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Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disease described by hyperglycemia, which is caused by insulin resistance or reduced insulin secretion. The interaction between various genetic variants and environmental factors triggers T2DM. The aim of this study was to find risk associated with genetic variants rs5210 and rs2237895 of KCNJ11 and KCNQ1 genes, respectively, in the development of T2DM in the Indian population. A total number of 300 cases of T2DM and 100 control samples were studied to find the polymorphism in KCNJ11 and KCNQ1 through PCR-RFLP. The genotype and allele frequencies in T2DM cases were significantly different compared to the control population. KCNJ11 rs5210 and KCNQ1 rs2237895 variants were found to be significantly associated with risk of T2DM in dominant (KCNJ11: OR, 2.07; 95% CI, 1.30–3.27; p − 0.001 ; KCNQ1: OR, 2.33; 95% CI, 1.46–3.70; p − 0.0003) and codominant models (KCNJ11: OR, 1.76; 95% CI, 1.09–2.84; p − 0.020 ; KCNQ1: OR, 1.85; 95% CI, 1.16–2.95; p − 0.009). We also compared clinicopathological characteristics between cases and control and observed a significant difference in all the parameters except HDL, gender, and family history. In this study, clinicopathological data with a carrier of a variant allele of both KCNJ11 and KCNQ1 genes were also analysed, and a significant association was found between the carrier of a variant allele with gender and PPG in KCNJ11 and with triglyceride in KCNQ1. We confirm the significant association of KCNJ11 (rs5210) and KCNQ1 (rs2237895) gene polymorphism with T2DM, indicating the role of these variants in developing risk for T2DM in Indian population. [ABSTRACT FROM AUTHOR]

Introduction: Glucokinase (GCK) gene alteration or inactivation leads to Maturity-Onset Diabetes of the Young (MODY) and Neonatal Diabetes. Alterations in GCK gene has been shown to be associated with increased risk of type 2 diabetes, hyperglycaemia and impaired beta cell function. Aim: To evaluate the GCK (-30G/A, rs1799884) alterations in Type 2 Diabetes Mellitus (T2DM) patients. Materials and Methods: After patients' selection, blood samples were taken and all biochemical parameters were analysed by auto-analyser using serum. Whole blood samples were used to extract DNA and RNA for genotyping of -30G/A polymorphism using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) as well as GCK mRNA expression using quantitative real time PCR. Results: Several parameters such as fasting sugar, serum uric acid, Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Triglyceride (TG), Cholesterol, high-sensitivity C-Reactive Protein (hs-CRP) were analysed among T2DM cases and healthy controls and differences among them were found to be significantly associated (p<0.0001). It was observed that patients who were smoking among T2DM cases, were found to be associated with increased fasting sugar (p=0.001), postprandial sugar (p<0.0001), HbA1c (p=0.003), blood urea (p=0.01), cholesterol (p=0.02) compared to those who were not smokers. T2DM patients who were alcoholic, showed increased LDL (p=0.006) and cholesterol (p=0.01) compared to non-alcoholic T2DM patients. T2DM cases which were reported hypertensive, showed increased hs-CRP (p=0.02) and cholesterol (p=0.02), compared to non-hypertensive T2DM cases and differences among them were found to be significantly associated. Significant differences were observed in distribution of GCK -30G/A genotypes among T2DM cases and healthy controls (p<0.0001). Odds ratio was calculated and it was observed that the heterozygous GA genotype had 4.66 odds ratio while odds ratio for mutant AA genotype was 35.98 in reference to wild type. Patients with homozygous GG showed 0.25 mean fold decreased GCK mRNA expression while heterozygous GA and mutant AA genotype showed more than 0.17 and 0.16 fold decreased. GCK mRNA was observed and differences among them was found to be significant (p<0.0001). Conclusion: Study revealed that GCK heterozygous GA and mutant AA genotypes were associated with T2DM risk and decreased expression may be responsible for disease progression and worsening of the disease. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus [T2DM] has been one of the common diseases and is characterized by increased blood glucose levels and suggested that cell-free non-coding RNAs and microRNAs (miRNAs) have been demonstrated to serve as important diagnostic/prognostic biomarkers in diabetes. Materials/Methods: The present study included clinically confirmed newly diagnosed 200 cases of T2DM and 200 healthy subjects, and all the parameters were taken care in diagnosis. Blood samples collected in plain vials were used for cell-free total RNA extraction and after that 100ng of total RNA was used to synthesize the cDNA for cell-free lncRNA H19, miRNA-29a, and miRNA-29b expression using quantitative real-time PCR method. Serum Biochemical parameters were analyzed after collection of the sample to observe the changes among T2DM cases and healthy controls. Results: It was observed that type 2 diabetic patients had decreased [0.59 fold] lncRNA H19 expression while increased miRNA-29a [5.62 fold] and miRNA-29b [5.58 fold] expression. Decreased expression of lncRNA H19 was observed to be associated with gender [p=0.004], hypertension [p< 0.0001], weight loss [p=0.02] and fatigue [p=0.02]. Increased miRNA29a expression was linked with hypertension [p< 0.0001], alcoholism [p=0.04], and smoking [p< 0.0001] as well as miRNA-29b expression was associated with hypertension [p=0.0001], weight loss [p=0.002], smoking [p=0.0002], alcoholism [p< 0.0001]. Low [≤ 1 fold] and high [> 1 fold] expression of lncRNA H19 expression was linked with miRNA-29a [p=0.005] and miRNA-29b [p< 0.0001] expression. lncRNA H19 expression showed negative correlation with miRNA-29a expression [r= − 27, p< 0.0001] and miRNA-29b [r= − 47, p< 0.0001]. Conclusion: The present study concluded that lower lncRNA H19 expression, and increased miRNA-29b, a miRNA-29b expression associated with the severity of T2DM patients. Decreased lncRNA H19 expression, and increased miRNA-29b, miRNA-29b expression observed to be interrelated with clinicopathological findings of T2DM patients could involve in pathogenesis disease. [ABSTRACT FROM AUTHOR]

