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Flashcards in Diabetes Deck (316):

What 3 end-organ complications are diabetes the leading cause of in Canadian adults? (CDA)

  • Blindness
  • ESRD
  • Nontraumatic amputation


What is the leading cause of death in individuals with diabetes? (CDA)

  • Cardiovascular disease – 2-4x higher incidence than in people without diabetes


What is the definition of diabetes mellitus? (CDA)

  • A metabolic disorder characterized by the presence of hyperglycemia due to defective insulin secretion, defective insulin action or both


What is the difference between Type 1, Type 2 and Gestational diabetes? (CDA)

  • Type 1 Diabetes: diabetes that is primarily a result of pancreatic beta cell destruction (immune-mediated process) and is prone to ketoacidosis
  • Type 2 Diabetes: diabetes may range from predominant insulin resistance with relative insulin deficiency to a predominant secretory defect with insulin resistance
  • Gestational Diabetes: glucose intolerance with onset or first recognition during pregnancy


What are the diagnostic criteria for diabetes based on? (CDA)

  • Thresholds of glycemia that are associated with microvascular disease, especially retinopathy


What are the diagnostic criteria for diabetes? (CDA)

Fasting Plasma Glucose

≥7.0 mmol/L

2-hour plasma glucose after a 75 g oral GTT

≥11.1 mmol/L

Glycated hemoglobin (A1c)



What are 5 reasons why A1c may be preferable to FPG or 2hPG? (CDA)

  • Measured at any time of day
  • More convenient
  • Reflects the average PG over the previous 2 to 3 months
  • Continuous cardiovascular (CV) risk factor
  • Better predictor of MACROvascular events than FPG or 2hPG


In which patients may A1c be misleading? (CDA)

  • Hemoglobinopathies
  • Iron deficiency
  • Hemolytic anemias
  • Severe hepatic disease
  • Severe renal disease
  • Ethnicities (African Americans, American Indians, Hispanics, Asians)
  • Age (increase by 0.1% per decade of life)

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In which type of patients is A1c not recommended for the diagnosis of diabetes? (CDA)

  • Children
  • Adolescents
  • Pregnant women
  • Suspected Type 1 Diabetes


When the result for one test for diabetes is in the diagnostic range, what should then be done to confirm the diagnosis? (CDA)

  • In the absence of symptomatic hyperglycemia, a REPEAT confirmatory laboratory test must be done on ANOTHER day
  • It is preferable that the SAME test be repeated for confirmation
  • If the results of more than one type of test for diabetes are available and are discordant, the test whose result is above the diagnostic cut point should be repeated


What are the diagnostic criteria for prediabetes? (CDA)

Impaired Fasting Glucose (IFG)

6.1-6.9 mmol/L

Impaired Glucose Tolerance (IGT)

7.8-11.0 mmol/L




What combination of plasma glucose tests are predictive of 100% progression to type 2 diabetes over a 5-year period? (CDA)

  • FPG 6.1 to 6.9 mmol/L AND A1c 6.0 to 6.4%


What is the definition of the metabolic syndrome? (CDA)

≥3 measures to make the diagnosis of metabolic syndrome

Waist Circumference

≥102 cm (Men) / ≥88 cm (Women)


≥1.7 mmol/L


<1.0 mmol/L (Men) / <1.3 mmol/L (Women)


SBP ≥130 mm Hg and/or DBP ≥85 mm Hg


≥5.6 mmol/L


What is the evidence to support a strategy of population-based screening for type 2 diabetes? (CDA)

  • No current evidence of clinical benefit


When does the CDA recommend that screening for diabetes begin? (CDA)

  • Screening for diabetes using FPG and/or A1c should be performed every 3 years in individuals ≥40 years of age or at high risk using a risk calculator?


What are 10 risk factors for type 2 diabetes? (CDA)

  • 1st degree relative with type 2 diabetes
  • Ethnicity (Aboriginal, African, Asian, Hispanic or South Asian)
  • History of prediabetes
  • History of gestational diabetes mellitus
  • History of delivery of a macrosomic infant
  • Presence of end organ damage complications associated with diabetes
    • Microvascular (retinopathy, neuropathy, nephropathy)
    • Macrovascular (coronary, cerebrovascular, peripheral)
  • Presence of vascular risk factors (Metabolic Syndrome)
  • Presence of associated diseases
    • PCOS
    • Acanthosis nigricans
    • OSA
    • Psychiatrics disorders (bipolar, depression, schizophrenia)
    • HIV
  • Use of drugs associated with diabetes
    • Glucocorticoids
    • Atypical antipsychotics
    • HAART


In what 2 circumstances does the CDA recommend using the 2hPG in a 75 g OGTT for diabetes screening? (CDA)

  • Individuals with a FPG 6.1-6.9 mmol/L and/or A1c 6.0-6.4% (Prediabetes)
  • Individuals with FPG 5.6-6.0 mmol/L and/or A1c 5.5-5.9% and ≥1 risk factor

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What does the CDA recommend as options to prevent type 2 diabetes in individuals with IGT? What is the evidence for these? (CDA)

  • Structured program of lifestyle modification and regular physical activity that includes moderate weight loss (Grade A, Level 1A)
    • Dietary modification (low-calorie, low-fat, low-saturated fat, high-fibre diet) and moderate-intensity physical activity (at least 150 minutes per week) resulted in moderate weight loss of approximately 5% of initial body weight
    • Reduced risk of DM2 by 58% at 4 years
  • Metformin 850 mg BID (Grade A, Level 1A)
    • ~30% reduction at 2.8 years
    • No effect in older age group (≥60 years) and in non-obese (BMI<35)
  • Acarbose 100 mg TID (Grade A, Level 1A)
    • ~30% reduction but did not persist when discontinued
    • 49% reduction in CV events


What target glucose level is recommended for treating patients with diabetes? (CDA)

  • Therapy in most individuals with type 1 or type 2 diabetes should be targeted to achieve an A1c 7.0% in order to reduce the risk of microvascular and, IF IMPLEMENTED EARLY in the course of disease, macrovascular complications [Grade B, Level 3]

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What are the glycemic targets for patients with diabetes in the fasting and postprandial states? (CDA)

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In which patients may less stringent A1c targets (7.1-8.5%) be appropriate? (CDA)

  • Limited life expectancy
  • High level of functional dependency
  • Extensive CAD at high risk of ischemic events
  • Multiple comorbidities
  • History of recurrent severe hypoglycemia
  • Hypoglycemia unawareness
  • Longstanding diabetes for whom it is difficult to achieve an A1c ≤7.0% despite effective doses of multiple antihyperglycemic agents, including intensified basal-bolus insulin therapy


What is the evidence regarding improved glycemic control in diabetes from randomized controlled studies? (CDA)

