CHAPTER ONE
INTRODUCTION
1.1 SCOPE OF STUDY
Diabetes mellitus is a group of metabolic disorders that is characterized by elevated levels of glucose in blood (hyperglycemia) and insufficiency in production or action of insulin produced by the pancreas inside the body (Maritim et al., 2013). Insulin is a protein (hormone) synthesized in beta cells of pancreas in response to various stimuli such as glucose, sulphonylureas, and arginine however glucose is the major determinant (Joshi et al., 2007). Long term elevation in blood glucose levels is associated with macro- and micro-vascular complications leading to heart diseases, stroke, blindness and kidney diseases (Loghmani, 2015). Sidewise to hyperglycemia, there are several other factors that play great role in pathogenesis of diabetes such as hyperlipidemia and oxidative stress leading to high risk of complications (Kangralkar et al., 2010).
Type 2 diabetes mellitus is a multifactorial disease characterized by chronic hyperglycemia, altered insulin secretion, and insulin resistance – a state of diminished responsiveness to normal concentrations of circulating insulin (Landas and Goldstein, 2008). T2DM is also defined by impaired glucose tolerance (IGT) that results from islet β-cell dysfunction, followed by insulin deficiency in skeletal muscle, liver, and adipose tissues (Radami et al., 2010). In individuals with IGT, the development of T2DM is governed by genetic predisposition and environmental variables (a hypercaloric diet and the consequent visceral obesity or increased adiposity in liver and muscle tissues) and host-related factors (age, imbalances in oxidative stress, and inflammatory responses) (Pickup et al., 2014). Clinical complications of T2DM include both microvascular diseases (eg, retinopathy, nephropathy, and neuropathy) and macrovascular complications (eg, myocardial infarction, peripheral vascular disease, and stroke). The macrovascular diseases are considered to be the leading cause of mortality among diabetics (Johanson et al., 2015).
A significant body of evidence highlights the key role of abnormal innate immune responses and chronic low-grade inflammation in the pathogenesis of insulin resistance and the development of T2DM (Houston et al., 2006). Inflammation results from the activation of the innate immune response – the body’s immediate, nonspecific reaction against environmental insults such as pathogens and chemical or physical injury (Bilan et al., 2009). Inflammation plays a role in prevention of tissue damage, restoration of tissue homeostasis, and destruction of infectious agents. It is the result of the acute phase response, a system wide process during which several pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, are released, primarily by macrophages (Medzhiton, 2000). These cytokines can enhance insulin resistance directly in adipocytes, muscle, and hepatic cells. leading to systemic disruption of insulin sensitivity and impaired glucose homeostasis (Hotamisigil, 2015). Increased levels of proinflammatory cytokines lead to hepatic production and secretion of acute-phase proteins such as C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), amyloid-A, α1-acid glycoprotein, and haptoglobin. These proteins, collectively known as inflammatory markers, appear in the early stages of T2D, and their circulating concentrations increase as the disease progresses (Fernandez and Pickup, 2008). Chronic inflammation is closely associated with oxidative stress, an exaggerated presence of highly reactive molecular species, which leads to potential tissue damage (Rosen et al, 2011). Oxidative stress results either from an increase in free radical production, a decrease in endogenous antioxidant defenses, or both (Landab and Goldstein, 2008). Obesity and the metabolic syndrome, conditions which are considered key steps in the progression of insulin resistance to T2DM, are associated with both oxidative stress and inflammation (Urakawa et al., 2013). Hyperglycemia, increases in plasma levels of free fatty acids (FFAs), and hyperinsulinemia have all been linked to increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS activate nuclear factor κB (NFκB), a proinflammatory transcription factor, that triggers a signalling cascade leading to a continued synthesis of oxidative species and the low-grade chronic inflammation (Calder et al., 2009).
Given that obesity and the metabolic syndrome are steps toward the development of T2DM, their link with oxidative stress and inflammation points to a potential causative role for these factors in the progression of the disease. Thus, aiming to reduce oxidative imbalances and inflammation could lead to improved insulin sensitivity and delayed disease onset. Measures that prevent the development of oxidative stress and inflammation may present a feasible strategy for T2DM prevention and control. Dietary intake of micronutrients has been associated with reduced levels of oxidative stress, proinflammatory cytokines, and risk of T2DM in various cross-sectional and interventional studies, an approach that may facilitate the development of novel strategies for the prevention of T2DM (Rizzo et al., 2008).
1.2 JUSTIFICATION
Diabetes mellitus a problem of glucose metabolism is associated with a lot of microvascular and macrovascular disorders. It is a global concern for its increase in endemicity is quite alarming. Type 2 diabetes mellitus pathogenesis has been linked with a lot of environmental factors and some metabolic disorders. So many research have been carried out linking its association with oxidative stress. Also its association with acute phase response or inflammatory response has been studied but there is scarcity of this research being done in Nigeria. Therefore this research is carried out to evaluate the level of C-reactive protein and antioxidant vitamins in type 2 diabetes in Owerri.
1.3 AIMS AND OBJECTIVE
Aim: To estimate the level of some C-reactive protein and antioxidant vitamin E and C in type 2 diabetes mellitus.
Objectives:
- To determine the level of C-reactive protein in type 2 diabetic patients.
- To determine the level of antioxidant vitamin C and vitamin E in type 2 diabetic patients.
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