Endocrine Flashcards
Diabetes Mellitus
Disease in which the body’s ability to produce or respond to insulin is impaired, resulting in hyperglycaemia -> micro and macrovascular complications
Epidemiology of Type I DM
- Younger onset (<30)
- More common in northern european ancestry
- Patients usually lean
- 10% of DM
Epidemiology of Type II DM
- Older onset (>30)
- More common in African/Asians
- Patients usually overweight
- 90% of DM
Risk factors of Type II DM
- Obesity
- Increasing age
- Family history
- HTN
- Hyperlipidaemia
- Alcohol excess
- Sedentary lifestyle
- Smoking
Pathophysiology of Type I DM
- Type IV hypersensitivity/cell mediated immune reaction -> T cell against antigen on beta cells
- Beta cells destroyed
- HLA DR3/4 gene mutation
Pathophysiology of Type II DM
- Insulin resistance
- B cells hyperplasia + hypertrophy until exhaustion -> hypoplasia + hypotrophy
- B cells unable to produce enough insulin to overcome insulin resistance
Signs and symptoms of Type I DM
- Polyphagia (weight loss from lipolysis and muscle breakdown -> hunger)
- Glycosuria (kidneys not able to reabsorb all glucose)
- Polyuria (water follows glucose in urine down water conc. gradient)
- Polydipsia (dehydration from polyuria -> thirst)
- Ketoacidosis (fruity breath)
Signs and symptoms of Type II DM
- Similar to Type I but longer period
- Fatigue + blurred vision
- Neuropathy
- Raised BP
- Elevated cholesterol
Investigations for DM
- Fasting plasma glucose (>7mmol/L) or random plasma glucose (>11.1mmol/L)
- HbA1c >6.5%/48mmol/mol (not used in pregnancy, children, haemolytic disease, type I, pancreatic surgery)
- Oral GTT 2hr >11.1mmol/mol
- C peptide reduces in type I, persists in type II
Management of Type I DM
Glycaemic control:
- Diet (low sugar, fat, high starch)
- Insulin (twice daily with meals) - DAFNE (dose adjustment for normal eating)
- Exercise encouraged
Management of Type II DM
- Lifestyle changes + regular HbA1c
- Monotherapy metformin
- Dual therapy metformin + DPP-4i, pioglitazone, SU, SGLT-2i
- Triple therapy
- Insulin
Secondary prevention Type II DM
- Eye screening
- Foot screening
- Kidney tests
- BP checks
- Reduce CV risks using statins and ACE-i
Metformin mechanism of action
- Sensitises GLUT4 receptors + helps lose weight
- SE: nausea, diarrhoea, anorexia
- Don’t give if eGFR < 36ml/min
Pioglitazone mechanism of action
- Increases insulin sensitivity
- SE: hypoglycaemia, fractures, fluid retention
- CI: CCF, osteoporosis, weight gain or oedema whilst on the drug
DPP-4i mechanism of action
- Inhibits DPP-4 (enzyme that destroys incretins)
- Incretins stimulate decrease in blood glucose levels
Sulphonylurea (SU) mechanism of action
- Increases insulin secretion
- SE: hypoglycaemia, weight gain
SGLT-2i mechanism of action
- Inhibits selective sodium-glucose cotransporter 2
- Reduced glucose reabsorption in the kidneys
- SE: yeast infection, UTI
Complications of Type II DM
Microvascular:
- Diabetic nephropathy
- Diabetic neuropathy
- Diabetic retinopathy (bloodshot eyes and aneurysms)
Macrovascular:
- Arterial disease (stroke, MI, limb ischaemia)
Other:
- Staph. skin infections
- Erectile dysfunction
- Hyperosmolar hyperglycaemic state (HHS)
Explain pathophysiology of diabetic ketoacidosis (DKA)
- Increased lipolysis -> ketogenesis in the liver creates acetoacetate and beta-hydroxybutyrate
- Decrease in blood pH causing renal hypoperfusion due to osmotic diuresis -> coma and circulatory failure
Symptoms of DKA
- Develops over days
- Polyuria + polydipsia
- Nausea + vomiting
- Weight loss
- Weakness
- Abdominal pain
- Drowsiness and confusion
Signs of DKA
- Hyperventilation (Kussmaul breath - deep + laboured)
- Dehydration
- Hypotension
- Tachycardia
- Coma
Management of DKA
- Rehydration (IV fluids)
- Insulin
- Replacement of electrolytes (K+)
- Treat underlying cause
Other types of DM
- Maturity-onset diabetes of the young (MODY)
- Diseases of the endocrine pancreas
- Endocrine causes (acromegaly, Cushing’s)
- Drug-induced
Maturity-onset diabetes of the young (MODY)
Refers to any of several hereditary forms of DM caused by single mutation in an autosomal dominant gene disrupting insulin production (alters beta cell function)
MODY 2
- Glucokinase gene mutation
- GCK = glucose-sensor of beta cells -> controls insulin release
- Higher set point
Patients that might be MODY
- Parent affected with diabetes
- Absence of islet autoantibodies
- Evidence of non-insulin dependence (good control on low dose insulin, no ketosis, measureable C-peptide)
- Sensitive to sulphonylurea
Pathophysiology of permanent neonatal diabetes
- Usually rising ATP causes channel closure, but mutation prevents this so beta cells unable to secrete insulin
- Tx = sulphonylurea - blocks channel
Signs of permanent neonatal diabetes
- Small babies
- Epilepsy
- Muscle weakness
Maternally inherited diabetes and deafness (MIDD)
- Mutation in mitochondrial DNA
- Loss of beta cell mass
- Similar presentation to type II
- Wide phenotype
DM causing diseases of the exocrine pancreas
- Hereditary haemochromatosis
- Pancreatic neoplasia
- Cystic fibrosis
Features of hereditary haemochromatosis
- Autosomal recessive - triad of cirrhosis, diabetes and bronzed hyperpigmentation
- Excess iron deposited in liver, pancreas, pituitary, heart and parathyroid
- Most need insulin
Features of pancreatic neoplasia
- Common cause of cancer death
- Require subcutaneous insulin
- Prone to hypoglycaemia due to loss of glucagon funciton