  • Reduces the risk of MICROvascular complications
  • NO significant effect on MACROvascular outcomes in recently diagnosed type 1 and type 2 diabetes, as well as more long-standing type 2 diabetes
    • Follow-up data from DCCT and UKPDS studies (conducted in RECENTLY DIAGNOSED diabetes) found benefit with CV outcomes in those originally randomized to intensive treatment [THIS IS WHY RECOMMENDATION SPECIFIES “IF IMPLEMENTED EARLY”]


What did the UKPDS trial find that supports the A1c target of <7.0%? (TFP)

  • NEWLY diagnosed diabetics, age ~50s, few co-morbidities, receiving single glucose-lowering therapy (to start) versus diet
    • Sulfonylurea or insulin – median 10 year A1c 7.0% vs 7.9%
      • Reduction in death (NNT=29) and MI (NNT=36)
    • Metformin – median 10 year A1c 7.4% vs 8.0%

Reduction in death (NNT=14) and MI (NNT=16


What are the 3 major trials that looked at the effect of intensive glycemic control on patients with long-standing type 2 diabetes? (CDA)

  • VADT


What was the significant outcome from the ACCORD trial? (CDA)

  • Intensive glucose control arm was prematurely terminated after 3.5 years due to HIGHER mortality associated with assignment to this treatment


What was the significant finding from these 3 (ACCORD, ADVANCE, VADT) trials? (CDA)

  • Intensive glycemic control improves MICROvascular outcomes
    • ACCORD improved albuminuria and diabetic retinopathy
    • ADVANCE improved nephropathy
    • VADT improved albuminuria
  • NO benefit on MACROvascular outcomes


What was the major risk associated with intensive glycemic control from these 3 trials? (CDA)

  • 2-fold increase in the risk of severe hypoglycemia
  • Higher mortality reported in participants with 1 or more episodes of severe hypoglycemia in both ACCORD and ADVANCE, irrespective of which treatment arm patients were in


How often should patients with diabetes have their A1c measured? (CDA)

  • Every 3 months
    • When glycemic targets are not being met and when diabetes therapy is being adjusted


When can patients with diabetes have their A1c measured every 6 months? (CDA)

  • Periods of treatment and lifestyle stability when glycemic targets have been consistently achieved


By what % does the mean plasma glucose in the previous 120 days contributed to the A1c value? (CDA)

  • <30 days prior = 50%
  • 31 to 90 days prior= 40%
  • 90 to 120 days prior = 10%


For which patients with diabetes does the CDA recommend should use self-monitoring of blood glucose (SMBG)? (CDA)

  • Type 1 Diabetes with Insulin >1x per day (Grade A, Level 1)
  • Type 2 Diabetes with Insulin >1x per day (Grade C, Level 3)
  • Type 2 Diabetes with Insulin 1x daily (Grade D, Consensus)
  • Type 2 Diabetes without Insulin but in whom glycemic control is NOT being achieved (Grade B, Level 2)
  • Consider in Type 2 Diabetes on an insulin secretagogue


How often should SMBG be performed per day in patients with diabetes? (CDA)

  • 3+ times per day (including both pre- and postprandial measurements)
    • Preprandial
    • 2-hour postprandial
    • Occasional nocturnal (unrecognized nocturnal hypoglycemia)
  • 1+ times per day (DM2 with once daily insulin)


What are 5 benefits of SMBG in patients with diabetes? (CDA)

  • Only way to confirm, and appropriately treat, hypoglycemia
  • Provide feedback on the results of lifestyle and pharmacological treatments
  • Increase patient empowerment and adherence to treatment
  • Provide information to both the patient and healthcare professional to facilitate longer-term treatment modifications and titrations as well as short-term treatment decisions


By how much has SMBG been shown to improve the A1c in type 2 diabetes not treated with insulin? (CDA)

  • 0.2-0.5%
    • Series of recent meta-analyses
    • Greater reductions in those performed SMBG when the baseline A1c was >8%
    • Most effective within the first 6 months after diagnosis


What is the evidence for routine SMBG in type 2 diabetes who do not use insulin? (TFP)

  • No clinical benefits
    • A1c reduced by 0.2 – 0.35% (0.5% considered minimum clinically important)
  • Not cost-effective
  • May reduce quality of life (depressive symptoms)
  • Should still know HOW to test their blood glucose in case it is low, they are feeling ill, or they are interested in seeing the impacts of lifestyle behaviours


How does SMBG affect patient satisfaction, general well-being or general health-related quality of life in patients with type 2 diabetes not treated with insulin? (CDA)

  • No evidence of any benefit


In which patients is ketone testing recommended for? (CDA)

  • Type 1 diabetes:
    • During periods of acute illness accompanied by elevated BG
    • When preprandial BG levels remain elevated (>14.0 mmol/L)
    • Symptoms of DKA (e.g. nausea, vomiting, abdominal pain)


What is the recommended amount of exercise for adults with diabetes? (CDA)

  • Minimum of 150 minutes of moderate- to vigorous-intensity aerobic exercise each week
    • Spread over at least 3 days of the week
    • No more than 2 consecutive days without exercise
  • Resistance exercise at least 2x per week (preferably 3x per week) IN ADDITION to aerobic exercise


What is the recommended amount of exercise for children with type 2 diabetes? (CDA)

  • 60 minutes daily of moderate to vigorous physical activity
  • Limit sedentary screen time to <2 hours per day


For patients that struggle with pain upon walking (e.g. due to osteoarthritis), what is an alternative form of aerobic exercise? (CDA)

  • Semi-recumbent cycling


What are examples of moderate and vigorous aerobic exercise for most middle-aged individuals? (CDA)

  • Moderate: brisk walking on level ground, semirecumbent cycling
  • Vigorous: brisk walking up an incline, jogging


In which patients with diabetes should medical evaluation be performed prior to engaging in exercise? (CDA)

  • People with diabetes with possible CVD or microvascular complications of diabetes who wish to undertake exercise that is substantially more vigorous than brisk walking


What medical evaluation is recommended for patients with diabetes prior to engaging in exercise? (CDA)

  • History
  • Physical examination
    • Fundoscopic exam
    • Foot exam
    • Neuropathy screening
  • Resting ECG
  • (Possibly) Exercise ECG Stress Testing


What is the evidence for exercise ECG stress testing in asymptomatic people with diabetes? (CDA)

  • 2 randomized trials found it had no impact on the risk of major cardiovascular events


What are 4 complications of diabetes that might pose an increased risk with certain type of exercise? (CDA)

  • Severe autonomic neuropathy
  • Severe peripheral neuropathy
  • Preproliferative or Proliferative Retinopathy
  • Unstable angina


What should patients with severe peripheral neuropathy be instructed to do prior to exercise? (CDA)

  • Inspect feet daily
  • Wear appropriate footwear
  • Do not engage in exercise with active foot ulcers


What should individuals with diabetes (type 1 or type 2 using insulin or insulin secretagogues) do if their pre-exercise blood glucose levels are <5.5 mmol/L? (CDA)

  • Ingest 15-30 g of carbohydrates before exercise


How does exercise acutely affect blood glucose levels? (CDA)

