Diabetes Mellitus: A Concise Review

Pathophysiology

Type 1 Diabetes Mellitus (T1DM) develops when the body’s own immune system attacks and destroys the insulin producing β-cells of the pancreas. As β-cell mass declines, insulin secretion decreases up until the insulin available is insufficient to maintain normal blood glucose levels (absolute insulin deficiency). In the absence of insulin, sugar is accumulated in the bloodstream instead of entering the cells. As a result, the body is unable to utilize this glucose for energy (Figure 1 and Figure 2). Once 80-90% of β-cells are destroyed, hyperglycemia initiates to develop and diabetes may be diagnosed (Harvard, 2018).

Figure 1.

Glucose mechanism of action in a healthy individual

Figure 2.

Glucose mechanism of action in type 1 diabetic patient

Type 2 Diabetes Mellitus (T2DM) is commonly associated with certain environmental factors, genetic elements, lifestyle choices and the dynamic between these varied aspects. It involves the dysfunction of insulin producing pancreatic β-cells, insulin hormone resistance in body cells or a combination of both. This condition initiates with resistance to insulin that gradually worsens over time. The resistance and the inadequate production of insulin by β-cells ultimately lead to β-cell failure. Once the β-cells fail, endogenous insulin can no longer be secreted. The inability of cells to utilize the hormone insulin, which inhibits the cell’s ability to absorb and utilize glucose in metabolic processes is known as insulin resistance. This is of primary matter in cells that are generally high in metabolic function such as: the liver, muscles and adipose tissues (Sun, 2014).

Majority of the type 2 diabetic patients, have abundant abdominal fat which can cause lipotoxicity. The abdominal fat is resistant to the antilipolytic effect of insulin thereby resulting in elevated levels of free fatty acids (FFAs). Raised free fatty acids exacerbates insulin resistance in the liver and muscle cells and thus increases the formation of glucose and impairs beta cell secretion. Excess fat tissues lead to enormous secretion of cytokines (adipokines and adipocytokines) associated with inflammation, endothelial dysfunction and thrombosis. Atherosclerosis due to insulin resistance is as a result of hypercoagulability, debilitated fibrinolysis and the combination of endothelial damage, oxidative stress and hyperglycemia. The pathophysiology of insulin dependent DM (type 1) and non-insulin dependent DM (type 2) is further portrayed in Figure 3 and Figure 4, respectively.