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Numerous studies disclosed the independent role of VDR genetic polymorphisms involved in pathogenesies of various metabolic disorders like type 2 diabetes mellitus in different populations, however no any conclusive or even key study conducted on South Asian population especially Pakistani population except on Indian population. Worldwidle, vitamin D defeciency and type 2 diabetes mellitus (T2DM) are two interlated and most common health problems. Such interlationship is involved complex inheritance pattern.The polymorphisms of various genes including vitamin D receptor (VDR) might affect genetic susceptibility of T2DM by developing malfunctioning of beta pancreatic cells or insulin resistance. Genetic architecture of T2DM is different among various ethnic populations. The present review will focus on concept that polymorphism of VDR gene may has role in susceptibilty of onset of T2DM and its pathogenesises.

BACKGROUND Diabetes Mellitus (DM) is an advanced and chronic endocrine disorder characterized by an insufficiency of insulin secretion from pancreatic β-cells and liver, adipose tissues, and skeletal muscles. OBJECTIVE The main objective of this study is to understand the mechanism and genes which are responsible for the prevalence of diabetes. The study also covers various types of diabetic complications with special reference to insulin role and defects. METHODS The scientific literature and patents were reviewed and analyzed based on their suitability and relevance to the theme of the study. The scientific literature was covered from the authentic databases such as Elsevier, Springer, and Bentham Science. The patents were reviewed from http://www.freepatentsonline.com. RESULTS Glucokinase (ATP: D-glucose-6-phosphotransferase; GCK), initiates glycolysis and acts as a glucose sensor and metabolic signal producer in liver and pancreas. PCR-sequencing showed qualitative differences in diabetic patients in comparison to healthy subjects. Glucokinase is the most important component in glucose detection of pancreatic islet beta cells in diabetes because glucokinase mutations can be one of the most common single gene disorders described. It is known that a genetic variation of a human glucokinase gene, including a point mutation, causes MODY, the concentration of plasma glucose increased and it is supposed to be the cause of diabetes of the present study subjects. Owing to hyperglycemia and individual components of the insulin resistance (metabolic) syndrome, people with Type II DM are prone to the high threat for microvascular complications (including nephropathy, retinopathy, and neuropathy) and macrovascular complications (such as Ischemic Heart Disease). There were also significant differences (P < 0.0001) in glycation levels (0.90, 0.4838mole/mole), random blood sugar (348.8, 105.8mg/dL), cholesterol levels (235.3, 161.8mg/dL), low density lipoprotein in diabetic subjects (155.3, 28.46mg/dL) and in healthy donors. GCK gene mutations were found in 70% of the patients while 30% are non-mutated. CONCLUSION In conclusion, lipids, glucose, and protein play an essential role in the initiation of AGE's or diabetic complications (Micro and Macrovascular Complications). The importance of the clinical results should also be recognized in the genetic analysis of heterogeneous disorders as NIDDM/ Type II DM.

An elderly woman presented with extensive bruising and a haemorrhagic stroke. Initial investigations revealed an abnormal clotting screen with a prolonged activated partial thromboplastin time. Further investigations revealed this to be due to antibodies that the patient had developed against clotting factor VIII also known as acquired haemophilia A.