Diabetes

Question 1

List some DDx for a presentation of polyuria and polydipsia?

Answer 1

• T1DM (late presentation, <35yo)
• Pre-diabetes
• Gestational diabetes
• Diabetes insipidus
o Central- insufficient ADH production
o Nephrogenic- inadequent renal response to ADH
• Secondary causes of diabetes
o Pancreas- haemochromatosis, chronic pancreatitis, pancreatic ca
o Endocrinopathies- acromegaly, Cushing syndrome, hyperthyroidism
o Drug-induced diabetes
- Hormonal therapy: Glucocorticoid excess -> stimulation of gluconeogenesis in liver AND inhibition of insulin sensivity
- Thiazide diuretics – weak inhibition of insulin release from beta cells (pancreas)
- B-blockers- impair insulin release
• UTI
• BPH (causes nocturia)

Question 2

Name 3 drugs used to treat T2DM?

Answer 2

• Metformin (Biguinide)
• Glibenclamide (Sulfonylureaas)
• Acarbose (a-glucosidase inhibitor)
• Pioglitazone (Glitazone)
• Sitagliptin (DDPP-4 inhibitor)
• Exentide (GLP-1 agonist)

Question 3

Describe the MAO of Metformin?

Answer 3

Metformin
o Class: Biguinide
o MA: decreased gluconeogenesis, increase glycolysis, increased peripheral glucose uptake -> increased insulin sensitivity

Question 4

Describe the MAO of Glibenclamide?

Answer 4

Glibenclamide
o Class: Sulfonylureas
o MA: Close K channel in B-cell membrane-> cell depolarizes -> insulin release via increase Ca influx

Question 5

Describe the MAO of Acarbose?

Answer 5

Acarbose
o Class: alpha glucosidase inhibitors
o MA: Inhibit intestinal brush-border a-glucosidases -> delayed carb hydrolysis and glucose absorption -> decreased postprandial hyperglycemia

Question 6

Describe the MAO of Pioglitazone?

Answer 6

Pioglitazone:
o Class: Glitazones
o MA: Binds to PPAR-y nuclear transcription regulator -> increase insulin sensitivity in peripheral tissue

Question 7

Describe the MAO of Sitagliptin?

hint: DDPP-4 inhib

Answer 7

Sitagliptin
o Class: DDPP-4 inhibitors
o MA: Inhibits DPP-4 enzyme that deactivates GLP-1 -> increase glucose-dependent insulin release, decrease glucagon release, decrease gastric emptying, increase satiety

Question 8

Describe the MAO of Exentide?

hint: GLP-1 agonist

Answer 8

Exenitide
o Class: GLP-1 agonists
o MA: stimulated glucagon-like peptide-1 (GLP-1) -> increase glucose-dependent insulin release, decreased glucagon release, decrease gastric emptying, increase satiety

Question 9

Differentiate between the treatment strategies for T1DM and T2DM?

Answer 9

• T1DM: low carb diet, insulin replacement
• T2DM: diet modification, exercise for weight loss, oral hypoglycaemic agents, non-insulin injectables, insulin replacement

Question 10

Describe the medication algorithm for T2DM?

Answer 10

1. Metformin.
   Alternatives: Sulfonylureas (US), insulin, Arcabose (a-glucosidase inhibitor)
2. Second line- Sulfonylureas, DPP-4 inhibitor, Sodium-glucose co-transporter 2 (SGLT-2) inhibitors
3. Third line- SU, DPP-4 inhibitor, SGLT-2 inhibitor, GLP-1 analogs, insulin

Question 11

Describe the LTM monitoring of diabetes control?

Answer 11

• HbA1C- provides indication of LTM control (3 months)
o checked by GP every 3/12
o self-monitoring for insulin users
• Regular GP check ups: BP, lipid levels (3/12)
• Annual medical checks:
o Eyes- retinal neuropathy (fundoscopy)
o Kidneys- glomerulonephritis (UEC)
o Peripheral vasculature (esp. feet)- peripheral neuropathy, vascular compromise -> reflexes, sensation (vibration), pulses, skin integrity
o Cholesterol- lipid levels

Question 12

How is DM diagnosed?

Answer 12

• Symptoms + 1 test
• 2 tests exceeding DM threshold (or same test done twice)

Diabetic thresholds:
• Fasting BSL: >7mmol/L
• Random BSL: >11.1 mmol/L
• HbA1c: >6.5% (glycosylated Hb, past 3/12)
• OGTT (2hrs post): >11.1mmol/L, done to confirm other test results

Question 13

List some lifestyle modifications you would suggest?

Answer 13

Non-pharm (can reverse insulin resistance)

• diet change (reduce sat fats, increase omega 3, reduced refined carbs, low GI)
• regular exercise (30mins, x5/7 days)
• weight loss (BMI 18.5-24.9)
• smoking cessation
• ETOH cessation
• comorbidity management (HTN, dyslipidaemia)
• referral to endocrinologist, dietician, exercise physio

Pharm management- when glycaemic control not achieved after 3/12 lifestyle intervention OR if symptoms severe

Question 14

Describe SE of metformin?

Answer 14

SE: lactic acidosis (rare but fatal), vit B12 malabsorption, N/V, anorexia, diarrhoea, severe GI disturbance,
taste disturbance

Question 15

What are your glycaemic targets in DM management?

Answer 15

• HbA1c <7% (elderly risk hypoglycaemia)
• Fasting BSL 4-8mmol/L
• OGTT <10mmol/L

Note: overly aggressive glycaemic control is associated with adverse effects