Introduction: Obesity plays a pivotal role in the development of metabolic syndrome—excessive body fat, spikes in blood glucose levels and hypertension—and ultimately leads to cardiovascular diseases and type 2 diabetes (T2D), if left unattended. The present study aimed to investigate the associated risk of T2D with obesity risk alleles of fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes. Methods: The study includes 400 subjects (300 T2D diabetic cases and 100 healthy controls). Genetic analysis was done by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Results: The findings of the study show no significant increase in odds of diabetes associated with the prevalence of FTO and MC4R minor alleles. Rare allele frequencies for "A" of FTO rs9939609 were 0.34 and 0.30 in cases and controls, respectively. Rare allele frequencies for A of MC4R rs12970134 were found to be more common in controls (0.45) than cases (0.41), but the difference was insignificant (p 0.246); however, an increase in body weight with the presence of allele "A" of the FTO gene (p value < 0.001) was found, indicating indirect involvement in the development of T2D. In addition, these were also correlated with the demographic/lifestyle and clinico-pathological parameters between T2D cases and controls. We found that T2D patients with a history of smoking and high consumption of alcohol, fast foods and sweetened beverages are at high risk of T2D compared to healthy controls (p < 0.01*). Conclusion: The present study concludes that there is no direct association of rs9939609 of the FTO gene with the occurrence of diabetes in the Indian population, but its role in T2D development cannot be overlooked altogether. Furthermore, we conclude that the rs9939609 of FTO carries a potential risk of obesity and because of this FTO rs9939609 T > A is widely considered an obesity-associated allele/single-nucleotide polymorphism (SNP). [ABSTRACT FROM AUTHOR]

Background. Type 2 diabetes mellitus (T2DM) has emerged as an epidemic affecting more than four hundred million people throughout the world. It is a multifactorial disease with range of environmental and genetic factors responsible for its prevalence. In search of novel biomarkers for recording progress of various metabolic diseases, small noncoding RNA in general and microRNAs (miRNAs) in particular have emerged as the most promising biomarkers for diagnosing variety of diseases including diabetes. An increasing number of studies have been published, reporting the quantification of miRNAs in blood of subjects with diabetes and mostly aimed at identifying miRNA modulation in chronic diabetic complications. Due to its association with immune system homeostasis and potential capability to predict diabetes development, the profile of circulating miRNAs may also provide useful information about diabetes pathogenic mechanisms. Thus, the present study aimed to understand the role and expression of microRNA330 and E2F1 mRNA expression in patients with T2DM. Methodology. The present study includes a total of 200 individuals: 100 "individuals with T2DM referred to as "cases" and 100 healthy individuals referred to as "controls". Extracted RNA was used to synthesise the cDNA for microRNA-330 and E2F1 mRNA expression. Taqman assay method has been used to analyse the microRNA-330 expression in the cases and controls and SYBR green dye was used to study the E2F1 mRNA expression. Results. Statistically significant difference was observed in all the selected 5 biochemical parameters among T2DM cases and healthy controls. Risk factors like hypertension were observed to be significantly associated with reduced HDL (p = 0.01), increased TG (p = 0.0008), and cholesterol (p < 0.0001) in hypertensive T2DM cases as compared to nonhypertensive T2DM cases. Obese patients showed significant increase in TG (p = 0.01) and cholesterol (p < 0.0001) as compared to nonobese patients. Similarly, increased TG (p = 0.001) and cholesterol (p < 0.0001) was observed in the case of alcoholic patients as compared to nonalcoholic patients. Also, patients with smoking habit showed increased TG (p = 0.009 p = 0.009), cholesterol (p < 0.0001), and VLDL (p = 0.01) as compared to nonsmokers and differences among them was found to be statistically significant. Besides this, significant impact of risk factors like hypertension, obesity, alcoholism, and smoking were observed on microRNA-330 expression and E2F1 mRNA expression. A 7.72-fold increased microRNA-330 and 0.05-fold decreased E2F1 mRNA expression was observed among T2DM cases as compared to healthy controls. Increased expression of microRNA-330 was observed in hypertensive cases (9.61-fold, p < 0.0001), obese cases (9.33-fold, p = 0.0008 , alcoholic cases (9.07-fold, p < 0.0001), and smoking cases (8.41-fold, p = 0.01) as compared to nonhypertensive, nonobese nonalcoholic, and nonsmoking cases, and differences among them were found to be significant. Decreased expression of E2F1 mRNA expression was observed in patients with alcoholism (0.03-fold, p = 0.002) and smoking (0.03fold, p < 0.0001) while patients who were nonalcoholic and nonsmokers showed 0.07-fold increase in expression, and differences among them were found to be statistically significant. Conclusion. The present study demonstrated that increased level of microRNA-330 and decreased level of E2F1 mRNA expression were found to be associated with pathogenesis of T2DM patients. Risk factors such as hypertension, obesity, alcoholism, and smoking may be were found to be associated with microRNA-330 and E2F1 mRNA expressions, and it can prove a reliable biomarker for T2DM disease progression could be linked to chronic diabetic complications. [ABSTRACT FROM AUTHOR]