Diabetes Mellitus Overview

Study Notes

Diabetes mellitus is derived from the Greek word "diabetes" (siphon) and the Latin word "mellitus" (sweet). The name reflects excess urination and the sweet taste of urine due to high sugar (glucose) levels.
The most noticeable sign of diabetes is excessive urination. Water passes through a person's body with this condition, like it's being siphoned out.

Ancient Chinese and Japanese physicians observed that dogs were drawn to the urine of people with diabetes due to its sweetness. Analysis revealed high glucose levels.
In 1679, physician Thomas Willis tasted the urine of a diabetic and described it as "wonderfully sweet" like honey, furthering the understanding of the condition.
The term "diabetes insipidus" describes a separate condition where the urine is tasteless, in contrast to the sweet urine of diabetes mellitus.

The concept of diabetes traces back to Apollonius of Memphis around 250-300 BC, with Ancient Greek, Indian, and Egyptian civilizations contributing to the recognition of the sweet nature of urine associated with the condition.
Mering and Minkowski (1889) identified the pancreas' role in the development of diabetes. Banting, Best, and Collip (1922) purified insulin from cow pancreases at the University of Toronto, leading to an effective treatment.

Diabetes is a group of metabolic disorders marked by elevated blood glucose (hyperglycemia) resulting from defects in insulin production or secretion, or decreased cellular response to insulin.

Fasting plasma glucose level ≥ 7.0 mmol/L (126 mg/dL)
Plasma glucose ≥ 11.1 mmol/L (200 mg/dL) after an oral glucose tolerance test (OGTT)
Symptoms of high blood sugar and a casual plasma glucose ≥ 11.1 mmol/L (200 mg/dL)
Glycated hemoglobin (HbA1c) ≥ 48 mmol/mol (≥ 6.5% DCCT)

The pancreas is a long, slender organ positioned behind the stomach.
The pancreas has an endocrine function, primarily through its islets of Langerhans, which secrete hormones.
The islets of Langerhans consist of differing cell types, important for the secretion of glucagon, insulin, somatostatin, and pancreatic polypeptide.

Insulin synthesis begins in the rough endoplasmic reticulum of beta cells within the islets of Langerhans.
It's initially produced as a preprohormone (preproinsulin), which is processed into proinsulin and subsequently insulin in the endoplasmic reticulum and Golgi apparatus.
Insulin is packaged in secretory vesicles then released when needed.

Glucose uptake:Insulin encourages glucose absorption by many cells. Essential for managing post-meal blood glucose levels.
Glycogenesis: Insulin boosts the liver and muscle's ability to store excess glucose as glycogen.
Breakdown inhibition: Insulin inhibits glycogenolysis (breakdown of glycogen) and gluconeogenesis (glucose production in the liver). This helps maintain blood glucose levels.
Action on fatty acids & proteins: Insulin encourages fatty acid and protein synthesis. Insulin stops the breakdown of fatty acids and proteins.

Insulin secretion is influenced by blood glucose concentrations and meal timing.
There are peaks of insulin secretion at meal times; otherwise, basal insulin secretion persists over time.

Insulin enhances amino acid intake and protein synthesis, it also impacts fat metabolism which helps it store and manufacture fatty acids.

GLUT-4 is the insulin-dependent glucose transporter in muscle and adipose tissues. When insulin is present, GLUT-4 is moved to the cell membrane, enabling glucose transport into the cells.