🩺 Endocrine, Diabetes and Metabolic Disorders

1. Which oral agent is usually started first for a newly diagnosed adult with type 2 diabetes and no contraindication?

1. An alpha-glucosidase inhibitor, because it acts locally and avoids systemic exposure entirely
2. A sulfonylurea such as gliclazide, because it produces the fastest fall in glycated haemoglobin
3. Metformin, titrated slowly and taken with food to limit gastrointestinal intolerance
4. A thiazolidinedione, because insulin resistance is the underlying defect in this disease

Metformin remains the usual initial agent because of its efficacy, weight neutrality, low hypoglycaemia risk and long safety record, with a second agent chosen according to comorbidity. Sulfonylureas, alpha-glucosidase inhibitors and thiazolidinediones are not preferred first choices. Source: Diabetes Canada clinical practice guidelines.

2. Which long-term nutritional deficiency is associated with metformin therapy?

1. Vitamin D deficiency, which presents as proximal muscle weakness and low bone density
2. Vitamin B12 deficiency, which may present as anaemia or as peripheral neuropathy
3. Vitamin C deficiency, which presents as bleeding gums and impaired wound healing
4. Vitamin K deficiency, which presents as easy bruising and a prolonged clotting time

Metformin reduces ileal absorption of vitamin B12, and long-term users may develop deficiency that mimics or worsens diabetic neuropathy, so periodic measurement is advised particularly in those on high doses for many years. The other vitamin deficiencies are not linked to the drug. Source: Diabetes Canada clinical practice guidelines.

3. A patient starting metformin asks how to reduce the diarrhoea he experienced on a previous attempt. What advice helps most?

1. Take the whole daily dose at once on an empty stomach to shorten intestinal contact time
2. Start at a low dose with food and increase slowly, or consider the extended-release form
3. Take the tablets with a large volume of fruit juice to speed transit through the bowel
4. Take an antidiarrhoeal with each dose indefinitely so that the metformin can be continued

Gastrointestinal intolerance is dose-related and is minimised by slow titration, administration with meals and, where needed, the extended-release formulation. Taking the full dose fasting worsens symptoms and chronic antidiarrhoeal use masks a problem that has a simpler solution. Source: Health Canada product monograph for metformin.

4. For a patient with type 2 diabetes and established atherosclerotic cardiovascular disease, which addition to metformin is best supported?

1. A GLP-1 receptor agonist or an SGLT2 inhibitor with demonstrated cardiovascular benefit
2. A sulfonylurea, because it lowers glycated haemoglobin more than any injectable agent
3. An alpha-glucosidase inhibitor, because postprandial glucose drives cardiovascular risk in this population
4. A thiazolidinedione, because it improves the lipid profile more than any other class

Agents in these two classes with proven outcome benefit reduce major cardiovascular events independently of their glucose-lowering effect, which is why comorbidity now drives the choice of second-line therapy. The other classes have no comparable outcome evidence. Source: Diabetes Canada clinical practice guidelines.

5. Which adverse effect is most characteristic of SGLT2 inhibitors?

1. Genital mycotic infection, related to the glucose present in the urine
2. Severe hypoglycaemia when used as monotherapy in a patient with normal renal function
3. Marked weight gain caused by fluid retention in the peripheral interstitial tissues
4. Persistent dry cough that resolves only when the drug is permanently discontinued

Glycosuria promotes candidal growth, making genital mycotic infection the commonest adverse effect of the class, alongside volume depletion and rare euglycaemic ketoacidosis. Monotherapy hypoglycaemia is uncommon, the class causes weight loss, and cough belongs to renin-angiotensin blockade. Source: Health Canada product monographs for the SGLT2 inhibitors.

6. How is a weekly GLP-1 receptor agonist injection best explained to a patient?

1. It is injected subcutaneously on the same day each week, with the site rotated each time
2. It is injected intramuscularly into the deltoid on any day of the week the patient chooses
3. It is taken orally with a large meal because absorption depends on the presence of fat
4. It is injected intravenously once a week by a nurse at the community health centre

Weekly agents are given subcutaneously on a consistent day with rotation of injection sites, and nausea is minimised by slow dose escalation. They are not intramuscular, intravenous or, in the weekly form, oral. Source: Health Canada product monographs for the GLP-1 receptor agonists.

