2014 L4 Glucose Disorders

Glycogenolysis

Breakdown of glycogen to glucose and other products

Glycogenesis

Conversion of glucose to glycogen (liver and muscle)

Insulin

Lowers blood glucose by promoting uptake and storage while inhibiting glycogenolysis, gluconeogenesis, lipolysis and genesis

Glucagon

Opposes insulin, raises glucose during fasting

Lipolysis

Breakdown of lipid in adipose tissue > triglycerides and glycerol, converted to glucose

Proteolysis

Breakdown of protein to amino acids, used to produce energy

Glycolysis

Conversion of glucose or other hexoses to lactate or pyruvate

Nocturnal Hypoglycaemia

• Nightmares

• Excessive sweating

• Waking up feeling irritated, fatigued, confused

Inborn Causes of Hypoglycaemia

Inborn metabolism errors e.g.

• Galactosaemia (galactokinase deficiency)

• Hereditary fructose intolerance (deficiency of fructose-1-phosphate aldolase)

• Glycogen storage diseases

Other Causes of Hypoglycaemia

• DM complication, from wrong insulin dose

• Insulinoma, pancreas tumour, secretes excess insulin

• Liver disease, unable to access stored glycogen > impaired hepatic glucose output

• Endocrine Disease

  • Adrenal failure, as glands produce hormones that help regulate blood > stress inc. and hormones signal for inc. in glucose for energy needed to respond to stress

  • Hormones help liver convert stored glycogen into blood glucose and support gluconeogenesis

Hyperglycaemia Symptoms

• Polyuria

• Polydipsia

• Polyphagia

T1 DM Hypo vs Hyper

Hypo (most common)

• exogenous insulin e.g. overdosing, skipping meals, inc physical activity

• during sleep or after alcohol

• more common than in T2

Hyper

• doses are missed/insufficient

• illness, infection or stress

T2 DM Hyper vs Hypo

Hypo

• less common, but can occur w sulfonylurea medications or insulin

• delayed meals, exercise or alcohol

Hyper (most common)

• insulin resistance and β-cell dysfunction

• chronic high sugar

Acute Metabolic Disturbances

• Diabetic ketoacidosis (DKA) - lack of insulin, high blood glucose, ketone buildup

• Hyperosmolar non-ketoic hyperglycaemia (HNKH) - severe hyperglycaemia without ketones, often in T2

DM Chronic Complications

• Nephropathy, kidney damage

• Retinopathy, blindness

• Neuropathy, nerve damage in extremeties

• Athersclerosis, arteries hardening, ↑ stroke and coronary artery disease

T1 DM

Autoimmune, antibodies react w β cells of islets of Langerhans in pancreas. Can be triggered by viruses.

T2 DM

• Obesity

• Insulin resistance and β cell dysfunction

• Could be due to abnormal insulin, lack of receptors, defective receptors, defective secondary messenger systems to glucose transporters

T1 Pathogenesis

β cell autoimmunity markers in serum before onset of hyperglycaemia

• Islet cytoplasmic antibodies, target islet cells and induce immune response

• Insulin autoantibodies, directed against protein

• Glutamic acid decarboxylase antibodies

• Tyrosine phosphatase antibodies

Genetics

• May be inherited

• MHC on C6 is implicated

• Human Leukocyte Antigens

• Viral infections e.g. coxsackie B

T1DM Staging