Type 2 Diabetes

• Type 2 diabetes


  A condition where a combination of insulin resistance and reduced insulin production cause persistently high blood sugar levels
• Simplified Pathophysiology of Type 2 diabetes

  Repeated exposure to glucose and insulin makes the cells in the body resistant to the effects of insulin. More and more insulin is required to stimulate the cells to take up and use glucose. Over time, the pancreas becomes fatigued and damaged by producing so much insulin, and the insulin output is reduced. A high carbohydrate diet combined with insulin resistance and reduced pancreatic function leads to chronic high blood glucose levels (hyperglycaemia)
• Complications of chronic hyperglycaemia

  • Microvascular
  • Macrovascular
  • Infectious
• Risk Factors for Type 2 diabetes

  • Non-modifiable: Older age, Ethnicity (Black African or Caribbean and South Asian), Family history
  • Modifiable: Obesity, Sedentary lifestyle, High carbohydrate (particularly sugar) diet
• Presenting features of diabetes

  • Tiredness
  • Polyuria and polydipsia (frequent urination and excessive thirst)
  • Unintentional weight loss
  • Opportunistic infections (e.g., oral thrush)
  • Slow wound healing
  • Glucose in urine (on a dipstick)
  • Acanthosis nigricans is characterised by the thickening and darkening of the skin (giving a “velvety” appearance), often at the neck, axilla and groin. It is often associated with insulin resistance
• TOM TIP: 'Consider type 2 diabetes in any patient fitting the risk factors above. It is easy to screen for diabetes with an HbA1c, and early treatment helps to prevent long-term complications. It is possible to reverse diabetes with the proper diet and lifestyle, especially at the pre-diabetes stage, so early detection is helpful'
• Diabetes screening


  1. Easy with an HbA1c test

  2. Early treatment helps prevent long-term complications
• Possible to reverse diabetes with proper diet and lifestyle, especially at the pre-diabetes stage
• Pre-diabetes is an indication that the patient is heading towards diabetes
• Pre-diabetes indicators


  • HbA1c of 42 – 47 mmol/mol
• HbA1c


  Blood test reflecting the average glucose level over the previous 2-3 months
• HbA1c of 48 mmol/mol or above indicates type 2 diabetes
• Diagnosis of diabetes


  HbA1c test repeated after 1 month to confirm diagnosis (unless symptoms or signs of complications)
• Management of type 2 diabetes

  • Structured education program
  • Low-glycaemic-index, high-fibre diet
  • Exercise
  • Weight loss (if overweight)
  • Antidiabetic drugs
  • Monitoring and managing complications
• Treatment targets for HbA1c

  • 48 mmol/mol for new type 2 diabetics
  • 53 mmol/mol for patients requiring more than one antidiabetic medication
• Measurement of HbA1c


  Every 3 to 6 months until under control and stable
• First-line medical management is metformin
• Medical management


  Add SGLT-2 inhibitor (e.g., dapagliflozin) if patient has existing cardiovascular disease or heart failure
• Second-line medical management is to add a sulfonylurea, pioglitazone, DPP-4 inhibitor, or SGLT-2 inhibitor
• Third-line options are triple therapy with metformin and two of the second-line drugs or insulin therapy
• If triple therapy fails and patient's BMI is above 35 kg/m2, consider switching to a GLP-1 mimetic (e.g., liraglutide)
• SGLT-2 inhibitors are increasingly recommended, especially for high-risk cardiovascular disease patients
• Metformin


  Increases insulin sensitivity, decreases glucose production by the liver, biguanide class, does not cause weight gain, does not cause hypoglycaemia
• Notable side effects of metformin include gastrointestinal symptoms, lactic acidosis, and modified-release options for gastrointestinal side effects
• SGLT-2 Inhibitors


  End with the suffix -gliflozin, block the action of the sodium-glucose co-transporter 2 protein in the kidneys, leading to glucose excretion in urine
• SGLT-2 Inhibitors


  • empagliflozin, canagliflozin, dapagliflozin, ertugliflozin
• Loss of glucose in the urine due to SGLT-2 inhibitors leads to lower HbA1c, reduced blood pressure, weight loss, and improved heart failure
• Reabsorption of glucose from the urine back into the blood

  SGLT-2 inhibitors block the action of a protein, causing more glucose to be excreted in the urine
• Loss of glucose in the urine

  Lowers the HbA1c, reduces the blood pressure, leads to weight loss, and improves heart failure
• SGLT-2 inhibitors


  Can cause hypoglycaemia when used with insulin or sulfonylureas
• SGLT-2 inhibitors


  Reduce the risk of cardiovascular disease
• Empagliflozin and dapagliflozin


  Are licensed for heart failure
• Dapagliflozin


  Is also licensed for chronic kidney disease
• Notable side effects of SGLT-2 inhibitors

  • Glycosuria (glucose in the urine)
  • Increased urine output and frequency
  • Genital and urinary tract infections (e.g., thrush)
  • Weight loss
  • Diabetic ketoacidosis
  • Lower-limb amputation may be more common in patients on canagliflozin (unclear if this applies to the others)
  • Fournier’s gangrene (rare but severe infection of the genitals or perineum)
• TOM TIP: 'Remember two side effects of SGLT-2 inhibitors. Firstly, an increased frequency of urinary tract infections and genital thrush due to lots of sugar passing through the urinary tract. Secondly, diabetic ketoacidosis. Patients starting SGLT-2 inhibitors are counselled about the features of DKA and when to seek emergency medical input'
• Pioglitazone is a thiazolidinedione
• Pioglitazone increases insulin sensitivity and decreases liver production of glucose
• Pioglitazone does not typically cause hypoglycaemia
• Notable side effects of pioglitazone

  • Weight gain
  • Heart failure
  • Increased risk of bone fractures
  • A small increase in the risk of bladder cancer
• Gliclazide is the most common sulfonylurea