This document discusses disorders of glucose homeostasis, including diabetes mellitus and hypoglycemia. It covers the key fuels in the body, glucose and fat metabolism, hormones that regulate glucose levels, symptoms and types of diabetes, pathogenesis of diabetic ketoacidosis and hyperosmolar hyperglycemic state, diagnosis of diabetes and hypoglycemia, and potential causes of hypoglycemia.

1. Disorders of glucose homeostasis
Language of medicine 2013
Division of chemical pathology
David Haarburger

2. Fuels
Carbohydrates Fat
(Polysaccharides)
Proteins
(Triacylglycerides)
Fatty Acids
Monosaccharide Amino acids
Glycerol
Glucose Ketones
Glucose
Ketones Glucose

3. Glucose
• Major energy substrate
• Essential for some tissues
– Erythrocytes
– Neurons
• Can be oxidised to lactate or CO2
• Glucose concentration is tightly controlled
between 2.5 and 8.0 mmol/L
– Glycolysis
– Glycogenolysis
– Gluconeogenesis

4. Glucose and fat metabolism
glucose
glucose-6-phosphate
phosphoenolpyruvate
pyruvate lactate
fatty acids
acetyl-CoA
+ ketones
oxaloacetate citric acid
ATP

5. Metabolism during starvation
triacylglycerides
free fatty acids
amino acids
glucose ketones
glycogen

6. Hormones involved in glucose control
Glucose Glucose
Counter-regulatory hormones Regulatory hormones
• Glucagon • Insulin
– Glycogenolysis
– Gluconeogenesis
– Glycogen synthesis
• Adrenaline – Protein synthesis
– Lipolysis – Fat synthesis
– Glycogenolysis
• Growth hormone – Allows glucose entry into cells
– Lipolysis
– Glycogenolysis
• Cortisol
– Proteolysis
– Gluconeogenesis

7. Diabetes mellitus
• Absolute or relative lack of – polyuria
insulin – polydipsia
• Types – polyphagia
– Type I • Complications
• IDDM, Juvenile-onset – Acute
• Autoimmune • DKA
– Type II • HONK
• NIDDM, Adult-onset – Chronic
• Insulin resistance • Macrovascular
– Gestational DM – Coronary heart disease
– Peripheral vascular disease
– Secondary to exocrine disease – Stroke
– Endocrinopathies • Microvascular
• Cushing syndrome, Acromegaly – Retinopathy
– Nephropathy
• Symptoms – Neuropathy
– loss of weight

8. Pathogenesis of DKA
No insulin
↑gluconeogenesis ↑glycogenolysis ↑lipolysis
hyperglycaemia
↑ketones acidosis
glycosuria
loss of water and
osmotic diuresis vomiting
electrolytes
Diagnosis
↓pH
dehydration ↑Glucose
↑Ketones

9. Pathogenesis of HONK state
Low insulin
Diagnosis
↑Glucose
↑gluconeogenesis ↑glycogenolysis ↑Osmolarity
↓pH (no ketones)
glycosuria hyperglycaemia
osmotic diuresis
↑↑ plasma
osmolarity
increased
loss of water and
blood
electrolytes
viscosity
cerebral
dehydration thrombosis dehydration

10. Diagnosis of diabetes
• Fasting plasma glucose level ≥ 7.0 mmol/l
– Normal < 6.1 mmol/l
• Glucose tolerance test
– Plasma glucose ≥ 11.1 mmol/l two hours after a
75 g oral glucose load
• Symptoms of hyperglycaemia and random
plasma glucose ≥ 11.1 mmol/l
• Glycated haemoglobin (Hb A1C) ≥ 6.5%

11. Hypoglycaemia
• Blood glucose < 2.2 – Drug Induced
mmol/L • Insulin
• Alcohol
• Symptoms
– Neoplasms
– Neuroglycopaenia • Insulinoma
• Tiredness
• Insulin-like growth factor
• Confusion secreting tumours
• Convulsions – Liver disease
• Coma
– Endocrine disease
– Sympathetic stimulation • Addison’s disease
• Palpations
• Growth hormone
• Tachycardia deficiency
• Sweating – Sepsis
• Causes