  • ↓BG (during and after) due to increased glucose disposal and insulin sensitivity
  • ↑BG (during and after) VERY INTENSE exercise (e.g. hockey, basketball, intense resistance training) due to increased glucose production that exceeds increases in glucose disposal


By how much has nutrition therapy been shown to reduce A1c in patients with diabetes? (CDA)

  • 1.0 to 2.0%


What guide are individuals with diabetes recommended to follow regarding their nutrition? (CDA)

  • Eating Well with Canada’s Food Guide
    • Emphasis on foods low in energy density and high in volume to optimize satiety and discourage overconsumption


What % of people with type 2 diabetes are overweight or obese? (CDA)

  • 80-90%


What macronutrient distribution as a % of total energy is recommended for adults with diabetes? (CDA)

  • Can vary to allow for individualization of nutrition therapy
    • Carbohydrates 45-60%
    • Protein 15-20%
    • Fat 20-35%


What is the evidence for CHO-restricted (4% to 45% of total energy per day) diets in people with type 2 diabetes? (CDA)

  • Improved A1c and TG
  • Did NOT improve TC, HDL, LDL or body weight compared to higher-CHO diet


What does the Glycemic Index (GI) represent? (CDA)

  • Assessment of the quality of the CHO-containing foods based on their ability to raise blood glucose


What are examples of low-GI and high-GI food sources? (CDA)

  • Low-GI
    • Beans, peas, lentils, pasta, pumpernickel or rye breads, parboiled rice, bulgur, barley, oats, quinoa
    • Temperate fruit (apples, pears, oranges, peaches, plums, apricots, cherries, berries)
  • High-GI
    • White or whole wheat bread, potatoes, highly extruded or crispy puffed breakfast cereals (corn flakes, puffed rice, puffed oats, puffed wheat)
    • Tropical fruit (pineapple, mango, papaya, cantaloupe, watermelon)


Why is soluble dietary fibre considered beneficial for patients with diabetes? (CDA)

  • Slows gastric emptying
  • Delays the absorption of glucose in the small intestine
  • Improves postprandial BG control


How many services of vegetables and fruit per day is recommended in Eating Well with Canada’s Food Guide? (CDA)

  • 7 to 10 servings per day


What is the maximum % of total daily energy adults with diabetes should get from saturated fats? (CDA)

  • 7%


What dietary recommendation should be considered for patients with diabetes who have chronic kidney disease (CKD)? (CDA)

  • Restricting dietary protein to 0.8 g/kg body weight per day
    • 1 to 1.5 g/kg body weight per day normal (15-20% of total energy intake)


What are 4 alternative dietary patterns that people with type 2 diabetes can follow that have been shown to improve glycemic control? (CDA)

  • Mediterranean-style
  • Vegan or Vegetarian
  • Incorporation of dietary pulses (beans, peas, chick peas, lentils)
  • Dietary Approaches to Stop Hypertension (DASH)


What study reported a significant benefit for the Mediterranean diet in regards to major cardiovascular events? (CDA)

  • PREDIMED study: Spanish multicenter, RCT of Mediterranean diet supplemented with EVOO or mixed nuts compared with a low-fat control diet
    • Stopped early for benefit
    • Reduced the incidence of MCE by ~30% over median follow-up of 4.8 years
    • No difference between those with and without diabetes (49% of participants had DM2)


What is the concern regarding the DASH diet in patients with diabetes? (CDA)

  • Low sodium intakes may be associated with increased mortality in people with type 1 and type 2 diabetes


What is the maximum amount of alcohol recommended? (CDA)

  • Males: ≤3 standard drinks per day and <15 drinks per week
  • Females: ≤2 standard drinks per day and <10 drinks per week


What is the concern with alcohol consumption in people with diabetes using insulin or insulin secretagogues? (CDA)

  • Risk of delayed hypoglycemia (if alcohol consumed with or after the previous evening’s meal)
    • Next morning after breakfast or as late as 24 hours after alcohol consumption


What is the insulin regimen of choice for all adults with type 1 diabetes? (CDA)

  • Basal-bolus insulin regiments
    • Multiple daily injections or continuous subcutaneous insulin infusion (CSII)


Why are rapid-acting bolus insulin analogues, in combination with adequate basal insulin, recommended instead of regular insulin in type 1 diabetes? (CDA)

  • Minimizes the occurrence of hypoglycemia
  • Improves A1c
  • Achieves postprandial glucose targets


Which rapid-acting insulin analogues should be used with CSII in adults with type 1 diabetes? (CDA)

  • Aspart or Lispro


Which long-acting insulin analogues should be used as basal insulin in adults with type 1 diabetes? (CDA)

  • Determir or Glargine


What is the advantage of using long-acting insulin analogues over NPH as basal insulin in adults with type 1 diabetes? (CDA/TFP)

  • Lower A1c
  • Reduced risk of hypoglycemia
  • Reduced risk of nocturnal hypoglycemia (Detemir)
  • ***TFP – no advantage in A1c, no evidence for hard outcomes, no difference in severe hypoglycemia ***


How often are long-acting insulin analogues administered in adults with type 1 diabetes and why? (CDA)

  • Twice-daily
  • 15-30% of patients using insulin glargine will experience preinjection hyperglycemia (on once daily regimen)


What are 3 rapid-acting insulin analogues? (CDA)

  • Insulin aspart (NovoRapid)
  • Insulin glulisine (Apidra)
  • Insulin lispro (Humalog)


What is the typical onset, peak and duration of the rapid-acting insulin analogues? (CDA)

  • Onset = 10-15 min
  • Peak = 1-1.5h (1-2h with Humalog)
  • Duration = 3-5h (3.5-4.75h with Humalog)


How does the administration of preprandial insulin differ between rapid-acting insulin analogues and short-acting insulin? (CDA)

  • Regular insulin: 30-45 minutes prior to a meal
  • Rapid-acting insulin: 0-15 minutes prior to or up to 15 minutes after a meal


What are 3 long-acting insulin analogues? (CDA)

  • Insulin detemir (Levemir)
  • Insulin glargine (Lantus)
  • Insulin glargine U300 (Toujeo)


What is the typical onset and duration for the long-acting insulin analogues? (CDA)

  • Onset = 90 min (up to 6h with Toujeo)
  • Duration =
    • 30h (Glargine U300/Toujeo)
    • 24h (Glargine/Lantus)
    • 16-24h (Demetir/Levemir)


What are the short-acting and intermediate-acting insulins? (CDA)

  • Short-acting insulins
    • Humulin-R
    • Novolin ge Toronto
  • Long-acting insulins
    • Humulin-N
    • Novolin ge NPH


What should patients with type 1 diabetes being initiated on insulin be educated on? (CDA)

  • How to care for and use insulin
  • Prevention, recognition and treatment of hypoglycemia
  • Sick-day management
  • Adjustments for food intake (e.g. carbohydrate counting) and physical activity
  • Self-monitoring of blood glucose (SMBG)