7. A patient on an SGLT2 inhibitor presents with nausea, vomiting and abdominal pain, with a capillary glucose of 9.4 mmol per litre and ketones present. What is the concern?

1. Hypoglycaemia, which typically presents with abdominal pain and vomiting in this class
2. Simple gastroenteritis, because ketoacidosis cannot occur below a glucose of 14 mmol per litre
3. Euglycaemic diabetic ketoacidosis, which can occur despite a near-normal glucose reading
4. Lactic acidosis caused by the SGLT2 inhibitor accumulating in the renal tubular cells

SGLT2 inhibitors can precipitate ketoacidosis with only modest hyperglycaemia, particularly during illness, surgery, fasting or reduced carbohydrate intake, so ketones must be measured whenever these symptoms appear. Normal glucose does not exclude the diagnosis. Source: Health Canada safety review of SGLT2 inhibitors.

8. Which second-line agent is most likely to cause hypoglycaemia when added to metformin?

1. Acarbose, because it directly stimulates the pancreatic beta cell to release insulin
2. Sitagliptin, because it produces a sustained glucose-independent rise in insulin release
3. Empagliflozin, because it increases hepatic glucose uptake in a glucose-independent way
4. Gliclazide, because it stimulates insulin secretion independently of the glucose level

Sulfonylureas close the ATP-sensitive potassium channel regardless of the prevailing glucose, which is why they cause hypoglycaemia and weight gain, whereas dipeptidyl peptidase-4 inhibitors, SGLT2 inhibitors and acarbose act in glucose-dependent or non-insulinotropic ways. Source: Diabetes Canada clinical practice guidelines.

9. How should a conscious adult with mild hypoglycaemia be treated?

1. Take a measured amount of fast-acting carbohydrate, then recheck the glucose in fifteen minutes
2. Eat a high-fat chocolate bar, because fat prolongs the rise in blood glucose usefully
3. Inject glucagon immediately, because oral treatment is never reliable in an adult
4. Wait thirty minutes without treatment, since mild episodes correct themselves reliably in most healthy adults

The standard approach is a defined quantity of rapidly absorbed carbohydrate followed by rechecking after fifteen minutes and repeating if needed, then a snack or meal if one is not due. Fat slows absorption, glucagon is for severe episodes with impaired swallowing, and waiting risks deterioration. Source: Diabetes Canada clinical practice guidelines.

10. Which patient is at greatest risk of hypoglycaemia unawareness?

1. A patient newly diagnosed with type 2 diabetes taking metformin as the only therapy
2. A patient with long-standing type 1 diabetes and frequent recent low glucose episodes
3. A patient on an SGLT2 inhibitor alone with an A1C consistently at the target value
4. A patient using an alpha-glucosidase inhibitor with a very high dietary fibre intake and irregular meal times

Repeated hypoglycaemia blunts the counter-regulatory and adrenergic response, so long duration of diabetes with recent frequent lows is the classic setting for unawareness, which is partly reversible by avoiding lows for several weeks. The other patients are at low risk of hypoglycaemia at all. Source: Diabetes Canada clinical practice guidelines.

11. Which insulin is designed to provide relatively flat basal coverage over approximately twenty-four hours?

1. Insulin glargine, which forms microprecipitates at physiological pH and releases slowly
2. Insulin lispro, which is absorbed rapidly and is intended for administration with meals
3. Regular human insulin, which is given thirty minutes before meals for prandial coverage
4. Insulin aspart, which has the fastest onset of the currently marketed prandial analogues

Glargine precipitates at subcutaneous pH and dissolves slowly, giving a relatively peakless basal profile, in contrast to the rapid-acting analogues and regular human insulin, which are prandial agents. Recognising basal from bolus insulin is fundamental to safe dispensing. Source: Health Canada product monograph for insulin glargine.

