Endocrinology

Question 1

What causes early morning hyperglycemia?

Answer 1

Physiological increase in growth hormone levels in the early morning hours stimulates gluconeogenesis and leads to a subsequent increase in insulin demand that cannot be met in insulin-dependent patients, resulting in elevated blood glucose levels.

Question 2

Diagnostic criteria for diabetes mellitus

Answer 2

Random blood glucose level >= 200mg/dL in patients with symptoms of hyperglycemia (ie. polydipsia, polyuria, polyphagia, unexplained weight loss) or hyperglycemic crisis
OR
>= 2 abnormal test results for hyperglycemia in asymptomatic individuals

Question 3

Describe the oral glucose tolerance test

Answer 3

Measurement of fasting plasma glucose and blood glucose 2 hours after the consumption of 75g of glucose

Question 4

Describe Hemoglobin A1C test

Answer 4

HbA1C test measures the concentration of glycated hemogloblin A1 in red blood cells (glucose in the blood binds to hemoglobin). HbA1C test measures the average blood glucose levels of the prior 8-12 weeks

Question 5

Which conditions and treatments may alter HbA1C results?

Answer 5

Sickle cell trait
CKD
Increased RBC lifespan (e.g. iron and/or vitamin B12 deficiency, splenectomy, aplastic anemia
Heavy alcohol use
Decreased RBC lifespan (e.g. due to acute blood loss, sickle cell trait, thalassemia, G6PD deficiency, cirrhosis, hemolytic anemia, splenomegaly, antiretrovial drugs)
Increased erythropoiesis (EPO therapy, pregnancy, iron supplementation)

Question 6

How often should you check HbA1C in a diabetic patient?

Answer 6

At least every 3-6 months

Question 7

Fasting glucose level target in diabetes

Answer 7

80-130 mg/DL (4.4-7.2 mmol/L)

Question 8

Contraindications for metformin

Answer 8

Severely impaired renal function (eGFR <30mL/minute/1.73m2)
Acute or chronic metabolic acidosis (including ketoacidosis)
Hypersensitivity to metformin

Question 9

Name glucose dependent and glucose independent insulinotropic agents

Answer 9

Glucose-dependent: GLP1 agonists, DPP4 inhibitors
Glucose-independent: Sufonylureas, meglitinides

Question 10

How do insulinotropic agents work?

Answer 10

Stimulate the secretion of insulin from pancreatic B cells - either stimulated by elevated blood glucose levels (postprandially) or irrespective of blood glucose levels (risk of hypoglycemia)

Question 11

Common contraindications of antidiabetic drugs

Answer 11

T1DM
Pregnancy and breastfeeding (all contraindicated - should be substituted with human insulin)
Renal failure (if GFR<30ml/min DPP4 inhibitors, incretin mimetic drugs, meglitinides and thiazolidinediones may be administered)
Major surgery under general anesthesia
Acute conditions requiring hospitalisation (infections, organ failure)
Elective procedures associated with an increased risk of hypoglycemia (periods of fasting)

Question 12

How do biguanides (metformin) work?

Answer 12

• Enhances effect of insulin
• Decreases hepatic gluconeogenesis and intestinal glucose absorption
• Increases peripheral insulin sensitivity which increases peripheral glucose uptake and glycolysis
• Reduces LDL, increases HDL

Question 13

Clinical characteristics of metformin:

Answer 13

• Lowers HbA1C by 1.2-2% over 3 months
• Weight loss
• No risk of hypoglycemia
• Reduces risk of macroangiopathic complications

Question 14

Side effects of metformin

Answer 14

• Metformin associated lactic acidosis
• GI symtoms (N+V, diarrhoea, vomiting, adominal pain, flatulence
• Severe symptoms: muscle cramps, hyperventilation, apathy, disorientation, coma

Question 15

How do thiazolidinediones (glitazones) work?

