*1.2.4 Endocrine system*

Changes occur in the endocrine system across the adrenal and thyroid glands, and also across the metabolic processes of the body. There is a change in how the

body metabolises glucose, protein and lipids. More details will be shed specifically on glucose metabolism further down in the chapter.

#### **1.3 Pathophysiology of diabetes**

Diabetes Mellitus develops majorly as a result of either defective insulin secretion from the beta cells of the pancreas or a defect in the insulin-sensitive cells which reduces the body's response to the available insulin [1]. A dysfunction in any of these two processes leads to abnormally high glucose levels.

#### *1.3.1 Glucose regulation in a healthy adult*

The human body utilises glucose as an immediate source of energy. The optimal level of glucose for proper body functioning is usually about 70–100 mg/dL [13]. Any value below or above this range constitutes a problem. Although the body can utilise other fuels, like protein and fat, as a source of energy, the breakdown of these alternative fuels creates ketoacids which makes the body acidic. This can lead to metabolic acidosis—which is a non-optimal state [14].

Regulation of glucose in the blood is largely carried out by the endocrine hormones in the pancreas via a process of continuous negative feedback loop. The main hormones involved in this process are insulin, glucagon, somatostatin and amylin. Insulin, formed in the beta cells of the pancreas, is the main hormone in this process and it lowers blood glucose levels. Conversely, Glucagon increases blood glucose levels. Somatostatin, produced by the pancreas's delta cells, helps balance insulin and glucagon levels, while the Delta cells of the pancreas help to balance the levels of insulin and glucagon. Amylin is the hormone that induces the feeling of fullness following a meal, thus preventing overeating.

For glucose to be utilised by the body, it is transported at a cellular level through the body tissues. This transportation is regulated by insulin which aids the diffusion rate of glucose into cells. After glucose enters the cell, it is converted to glucose-6-phosphate which can either be used immediately or be stored as glycogen.

#### *1.3.2 Glucose regulation during pregnancy*

As earlier explained, during a healthy pregnancy, a woman's body undergoes various physiological changes to meet the demands of the growing foetus in her womb. The adaptive change that is important for glucose metabolism occurs in the metabolic systems. During this period the insulin sensitivity of the woman's body varies to meet the requirements of pregnancy. In the early phase of gestation, insulin sensitivity is increased thus promoting the uptake of glucose into storage for the later part of pregnancy. As gestation progresses, there is a surge of several hormones including placental hormones, oestrogen, cortisol, placental growth hormone, placental lactogen, progesterone and leptin. This surge leads to a state of insulin resistance which elevates blood glucose levels. This insulin-resistant state leads to the endogenous production of glucose via the breakdown of protein and fats, further increasing the level of blood glucose. The glucose is transported to the foetus via the placenta to aid growth in-utero.

Some evidence shows that the maternal body compensates for this state of resistance through hypertrophy and hyperplasia of pancreatic beta-cells to produce more insulin. Placental hormones are important in this process as the maternal state of insulin sensitivity is reversed after a few days following the foetus and placenta delivery. Gestational Diabetes often occurs when there is an imbalance in this process.
