diabetes

• Insulin


  A polypeptide synthesised in the beta cells of islets of langerhams of the pancreas
• Insulin


  • Involved in the storage of nutrients in the form of glycogen in liver and muscle and triglycerides in fat
• Diabetes mellitus


  Disorder where the circulating levels of the hormone insulin is insufficient to maintain blood glucose concentration within the normal range
• Normal blood glucose range: 4-5.6mmol/L
• Type 1 Diabetes Mellitus (T1DM)

  Lack of insulin as a consequence of the autoimmune destruction of insulin producing beta cells. The presence of islet cells antibodies in serum can predict future development of diabetes
• Clinical features of T1DM


  • Thirst, polyuria, weight loss, lethargy, ketoacidosis
• Polyuria


  Result of osmotic diuresis when blood glucose levels exceed the renal tubular reabsorptive capacity
• Thirst


  Stimulated by fluid and electrolyte losses
• Weight loss


  Caused by fluid depletion and breakdown of muscle and fat as a result of insulin deficiency
• Diagnostic criteria for T1DM: fasting plasma glucose more than 7 mmol/L or random plasma glucose more than 11.1 mmol/L
• One abnormal laboratory value is diagnostic in symptomatic individuals; two values are needed in asymptomatic people
• Glucose tolerance test


  After an overnight fast, 75g of glucose is taken in 250-350ml of water. Blood samples are taken before and 2hours after the glucose has been given
• Insulin uses


  • First line treatment for T1DM
  • T2DM when other methods have failed
  • Temporarily in the presence of intercurrent illness or peri-operatively
  • In pregnant women with T2DM when diet or oral meds fail
• Types of insulin


  • Short acting: soluble insulin, rapid acting insulin analogues
  • Intermediate: isophane insulin, insulin glargine, insulin degludec, insulin detemir
• Soluble insulin


  Works within 30-60 mins and lasts for 8 hrs with a peak between 1-4 hrs, iv works in 5 min and disappears after 30mins - only to be used in emergencies
• Rapid acting insulin analogues

  Onset of action 15 mins, duration 2-5hrs
• Isophane insulin


  Onset of action 1-2hrs, maximal effect 3-11hrs, duration 11-24 hours
• Insulin glargine, insulin degludec, insulin detemir


  Human insulin analogues with a prolonged duration of action up to 36 hours, steady state in 2-4 days
• NICE (December 2002) has recommended that insulin glargine should be available as an option for patients with T1DM
• Insulin regimens


  • Multiple injection regimen: short-acting insulin or rapid-acting insulin analogue, before meals with long-acting insulin, once or twice daily (basal-bolus)
  • Short-acting insulin or rapid-acting insulin analogue mixed with intermediate-acting once or twice daily (before meals)
  • Intermediate-acting once or twice daily without short-acting insulin or rapid-acting insulin before meals
  • Continuous subcutaneous insulin infusion via pump
• Continuous subcutaneous insulin infusion via pump is recommended for adults and children over 12 years with type 1 diabetes who suffer from repeated hypoglycaemia, with multiple injection regimens OR whose glycaemic control remains inadequate despite optimum multiple-injection regimen
• Home blood glucose monitoring targets


  • Fasting blood glucose of 5-7 mmol/L on waking
  • Blood glucose of 4-7mmol/L before meals
  • Blood glucose of 5-9mmol/L at least 90 mins after eating
  • Blood glucose of at least 5mmol/L when driving
• Urine testing is a good measure for glycaemic control and usually for elderly
• Urine ketones are useful if the patient is unwell and ketonuria indicates diabetic ketoacidosis
• Microalbuminuria


  Albumin excretion rate intermediate between normality (<30mg/day) and macroalbuminaemia (>300mg/day). It is a marker of early (reversible) diabetic nephropathy and is thus used to screen for renal damage
• Glycosylated haemoglobin (HbA1c)


  Measures control over a period of 2-3 months. Ideal to aim for an HbA1c concentration of 48 mmol/mol (6.5%) or lower in patients with type 1 diabetes
• HbA1c should be measured every 3–6 months
• Driving advice: reading should be above 5mmol/l to drive, if below 4mmol/l then wait and treat until it reaches target. Leave 45 mins before you drive again. Bring snacks, don't delay meals, take breaks
• Type 2 Diabetes Mellitus (T2DM)

  There is resistance of peripheral tissues to the actions of insulin, so that insulin levels may be normal or even high. Hyperglycaemia can also be the result of reduced insulin secretion
• Diet for T2DM

  First approach is a well balanced diet whereby main nutrient load should be spread throughout the day to reduce swings in blood glucose
• Medication for T2DM should be prescribed only if the patient fails to respond adequately to at least 3 months of restriction of energy and carbohydrates intake and increased physical energy
• Biguanides (metformin)

  Decreases gluconeogenesis and increases peripheral utilisation of glucose by increasing sensitivity to insulin. First line for both obese and non obese patients as it doesn't increase appetite
• Sulphonylureas (gliclazide)

  Stimulates pancreatic insulin secretion by blocking potassium channels in pancreatic beta cells. Considered for patients NOT obese or metformin contra-indicated/not tolerated
• DPP4 inhibitors (linagliptin)

  Delay inactivation of GLP-1 which increases insulin secretion from the pancreas after meals and reduces glucagon release
• SGLT-2 inhibitors (dapagliflozin)

  Inhibit renal reabsorption of glucose/promote renal excretion of glucose by reversibly inhibiting the sodium-glucose co-transporter 2 in the renal proximal convoluted tubules
• Thiazolidinediones (pioglitazone)

  Potentiate insulin action in muscle/fat/liver = increased peripheral glucose uptake and utilisation and reducing hepatic gluconeogenesis
• Alpha-glucosidase inhibitors (acarbose)

  Inhibit intestinal glucosidase, thus impairing carbohydrates digestion and slowing glucose absorption
• Lifozin

  10mg daily
• Adverse effects of lifozin


  • Increases UTI especially in women
  • Euglycaemic DKA
• Advantages of lifozin

  • Weight loss
  • Can improve BP