12. Which practice reduces the risk of a serious insulin dispensing error?

1. Dispensing whichever insulin is in stock when the prescribed brand is temporarily unavailable
2. Assuming that all insulin pens contain the same concentration of one hundred units per millilitre
3. Abbreviating the word units as a capital U on the label to save space on the container
4. Confirming concentration and product name in full, since look-alike names differ in strength

Concentrated insulins exist alongside standard strength products and several brand names are visually similar, so the full product name and concentration are verified at every step. Abbreviating units has caused tenfold overdoses and insulins are not freely interchangeable. Source: ISMP Canada medication safety bulletins.

13. What advice is given about storage of an insulin pen currently in use?

1. Keep the in-use pen in direct sunlight so that it warms before each administration
2. Keep the in-use pen in the freezer between doses to prolong its chemical stability
3. Keep the in-use pen at room temperature and discard it after the stated in-use period
4. Keep the in-use pen refrigerated at all times and inject the insulin while still cold straight from the refrigerator

Unopened insulin is refrigerated, but the pen in use is kept at room temperature and discarded after the period stated in the monograph, since injecting cold insulin is uncomfortable and repeated warming and cooling degrades the product. Freezing destroys insulin and light exposure is avoided. Source: Health Canada product monographs for insulin products.

14. A patient on basal insulin has fasting glucose values that are consistently high but daytime values at target. What adjustment is most logical?

1. Increase the mealtime rapid-acting insulin at lunch, since that dose covers the night
2. Increase the basal insulin dose gradually, guided by repeated fasting measurements
3. Add an alpha-glucosidase inhibitor at bedtime to blunt the overnight glucose rise
4. Reduce the basal insulin dose, because a high fasting value indicates overnight excess

Basal insulin is titrated against the fasting glucose, so persistent fasting hyperglycaemia with acceptable daytime values calls for a gradual increase in the basal dose, after excluding nocturnal hypoglycaemia with rebound. Adjusting a lunchtime bolus does not address the overnight period. Source: Diabetes Canada clinical practice guidelines.

15. Which group of medicines is held during an acute illness with vomiting and dehydration?

1. Inhaled corticosteroids, antihistamines, topical emollients and artificial tear products
2. Sulfonylureas, ACE inhibitors, diuretics, metformin, ARBs, NSAIDs and SGLT2 inhibitors
3. Levothyroxine, oral contraceptives, proton pump inhibitors and antidepressant therapy
4. Statins, calcium supplements, vitamin D and low-dose acetylsalicylic acid for prevention

These agents either reduce renal perfusion, promote volume depletion or accumulate when filtration falls, so holding them during a dehydrating illness prevents acute kidney injury, lactic acidosis and ketoacidosis. The other groups are not part of sick-day guidance. Source: Diabetes Canada clinical practice guidelines.

16. What should a patient with type 1 diabetes be told about insulin during an illness with fever?

1. Never stop the insulin, monitor glucose and ketones more often, and maintain fluid intake
2. Stop the insulin while unable to eat, since insulin without food always causes hypoglycaemia
3. Halve every dose automatically for the duration of any febrile illness, whatever the readings
4. Replace the insulin with an oral agent until the illness has completely resolved

Illness raises counter-regulatory hormones and insulin requirements, so basal insulin is never stopped in type 1 diabetes; monitoring of glucose and ketones is increased and hydration maintained, with doses adjusted on measurements. Stopping insulin precipitates ketoacidosis. Source: Diabetes Canada clinical practice guidelines.

17. What does glycated haemoglobin reflect?

1. Glucose control over the previous twenty-four hours, measured directly from plasma on the day of the test
2. Average glycaemia over the preceding two to three months, weighted towards recent weeks
3. The peak postprandial glucose reached after the largest meal of the previous week
4. The total quantity of insulin secreted by the pancreas over the preceding month

Glycated haemoglobin reflects average exposure over the lifespan of the red cell, roughly two to three months, with recent weeks contributing most, which is why it is misleading in haemoglobinopathy, haemolysis and recent transfusion. It is not a measure of a single day, a single peak or insulin secretion. Source: Diabetes Canada clinical practice guidelines.