What can some patients with type 1 diabetes experience after insulin initiation? (CDA)

  • “Honeymoon period” – insulin requirements decrease transiently (weeks to months)


What is the evidence for using metformin in type 1 diabetes? (CDA)

  • Off-label
  • Potentially harmful in patients with renal or heart failure
  • No improvement in A1c
  • May improve insulin sensitivity
  • Reduces insulin requirements
  • Reduces TC/LDL ratio
  • May lead to modest weight loss


What is the most common adverse effect of intensive insulin therapy in patients with type 1 diabetes? (CDA)

  • Hypoglycemia


What is hypoglycemia unawareness? (CDA)

  • Threshold for the development of autonomic warning symptoms is close to, or lower than, the threshold for the neuroglycopenic symptoms
  • First sign of hypoglycemia is confusion or loss of consciousness


What are 3 strategies for hypoglycemia unawareness to reduce the risk of hypoglycemia in type 1 diabetes patients? (CDA)

  • Increased frequency of SMBG, including periodic assessment during sleeping hours
  • Less stringent glycemic targets with avoidance of hypoglycemia for up to 3 months
  • A psychobehavioral intervention program (blood glucose awareness training)


What % of patients with type 2 diabetes present with microvascular and/or macrovascular complications at the time of diagnosis? (CDA)

  • 20 to 50%


In patients with type 2 diabetes, when should antihyperglycemic agent therapy be started if glycemic targets are not achieved using lifestyle management? (CDA)

  • 2-3 months


When should target A1c levels be attained once starting pharmacotherapy for type 2 diabetes? (CDA)

  • 3 to 6 months


When will the maximum effect of oral antihyperglycemic agent monotherapy be seen at? (CDA)

  • 3 to 6 months


Which is better, maximal dose monotherapy or combinations of submaximal doses of antihyperglycemic agents and why? (CDA)

  • Combination of submaximal doses of antihyperglycemic agents
    • More rapid and improved glycemic control
    • Fewer side effects


What are 5 patient characteristics and 6 treatment characteristics that should be taken into account when starting pharmacotherapy for patients with type 2 diabetes? (CDA)

  • Patient
    • Degree of hyperglycemia
    • Overweight or obese
    • Patient preference
    • Presence of comorbidities (renal, cardiac, hepatic)
    • Ability to access treatments
  • Treatment
    • Effectiveness and durability of lowering BG
    • Risk of hypoglycemia
    • Effectiveness at reducing diabetes complications
    • Effect on body weight
    • Side effects and contraindications
    • Cost and coverage


What should be the initial drug use for overweight patients with type 2 diabetes? (CDA)

  • Metformin


How does metformin work to treat diabetes? (CDA)

  • Enhances insulin sensitivity in liver and peripheral tissues by activation of AMP-activated protein kinase


Why is metformin recommended as the initial agent in most patients with type 2 diabetes? (CDA)

  • Effectiveness in lowering BG
  • Relatively mild side effect profile
  • Long-term safety track record
  • Negligible risk of hypoglycemia
  • Lack of causing weight gain
  • Cardiovascular benefit in overweight patients


By how much is metformin expected to decrease A1c? (CDA)

  • 1.0-1.5%


What is the risk of hypoglycemia with metformin? (CDA)

  • Negligible


How does metformin affect weight? (CDA)

  • Weight neutral


What are 4 contraindications to metformin use? (UTD)

  • Renal Failure (eGFR <30)
    • ½ dose eGFR 30 to <60
  • Lactic acidosis
  • Decompensated CHF
  • Hepatic dysfunction


What are 8 classes of antihyperglycemic medications? (CDA)

  • Alpha-glucosidase inhibitor
  • Incretin agents
  • Insulin
  • Insulin secretagogue
  • Metformin
  • SGLT2 inhibitor
  • Thiazolidinedione (TZD)
  • Weight loss agent (Orlistat)


In patients with clinical cardiovascular disease (prior MI, CAD, unstable angina, stroke, occlusive PAD) in whom glycemic targets are not met, what medication should be added to antihyperglycemic therapy? (CDA)

  • SGLT2 inhibitor (Empagliflozin)


What is an example of an alpha-glucosidase inhibitor? (CDA)

  • Acarbose (Glucobay)


By how much is acarbose expected to decrease A1c? (CDA)

  • 0.6%


What is the risk of hypoglycemia with acarbose? (CDA)

  • Negligible


How does acarbose affect weight? (CDA)

What are the main side effects associated with acarbose? (CDA)


What are the two types of incretin agents used in diabetes? (CDA)

  • DPP-4 inhibitor
  • GLP-1 receptor agonist


What are 2 examples of DPP-4 inhibitors? (CDA)

  • Sitagliptin (Januvia)
  • Linagliptin (Trajenta)


By how much are DPP-4 inhibitors expected to decrease A1c? (CDA)

  • 0.7%


What is the risk of hypoglycemia with DPP-4 inhibitors? (CDA)

  • Negligible


How do DPP-4 inhibitors affect weight? (CDA)

  • Weight neutral


What are the main side effects associated with DPP-4 inhibitors? (CDA)

  • Rare cases of pancreatitis


What is the evidence for DPP-4 inhibitors modifying CVD or mortality? (TFP)

  • No evidence of benefit or harm
  • Possible increased risk in pancreatitis (NNH = 798)


What is an example of a GLP-1 receptor agonist? (CDA)

  • Liraglutide (Victoza)


By how much are GLP-1 receptor agonists expected to decrease A1c? (CDA)

  • 1.0%


What is the risk of hypoglycemia with GLP-1 receptor agonists? (CDA)

  • Negligible


How do GLP-1 receptor agonists affect weight? (CDA)

  • Significant weight loss


What might deter patients from using GLP-1 receptor agonists? (CDA)

  • Parenteral administration


What are the main side effects associated with GLP-1 receptor agonists? (CDA)

  • Nausea and vomiting
  • Rare cases of pancreatitis


In whom would GLP-1 receptor agonists be contraindicated? (CDA)

  • Personal/family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2)


By how much would insulin be expected to decrease A1c? (CDA)

  • 0.9-1.1%


How do insulin secretagogues work to treat diabetes? (CDA)

  • Activate sulfonylurea receptor on beta cell to stimulate endogenous insulin secretion


What are 2 types of insulin secretagogues? (CDA)

  • Sulfonylureas
  • Meglitinides


What are 2 examples of sulfonylureas? (CDA)

  • Gliclazide (Diamicron, Diamicron MR)
  • Glyburide (Diabeta)


By how much would sulfonylureas be expected to decrease A1c? (CDA)

  • 0.8%


What is the risk of hypoglycemia with sulfonylureas? (CDA)

  • Gliclazide = Minimal/moderate risk
  • Glyburide = Significant risk


What are two common side effects of glyburide? (CDA)

  • Hypoglycemia
  • Weight gain


What is an example of a meglitinide? (CDA)

