Physiology of diabetes and ketoacidosis !

Mechanism
Exam priority: high

In diabetes insulin is missing or does not work well: glucose stays in the blood and, if insulin is gone, the body makes acids (ketones).

Updated 2026-11-01

Also called: Diabetes mellitus, Diabetic ketoacidosis

See it in 3D: Pancreas

What it is

Diabetes is chronic hyperglycemia from lack of insulin (type 1) or insulin resistance with progressive β-cell failure (type 2). With low insulin and high glucagon the body behaves as in extreme fasting while glucose is plentiful. When insulin is almost absent, unchecked lipolysis floods the liver with fatty acids and ketoacidosis follows.

How it works, step by step

Without insulin, muscle and fat take up no glucose and the liver keeps making it (unopposed glucagon): hyperglycemia.
Filtered glucose exceeds the proximal tubule's transport maximum; it drags water and sodium: osmotic diuresis and dehydration.
Hormone-sensitive lipase, freed from insulin's brake, sends free fatty acids to the liver.
Glucagon lowers malonyl-CoA: carnitine palmitoyltransferase I is released and fatty acids enter the mitochondria.
β-oxidation makes more acetyl-CoA than the Krebs cycle can use: acetoacetate and β-hydroxybutyrate form.
Keto-acids consume bicarbonate: high anion gap metabolic acidosis; deep breathing (Kussmaul) compensates.
Acidosis and lack of insulin shift potassium out of cells; diuresis loses it in urine: total potassium depletion.

Equations

Anion gapAG = Na⁺ − (Cl⁻ + HCO₃⁻)

AG: anion gap, normal ≈8–12 mEq/L

In ketoacidosis it rises because of unmeasured keto-acids.

Effective plasma osmolalityOsm_eff = 2 × Na⁺ + glucose/18

Na⁺: mEq/L
glucose: mg/dL

Above ≈320 mOsm/kg consciousness becomes impaired (hyperosmolar state).

Glucose-corrected sodiumNa_corr = Na⁺ + 1.6 × (glucose − 100)/100

High glucose pulls water out of cells and dilutes sodium; the correction shows the true sodium.

Type 1 versus type 2 diabetes

Feature	Type 1	Type 2
Mechanism	Autoimmune β-cell destruction	Insulin resistance + progressive β-cell failure
Insulin and C-peptide	Very low	Normal or high early, falling over the years
Typical onset	Childhood or youth, sometimes with ketoacidosis	Adulthood, insidious, linked to obesity
Typical acute complication	Ketoacidosis	Hyperosmolar hyperglycemic state
Inheritance	HLA DR3/DR4; low twin concordance	Polygenic; high twin concordance

Clinical notes

Ketoacidosis: polyuria, vomiting, abdominal pain, fruity breath, Kussmaul breathing and dehydration; typical triggers are infection and missed insulin.
Insulin resistance is the core of metabolic syndrome (central obesity, hypertension, high triglycerides, low HDL).
Metformin lowers hepatic glucose output; it does not stimulate insulin, so on its own it rarely causes hypoglycemia.

Test yourself

Think of the answer, then tap the question to see it.

Why does a patient in ketoacidosis have normal or high plasma potassium when body potassium is low?

Lack of insulin and acidosis shift potassium out of cells while osmotic diuresis loses it in urine. Once insulin is given, potassium moves back into cells and plasma potassium falls.

Why is ketoacidosis uncommon in type 2 diabetes?

Some insulin usually remains, enough to brake lipolysis and hepatic ketogenesis though not to control glucose; so the hyperosmolar state dominates instead.

What role does glucagon play in ketone body formation?

It lowers malonyl-CoA and releases carnitine palmitoyltransferase I; fatty acids enter the mitochondria and are oxidized to ketones. Without insulin to brake it, the process runs away.

Why does a person with uncontrolled diabetes urinate a lot and feel thirsty?

Filtered glucose exceeds the tubular transport maximum; glucose in the lumen holds water (osmotic diuresis), and the water loss raises osmolality and triggers thirst.

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See it in 3D

The structures of Durgical's 3D anatomy where it happens.

Pancreas

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Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: Diabetic ketoacidosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2024); Type 1 Diabetes (StatPearls (NCBI Bookshelf), 2024); Type 2 Diabetes (StatPearls (NCBI Bookshelf), 2024); Hemoglobin A1C (HbA1c) Test: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 79). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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