Diabetes Mellitus

Topic Overview

Diabetes Mellitus is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. For MCCQE1 preparation, understanding the Diabetes Canada Clinical Practice Guidelines (CPGs) is crucial, as management strategies and screening protocols specific to the Canadian population (including Indigenous health considerations) are frequently tested.

Classification and Pathophysiology

Understanding the etiology is the first step in diagnosis and management. The MCCQE1 expects candidates to differentiate between types based on clinical presentation and demographics.

Type 1 Diabetes

Type 1 Diabetes (T1DM)

Pathophysiology: Autoimmune destruction of pancreatic beta-cells leading to absolute insulin deficiency.
Epidemiology: Typically childhood/adolescent onset, but can occur at any age. Canada has one of the highest incidence rates of T1DM globally.
Markers: Anti-GAD, anti-islet cell antibodies, low C-peptide.
Presentation: Polyuria, polydipsia, polyphagia, weight loss, DKA.

Diagnosis of Diabetes

The MCCQE1 strictly follows the Diabetes Canada diagnostic criteria. Memorize these values.

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Crucial Rule: In the absence of symptomatic hyperglycemia, a repeat confirmatory test must be done on another day. If two different tests are done (e.g., FPG and A1C) and both are above the threshold, the diagnosis is confirmed. If only one is above the threshold, repeat that specific test.

Diagnostic Criteria Table

Test	Diabetes Threshold	Prediabetes Threshold	Notes
Fasting Plasma Glucose (FPG)	≥ 7.0 mmol/L	6.1 – 6.9 mmol/L	Fasting = no caloric intake for at least 8 hours.
Hemoglobin A1C	≥ 6.5%	6.0 – 6.4%	Not used for suspected T1DM, children, pregnancy, or conditions affecting RBC turnover (e.g., sickle cell).
2h Plasma Glucose (75g OGTT)	≥ 11.1 mmol/L	7.8 – 11.0 mmol/L	The gold standard, though less convenient.
Random Plasma Glucose	≥ 11.1 mmol/L	N/A	Must be accompanied by classic symptoms of diabetes (polyuria, polydipsia, weight loss) to be diagnostic without confirmation.

Screening Guidelines (Canadian Context)

Screening protocols are high-yield for MCCQE1 Preventive Medicine questions.

General Population

Screen every 3 years in individuals ≥ 40 years of age.
Use FPG or A1C.

High-Risk Populations

Screen earlier and/or more frequently (e.g., every 6–12 months) in individuals with risk factors:

First-degree relative with T2DM.
High-risk ethnic group (e.g., Indigenous, South Asian).
History of prediabetes (IGT, IFG, or A1C 6.0–6.4%).
History of GDM.
Presence of end-organ damage (retinopathy, neuropathy).
Vascular risk factors (HDL < 1.0 mmol/L in males or < 1.3 mmol/L in females, Triglycerides ≥ 1.7 mmol/L, Hypertension).
Associated diseases (PCOS, Acanthosis nigricans, Psychiatric disorders on antipsychotics).

Indigenous Health Consideration

Indigenous peoples in Canada have a 3–5 times higher prevalence of T2DM compared to the general population. Screening should be considered earlier (screening guidelines suggest considering screening at any age with additional risk factors) and culturally safe care is a mandatory component of management (CanMEDS Health Advocate).

Management: The ABCDES of Diabetes Care

The primary goal is to prevent complications. The ABCDES mnemonic is standard in Canadian medical education.

A - A1C: Target usually ≤ 7.0%. (Target ≤ 6.5% for T2DM to reduce CKD/Retinopathy risk if achievable safely; 7.1–8.5% for frail elderly/limited life expectancy).
B - Blood Pressure: Target < 130/80 mmHg.
C - Cholesterol: LDL < 2.0 mmol/L or >50% reduction. Statins generally indicated for age ≥ 40 with diabetes.
D - Drugs: Cardioprotective agents (ACEi/ARB, SGLT2i, GLP-1 RA).
E - Exercise/Eating: 150 mins/week moderate-vigorous activity; resistance training 2-3 times/week.
S - Screening for Complications / Smoking Cessation: Retinopathy, Neuropathy, Nephropathy.

Pharmacotherapy for Type 2 Diabetes

The 2018/2023 Diabetes Canada guidelines emphasize cardiorenal protection.

Step 1: Lifestyle + Metformin

Metformin is the first-line agent unless contraindicated (e.g., eGFR < 30 mL/min).

Step 2: Assess Cardiorenal Status

Does the patient have Atherosclerotic Cardiovascular Disease (ASCVD), Heart Failure (HF), or Chronic Kidney Disease (CKD)?

If YES: Start an agent with proven benefit independent of A1C.
- ASCVD: GLP-1 RA or SGLT2i.
- Heart Failure (HFrEF): SGLT2i (Grade A evidence).
- CKD: SGLT2i (preferred) or GLP-1 RA.
If NO: Choose second-line agent based on patient priorities (hypoglycemia avoidance, weight loss, cost).

Step 3: Add-on Therapy

If A1C targets are not met, add additional agents (DPP-4 inhibitors, Insulin, Sulfonylureas, etc.).

Step 4: Insulin Therapy

Basal insulin (e.g., Glargine, Detemir) is usually added first. If targets are still not met, progress to basal-bolus regimens.