  • Repaglinide (GlucoNorm)


By how much would meglitinides be expected to decrease A1c? (CDA)

  • 0.7%


What is the risk of hypoglycemia with meglitinides? (CDA)

  • Minimal/moderate risk


Which of sulfonylureas or meglitinides are associated with less hypoglycemia and why? (CDA)

  • Meglitinides – shorter duration of action allowing medication to be held when forgoing a meal


How do sodium-glucose linked transporter 2 (SGLT2) inhibitors work to treat diabetes? (CDA)

  • Enhances urinary glucose excretion by inhibiting glucose reabsorption in the proximal renal tubule


What are 3 examples of SGLT2 inhibitors? (CDA)

  • Canagliflozin (Invokana)
  • Dapagliflozin (Forxiga)
  • Empagliflozin (Jardiance)


By how much would SGLT2 inhibitors be expected to decrease A1c? (CDA)

  • 0.7-1.0%


What is the risk of hypoglycemia with SGLT2 inhibitors? (CDA)

  • Negligible


How do SGLT2 inhibitors affect weight? (CDA)

  • Weight loss


What are the main side effects associated with SGLT2 inhibitors? (CDA)

  • Genital infections (Fungal)
  • UTI
  • Hypotension (Osmotic diuresis)
  • Increase in LDL
  • Caution with renal dysfunction and loop diuretics
  • Rare diabetic ketoacidosis (may occur with no hyperglycemia


In which patients on an SGLT2 inhibitor would you suspect DKA and what should be done? (CDA)

  • Symptoms of breathing difficulty, nausea, vomiting, abdominal pain, confusion or fatigue
  • +/- hyperglycemia
  • Evaluate for ketoacidosis


How do thiazolidinediones (TZD) work to treat diabetes? (CDA)

  • Enhances insulin sensitivity in liver and peripheral tissues by activation of peroxisome proliferator-activated receptor-gamma receptors
    • Similar to metformin which activates AMP-activated protein kinase


What are 2 examples of TZDs? (CDA)

  • Pioglitazone (Actos)
  • Rosiglitazone (Avandia)


By how much would TZDs be expected to decrease A1c? (CDA)

  • 0.8%


What is the risk of hypoglycemia with TZDs? (CDA)

  • Negligible


How do TZDs affect weight? (CDA)

  • Weight gain


What are the main side effects associated with TZDs? (CDA)

  • CHF
  • Edema
  • Fractures
  • ALT elevations – must monitor and discontinue at 3x ULN
  • ?MI (Rosiglitazone)
  • Bladder cancer (Pioglitazone)


By how much would Orlistat be expected to decrease A1c? (CDA)

  • 0.5%


What is the risk of hypoglycemia with Orlistat? (CDA)

  • Negligible


What is the main side effect associated with Orlistat? (CDA)

  • Abdominal bloating, pain and cramping
  • Steatorrhea
  • Fecal incontinence


Rank the antihyperglycemic medications based on relative A1c lowering. (CDA)

  1. Metformin = 1.0-1.5%
  2. Insulin = 0.9-1.1%
  3. GLP-1 receptor agonist (Liraglutide – Victoza) = 1.0%
  4. SGLT2 inhibitors (Empagliflozin – Jardiance or Canagliflozin – Invokana) =
  6. Sulfonylureas (Gliclazide – Diamicron) = 0.8%
  7. TZD (Pioglitazone or Rosiglitazone) = 0.8%
  8. DPP-4 inhibitors (Sitagliptin – Januvia or Linagliptin – Trajenta) = 0.7%
  9. Meglitinides (Repaglinide – Gluconorm) = 0.7%
  10. Alpha-glucosidase inhibitor (Acarbose) = 0.6%
  11. Orlistat = 0.5%


Which class of antihyperglycemic medications, other than insulin, have the highest risk of hypoglycemia? (CDA)

  • Insulin secretagogues
    • Glyburide > Gliclazide > Repaglinide (GlucoNorm)


Which antihyperglycemic medications typically are associated with weight gain? (CDA)

  • Insulin (fast acting, NPH) > TZDs > Sulphonylureas > Meglitinides
    • TZDs
    • Insulin secretagogues
    • Insulin


In patients with type 2 diabetes marked hyperglycemia (A1c 8.5%), what therapy should be considered? (CDA)

  • Initiating combination therapy with 2 agents – 1 of which may be insulin


How do the antihyperglycemic medications compare in cost? (CDA)

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How does renal function affect the use of antihyperglycemic medications? (CDA)

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What is the evidence for pioglitazone in preventing CVD? (NEJM 2016)

  • IRIS Trial
  • Double-blind RCT of 3876 patients with a recent ischemic stroke or TIA randomized to pioglitazone 45 mg daily or placebo
  • Patients did NOT have diabetes but had insulin resistance (score >3.0 on HOMA-IR index)
  • At 4.8 years, pioglitazone group had lower rate of primary outcome (fatal or nonfatal stroke or MI) 9.0% vs 11.8%, HR 0.76
  • No significant difference in all-cause mortality
  • Pioglitazone associated with a lower risk of diabetes (???)
  • Pioglitazone associated with a greater frequency of weight gain exceeding 4.5 kg (10 lbs!), edema and bone fracture requiring surgery or hospitalization


What study demonstrated a cardiovascular benefit with SGLT2 for patients with type 2 diabetes and clinical cardiovascular disease (CVD)? Describe the study, patients and findings. (CDA)

  • The Empagliflozin Cardiovascular Outcome Event Trial (EMPA-REG OUTCOME)
  • Randomized 7020 patients with DM2 and clinical CVD (prior MI, CAD, unstable angina, stroke or occlusive PAD) and eGFR ≥30 mL/min to empagliflozin (10mg or 25mg) or placebo
    • 98% of patients were receiving antihyperglycemic agents prior to randomization
      • 75% taking metformin
    • Baseline A1c levels between 7 and 10%
      • Mean 8.1%
    • 82% had had diabetes for more than 5 years
    • 80% were taking RAAS inhibitors, statins and ASA
  • 1.6% ARR (10.5% vs 12.1%, HR 0.86) for the composite cardiovascular end-point of death from cardiovascular causes, nonfatal MI or nonfatal stroke
    • Driven mainly by a 38% RRR in cardiovascular death
    • No reduction in the rate of nonfatal MI or nonfatal stroke
  • 1.4% ARR (2.7% vs 4.1%, HR 0.65, NNT = 71 in hospitalization for heart failure
  • 2.6% ARR (5.7% vs 8.3%, NNT = 38) in total mortality


What did the EMPA-REG OUTCOME study demonstrate in regards to progression of renal disease? (NEJM)

  • Primary outcome was a composite of progression to microalbuminuria, a doubling of serum creatinine, having to start renal replacement therapy, or death due to renal disease
  • Improvement in progression to microalbuminuria
    • 11.2% vs 16.2%, NNT = 20
  • Improvement in doubling of serum creatinine
    • 1.5% vs 2.6%, NNT = 90
  • Improvement in need for RRT
    • 0.3% vs 0.6%, NNT = 333


