**5. An overview of pathogenesis of type 2 diabetes mellitus**

Several pathogenic processes are involved in the development of diabetes. Type 2 diabetes is characterized by excessive hepatic glucose production, reduced insulin action and insulin resistance. These alter the utilization of endogenously produced insulin at the target cells. These precipitate hyperglycaemia [60]. The pathogenesis of type 2 diabetes rests on the relationship between carbohydrate metabolism and insulin action. Consumed complex carbohydrates are metabolized to their monosaccharide constituents (glucose, galactose and fructose) in the gut. These monosaccharides have roles in nutrition. Glucose metabolism and absorption receive more attention in relation to diabetes. Glucose, absorbed into the blood stream, elevates blood glucose level. This rise in blood glucose stimulates the secretion of insulin from the beta-cells of the pancreas to regulate blood sugar levels by increasing active transport of glucose into fat and muscle cells. Post-prandially, blood glucose is absorbed and transported via the portal vein to the liver. The liver maintains blood glucose levels by converting glucose into glucose-6-phosphate and glycogen (glucogenesis). The increased insulin secretion from the pancreas and subsequent cellular utilization of glucose lowers blood glucose levels. Lower blood glucose level decreases insulin secretion. In diseased condition, insulin production is decreased to inhibit glucose uptake into the cells, which precipitates hyperglycaemia. The insulin secreted by the pancreas at this time is not used by the target cells. Hyperglycaemia is a common effect of uncontrolled diabetes and overtime, it causes serious damage to many body systems, particularly, the blood vessels and nerves. Common symptoms include glucosuria, frequent urination (polyuria), excessive thirst (polydypsia), excessive hunger (polyphagia), sudden weight loss, extreme tiredness and blurred vision.

There is enormous and escalating economic and social cost of treating type 2 diabetes. Sifelani [54] observed that the number of people seeking medical assistance for diabetes is rising in Africa at a time when health experts reported the continent's overburdened health systems are ill equipped to diagnose the disease. Majority of the poor cannot afford the cost of treat‐ ment. Cost of treating diabetes accounts for about 10% of the national income of most countries in Sub-Saahara Africa. National surveys in most parts of Africa indicate that diabetes cases are on the rise due to rapid urbanization as well as fast changing diets which are displacing the traditional ones in favour of the western diets [55]. This makes a compelling case for attempts

Nigeria is among the top 5 countries that have the highest number of people affected by type 2-diabetes in sub-Saharan Africa. Nigeria has about 1.2 million people; South Africa, 841,000; the Democratic Republic of Congo, 552,000; Ethiopia, 550,000 and Tanzania, 380,000 living with diabetes. A national survey had an average prevalence rate of 2.7% with similar pattern in both sexes. There are slightly varying prevalence rates in different geographical locations [12]. Some sporadic figures on prevalence rates of diabetes in Nigeria were published. Cooper *et al.* [56] studied rural areas in Nigeria and found the prevalence of diabetics to be 2.8%. Wokoma [57] reported that the prevalence of diabetes in Nigeria ranges from 1% to 6%. International Diabetes Federation (IDF) [13] and [51] reported 2.2% and 3.9%, respectively, for type 2 diabetes in Nigeria. The annual increase was 0.3% in prevalence rate. A good number of people still live with it undiagnosed. The prevailing trend to replace the consumption of more complex forms of traditional diets with high intake of refined carbohydrates (Western) diets, in Nigeria, calls for great concern and urgent action. This is because carbohydrate (CHO) foods form over 70% of the local diets. The bleak account of national prevalence poses great challenges to individuals and the nation. Diabetes mellitus is a significant contribution to medical morbidity and mortality risk worldwide. Many factors are involved in its aetiology. The general risk factors include age, obesity, physical inactivity and family history/ previous history of gestational diabetes and poor eating habits. This is because intakes of good sources of dietary fibre such as fruits, vegetables, whole and high fibre grain products and legumes are low due to changes in dietary habit (nutrition transition) across the globe [58]. The main diabetes related risk factors include hyperglycaemia, hyperinsulinaemia/insulin resistance and microalbumi‐

**5. An overview of pathogenesis of type 2 diabetes mellitus**

Several pathogenic processes are involved in the development of diabetes. Type 2 diabetes is characterized by excessive hepatic glucose production, reduced insulin action and insulin resistance. These alter the utilization of endogenously produced insulin at the target cells. These precipitate hyperglycaemia [60]. The pathogenesis of type 2 diabetes rests on the relationship between carbohydrate metabolism and insulin action. Consumed complex carbohydrates are metabolized to their monosaccharide constituents (glucose, galactose and fructose) in the gut. These monosaccharides have roles in nutrition. Glucose metabolism and absorption receive more attention in relation to diabetes. Glucose, absorbed into the blood

to reduce the risk of developing diabetes.

66 Antioxidant-Antidiabetic Agents and Human Health

nuria/proteinuria [59].

Decreased amount of insulin in circulation decreases lipogenesis and increases lipolysis. Increased lipolysis releases fatty acids from adipose tissues. Fatty acids are also absorbed from the intestinal tract. The rapid release of fatty acids in the blood leads to hyperlipidaemia. The blood level of cholesterol increases, causing the development of atherosclerosis to occur at an earlier age than in non-diabetics and is more pronounced [61]. Elevated circulating levels of free fatty acids derived from adipocytes are the most likely link between insulin resistance and type 2 diabetes [60]. They contribute to insulin resistance by inhibiting glucose uptake, glycogen synthesis and glycolysis, and increasing hepatic glucose production. This leads to a decrease in intracellular concentration of glucose by a reduction in glucose-6-phosphate levels, implicating the glucose transport system as the rate-controlling step for free fatty acid-induced insulin resistance [62].

Free radicals and enhanced oxidative stress with reduced blood levels of anti-oxidants were implicated in the pathogenesis of diabetes and more importantly, in the development of diabetic complications [60, 63]. Free radicals are highly reactive molecules (charged superox‐ ide, hydroxyl radical and nitric oxide). The uncharged hydrogen peroxide species is capable of damaging cellular molecules, DNA, proteins and lipids. These produce altered cellular functions. Oxidative stress is a serious imbalance between the production of free radicals and antioxidant defences. This causes potential tissue damage [64]. Antioxidants play protective role against the effects of hyperglycaemia and free fatty acids *in vitro*. They neutralize free radicals effects in experimentally-induced diabetes in animal models [60] and reduce the severity of diabetic complications [63].