Key Drug Classes & Considerations

Class	Examples	Mechanism	Key Side Effects/Notes
Biguanides	Metformin	$\downarrow$ Hepatic glucose production	GI upset, B12 deficiency, Lactic acidosis (rare).
SGLT2 Inhibitors	Empagliflozin, Dapagliflozin	$\uparrow$ Urinary glucose excretion	Genital mycotic infections, DKA (euglycemic), volume depletion. Cardiorenal protection.
GLP-1 RAs	Liraglutide, Semaglutide	$\uparrow$ Insulin, $\downarrow$ Glucagon, slows gastric emptying	Nausea/Vomiting, weight loss. CV protection. Injection (mostly).
DPP-4 Inhibitors	Sitagliptin, Linagliptin	$\uparrow$ Incretin levels	Well tolerated, weight neutral. No CV benefit.
Sulfonylureas	Gliclazide, Glyburide	$\uparrow$ Insulin secretion	Hypoglycemia, weight gain.

Acute Complications

Differentiation between DKA and HHS is critical for emergency medicine questions on the MCCQE1.

Feature	Diabetic Ketoacidosis (DKA)	Hyperosmolar Hyperglycemic State (HHS)
Patient Profile	Usually T1DM	Usually T2DM, Elderly
Onset	Rapid (< 24 hours)	Insidious (Days to weeks)
Glucose	> 14 mmol/L (often higher)	> 34 mmol/L (Severe hyperglycemia)
pH / Bicarb	pH ≤ 7.3, HCO3 ≤ 15	pH > 7.3, HCO3 > 15
Ketones	Positive (Serum/Urine)	Small or Negative
Osmolality	Variable	> 320 mOsm/kg
Mental Status	Alert to drowsy	Stupor/Coma common
Management	IV Fluids, IV Insulin, K+ replacement	Aggressive IV Fluids, IV Insulin

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Potassium Rule: In DKA management, if Serum K+ < 3.3 mmol/L, hold insulin and replace potassium first to prevent life-threatening arrhythmias.

Sample Question

Clinical Scenario

A 62-year-old male presents to his family physician for a diabetes follow-up. He has a history of Type 2 Diabetes (diagnosed 5 years ago), hypertension, and a myocardial infarction 2 years ago. His current medications include Metformin 1000 mg BID, Ramipril 10 mg daily, Atorvastatin 40 mg daily, and ASA 81 mg daily.

Vitals: BP 132/78 mmHg, HR 72 bpm, BMI 31 kg/m². Labs:

A1C: 7.8% (Target ≤ 7.0%)
eGFR: 55 mL/min/1.73m²
LDL: 1.6 mmol/L

According to the Diabetes Canada Clinical Practice Guidelines, which of the following is the most appropriate next step in the management of his antihyperglycemic therapy?

Explanation

The correct answer is:

C. Add Empagliflozin

Detailed Explanation: This patient has Type 2 Diabetes with established Atherosclerotic Cardiovascular Disease (ASCVD) (history of MI) and is not at his glycemic target (A1C 7.8%).

Option C (Correct): Diabetes Canada guidelines recommend that for patients with established ASCVD, an antihyperglycemic agent with demonstrated cardiovascular benefit should be added. SGLT2 inhibitors (like Empagliflozin) and GLP-1 receptor agonists (like Liraglutide) have Grade A evidence for reducing Major Adverse Cardiovascular Events (MACE) in this population. SGLT2 inhibitors are also indicated for renoprotection, which is beneficial given his eGFR of 55.
Option A: Increasing Metformin might lower glucose, but it does not provide the specific cardioprotective benefit mandated by the guidelines for a patient with prior MI.
Option B: DPP-4 inhibitors (Sitagliptin) have demonstrated cardiovascular safety but not benefit. They are not the preferred second-line agent in patients with ASCVD.
Option D: Sulfonylureas (Gliclazide) carry a risk of hypoglycemia and weight gain and do not offer the specific CV mortality benefits seen with SGLT2 inhibitors or GLP-1 RAs.
Option E: Insulin is generally reserved for when non-insulin agents fail to achieve targets or if there is severe symptomatic hyperglycemia. It is not the preferred next step for CV risk reduction here.

Key Points to Remember for MCCQE1

Screening: Screen everyone ≥ 40 years old every 3 years. Screen high-risk groups earlier.
Diagnosis: Requires confirmatory testing unless symptomatic hyperglycemia is present. Know the numbers (FPG ≥ 7.0, A1C ≥ 6.5%).
Vascular Protection: Statin therapy is indicated for almost all diabetics ≥ 40 years old. ACEi/ARBs are indicated for diabetics ≥ 55 years old OR those with microvascular complications.
Drug Selection: If the patient has Heart Disease or Kidney Disease, prioritize SGLT2i or GLP-1 RA regardless of current A1C.
Hypoglycemia: Defined as < 4.0 mmol/L. Treat with 15g fast-acting carbohydrate, recheck in 15 mins.
Driving: Physicians in Canada have a duty to report patients who are unfit to drive due to uncontrolled hypoglycemia or lack of awareness (varies slightly by province, but the principle of public safety is paramount).

References

Diabetes Canada Clinical Practice Guidelines Expert Committee. Diabetes Canada 2018 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can J Diabetes. 2018;42(Suppl 1):S1-S325. Available online
Diabetes Canada Clinical Practice Guidelines Steering Committee. 2023 Update on Pharmacologic Management of Type 2 Diabetes. Available online
Medical Council of Canada. MCCQE Part I Clinical Decision-Making and Multiple-Choice Question Objectives. Available online