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Lom disordersofglucosehomeostasis2013

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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.

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Disorders of glucose homeostasis Language of medicine 2013 Division of chemical pathology David Haarburger
Fuels Carbohydrates Fat (Polysaccharides) Proteins (Triacylglycerides) Fatty Acids Monosaccharide Amino acids Glycerol Glucose Ketones Glucose Ketones Glucose
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
Glucose and fat metabolism glucose glucose-6-phosphate phosphoenolpyruvate pyruvate lactate fatty acids acetyl-CoA + ketones oxaloacetate citric acid ATP
Metabolism during starvation triacylglycerides free fatty acids amino acids glucose ketones glycogen
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
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
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
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
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%
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

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Lom disordersofglucosehomeostasis2013

  • 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