TYPE 2 DIABETES
Diabetes mellitus (DM) is a chronic disease characterised by persistent hyperglycaemia (raised blood sugar levels), resulting from defective insulin secretion, resistance to insulin, or both (1). Both are required to be present before being diagnosed with type 2 DM (T2DM) (2). Yet, while insulin resistance is entirely evident from the pre-diabetic stage, defective insulin secretion develops over time, aligned with a gradual decline in both beta cell (insulin secreting cell) function. Insulin is a hormone that signals the uptake of glucose into the body’s cells and inhibits glucose production from the liver, thus plays a key role in the regulation of blood glucose levels (3).
Hyperglycaemia if left untreated, will lead to the long-term damage of numerous bodily systems, in particular the nerves and blood vessels, resulting in the development of potentially serious health implications, most notably microvascular (retinopathy, nephropathy, and neuropathy) and macrovascular complications leading to a 2-fold to a 4-fold increased risk of cardiovascular diseases (4).
Type 2 Diabetes Mellitus
Type 2 diabetes is the most common type of diabetes, accounting for up to around 90% of all cases (5). T2DM largely results from the interaction among genetic, environmental, and behavioural risk factors (6). Many who develop T2DM are genetically predisposed, however T2DM is largely related to obesity or excess body fat, mainly distributed in the mid-section (2). T2DM is most common in adults (> 45 years), however, is now more frequently being seen in young adults, adolescents, and even children, which can be attributed to rising levels of obesity, physical inactivity, and energy-dense diets (7).
The primary pathophysiological factor of T2DM is insulin resistance, and essentially this is when the body tissues, primarily muscle and liver, have an insensitivity to insulin, in other words the ability for insulin to stimulate uptake of glucose into cells is impaired (8). However, initially, there is an increase in insulin production to compensate in order to maintain near normal blood glucose levels, but after a while, in the presence of defective beta cell function, insulin production begins to decline and hyperglycaemia is the end result (9).
If not treated, blood glucose levels remain chronically elevated. However, T2DM often presents with no symptoms initially, thus as a result can go undiagnosed for a number of years following onset, and by then complications have generally entered into the frame (4). However, like type 1 DM, the most common symptoms include increased thirst, frequent urination, lethargy, delayed wound healing, and sometimes blurred vision (10).
Prevention and Treatment
Since T2DM is strongly associated with overweight or obesity and insulin resistance, weight loss and maintaining a normal body weight is the primary target of its clinical management (11). Reduction in body weight is also associated with improvements in glycaemia, blood pressure, and lipid profile and hence can delay or prevent complications, especially incidence of cardiovascular events (12).
Simple lifestyle measures including diet modification (calorie restriction) to reduce energy intake, and regular exercise (at least 30 minutes, moderate-intensity five days per week) to increase energy expenditure, have been shown to be effective in the prevention or delayed onset of T2DM (13, 14). In people at an increased risk of developing T2DM, prevention of the disease through lifestyle modification isn’t a given, however can help delay the onset of diabetes for several years (15).
Type 2 diabetes is traditionally treated in a stepwise manner. Initial therapy is usually diet and increased exercise to promote weight loss (16, 17, 18). This weight reduction may improve insulin sensitivity, and in turn result in better regulation of blood glucose (19). However, for the majority, lifestyle measures generally fail to completely control glycaemia and, therefore, pharmacological treatment is instigated (20).
Initial therapy is with a single oral drug, usually Metformin (inhibits glucose production in the liver), and Sulfonylureas are generally the second-line therapy in T2DM patients, however, can be used in place of metformin if the patient is not overweight, or cannot tolerate metformin (21). Monotherapy often fails over a period of time and a combination of two or more oral therapies is used (22). Eventually, failure of all oral combination therapy may occur when β-cell failure has progressed to such a degree that additional, exogenous insulin is then required (21).
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