revealed that Vescalagin was more effective than Metformin in stabilizing the system. The present study suggests that the associations of the investigated nsSNPs in LEP [rs200915360 (D76Y)] and others can be key factors in the predominant role of T2DM morbidity in the Indian population that can be used as potential markers and drug targets for T2DM therapeutics. Communicated by Ramaswamy H. Sarma

Association of SLC30A8 (rs13266634) and GLIS3 (rs7034200) gene variant in development of type 2 diabetes mellitus in Indian population: A case-control study

ObjectiveType 2 diabetes mellitus (T2DM) is a chronic disorder characterized by pancreatic beta-cell dysfunction and insulin resistance because of unsettled hyperglycemia. The present study was designed to understand the association of genetic variations in SLC30A8 and GLIS3 genes with T2DM. MethodA total of 600 samples were taken with 400 T2DM cases (240 males and 160 females; mean age 42.4 ± 9.3) and 200 control cases (130 males and 70 females; mean age 40.7 ± 8.2) in the study from regions across North India. A genetic study was conducted by PCR-RFLP methods. P parametric and non-parametric tests were used to analyze the data based on the qualitative and quantitative data. ResultsSignificant difference was found in biochemical parameters and sedentary lifestyle compared between T2DM patients and healthy controls such as triglycerides, HbA1c, T-cholesterol, LDL-C, BMI, systolic and diastolic BP, PPG, FPG, weight loss, fatigue, slow wound healing, blur vision, urination, appetite, urination, consumption of alcohol, non-veg, fast food and sugary drink, excessive consumption of calorie, normal and brisk (20 min) walk, prolonged sitting 3 h work, leisure sitting (3 h) and standing work (3 h) while no significant differences were observed in parameters such as HDLC, WHR, family history, household chores and exercise among T2DM patients and controls. In SLC30A8 rs13266634 variant, it was observed that TC and CC genotypes frequencies were significantly higher in T2DM cases as compared to healthy controls (OR- 2.88; 95%CI- 1.93–4.31; p < 0.0001 and OR- 5.6; 95%CI- 2.33–13.55; p = 0.0001). C allele frequency was higher as compared to healthy controls. For the GLIS3 rs7034200 variant, no significant difference was found in allelic frequency in cases and controls (p-0.434). We did not find any significant association of T2DM with GLIS3 gene variant under dominant as well as recessive models. ConclusionPresent study concludes that the association of genetic variations between T2DM cases and control was found to have a significant difference and play a vital role in T2DM risk based on odds ratio. However, the difference in frequency of alleles in the GLIS3 variant was non-significant among T2DM patients and healthy controls.

Insulin gene mutations linked to permanent neonatal diabetes mellitus in Indian population.

Neonatal diabetes mellitus (NDM) is a rare monogenic disorder of pancreatic beta cell mass and/or function. In the present study we aimed to evaluate the INS gene mutations in a cohort of children with Permanent Neonatal Diabetes Mellitus (PNDM) and to explore the clinical and genetic characteristics of PNDM caused by INS mutations. Direct sequencing of all exons of INS genes was carried out in 189 children with PNDM. Clinical and biochemical data were collected and correlated. The pathogenicity of mutations was determined based on the American College of Medical Genetics and Genomics and Association of Medical Pathology guidelines. Two novel mutations (His34Pro, Leu35Met) in a compound heterozygous state and seven known mutations (Gly32Ser, Phe48Cys, Arg89Cys, Cys96Tyr, Ser98Ile, Try108Asp and Cys109Phe) in the INS gene were identified in 8 patients out of the total of 189 PNDM children studied. Four mutations were involved in defects with disulphide bond formation and hence were in crucial regions of the gene. All the mutations were de novo in origin. This is the first comprehensive study from India to investigate the insulin gene mutations in PNDM and to show that INS gene mutations also contribute to the causation of PNDM.

Association of nod-like receptor pyrin domain containing 3 (rs10754558) and protein kinase C zeta (rs2503706) gene polymorphisms with the risk of type 2 diabetes mellitus in Indian population

