Delve into the etiology and pathogenesis of Type 1 Diabetes Mellitus, including the autoimmune processes that lead to beta-cell destruction and insulin deficiency.
Understand the hallmark symptoms, diagnostic criteria, and the stages of T1DM, providing a clear picture of the disease progression ...
Natural History of Diabetes Mellitus Type 1
02 January 2021 18:00
Type 1 diabetes was an awful disease prior to 1921 when insulin was administered for the first
time. Treatment at that time prior to the availability of insulin was simply to avoid all intake of
carbohydrates containing foods. As effect children were starving, it was usually children who
presented it would starve to death.
Diabetes- a pancreatic islet disease:
Paul Langerhans - First identified the islets
Oskar Minkowski - Identified that removing the pancreas in dogs caused diabetes mellitus
Fredrick Banting- Brought in the idea of isolating the islets from the pancreas of the dog
James Collip and John Maccloud - Isolated insulin hormone from pancreatic materials
Lean and obese participants had very similar glucose levels in blood. But there is a large difference
in insulin levels between the lean and obese group.
Ove the course of the fed and fast states there is variability in insulin production between the lean
and the obese groups.
The early onset of DKA after withdrawal of insulin in people with type 1 diabetes:
• Increased glucose levels
• Increased glycerol levels
• Increased non-esterified fatty acids
• Increased beta hydroxybutyrate
Mechanism of diabetic ketoacidosis
Glucagon excess <-----Absolute insulin deficiency-----> Cortisol and Catecholamine excess
The hormone imbalance leads to glycogenolysis, gluconeogenesis, lipolysis and decreased glucose
oxidation. All these leads to the development of hyperglycaemia. Lipolysis leads to production on
non-esterified fatty acids and glycerol, which then contributes to gluconeogenesis.
Gluconeogenesis draws in oxaloacetate from the Krebs cycle. This is important because non-
esterified fatty acids cannot be oxidised via the Krebs cycle, so instead they're diverted into ketone
formation.
Non-esterified fatty acids -----> Acetyl CoA -------> beta-hydroxybutyrate and acetoacetate ------>
Metabolic acidosis
Ketone bodies are synthesised in vast excess and that results in metabolic acidosis. Alongside,
hyperglycaemia causes osmotic diuresis, which results in dehydration and also result of vomiting
due to the acidosis.
Diagnosing diabetic ketoacidosis:
• Ketonemia >3.0mmol/L or significant ketonuria (more than 2+ on standard urine sticks)
• Blood glucose >11.0mmol/L or known as diabetes mellitus
• Serum bicarbonate <15.0mmol/L and/ or venous pH<7.3
Diabetic ketoacidosis - epidemiology
23% of new type 1 diabetes in children presents as DKA (diabetic ketoacidosis).
In established type 1 diabetes, most common in adolescents (insulin omission)
Also precipitated by:
• Infection
• Surgery
• Trauma
• Insulin resistance -catamenial, pubertal
Diabetic ketoacidosis Page 1
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