Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by increased production of free radicals and oxidative stress. Oxidative stress can be defined as an imbalance between the removal of free radical production and altered activity levels of antioxidant enzymes. The aim of this study was to evaluate the antioxidant enzyme activity such as superoxide dismutase (SOD), catalase (CAT) and glutathione S transferase (GST) in T2DM patients and healthy subjects in a North Indian population. The study was conducted on 474 T2DM and 301 healthy subjects. Blood lysates were prepared and levels of antioxidant enzymes viz. SOD, CAT and GST were measured by spectrophotometric method. Data were analyzed by using Prism software (v 5.01) and expressed as Mean ± SE. The activity levels of SOD and GST were significantly lower in T2DM patients than in healthy subjects (P<0.05) whereas that of catalase was higher in T2DM patients (15.56±1.53 units/mg) than in healthy subjects (12.12±1.212 units/mg). Analysis of data also showed that enzyme activity levels decreased with increasing age both in normal and T2DM conditions. Only GST level showed significant decrease in diabetic males while both GST and SOD decreased in diabetic females. Assay of enzyme activity levels in erythrocytes could be used as markers to identify individuals predisposed to T2DM.

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Antioxidant enzyme levels as markers for type 2 diabetes mellitus

Background: Type 2 diabetes mellitus (T2DM) is a multifactorial disease resulting from ineffective use of insulin in the body. Single nucleotide polymorphisms (SNPs) in genes for scavenger receptors such as CD36 have been implicated in the pathogenesis of atherosclerosis and cardiovascular diseases in diabetes. The present study evaluated the effect of genetic polymorphisms of the CD36 gene on the risk of developing T2DM. Four SNPs in the CD36 gene (–178A→C in the promoter region, rs1984112 [A→G in exon 1A], rs1527479 [T→C in intron IB], and rs3211938 [T→G in exon 10]) were screened in T2DM patients and healthy controls (n=100 each). Materials and Methods: Analysis of CD36 gene polymorphisms was performed by polymerase chain reaction–restriction fragment length polymorphism. Statistical analysis was done by Fisher's exact test and χ2 statistics using SPSS version 15.0 software (SPSS, Inc., Chicago, IL), whereas SHEsis software (available at http://analysis.bio-x.cn/myAnalysis.php) was used for ha...

CD36 gene variants and their association with type 2 diabetes in an Indian population.

-------------------------------------------------------------------------------------------------------------------------II ACKNOWLEDGEMENTS --------------------------------------------------------------------------------------------------------IV TABLE OF CONTENTS -------------------------------------------------------------------------------------------------------------V LIST OF FIGURES -----------------------------------------------------------------------------------------------------------------XII LIST OF TABLES ------------------------------------------------------------------------------------------------------------------XVI ABBREVIATIONS ----------------------------------------------------------------------------------------------------------------XIX CHAPTER 1: INTRODUCTION-------------------------------------------------------------------------------------------------1 GENETICS OF COMPLEX DISEASES ---------------------------------------------------------------------------------------------------2 Approaches to gene mapping -------------------------------------------------------------------------------------------------------2 GOUT ---------------------------------------------------------------------------------------------------------------------------------4 1.1Brief history of gout --------------------------------------------------------------------------------------------------------------5 1.2Epidemiology of gout ------------------------------------------------------------------------------------------------------------6 1.3Synthesis of uric acid in the body ---------------------------------------------------------------------------------------------8 1.4Loss of uricase---------------------------------------------------------------------------------------------------------------------10 1.5Urate transport in the kidney -------------------------------------------------------------------------------------------------11 1.6Stages of gout ---------------------------------------------------------------------------------------------------------------------14 1.7Uric acid crystals and inflammation ----------------------------------------------------------------------------------------17 1.8Risk factors for gout -------------------------------------------------------------------------------------------------------------19 1.9Role of genetics in the development of hyperuricaemia and gout --------------------------------------------------23 1.10Treatment of gout --------------------------------------------------------------------------------------------------------------28 1.11Complications of gout ---------------------------------------------------------------------------------------------------------32 TYPE 2 DIABETES -------------------------------------------------------------------------------------------------------------------33 1.12Control of blood glucose ------------------------------------------------------------------------------------------------------33 1.13Epidemiology of type 2 diabetes worldwide ----------------------------------------------------------------------------34 1.14Pathophysiology of type 2 diabetes ---------------------------------------------------------------------------------------36 1.15Risk factors for type 2 diabetes ---------------------------------------------------------------------------------------------39 1.16Genetics of type 2 diabetes --------------------------------------------------------------------------------------------------43

Investigation of the Genetic Link Between the Metabolic Diseases Gout and Type 2 Diabetes

Obesity is driving the cardiovascular disease epidemic: however, should obesity be classified as a disease?

Study of CI962235 (Ins1361A), rs3212018 (16 bp del) and rs1049673 (G>C) CD36 Gene Polymorphisms in T2DM Patients of North India

Background: Type 2 diabetes mellitus (Type 2 DM) has been recognized as the recent pandemic; India and China competing each other for the title--Diabetes Capital of the World. A number of new drugs have been recently available and has lead to a boom in the clinical drug trial industry. We intend to evaluate the trend of clinical drug trials in Type 2 DM over last one decade. Materials and Methods: Clinical drug trial registry of USA was used for getting the data regarding number of drug trials conducted in each country over last decade. India, China, and USA being the countries with highest prevalence of diabetes were included in the analysis. The percentage share of each country in clinical drug trials in Type 2 DM was compared with their percentage share in prevalence of Type 2 DM. Discussion: A significant growth in the drug trials in Type 2 DM was observed during 2005 to 2008, after which there has been a plateau. It was also recognized that India and China which contribute to around 30% of diabetic population of the world contributed in only 9.73% and 5.15% of drug trials in Type 2 DM during 2010, respectively. USA comprising of 15.15% of diabetic population of world was seen to have contributed in 38.36% of clinical drug trials in Type 2 DM. This raises a question of skewing in the data generated from various drug trials conducted in Type 2 DM.

Trend of clinical drug trials in type 2 diabetes mellitus over last decade

Context: Though India has been thought to be an ideal destination for conduct of clinical drug trials, other smaller countries seem to be doing better. The pace of growth observed during 2005-2009 seems to be plateaued in 2010. Aims: There is an urgent need for introspection and corrective actions. Materials and Methods: An online survey was conducted among various stakeholders from clinical drug trial industry in India regarding their perception about clinical drug trial industry in India. Respondents were requested to rate training of investigator sites, industry, performance of regulatory, etc. Results: Majority of respondent felt that the clinical drug trial industry in India is growing, though India is not utilizing its full potential. Lack of trained investigators and delay in regulatory approvals came out as biggest hurdles. Conclusions: Urgent steps need to be taken in terms of proper training of all stakeholders. Regulatory bodies ought to bring about some radical changes in the system so as to match the other competing nations.

M S Dolima

Papers

Trend of clinical drug trials in type 2 diabetes mellitus over last decade

Perception of various stakeholders regarding clinical drug trial industry in India.