BackgroundType 2 diabetes mellitus (T2DM) is a multifactorial chronic disease, characterized by hyperglycemia due to defect in insulin action, secretion or both. Nod-like receptor pyrin domain containing 3 (NLRP3) and protein kinase C zeta (PRKCZ) genes show a significant role in obesity-induced inflammation and insulin resistance. Polymorphisms of NLRP3 and PRKCZ genes have been reported with contradictory results as genetic risk factor for T2DM in different populations. Therefore, the current study was conducted in North Indian population to investigate the association of single nucleotide polymorphism (SNP) of NLRP3 (rs10754558) and PRKCZ (rs2503706) gene with T2DM. MethodThe study included a total of 270 subjects comprised of 102 healthy controls and 168 T2DM cases and SNPs were genotyped by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) method. Clinical parameters like glycated hemoglobin (HbA1c), fasting blood glucose (FBG), high density lipoprotein cholesterol (HDLC), triglycerides (TG), total cholesterol (CHL) and fasting insulin were determined by enzymatic methods. Result and conclusionA statistically significant association was observed between NLRP3 gene at SNP rs10754558 (C vs. G, OR (95% C.I.) = 1.77 (1.21–2.58), P = 0.002) and T2DM while significant association could not be observed between PRKCZ gene at SNP rs2503706 (C vs. T OR (95% C.I.) = 1.86 (0.94–3.67), P = 0.070) and T2DM. It can be concluded from these results that NLRP3 gene polymorphism at SNP rs10754558 is associated with the development of T2DM.

Association of Metallothionein 1A gene polymorphisms at rs11640851 and rs8052394 with risk of type 2 diabetes mellitus in Indian population

BackgroundMetallothioneins (MTs) are cysteine rich metal binding proteins that protect the cell proteins from oxidative damages. The studies have shown ambiguous findings regarding the association of SNPs in MT1A gene with type 2 diabetes mellitus (T2DM), therefore the present study was conducted to investigate the relationship of two SNPs (rs11640851 and rs8052394) of MT1A gene and haplotypes derived from these SNPs with T2DM in North Indians. MethodsThe present case-control study, conducted from August 2017 to July 2020, involved 168 T2DM patients and 102 healthy controls. SNPs rs11640851 and rs8052394 were genotyped from genomic DNA in the studied samples using PCR-RFLP method. ResultOut of two SNPs, only one SNP rs11640851 (+647 A/C) was found to be associated with T2DM and frequency of C allele was found to be higher in T2DM subjects (C vs A, OR = 1.58, 95% CI 1.07–2.33, p = 0.02). Among the four haplotypes (A/A, A/G, C/A, C/G), only C/A haplotype was found to be significantly associated with increased T2DM risk (C/A, OR = 1.97, CI 1.28–3.04, p = 0.001). ConclusionIt can be concluded from these results that MT1A gene polymorphism at SNP rs11640851 was associated with T2DM and C allele may be a predisposing factor in the development of T2DM.

Association of resistin (rs3745367) and urotensin II (rs228648 and rs2890565) gene polymorphisms with risk of type 2 diabetes mellitus in Indian population.

Insulin resistance may become the most powerful predictor of future development of type 2 diabetes mellitus (T2DM) and a therapeutic target for the treatment of the same. Both Resistin, an adipose derived peptide hormone and Urotensin II a potent vasoconstrictor, are reported to be involved in the development of insulin resistance and T2DM but the results remain contradictory. Therefore, investigations were carried out to study the association of T2DM and single nucleotide polymorphism (SNP) in Resistin (RETN) gene at rs3745367 (+ 299 G > A) and Urotensin II (UTS2) gene at rs228648 (+ 143 G > A) and rs2890565 (+ 3836 C > T) in a North Indian population. Method: The present case-control study, conducted from August 2017 to July 2020, involved 168 T2DM patients and 102 healthy controls. SNPs rs3745367, rs228648 and rs2890565 were amplified from genomic DNA in the studied samples by polymerase chain reaction (PCR) using specific primers. The amplified products were genotyped by restriction fragment length polymorphism (RFLP) using particular restriction endonucleases. Clinical parameters viz. glycosylated haemoglobin (HbA1c), fasting blood glucose (FBG), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), total cholesterol (CHL) and fasting insulin were determined by enzymatic methods. Result and conclusion: A statistically significant association between T2DM and RETN gene at SNP rs3745367 (p = 0.001) and UTS2 gene at SNP rs2890565 (p = 0.001) was observed. In RETN gene SNP rs3745367, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were found to be higher in GA + AA combined genotype than in GG genotype for T2DM subjects. Regression analysis revealed that SNP rs2890565 and HOMA-IR were independently associated with the risk of development of T2DM when three SNPs were taken as independent variable adjusted for clinical variables. Among four haplotypes, A/T was found associated with increased risk of T2DM as determined for rs228648 and rs2890565 of UTS2 gene. It can be concluded from these results that polymorphism at rs3745367 of RETN gene and at rs2890565 of UTS2 gene are associated with risk of T2DM in North Indian population.