18. In which situation is glycated haemoglobin least reliable as a measure of control?

1. A patient with well controlled hypertension taking a thiazide and an ACE inhibitor daily
2. A patient with haemolytic anaemia, in whom red cell survival is substantially shortened
3. A patient who has recently changed from one brand of metformin to a different generic
4. A patient who works night shifts and therefore eats the main meal in the early morning

Any condition that alters red cell lifespan, including haemolysis, recent transfusion, iron deficiency and some haemoglobin variants, distorts the glycated haemoglobin result, so alternative measures are used. Antihypertensives, generic substitution and shift work do not affect the assay itself. Source: Diabetes Canada clinical practice guidelines.

19. How should levothyroxine be taken to obtain consistent absorption?

1. With an antacid, which raises gastric pH and increases the absorption of the hormone
2. With a large breakfast including dairy products, which improves dissolution of the tablet
3. At bedtime together with the evening calcium supplement, to simplify the daily routine
4. On an empty stomach with water, separated from calcium and iron by several hours

Levothyroxine absorption is reduced by food and by calcium, iron, proton pump inhibitors and several other products, so a consistent empty-stomach routine with adequate separation is the standard advice. Taking it with dairy, calcium or an antacid reduces absorption. Source: Health Canada product monograph for levothyroxine.

20. How long after a change in levothyroxine dose is thyroid stimulating hormone usually rechecked?

1. On the same day as the dose change, to establish a baseline for the new dose level
2. After twenty-four hours, since the pituitary responds immediately to circulating thyroxine
3. After twelve months, because shorter intervals produce results that cannot be interpreted
4. After about six to eight weeks, because the pituitary axis responds slowly to the change

Thyroid stimulating hormone takes weeks to equilibrate after a dose change, so measuring too early produces a value that does not reflect the new steady state and can lead to inappropriate adjustment. A full year is an unnecessarily long interval. Source: CPhA Therapeutic Choices, thyroid disorders chapter.

21. A woman on levothyroxine becomes pregnant. What usually happens to her requirement?

1. The requirement rises, so the dose is increased and thyroid function is monitored closely
2. The requirement falls sharply, so the dose is halved as soon as pregnancy is confirmed
3. The requirement is unchanged throughout pregnancy and no additional monitoring is needed
4. The drug is stopped for the first trimester because it crosses the placenta and harms the fetus

Increased thyroxine-binding globulin and fetal demand raise levothyroxine requirements early in pregnancy, so the dose is increased promptly and thyroid function is monitored each trimester. Stopping the hormone would harm fetal neurodevelopment. Source: CPhA Therapeutic Choices, thyroid disorders chapter.

22. Which symptom in a patient taking an antithyroid drug requires urgent medical assessment?

1. Sore throat with fever, which may signal agranulocytosis and requires a blood count
2. Mild constipation, which is an expected effect of the drug in the first fortnight
3. A slight increase in appetite, which reflects the return of normal thyroid function
4. Dry skin developing gradually over several months of continuous antithyroid therapy in almost every treated patient

Methimazole and propylthiouracil can cause agranulocytosis, so any sore throat, fever or mouth ulceration prompts immediate assessment with a white cell count and temporary cessation. The other symptoms are not markers of this reaction. Source: Health Canada product monograph for methimazole.

23. Which administration instruction applies to an oral bisphosphonate?

1. Take on rising with a full glass of plain water and remain upright without food for the stated period
2. Take with the evening meal and lie down immediately afterwards to improve absorption, which increases the contact time
3. Take with a glass of milk to reduce the gastric irritation that the tablet causes, as the calcium buffers the acid
4. Crush the tablet and mix it with yoghurt if swallowing whole tablets is difficult

Bisphosphonates are poorly absorbed and irritant to the oesophagus, so they are taken on an empty stomach with plain water while remaining upright for the stated interval. Milk and food prevent absorption, and crushing increases mucosal contact. Source: Health Canada product monographs for the oral bisphosphonates.

