Week 6

• T2DM


  Occurs due to cell receptor resistance to the action of insulin, resulting in a reduction in the efficacy of insulin on target organs
• T2DM


  Over time insulin resistance leads to a gradual loss of insulin-producing capacity from the pancreatic beta cells
• T2DM


  A combination of ineffective insulin and not enough insulin
• T2DM is a progressive disease in most cases
• Failure of beta cells to meet requirements in T2DM

  1. Initially normal glucose tolerance

  2. Ultimately clinically defined diabetes
• T2DM is often asymptomatic and only detected during routine investigation for other health problems
• At the time of diagnoses, beta cell function is often already reduced by 50%
• Up to 50% of people will require insulin replacement within 10 to 15 years of being diagnosed with T2DM
• Insulin resistance


  Leads to glucose intolerance which leads to T2DM and, if left untreated, complications
• Most people would not be screened for diabetes unless they had other cardiovascular risk factors (e.g. hypertension, obesity, or dyslipidaemia)
• Investigation of related complications may also uncover a diagnosis of diabetes
• Risk assessment for diabetes should begin for non-indigenous Australians from the age 40 years, and for indigenous Australians from age 18
• Specific treatment goals in T2DM

  • Relieve the symptoms associated with hyperglycaemia
  • Reduce the immediate hyperglycaemia-associated risks
  • Avoid complications of severe hyperglycaemia
  • Reduce the risk of, and prevent or delay long-term complications
  • Reduce overall morbidity and mortality
  • Ensure the risk-benefit of therapy is favourable by avoiding any treatment complications
• Signs and symptoms of T2DM are usually less acute and less severe than T1DM, providing less motivation for individuals to adhere to treatment plans
• Complications of diabetes, alongside other comorbidities of advancing age and poor lifestyle choices, are often already present at the time of diagnosis
• First-line non-pharmacological strategies (diet, exercise) are often harder to implement later in life
• Monotherapy (i.e. using one medication only) is often insufficient to achieve good BGL control and effectively reduce the risk of complications
• Polypharmacy (i.e. at least two medications) is needed in most people. Often three BG-lowering agents are prescribed to achieve and maintain optimal BG control
• Optimal BG control


  • Attainment of BG levels within therapeutic targets, including HbA1c levels
  • Reduction in hyperglycaemia symptoms without hypoglycaemia (i.e. euglycemia)
• HbA1c levels should be monitored every 3 to 6 months in T2DM
• HbA1c target


  Equal to or less than 7% in most patients. This is a target not a mandate
• In practise the target HbA1c needs to be balanced against the risk of hypoglycaemia, the likelihood of treatment adherence, and the current lack of robust evidence that HbA1c ≤7% improves overall patient outcomes
• Achieving an HbA1c in the range of 7% to 8% may be more reasonable. Aiming for ≤7% in patients if it is feasible and clinically appropriate
• Patients tend to say that they feel better when their HbA1c is between 7% and 8%, rather than below 7%, making treatment more sustainable and improving adherence
• As pharmacists, we should always monitor a patients response to treatment to gauge how they are feeling alongside any clinical measures
• In elderly, the target HbA1c may be greater than 7% (i.e. staying slightly above 7%) to avoid hypoglycaemia
• BGLs


  Monitored as part of the day-to-day management of DM, and help with adjustment of treatment doses against the body's glucose needs (relating to diet, physical activity)
• HbA1c levels


  Indicate long-term BGL control and the likelihood of long-term complications
• The UKPDS study has demonstrated that even a small 1% decrease in HbA1c, working toward the desired target, decreases the risk of diabetes related deaths, myocardial infarction, microvascular complications, and peripheral vascular disease
• Being overweight and obese is a major factor for the development of T2DM - although it is not a risk factor at all for T1DM, and lesser risk factor for gestational diabetes
• Metabolic syndrome


  • Not a condition itself, but rather a cluster of factors/conditions occurring together
  • An epidemiological clustering of risk factors with a common underlying pathophysiological cause: insulin resistance associated with central adiposity. It is not the same as DM but can lead to T2DM
• Type 2 diabetes (T2DM)


  Patients are usually asymptomatic initially, not typically associated with ketoacidosis, insulin treatment not essential until other medications fail
• Management of T2DM


  • Lifestyle modifications (weight loss, dietary changes, exercise)
  • Metformin (first-line unless contraindicated)
  • Additional antihyperglycemic agents over time
  • Minimise risk of microvascular and macrovascular complications
• Clinical management goals for T2DM

  • Multifactorial
  • Specific
• These goals should be the basis of an individualised diabetes management plan and sick day management plan
• First line treatment of T2DM

  • Lifestyle modification (foundation, never ceased)
  • Initiate metformin (unless contraindicated)
• Lifestyle modifications - diet

  Include lots of veggies and some fruit, good fats in moderation, low in salt/saturated/trans fats/sugar
• Lifestyle modifications - exercise

  150min/week can delay/prevent T2DM, increases insulin sensitivity, 5-20% weight loss improves glycaemic control
• Pharmacotherapy used to treat diabetes can impact patient's weight (weight gain or loss)
• Anti-hyperglycaemia agents


  • Biguanide (metformin)
  • Sulfonylureas
  • SGLT2 inhibitors
  • DPP-4 inhibitors
  • GLP-1 receptor agonists
  • Acarbose, pioglitazone