Diabetes Mellitus: Type 1 and 2 Classification

Study Notes

Definition: A metabolic disorder caused by an absolute or relative insulin deficiency.

Type I (Insulin Dependent Diabetes Mellitus) IDDM
- Caused by an absolute deficiency of insulin.
- Typically develops before the age of 40.
- Not associated with obesity.
- Treated with insulin and oral antidiabetic drugs if not controlled.

Insulin is a polypeptide hormone secreted from ß-cells of the pancreas.
Insulin secretion is stimulated by:
- High plasma concentrations of glucose, free fatty acid, and amino acids.
- Gastrointestinal hormones, such as secretin, gastrin, and cholecystokinin.
- Systemic hormones, such as glucagon and growth hormone.
- Certain drugs, such as sulphonylureas, alpha blockers, Beta 2 agonists, and muscarinic agonists.
Insulin secretion is inhibited by:
- Fasting and starvation.
- Certain drugs, such as alpha agonists, beta blockers, thiazide, diazoxide, anti-cholinergics, and Phenytoin.

Brain: Initiates hunger and hepatic glucose production, as well as lipoprotein production.
Liver: Responds to insulin by mediating peripheral muscle glucose synthesis, glycogen synthesis, and lipid accumulation, alongside inducing inflammation.
Adipose Tissue: Responds to insulin by mediating glucose metabolism, lipogenesis, glycogen synthesis, muscle mass, mitochondrial dysfunction, inflammation, and the switch from M2 to M1 macrophages.

Insulin release is triggered when high blood glucose enters beta cells through the Glut-2 glucose transporter.
This stimulates glycolysis, generating ATP, which blocks ATP-sensitive K+ channels, resulting in depolarization and stimulation of voltage-dependent Ca++ channels, leading to an influx of Ca++ and exocytosis of insulin.

Insulin is not effective orally due to digestion by proteolytic enzymes.
It is administered parenterally, usually subcutaneously (S.C.) or intravenously (I.V.) in emergency situations.
Insulin undergoes extensive hepatic metabolism, with 50% first-pass metabolism, primarily by the insulinase enzyme.

Insulin binds to specific membrane receptors consisting of alpha and beta subunits linked by disulphide bridges.
Alpha-subunits are extracellular, while beta-subunits are transmembrane and have tyrosine kinase activity.
Insulin binding to alpha-subunits produces conformational changes in beta-subunits, activating tyrosine kinase activity, phosphorylating intracellular proteins, and changing enzyme activity.

Insulin facilitates glucose uptake in adipose tissue and skeletal muscles.
It causes hypoglycemia by facilitating glucose entry, stimulating glycolysis, glucose utilization, glycogenesis, and inhibiting glycogenolysis and gluconeogenesis.
Insulin increases lipogenesis in the liver and decreases lipolysis, reducing plasma levels of free fatty acids.
It stimulates ketone body formation in the liver and has anabolic effects by increasing protein synthesis and inhibiting protein breakdown.
Insulin also increases the uptake of potassium, calcium, and phosphate by cells.