Answer 15

Increased storage of fatty acids in adipocytes, decreased free fatty acids in circulation, increased glucoe utilisation and decreased hepatic glucose production

Question 16

Side effects of glitazones

Answer 16

Increased risk of heart failure
Increased risk of fractures (osteoporosis)
Fluid retention and oedema
Weight gain
Rosiglitazone: Increased risk of CV complications like cardiac infarction or death

Question 17

How do sulfonylureas work?

Answer 17

Block ATP-sensitive potassium channels of the pancreatic B cells -> depolarisation of the cell membrane -> calcium influx -> insulin secretion

Question 18

Contraindications to sulfonylureas

Answer 18

Beta blockers (can mask hypoglycemic symptoms while lowering serum glucose levels)
Severe CV comorbidity
Obesity
Sulfonamide allergy
Liver and kidney failure

Question 19

Names of sulfonylureas

Answer 19

Chlorpropamide
Tolbutamide
Glyburide
Glipizide
Glimepiride

Question 20

How do glucagon-like peptide 1 receptor agonists (incretin mimetics) work?

Answer 20

Incretin mimetic drugs bind to the GLP-1 receptors and are resistant to degradation by DPP4 enzyme -> increased insulin secretion, decreased glucagon secretion, slow gastric emptying (increased feeling of satiety, decreased weight)

Question 21

Side effects of GLP1 receptor agonists

Answer 21

N+V
Strong feeling of satiety
Pancreatitis and potentially pancreatic cancer

Question 22

Contraindications for GLP1 receptor agonists

Answer 22

GI motility disorders
Chronic pancreatitis or a family history of pancreatic tumors
Personal or family history of MTC or multiple endocrine neoplasia syndrome type 2 (MEN 2)

Question 23

How do Dipeptidyl peptidase-4 inhibitors (gliptins) work?

Answer 23

Indirectly increase the endogenous incretin effect by inhibiting the DPP-4 that breaks down GLP-1 -> increased insulin secretion -> decreased glucagon secretion, delayed gastric emptying

Question 24

Side effects of DPP-4 inhibitors

Answer 24

GI symptoms
Arthralgia
Nasopharyngitis and URTI
Increased feelings of satiety
Urinary infections (mild)
Increased risk of pancreatitis
Worsening renal function, acute renal failure
Headaches, dizziness

Question 25

How do SGLT2 inhibitors (glifozins) work?

Answer 25

Reversible inhibition of SGLT2 in the proximal tubule of the kidney -> decreased glucose reabsorption in the PCT of the kidney -> glycosuria and polyuria

Question 26

Side effects of SGLT2 inhibitors

Answer 26

UTIs, genital infections (vulvovaginal candidiasis, balantitis) due to glucosuria
Dehydration, weight loss, orthostatic hypotension
Severe diabetic ketoacidosis

Question 27

Describe a hyperosmolar hyperglycemic state

Answer 27

Condition primarily seen in T2DM due to extreme hyperglycemia. Unlike in DKA, there is some insulin available to suppress fat breakdown so ketosis does not result, rather, severe hyperglycemia (>600mg/dL) may develop

Question 28

Clinical manifestations of hyperosmolar hyperglycemic state

Answer 28

Polyuria, polydipsia, nausea, vomiting, volume depletion and eventually mental status changes and coma

Question 29

Describe diabetic ketoacidosis

Answer 29

Primarily seen in patients with T1DM
Caused by insufficient insulin levels (often secondary to acute infection).
Hyperglycemia (usually 300-600 mg/dL)

Question 30

Macrovascular complications of diabetes

Answer 30

Atherosclerosis - related more to metabolic risk factors including obesity, dyslipidemia, arterial HTN rather than hyperglycemia

Manifestations:
- Coronary heart disease
- Cerebrovascular disease
- Peripheral artery disease
- Monckeberg arteriosclerosis
- Gangrene

Question 31

Microvascular complications of diabetes

Answer 31

Diabetic nephropathy
Diabetic retinopathy, glaucoma
Diabetic neuropathy including diabetic gastroparesis
Diabetic foot

Question 32

Pathophysiology of microvascular disease

Answer 32

Chronic hyperglycemia -> nonenzymatic glycation of proteins and lipids -> thickening of the basal membrane with progressive function impairment and tissue damage