Diabetes Mellitus

–Pratyay Islam, Calcutta Medical College

Diabetes mellitus is one of the most commonly seen metabolic disorders observed in humans. The underlying cause for this type of diabetes is defective action or secretion of the endocrine hormone insulin, which leads to a rise in blood glucose levels. It is mainly of two types:

1) Type 1 or Insulin Dependent Diabetes Mellitus

2) Type 2 or Non-Insulin Dependent Diabetes Mellitus

Type 1 Diabetes Mellitus or IDDM:

IDDM is mostly observed in children or teenagers and therefore earlier it was also known as juvenile diabetes. It is caused due to the development of auto-immunity against the beta-cells of the pancreas. The beta-cells are concerned with the production and secretion of insulin and their selective destruction occurs in type 1 diabetes, leading to insulin deficiency. The other types of cells present in the pancreas remain unharmed and therefore hormones like glucagon, pancreatic polypeptide, etc don’t show any change in their secretion or synthesis.

Normally, insulin inhibits the secretion of glucagon hormone from alpha-cells of the pancreas. This glucagon is responsible for the conversion of glycogen to glucose. 

In IDDM as there is no production and secretion of insulin, the amount of glucose and ketone body production increases greatly in the liver and the rate of production exceeds the rate of utilization, which results in the accumulation of these substances in our blood. This rise in solutes in blood exerts immense pressure over the kidney functions which reduces its functionality and efficiency.

Clinical Symptoms of IDDM:

• Osmotic Diuresis: The patients suffering from IDDM show osmotic diuresis. This is because the blood glucose level is elevated and it surpasses the renal threshold and therefore complete reabsorption of glucose in the proximal convoluted tubules of nephron does not take place. Further glucose is highly osmotically active which therefore results in loss of water along with the glucose.

• Polydipsia: Due to osmotic diuresis, a large amount of water loss from the body occurs and this stimulates thirst, resulting in polydipsia.

• Diabetic Ketoacidosis or DKA: This is only seen in Type 1 diabetes mellitus. Fatty acids breakdown in the liver results in the formation of ketone bodies, which include acetoacetate, beta-hydroxybutyrate, and acetone. These ketoacids have a pH<4 and therefore are moderately acidic. This results in metabolic acidosis, which leads to an increase in the anion gap. In response to this acidosis, the rate and depth of respiration increase, this type of breathing is known as Kussmaul breathing. 

Type 2 Diabetes Mellitus or NIDDM:

Type 2 diabetes is more common in adults and older persons usually around the age of 40 years. In this type of diabetes, secretion of the insulin hormone and the effects on insulin hormone on glucose metabolism both are defective. Even though the beta-cells are present they do not show appropriate feedback in response to a rise in blood glucose level by increasing insulin production. Further the tissues of the liver, muscles, etc show resistance towards insulin hormone and therefore these cells do not take up glucose present in the blood for active metabolism. In type 2 diabetes mellitus the secondary messenger is affected. The level of insulin is sufficient and the insulin receptors are also present but the signal generated by the hormone-receptor complex is defective and therefore insulin resistance is seen. The GLUT4, a type of glucose transporter shows a defect in type 2 diabetes mellitus.

It is important to understand that DKA or diabetic ketoacidosis is not seen in NIDDM as the circulating levels of insulin are sufficient and active enough.

Clinical Symptoms of IDDM:

• Hypertension: Increase in the systolic and diastolic blood pressure.

• Obesity

• Specific Dyslipidemia: Increased amounts of TAGs or triacylglycerol is seen, along with the depression of high-density lipoproteins.

• Metabolic Syndrome: Insulin resistance and metabolic abnormalities are observed even before the onset of type 2 diabetes mellitus, all these symptoms are together referred to as the metabolic syndrome.

Sources:

1. Medical Physiology Third Edition, Boron and Boulpaep
2. Leninger Principles of Biochemistry Sixth Edition, Nelson and Cox
3. CRISP Physiology, S Krishna Kumar