Diabetes Mellitus

Question 1

Definition of DM

Answer 1

• A metabolic disorder of multiple aetiology characterised by chronic hyperglycaemia with disturbances of carbohydrate, protein and fat metabolism resulting from defects in insulin secretion, insulin action, or both

Question 2

Diagnostic criteria for DM

Answer 2

• One abnormal value diagnostic is symptomatic or two if asymptomatic
• HbA1c >6.5% or >48mmol/mol

Question 3

Pathophysiology of T1DM

Answer 3

• Immune pathogenesis
• Severe insulin deficiency
• Islet autoantibodies are markers of the autoimmune process associated with T1DM
• GAD and IA2 also measured

Question 4

Pathophysiology of T2DM

Answer 4

• Combination of insulin resistance and deficiency
• Some patients with phenotype of T2DM have positive antibodies
• C-peptide is secreted in equimolar concentrations to insulin and is a useful marker of endogenous insulin secretion

Question 5

Differences in presentation of T1DM and T2DM

Answer 5

• Ketones <0.6mmol/L normal, 0.6-1.5mmol/L development of problem and >1.5mmol/L indicaed high risk of DKA

Question 6

Causes of secondary diabetes

Answer 6

• Genetic defects of beta-cell function
• Genetic defects in insulin action
• Disease of exocrine pancreas (i.e. pancreatitis, haemochromatisis, carcinoma, CF)
• Endocrinopathies (Acromegaly, Cushings, phaeochromocytoma)
• Immunosuppressive agents (glucocorticoids, tacrolimus, ciclosporin)
• Anti-psychotics (clozapine, olanzapine)
• Genetic syndromes associated with DM (Downs syndrome, Friedreich’s ataxia, Turner’s, Myotonic distrophy, Kleinfelter’s syndrome

Question 7

Clinical criteria for gestational diabetes

Answer 7

• Fasting venous plasma glucose ≥5.1mmol/l
• One hour value ≥10mmol/l
• Two hours after OGTT ≥8.5mmol/l

Question 8

Monogenic diabetes (MODY)

Answer 8

• Caused by change in single gene (AD)
• 6 genes identified for around 87% of cases (HNF1-A most common)

Question 9

Symptoms of hyperglycaemia

Answer 9

• Glycosuria (depletion of energy stores - tired, fatigue, weight loss, difficulty concentrating, irratibility)
• Glycosuria (osmotic diuresis - polyuria, polydypsia, thirst, dry mucous membranes, reduced skin turgor, postural hypotension)
• Glucose shifts (swollen ocular lenses - blurred vision)
• Ketone production (nausea, vomiting, abdominal pain, heavy/rapid breathing, acetone breath, drowsiness, coma)
• Depletion of energy stores (muscle - weakness, polyphagia, weight loss, growth retardation in young)
• Complications (macrovascular, microvascular, neuropathy, infection)

Question 10

Treatment of T1DM

Answer 10

• Patient education on management is essential (i.e. Dose Adjustment For Normal Eating/DAPHNE)
• Subcutaneous insulin regimens
  
  • Once daily basal insulin
  • Twice-daily mixed insulin
  • Basal-bolus therapy
• Monitoring of carbohydrate intake
• Monitoring of BMs
• Monitoring for and managing complications

NB - Injecting into the same spot can cause a condition called “lipodystrophy”, where the subcutaneous fat hardens and patients do not absorb insulin properly from further injections into this spot - patients should cycle injection sites.

Question 11

Treatment of T2DM

Answer 11

• Patient education about lifestyle changes
  
  • Dietary (i.e. vegetables and oily fist, low glycaemic, high fibre, low carbohydrate may help)
  • Optimise risk factors (i.e. exercise and weight loss, stop smoking, optimise management for comorbidities)
  • Monitoring for complications
• Treatment targets
  
  • HbA1c 48mmol/mil for new type 2 diabetics
  • HbA1c 53 mmol/mol for diabetics that have been moved beyond metformin alone
• SGLT-2 inhibitors and GLP-1 inhibitors are preferential in patients with CV disease.

Question 12

Monitoring of DM

Answer 12

• HbA1c every 3-6 months
• Capillary blood glucose
• Flash glucose monitoring

Question 13

Notable side effects of T2DM medications

Answer 13

• Metformin - GI upset, lactic acidosis
• Pioglitazone - weight gain, fluid retention, anaemia, HF, increased risk of bladder cancer
• Sulfonylurea - weight gain, hypoglycaemia, increased risk of CV disease and MI when used as monotherapy
• DPP-4 inhibitors - GI upset, symptoms of URTI, pancreatitis
• GLP-1 mimetics - GI upset, weight loss, dizziness, low risk of hypoglycaemia
• SGLT-2 inhibitors - glucosuria, DKA with moderately raised glucose, lower limb amputation more common