T2DM

• What is T2DM?


  Chronic metabolic condition

  Characterised by inadequate insulin production from pancreatic beta cells -> insulin resistance -> elevation in blood glucose levels -> hyperglycaemia
• Pathophys - T2DM


  Repeated exposure to glucose & insulin -> body cells become resistant to effects of insulin -> more insulin is required to stimulate the cells to take up glucose -> less glucose uptake in muscle, liver & adipose tissue -> beta cells begin to fail -> cannot produced enough insulin to bring glucose to all cells -> hyperglycaemia -> glucose becomes lost in urine
• What are the RFs of T2DM?


  Older age

  Ethnicity (Black African or Caribbean & South Asian)

  FHx

  Obesity

  Sedentary lifestyle

  High carbohydrate diet
• What are the signs & symptoms of T2DM?


  Fatigue

  Polyuria

  Polydipsia

  Unintentional weight loss

  Opportunistic infections (e.g. oral thrush)

  Slow wound healing

  Glucose in urine

  Blurry vision

  Acanthosis nigricans (often associated with insulin resistance)
• What is pre-diabetes?


  A condition where blood sugar levels are higher than normal but not high enough for a diabetes diagnosis.

  HbA1c of 42-47 mmol/mol
• What are the DDx of T2DM?


  T1DM

  MODY (Maturity Onset Diabetes of the Young)

  Secondary Diabetes Mellitus
• What is the criteria for T2DM diagnosis?


  If symptomatic, one of the following results is sufficient for diagnosis:

  • Random blood glucose ≥ 11.1mmol/l
  • Fasting plasma glucose ≥ 7mmol/l
  • 2-hour glucose tolerance ≥ 11.1mmol/l
  • HbA1C ≥ 48mmol/mol (6.5%)

  If pt is asymptomatic, 2 results required on different days
• What is the management of T2DM?


  Education

  Low glycaemic index, high fibre diet

  Exercise

  Weight loss (if overweight)

  Antidiabetic drugs (metformin, SGLT2i, sulfonylurea, pioglitazone, DPP-4 inhibitor, insulin)

  Monitoring & managing complications
• What are the HbA1c targets in T2DM?


  48 mmol/mol in new T2DM

  53 mmol/mol in pts requiring more than 1 antidiabetic medication
• What are the possible complications of T2DM?


  Infections

  PAD

  Cerebrovascular disease

  Diabetic retinopathy

  Diabetic nephropathy

  Diabetic neuropathy

  Gastroparesis (slow emptying of the stomach)

  Sexual dysfunction

  Hyperosmolar hyperglycaemic state
• What does metformin do?


  CLASS: Biguanide

  MOA: Increases insulin sensitivity & decreases glucose production by the liver. Does not cause weight gain or hypoglycaemia

  SEs: GI symptoms (pain, nausea & diarrhoea), lactic acidosis
• What do SGLT-2 inhibitors do?


  Inhibits SGLT-2 protein (in proximal tubules of kidneys) -> more glucose is excreted in urine -> lowers HbA1c -> lowers BP, weight loss & improves HF

  Can cause hypoglycaemia when used with insulin or sulfonylureas

  Also reduced the risk of CVD
• What are the side effects of SGLT2i?


  Glycosuria

  Increased urine output & frequency

  Genital & urinary tract infections

  Weight loss

  DKA

  Lower-limb amputation

  Fournier's gangrene (rare but severe infection of the genitals or perineum)
• What do thiazolidinediones do?


  Increase insulin sensitivity & decreased liver production of glucose
• What are the side effects of pioglitazone (thiazolidinedione)?


  Weight gain

  HF

  Increased risk of bone fractures

  Small increase in risk of bladder cancer
• What do sulfonylureas do? What are there side effects?


  Stimulates insulin release from pancreas

  SEs

  • weight gain
  • hypoglycaemia
• What is hyperosmolar hyperglycaemic state (HHS)?


  Rare but potentially fatal complication of T2DM

  Characterised by hyperosmolarity (water loss -> very concentrated blood), hyperglycaemia & absence of ketones

  Presents: polyuria, polydipsia, weight loss, dehydration, tachycardia, hypotension & confusion

  Treatment: IV fluids & monitoring