24. Which rare adverse effect is associated with long-term bisphosphonate or denosumab therapy?

1. Irreversible sensorineural hearing loss developing in the first month of therapy in a substantial minority of users
2. Acute haemolytic anaemia occurring within the first two weeks of the first dose
3. Osteonecrosis of the jaw, particularly after invasive dental procedures in at-risk patients
4. Rapidly progressive interstitial lung disease appearing after the second annual dose of the intravenous formulation

Osteonecrosis of the jaw and atypical femoral fracture are the recognised rare risks of long-term antiresorptive therapy, which is why dental assessment before starting and reporting of new thigh or groin pain are part of counselling. The other reactions are not associated with these drugs. Source: Health Canada product monographs for the antiresorptive agents.

25. A patient stops denosumab without any replacement therapy. What is the specific concern?

1. A rapid loss of bone density with a risk of multiple vertebral fractures after cessation
2. A permanent suppression of bone turnover that continues for the remainder of life
3. An immediate rise in serum calcium requiring urgent treatment with intravenous fluids
4. A withdrawal syndrome with fever and joint pain lasting several weeks after the last dose

Denosumab produces a rebound increase in bone resorption when stopped, with a documented risk of multiple vertebral fractures, so transition to another antiresorptive is planned rather than simply discontinuing. Suppression is reversible and the other described reactions do not occur. Source: Health Canada safety review of denosumab.

26. Why is a systemic corticosteroid tapered rather than stopped abruptly after prolonged use?

1. Sudden withdrawal produces a rebound rise in blood glucose that persists for many months after the last dose is taken
2. Abrupt cessation causes an immediate and permanent loss of bone mineral density
3. Suppression of the hypothalamic-pituitary-adrenal axis can leave the patient unable to respond to stress
4. The drug crystallises in the renal tubule if the plasma concentration falls too quickly, causing an obstructive nephropathy

Exogenous glucocorticoid suppresses endogenous cortisol production, and recovery takes time, so tapering avoids adrenal insufficiency and a flare of the underlying disease. The other explanations do not describe corticosteroid pharmacology. Source: CPhA Therapeutic Choices, corticosteroid chapter.

27. Which counselling point applies to a patient taking prednisone for several weeks?

1. Stop the drug on any day when symptoms are absent, then resume when they return
2. Take the dose at bedtime, since night-time administration prevents insomnia entirely
3. Take the dose in the morning, monitor glucose if diabetic, and never stop suddenly
4. Avoid all vaccination for life once a course of oral corticosteroid has been completed

Morning dosing mimics the physiological cortisol rhythm and reduces insomnia, glucose rises are common and matter in diabetes, and abrupt cessation risks adrenal insufficiency. Intermittent self-directed use and lifelong vaccine avoidance are both incorrect. Source: CPhA Therapeutic Choices, corticosteroid chapter.

28. Which finding is an absolute contraindication to a combined hormonal contraceptive?

1. Irregular menstrual cycles in an otherwise healthy woman of twenty-two years
2. Mild acne that has not responded to a topical retinoid used for three months at the recommended strength
3. A family history of type 2 diabetes in a first-degree relative aged over sixty who required insulin therapy
4. Migraine with aura, because of a substantially increased risk of ischaemic stroke

Migraine with aura, a history of venous thromboembolism, smoking above a defined age, uncontrolled hypertension and several other conditions contraindicate combined hormonal contraception, and a progestin-only method is used instead. Acne, family history of diabetes and irregular cycles are not contraindications. Source: Canadian Contraception Consensus.

29. What should a woman be told if she misses two consecutive active combined oral contraceptive tablets?

1. Stop the pack entirely and wait for the next menstrual period before starting again, using a barrier method meanwhile
2. Take the most recent missed tablet at once, continue the pack, and use backup contraception
3. Take all missed tablets together with the next four days of tablets to catch up quickly, then resume the usual schedule
4. Do nothing, because missing two tablets never affects contraceptive protection at all

Missing two or more active tablets requires taking the most recent missed dose immediately, continuing the pack, using a backup method for the specified number of days, and considering emergency contraception depending on the timing in the cycle. Stopping the pack or taking multiple extra tablets is not correct. Source: Canadian Contraception Consensus.

