E10

• Diabetes


  • A disease of high glucose (and blood pressure and lipids...)
  • Caused by insufficient action of the hormone insulin
  • Common
  • Associated with significant morbidity
  • Expensive to treat
  • Part of the Metabolic Syndrome
• Classification of diabetes


  • Type 1
  • Type 2
  • Monogenic diabetes- maturity-onset diabetes of the young (MODY), mitochondrial diabetes, neonatal diabetes
  • Other- gestational diabetes, drug-induced, endocrinopathies, secondary diabetes
• Type 1 diabetes


  • Insulin dependent
  • Childhood onset- under 40
  • Absolute insulin deficiency
  • Normal weight-slim
  • Family history less common
  • KETONES present
  • Insulin required to sustain life
• Cause of Type 1 diabetes

  Insulitis, autoimmune destruction of pancreatic beta cells
• Type 2 diabetes


  • Insulin resistance
  • Mature onset- over 40
  • Relative insulin deficiency
  • Genetic
  • Obesity associated
  • Insulin not required to sustain life
  • NO KETONE
• Cause of Type 2 diabetes


  Insulin resistance and pancreatic beta cell dysfunction
• Symptoms of diabetes


  • Weight loss
  • Extreme fatigue
  • Prone to infections
  • Osmotic symptoms (polyuria, thirst, blurred vision)
  • Slow healing wounds
  • Tingling pain or numbness in the hands/feet
• Diagnosing diabetes


  1. Measure urine glucose

  2. HbA1c (≥ 6.5% or 48 mmol/mol)
• HbA1c


  Glucose + haemoglobin
• What insulin does


  • When blood sugar rises, pancreas releases insulin into blood
  • It helps absorb glucose from blood, reducing blood sugar levels
  • Signals liver and muscle cells to store excess glucose as glycogen
  • Promotes storage of fatty acids and inhibits breakdown of fat stores
• Treating Type 1 diabetes


  1. Lifestyle

  2. Capillary blood glucose testing and insulin administration

  3. Insulin injections
• Treating Type 2 diabetes


  1. Lifestyle

  2. Reduce insulin resistance

  3. Increase insulin secretion

  4. Insulin injection

  5. Incretins

  6. Bariatric surgery
• Types of drugs to treat diabetes


  • To increase insulin secretion: Sulfonylureas, Meglitinides, Incretins
  • To decrease glucagon secretion (and for appetite control): Incretins, Amylin
  • Glucose uptake and utilisation: Thiazolidinediones, Metformin
• Metformin


  • Biguanide
  • 1st line in T2DM with increased BMI
  • Also used in polycystic ovary syndrome
  • Insulin sensitiser
  • Benefits: no hypoglycaemia, weight loss
  • Side effects: nausea + Gastrointestinal effects, lactic acidosis, caution in kidney disease
• Metformin action


  • Via activation of AMP kinase (among other effects)
  • Blocks gluconeogenesis by liver
  • Increases glucose uptake by muscle
  • AMPK in liver, skeletal muscle + brain
  • Also, lipid-lowering effects within liver
• Sulphonylureas


  • E.g. Gliclazide which is currently used
  • Stimulates insulin release from beta cells of islets
  • Benefits: quick onset of action, effective at lowering glucose in early T2DM
  • Side effects: hypoglycaemia, weight gain
  • Not effective in later T2DM where beta cell function cease
• Thiazolidinediones


  • E.g. glitazone
  • Ligands of peroxisome-proliferator-activated receptor gamma (PPAR g)
  • PPAR g belongs to subfamily of nuclear receptors that is involved in the regulation of adipogenesis and lipid uptake
  • Drug class with effects in multiple tissues
  • Lower insulin, glucose, free fatty acids
• SGLT2 inhibitors


  • Sodium-glucose cotransporter 2 inhibitors
  • Inhibit glucose reabsorption in the proximal renal tubule
  • Kidney filters 180g glucose /day, almost all reabsorbed
  • Phlorizin = naturally-occurring SGLT2 inhibitor
• Insulin-based therapies


  • Glucagon-Like Peptide 1 (GLP-1) (and Glucose dependant Insulinotropic Polypeptide (GIP))
  • Hormones released during food ingestion from L cells in ileum and colon and K cells in duodenum
  • Stimulate glucose-dependent insulin secretion – ie no hypoglycaemia
  • GLP-1 analogues or DPP4 - Inhibitors
• Complications of diabetes


  • Everything's EXPENSIVE
  • Macrovascular complications: Stroke, Heart disease, Peripheral vascular disease, Limb amputation
  • Microvasculature complications: Eyes- diabetic retinopathy, Kidneys- failure, Nerves, Diabetic neuropathy
• History of complications in Type 1 diabetes


  Usually develop within 15-20 years of diabetes onset
• History of complications in Type 2 diabetes


  • Many patients present with complications
  • Incidence of complications increases with increasing disease duration
  • Major problem as mean age of diabetes onset is falling
• Strategies to minimise risk of complications


  1. Education: self-monitoring, self-management, diet

  2. Aim for tight glycaemic control: HbA1c<48

  3. Blood pressure control – antihypertensives

  4. Lipid profile – statins

  5. Annual review: retinal screening, urinary albumin excretion, foot care