Malnutrition Related Diabetes Mellitus in Indian Population

Malnutrition related diabetes mellitus (MRDM) is rare type of diabetes associated with long term malnutrition and is not uncommon in India. Diabetes mellitus is the most common endocrine disorder of multifactorial aetiology and has been linked to both chronic under nutrition and obesity. Malnutrition is often related to deficient micro and macro nutrients, unhealthy behaviours and low socioeconomic status. Various clinical studies have underlined the relationship between malnutrition and diabetes mellitus. In the present review, we mainly explored malnutrition related diabetes mellitus in Indian population. Maternal under nutrition during pregnancy causes a decrease in the fetal intrauterine development rate known as intrauterine growth retardation (IUGR). Malnutrition majorly causes persistent insulin deficiency, glucose intolerance and insulin resistance and there by increases the risk of diabetes in Indian population. In this study we have also discussed the pathogenesis of MRDM and their management like self- dietary management and evidence based individualized nutritional therapy.

Association of EGF A61G polymorphism and EGF expression with type 2 diabetes mellitus in Indian population

BackgroundEpidermal Growth Factor (EGF) plays critical role in regeneration of pancreatic β-cells and insulin secretion. The deficiency in EGF expression affects pancreatic β-cell's proliferation, maintenance and its function like insulin secretion which may result in individual susceptibility to Type 2 Diabetes Mellitus (T2DM). EGF A61G is a functional SNP that modulate EGF levels and eventually affects activity of β-cells. ObjectiveThe present study explores EGF A61G polymorphism (rs4444903) and correlates it with the risk of developing T2DM and mRNA expression. MethodsThe study included 90 subjects, T2DM patients (n = 30) and healthy controls (n = 60). Blood sample was collected from subjects to study EGF A61G polymorphism by PCR-RFLP and EGF mRNA expression level by Real-time PCR. ResultsThe EGF gene A61G polymorphism was found to be in significant association with T2DM. A/G genotype (OR = 4.07, 95%CI = 1.303 to 12.71, p = 0.0206) and ‘A’ allele (OR = 1.91, 95%CI = 1.017 to 3.568, p = 0.043) were significantly associated with risk of T2DM. The prevalence of allele ‘A’ was found to be higher in diabetic males and females (52.5% and 55% respectively). As compared to healthy subjects EGF mRNA expression levels showed significant down-regulation in T2DM patients (p = 0.005). The relative EGF mRNA expression in A/A and A/G genotype was significantly lower than G/G genotype. ConclusionThe present study suggests that EGF gene A61G polymorphism may be a genetic risk factor for susceptibility of T2DM in Indian population. However, this marker deserves further investigation using more sample size.

A study of CBS gene polymorphism, plasma H2S levels and their association in type-2 diabetes mellitus

Background: Hydrogen Sulphide (H2S), in recent years, is getting significant attention, as more evidences are emerging about its diverse biological roles. There are evidences of H2S having anti-inflammatory, neuro-modulator, vasodilator, anti-apoptotic and mitochondrial protective roles in various tissues. Among different tissues, β-cells of pancreas, according to some recent studies, get significantly affected by the imbalance in H2S homeostasis, leading to β-cell dysfunction and Diabetes Mellitus (DM). Cystathionine- β-synthase (CBS) enzyme is involved in the synthesis of H2S from cysteine in various tissues. Among various possible mutations in the CBS gene, a particular 833T-C mutation, has been found to be associated with various diseases.&#x0D; Aims and Objectives: The present study was aimed to determine the extent of abnormality of H2S homeostasis in type-2 DM patients, and to find out presence and association (if any) of 833T-C mutation in CBS gene, in the patients of type-2 DM, in comparison to healthy control subjects, in the Indian population.&#x0D; Materials and Methods: A cross sectional study was done with 40 clinically and biochemically diagnosed DM type II patients attending OPD of Endocrinology department of NRS Medical College &amp; Hospital, Kolkata, and 40 age and gender matched non-diabetic control subjects. DNA was isolated from EDTA blood of all the study subjects, PCR done and results compared. Plasma H2S was measured by the N,N-dimethyl-p-phenylene-diamine method. Plasma glucose and serum insulin were measured by standardized commercial kits.&#x0D; Results: Our study found the plasma H2S levels in the patients of type II DM to be significantly higher(P&lt;0.001) than the control subjects. The results also found significant positive correlation between plasma H2S level with fasting serum Insulin level (P&lt;0.001) and fasting plasma glucose level (P&lt;0.001) in the diabetic patients. Among 40 DM patients, only two were heterozygous for the mutation, and had both mutated allele (242bp) and normal allele (174bp). Rest of the patients and all the control subjects were homozygous for the normal allele (174bp). This marginal difference in the incidence of mutated allele was not found to be statistically significant.&#x0D; Conclusion: our study shows significant association of H2S dys-regulation with the type-2 Diabetes Mellitus in Indian population. The marginal but insignificantly higher incidence of 833T-C mutation in CBS gene, found in our study, warrants further research with higher number of study population, to more conclusively infer about the role of this mutation in the pathogenesis of type-2 DM.