Role of oral hypoglycemic drugs on inflammatory condition associated with type 2 diabetes mellitus

Abstract

Diabetes Mellitus is one of the most common major public health problems having worldwide distribution with a prevalence of 382 million human cases, and the incidence is expected to increase to 592 million by 2035. Accord ing to the Centers for Disease Control, present trends of diabetes incidence suggest one in three Americans will be diagnosed with diabetes by the year 2050.1 The vast majority of diabetes patients (90%–95%) suffer from type 2 DM (T2DM). Depending on the etiology of diabetes mellitus, factors contributing to hyperglycemia may include; reduced insulin secretion, decreased glucose usage and increased glucose production. Although hyperglycemia is the main characteristic of all form of diabetes mellitus, the pathogenic mechanism by which hyperglycemia arises differs widely. Some forms of Diabetes mellitus are characterized by an absolute insulin deficiency or a genetic defect leading to defective insulin secretion; where as other forms share insulin resistance as their underlying etiology.2 Recently, there in increasing evidence that an ongoing cytokine induced acute phase response which is sometimes called low grade inflammation, but part of a widespread activation of the innate immune system, is closely involved in the pathogenesis of type 2 diabetes mellitus and associated complications such as dyslipidemia and atherosclerosis. Current literature recognizes that chronic low-grade subclinical inflammation is a part of insulin resistance and strongly related to the features of metabolic syndrome.3–5 In addition; inflammatory processes are also involved in the micro vascular complications of diabetes including diabetic nephropathy and retinopathy. 9 Inflammatory factors, which play a critical role in the development of atherothrombosis, are often found to be at elevated levels in patients suffer ing from diabetes. Elevated circulatory inflammatory markers such as C-reactive protein and interleukin-6 predict the development of type 2 Diabetes mellitus and several drugs with anti-inflammatory properties both lower both acute phase reactants and glycemia and possibility decrease the risk of developing type 2 diabetes mellitus. Age, inactivity, certain dietary components, smoking, psychological stress and low birth weight are among the risk factors for type 2 diabetes mellitus, which are also known to be associated with activated innate immunity. Activated immunity may be the common antecedent of developing type 2 diabetes mellitus.6 Other features of type 2 diabetes mellitus such as fatigue, sleep disturbance and depression are likely to be at least partly due to hypercytokinemia and activated innate immunity. This recent explosion of interest in the notion that chronic low grade inflammation and activation of the innate immune system are closely involved in the pathogenesis of type 2 diabetes mellitus was first proposed in 1997-987 several studies after that have shown that circulating markers of inflammation, acute phase reactants or interleukin-6 (IL-6) are strong predictors of the development of type 2 diabetes.8,9 The role of acute phase reactants in the development of type 1 diabetes mellitus is not very clear. For the management of Type 2 Diabetes Mellitus, many approach have been investigated which can mainly target to reduce inflammation but no approach concluded as successful.10,11 The current pharmacotherapy of Type 2 Diabetes Mellitus is derived from the ominous octet concept described by