What study demonstrated a cardiovascular benefit with a GLP-1 receptor agonist for patients with type 2 diabetes and high cardiovascular risk? Describe the study, patients and findings. (NEJM)

  • Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER)
  • Randomized 9340 patients with DM2 and high cardiovascular risk to maximum tolerated dose liraglutide (0.6 to 1.8 mg) or placebo
    • Age 50 years or more with at least one cardiovascular coexisting condition (coronary heart disease, cerebrovascular disease, PVD, CKD of stage 3 or greater, CHF NYHA class II or III)
    • Age 60 years or more with at least one cardiovascular risk factors (microalbuminuria or proteinuria, hypertension and LVH, left ventricular systolic or diastolic dysfunction, ABI <0.9)
    • Mean duration of diabetes was 12.8 years
    • Mean A1c level 8.7%
  • 1.9% ARR (13.0% vs 14.9%, HR 0.87, 13% RRR, NNT=53) for the primary composite outcome of the first occurrence of death from cardiovascular causes, nonfatal MI or nonfatal stroke after 3.5 years
    • Driven mainly by a 22% RRR (1.3% ARR) in cardiovascular death
    • No reduction in the rate of nonfatal MI or nonfatal stroke
  • 15% RRR (1.4% ARR – 8.2% vs 9.6%, NNT=71) in total mortality


What type of basal insulin should be used when added to antihyperglycemic agents in patients with type 2 diabetes and why? (CDA)

  • Long-acting insulin analogues (e.g. detemir or glargine)
  • Reduces the risk of nocturnal and symptomatic hypoglycemia compared to intermediate-acting NPH


What should all patients with type 2 diabetes be counseled on when using or starting therapy with insulin or insulin secretagogues? (CDA)

  • Prevention, recognition and treatment of drug-induced hypoglycemia


In what % of patients taking insulin secretagogues does hypoglycemia occur annually? (CDA)

  • 20%


What type of bolus insulin should be used when added to antihyperglycemic agents in patients with type 2 diabetes and why? (CDA)

  • Rapid-acting insulin analogues (e.g. Aspart or Lispro)
  • Improves glycemic control and reduces the risk of hypoglycemia compared to regular (short-acting) insulin


In general, when bolus insulin is added to the treatment regimen in patients with type 2 diabetes, what class of medication is usually discontinued? (CDA)

  • Insulin secretagogues
    • Sulfonylureas
    • Meglitinides


How should patients with type 2 diabetes be started on basal insulin? (CDA)

  • Start at 10 nits at bedtime (lower if <50 kg)
  • Self-titrate by increasing the dose by 1 unit every night until fasting BG target of 4-7 mmol/L is achieved
  • Can continue metformin +/- secretagogue
  • Should monitor blood sugar once daily (fasting most indicative of effect)


What is the evidence for initiating basal insulin in poorly controlled type 2 diabetes with oral agents compared to prandial or biphasic insulin? (TFP)

  • Similar A1c reductions
  • Less weight gain
  • Less hypoglycemia


How should patients with type 2 diabetes be started on basal and bolus insulin? (CDA)

  • Current Basal Users
    • Add 10% bolus insulin at each meal
  • New Basal + Bolus Users
    • Calculate total daily insulin dose 0.5 units/kg
      • 40% of TDI dose as basal insulin
      • 20% of TDI dose as bolus insulin prior to each meal
    • Titrate BASAL to FASTING BG level
    • Titrate BOLUS to POSTPRANDIAL BG levels
    • Continue Metformin but likely stop secretagogue
    • Monitor blood sugar at least 3 times per day, both pre- and post-prandial


How is hypoglycemia defined? (CDA)

  1. Development of autonomic or neuroglycopenic symptoms
  2. Low plasma glucose level (<4.0 mmol/L for patients treated with insulin or an insulin secretagogue)
  3. Symptoms responding to the administration of carbohydrate


What are 7 neurogenic (autonomic) symptoms of hypoglycemia? (CDA)

  • Trembling
  • Palpitations
  • Sweating
  • Anxiety
  • Hunger
  • Nausea
  • Tingling


What are 8 neuroglycopenic symptoms of hypoglycemia? (CDA)

  • Difficulty concentrating
  • Confusion
  • Weakness
  • Drowsiness
  • Vision changes
  • Difficulty speaking
  • Headache
  • Dizziness


What are the 3 levels of severity of hypoglycemia? (CDA)

  • Mild – autonomic symptoms present – individual able to self-treat
  • Moderate – autonomic and neuroglycopenic symptoms present – individual able to self-treat
  • Severe – individual requires assistance of another person – PG typically <2.8 mmol/L
    • May become unconscious


What is the potential long-term complication of severe hypoglycemia in patients with type 2 diabetes? (CDA)

  • Dementia


What are 10 risk factors for hypoglycemia? (CDA)

  • Prior episode of severe hypoglycemia
  • Current low A1c (<6.0%)
  • Hypoglycemia unawareness
  • Long duration of insulin therapy
  • Autonomic neuropathy
  • Low economic status
  • Food insecurity
  • Low health literacy
  • Cognitive impairment
  • Adolescence
  • Preschool-age children unable to detect and/or treat mild hypoglycemia on their own


What should patients at high risk for severe hypoglycemia be counseled on? (CDA)

  • Preventing and treating hypoglycemia (including use of glucagon)
  • Preventing driving and industrial accidents through SMBG and taking appropriate precautions prior to the activity
  • Documenting BD readings taken during sleeping hours


How should mild to moderate hypoglycemia be treated? (CDA)

  • Oral ingestion of 15 g carbohydrate
  • Retest BG in 15 minutes and re-treat with another 15 g carbohydrate if the BG level remains <4.0 mmol/L


How should severe hypoglycemia be treated in a conscious person? (CDA)

  • Oral ingestion of 20 g carbohydrate
  • Retest BG in 15 minutes and re-treat with another 15 g carbohydrate if the BG level remains <4.0 mmol/L


How should severe hypoglycemia be treated in an unconscious person? (CDA)

  • No IV Access: Glucagon 1 mg SC or IM
  • IV Access: 10-25 g (20-50 cc of D50W) of glucose given IV over 1-3 minutes


What should be done after hypoglycemia has been reversed? (CDA)

  • Should have the usual meal or snack that is due at that time of the day to prevent repeated hypoglycemia
  • If a meal is >1 hour away, a snack (including 15 g carbohydrate and a protein source) should be consumed


By how much does 15 g and 20 g glucose increase the BG? (CDA)

  • 15 g – 2.1 mmol/L within 20 minutes
  • 20 g – 3.6 mmol/L within 45 minutes


What are 5 examples of 15 g carbohydrate for the treatment of mild to moderate hypoglycemia? (CDA)