30. Which drug most clearly reduces the effectiveness of a combined oral contraceptive?

1. Amoxicillin, which reliably reduces contraceptive steroid levels through gut flora effects
2. Rifampin, a potent inducer that accelerates metabolism of both hormonal components
3. Cetirizine, which competes with ethinyl estradiol for the same hepatic enzyme system
4. Pantoprazole, which prevents dissolution of the contraceptive tablet in the stomach

Rifampin and rifabutin are established enzyme inducers that lower contraceptive steroid concentrations and require an alternative or additional method, as do several anticonvulsants and some antiretrovirals. Broad-spectrum antibiotics other than the rifamycins are no longer considered to reduce efficacy. Source: Canadian Contraception Consensus.

31. Which therapy is first-line for painful diabetic peripheral neuropathy?

1. A short course of an oral corticosteroid tapered over the following two weeks with a proton pump inhibitor
2. A long-acting opioid started at a moderate dose and titrated upward every three days until the pain is controlled
3. A topical antifungal preparation applied to the feet twice daily for several weeks to the affected areas of skin
4. A gabapentinoid, a tricyclic antidepressant or a serotonin-norepinephrine reuptake inhibitor

Pregabalin, gabapentin, amitriptyline and duloxetine are the recognised first-line options for painful diabetic neuropathy, with opioids reserved because of poor long-term benefit and substantial harm. Antifungals and corticosteroids have no role in neuropathic pain. Source: Diabetes Canada clinical practice guidelines.

32. Which foot care advice is given to a patient with diabetic peripheral neuropathy?

1. Wear new shoes for a full day immediately so that they mould to the shape of the foot
2. Soak the feet in very hot water each evening to improve the circulation to the toes
3. Use a sharp blade to remove callus at home to prevent pressure ulcers from forming
4. Inspect the feet daily, avoid walking barefoot, and check water temperature by hand

Loss of protective sensation means injuries go unnoticed, so daily inspection, protective footwear, professional nail and callus care and caution with heat are central to preventing ulceration and amputation. Hot soaks, self-cutting of callus and prolonged wear of new shoes all cause injury. Source: Diabetes Canada clinical practice guidelines.

33. Which mechanism explains the weight loss produced by a GLP-1 receptor agonist?

1. A direct increase in resting metabolic rate produced by uncoupling of mitochondria
2. Delayed gastric emptying with central effects on appetite and increased satiety
3. Blockade of intestinal lipase, which prevents absorption of about a third of dietary fat
4. Competitive antagonism at the leptin receptor within the hypothalamic satiety centre

GLP-1 receptor agonists slow gastric emptying and act on hypothalamic appetite pathways, producing reduced energy intake and clinically significant weight loss. Lipase inhibition describes orlistat, and neither uncoupling nor leptin antagonism is involved. Source: Health Canada product monographs for the GLP-1 receptor agonists.

34. Which adverse effect should be discussed before dispensing orlistat?

1. Marked hypertension that develops during the first month of continuous therapy
2. Severe hypoglycaemia occurring within an hour of each dose in non-diabetic users
3. Persistent dry cough that continues for several weeks after the drug is stopped
4. Oily stools and faecal urgency, which worsen markedly with a high-fat meal

Orlistat blocks intestinal lipase, so unabsorbed fat produces steatorrhoea, urgency and flatus with discharge, all of which are proportional to dietary fat intake, and fat-soluble vitamin supplementation is advised. The other effects are not associated with the drug. Source: Health Canada product monograph for orlistat.

35. A patient with type 1 diabetes using multiple daily injections asks about carbohydrate counting. What is the principle?

1. Carbohydrate is avoided entirely so that mealtime insulin becomes unnecessary and glucose stays flat all day
2. The same fixed mealtime dose is used regardless of what the meal actually contains, which simplifies the regimen
3. The mealtime insulin dose is matched to the carbohydrate content using a personal ratio
4. The basal insulin dose is adjusted at each meal according to the carbohydrate eaten rather than the mealtime dose

Carbohydrate counting matches the rapid-acting insulin dose to the carbohydrate load using an individualised insulin-to-carbohydrate ratio, with a correction factor for the pre-meal glucose. Fixed dosing, carbohydrate elimination and adjusting basal insulin at meals are all incorrect. Source: Diabetes Canada clinical practice guidelines.