  • 15 g glucose (e.g. glucose tablets)
  • 3 packets of table sugar dissolved in water
  • ¾ cup of juice or regular soft drink
  • 6 LifeSavers
  • 1 tablespoon of honey


Why are glucose or sucrose tablets or solution preferred to orange juice and glucose gels? (CDA)

  • Orange juice = slower to increase BG levels
  • Glucose gel = slow and must be swallowed to have a significant effect


By how much does 1 mg Glucagon SC/IM increase the BG? (CDA)

  • Increase from 3.0 to 12.0 mmol/L within 60 minutes


How does hyperglycemia lead to DKA? (CDA)

  • Hyperglycemia causes urinary losses of water and electrolytes (Na, K, Cl)
  • Results in extracellular fluid volume (ECFV) depletion
  • Potassium shifted out of cells (potassium deficit and abnormal concentration)
  • Metabolic acidosis
  • Hyperosmolality (water deficit leading to increased corrected sodium concentration plus hyperglycemia


What are 6 risk factors or precipitating causes of DKA/HHS? (CDA)

  • New diagnosis of diabetes
  • Insulin omission
  • Infection
  • Myocardial infarction
  • Thyrotoxicosis
  • Drugs (e.g. cocaine, atypical antipyschotics, lithium)
  • 6 Is (Infection, Infarction, Intoxication, Insulin missed, Iatrogenic/Steroids, Intra-abdominal mass – pancreatitis, cholecystitis)


What are 7 symptoms or signs of DKA? (CDA)

  • Symptoms of hyperglycemia (polyuria, polydipsia, blurred vision)
  • Kussmaul respiration (deep labored breathing with severe metabolic acidosis)
  • Acetone-odoured breath
  • ECFV contraction (tachycardia, hypotension, confusion)
  • Nausea/Vomiting
  • Abdominal pain
  • Decreased LOC


  • Hyperglycemia – polyuria, polydipsia, blurred vision
  • Ketosis – nausea/vomiting, abdominal pain, fruity odor
  • Dehydration – tachycardia, hypotension, confusion
  • Metabolic acidosis – tachypnea, Kussmaul respiration


How does HHS typically present different than DKA? (CDA)

  • HHS more profound ECFV contraction and decreased LOC
    • Seizures
    • Stroke-like state


What test can be done in the hospital to screen for DKA in patients with type 1 diabetes with capillary glucose >14.0 mmol/L? (CDA)

  • Point-of-care capillary beta-hydroxybutyrate
    • >1.5 mmol/L warrants further testing


What is unique to pregnant women presenting with DKA? (CDA)

  • Lower glucose levels
    • Case reports of euglycemic DKA


In individuals suspected of having DKA or HHS, what 8 investigations should be done? (CDA)

  • Electrolytes
  • Anion gap – >10
    • AG = (Na + K) – (Cl + HCO3)
  • Glucose – typically >14
  • Creatinine
  • Osmolality
  • Beta-hydroxybutyric acid
  • Blood gases – pH < 7.3
  • Serum and urine ketones


How does plasma osmolality typically differ between DKA and HHS? (CDA)

  • ≤320 mmol/kg – DKA
  • >320 mmol/kg - HHS


In adults presenting with DKA, what are 5 principles of treatment? (CDA)

  1. Fluid resuscitation
  2. Avoidance of hypokalemia
  3. Insulin administration
  4. Avoidance of rapidly falling serum osmolality
  5. Search for precipitating cause

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In adults presenting with HHS, what are 5 principles of treatment? (CDA)

  1. Fluid resuscitation
  2. Avoidance of hypokalemia
  3. Avoidance of rapidly falling serum osmolality
  4. Search for precipitating cause
  5. Possibly insulin administration to further reduce hyperglycemia


In individuals with DKA, how should fluid administration be given? (CDA)

  • IV 0.9% NS at 500 mL/h for 4 hours THEN
    • Consider higher rate (1-2 L/h) in the presence of shock
  • 250 mL/h for 4 hours


What is the concern with overly rapid correction of hyponatremia in HHS? (CDA)

  • Central pontine myelinolysis


How should potassium be managed in patients with DKA? (CDA)

True K is MUCH LOWER as acidosis shifts potassium OUT of cells (i.e. artificial elevation)

  • Hyperkalemia
    • Start K supplementation when plasma gets <5.0 to 5.5 mmol/L
  • Hypokalemia/Normokalemia
    • Give K immediately with IV fluid (between 10 and 40 mmol/L)
  • Hypokalemia <3.3 mmol/L
    • Withhold insulin until K ≥3.3 mmol/L


How should insulin be given in patients with DKA? (CDA)

  • Infusion of short-acting IV insulin of 0.10 U/kg/h
  • Insulin infusion rate should be maintained until the resolution of ketosis as measured by the normalization of the plasma anion gap


How should hypoglycemia be avoided in patients with DKA receiving an insulin infusion? (CDA)

  • IV dextrose started once plasma glucose concentration reaches 14.0 mmol/L


When would bicarbonate therapy be used for DKA? (CDA)

  • Only in extreme acidosis of pH ≤ 7.0


Which 3 antidepressants have been shown to cause weight gain of between 2 to 3 kg within a 1-year time frame? (CDA)

  • Amitriptyline
  • Mirtazapine
  • Paroxetine


What are the 4 types of bariatric surgery? (CDA)

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What is the recommendation for immunizations in patients with diabetes? (CDA)

  • Annual influenza immunization
  • Pneumococcal immunization
    • Single dose for those >18 years of age
    • 1-time revaccination for those >65 years of age (if the original vaccine was given when they were <65 years of age) with at least 5 years between administrations


What % of patients with diabetes report taking a natural health product for various indications? (CDA)

  • 78%


What does the CDA recommend regarding the use of natural health products for glycemic control for individuals with diabetes? (CDA)

  • Against – insufficient evidence regarding efficacy and safety
  • Some NHPS have been shown to lower A1c by ≥0.5% in trials lasting at least 3 months in adults with type 2 diabetes


By how much do persons with diabetes generally have a cardiovascular age in advance of their chronological age? (CDA)

  • 10 to 15 years


Which trial showed the long-term benefits of an intensive multifactorial management strategy in patients with type 2 diabetes and microalbuminuria? (CDA)

  • STENO-2 trial


What is the target BP for patients with diabetes? (CDA)

  • <130/80


Which patients with diabetes should be treated with statins? (CDA)

  • Clinical macrovascular disease
  • Age ≥ 40 years for type 2 diabetes
  • Age < 40 years and 1 of the following:
    • Diabetes duration >15 years and age >30 years
    • Microvascular complications
    • Warrants therapy based on the presence of other risk factors according to the CCS guidelines


What studies supported the use of statins for all patients with diabetes ≥40 years of age with or without 1 CV risk factor? (CDA)

  • HPS – Simvastatin 40 mg daily
  • CARDS (1 CV risk factor) – Atorvastatin 10 mg daily


Which patients with diabetes but without hypertension should be treated with an ACEi or ARB? (CDA)

  • Clinical macrovascular disease
  • Age ≥ 55 years
  • Age < 55 years and microvascular complications
    • Should only be used if there is reliable contraception for women with childbearing potential


Which trials showed a benefit for ACEi and ARBs in patients with type 2 diabetes? (CDA)

  • HOPE trial
    • Ramipril 10 mg
    • Ramipril 10 mg
    • Telmisartan 80 mg


What is the recommendation for ASA for the primary prevention of CVD in people with diabetes? (CDA)

  • No ASA
    • No reduction of CAD event s and stroke
    • Increase in GI hemorrhage


For patients for whom ASA is recommended for secondary prevention of CVD, what can be used as an alternative in people unable to tolerate ASA? (CDA)

  • Clopidogrel 75 mg daily


What % of people with diabetes will die from heart disease? (CDA)

  • 65-80%


What % of MIs in diabetics occur without recognized or typical symptoms (silent MIs)? (CDA)

  • 1/3


In which patients with diabetes is it recommended to have a baseline resting ECG? (CDA)

  • Age >40 years
  • Duration of diabetes >15 years and age >30 years
  • End organ damage (microvascular, macrovascular)
  • Cardiac risk factors


How often should a repeat resting ECG be performed in patients with diabetes? (CDA)

  • Every 2 years


What are 3 reasons for patients with diabetes to undergo exercise ECG stress testing as the initial test for CAD investigation? (CDA)

  • Typical or atypical cardiac symptoms (e.g. unexplained dyspnea, chest discomfort)
  • Signs or symptoms of associated disease
    • Peripheral arterial disease (abnormal ABI)
    • Carotid bruits
    • TIA
    • Stroke
  • Resting abnormalities on ECG (e.g. Q waves)


In which patients with diabetes should pharmacological stress echocardiography or nuclear imaging be used instead of exercise ECG stress testing based on the resting ECG? (CDA)

  • Resting ST depression (≥1 mm)
  • LBBB or RBBB
  • Intraventricular conduction defect with QRS duration >120 ms
  • Ventricular paced rhythm or preexcitation


What lipid testing should be done at the time of diabetes diagnosis? (CDA)

  • Fasting (8-hour fast) lipid profile (TC, HDL-C, TG, calculated LDL-C) OR
  • Nonfasting lipid profile (apo B, non-HDL-C calculation)


If lipid lowering treatment is not initiated in patients with diabetes, how often is repeat testing recommended? (CDA)

  • Yearly


What is the target LDL-C level for patients with diabetes? (CDA)

  • ≤2.0 mmol/L


Why is a treatment target of ≤2.0 mmol/L for LDL-C advised for patients with diabetes? (CDA)

  • Linear relationship between the proportional CVD risk reduction and LDL-C lowering à suggests that there is NO lower limit of LDL-C
  • CARDS (Collaborative Atorvastatin Diabetes Study) trial randomized type 2 diabetics without known vascular disease but with at least 1 CVD risk factor (hypertension, retinopathy, microalbuminuria or microalbuminuria, current smoking) to Atorvastatin 10 mg daily or placebo
    • Treatment resulted in a mean LDL-C of 2.0 mmol/L from a mean baseline of 3.1 mmol/L
    • Reduced risk for CV events and stroke of 37% and 48%
  • TNT (Treating to New Targets) trial subgroup analysis of diabetics with stable CAD
    • Randomized to Atorvastatin 80 mg daily vs Atorvastatin 10 mg daily
    • Atorvastatin 80 mg daily achieved a mean LDL-C of 2.0 mmol/L had 25% fewer major CVD events than those treated with Atorvastatin 10 mg daily who achieved a mean LDL-C of 2.5 mmol/L


For every 1.0 mmol/L reduction in LDL-C, what % reduction is seen in CVD events, regardless of baseline LDL-C? (CDA)

  • 20%
    • Based on Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis of >170,000 statin-treated subjects
    • Similar for those with and without diabetes


For diabetes patients NOT at LDL-C target despite statin therapy, which second-line agents can be considered? (CDA)

  • Bile acid sequestrants – e.g. Cholestyramine (Questran)
  • Cholesterol absorption inhibitor – e.g. Ezetimibe (Ezetrol)
  • Fibrates – e.g. Fenofibrate (Lipidil)
  • Nicotinic – e.g. Niacin


What is the evidence supporting the addition of lipid-modifying agents to statin therapy for patients with diabetes? (CDA)

  • No evidence
    • ACCORD trial found no benefit with the addition of fenofibrate to statin therapy in patients already meeting LDL-C targets


What is the recommended management for diabetics with a serum TG >10.0 mmol/L and why? (CDA)

  • Fibrate
    • Reduces the risk of pancreatitis


What TG level is considered optimal for patients with diabetes? (CDA)

  • <1.5 mmol/L


What is the blood pressure treatment threshold and blood pressure target for patients with diabetes? (CDA)

  • < 130/80 mm Hg


When would combination therapy using 2 first-line agents be considered as initial treatment of hypertension in diabetes? (CDA)

  • SBP ≥20 mm Hg above target
  • DBP ≥10 mm Hg above target


What is recommended as first-line initial therapy for hypertension in patients with diabetes? (CDA)

  • ACEi or ARB


After an ACEi or ARB, what are two other antihypertensive classes to consider next for patients with diabetes? (CDA)

  • Dihydropyridine CCBs (e.g. Amlodipine, Nifedipine)
  • Thiazide/Thiazide-like diuretics


For diabetes patients being treated with an ACEi for hypertension, what is recommended for combination therapy: dihydropyridine CCB or thiazide? (CDA)

  • Dihydropyridine CCB


What were the main findings of the ACCORD trial? (CDA)

  • Randomized diabetic patients to target SBP <140 mm Hg or <120 mm Hg
  • No benefit in primary outcome (MI, stroke, and cardiovascular death) with intensive treatment
  • 41% reduction in risk of stroke with intensive treatment
  • Increased risk of hypotension and hyperkalemia with intensive treatment


What is considered the earliest clinical sign of diabetic nephropathy? (CDA

  • Albuminuria


What are the stages of diabetic nephropathy based on urinary albumin level? (CDA)

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What are two other common types of kidney disease that can occur in diabetics? (CDA)

  • Hypertensive nephropathy
  • Ischemic nephropathy


How should screening for CKD in diabetes be conducted and how often? (CDA)

  • Random urine ACR and serum creatinine (eGFR)
  • Yearly
  • Commence at diagnosis of type 2 diabetes or 5 years after diagnosis in type 1 diabetes


How should individuals be counseled to perform a 24-hour urine collection? (CDA)

  • Discard 1st morning urine on the day of collection
  • Collect all subsequent urine for a 24-hr period
  • Include the 1st morning urine of the next day


What is the most common method of estimating renal function in Canada using the eGFR? (CDA)

  • MDRD (Modification of Diet in Renal Disease)
    • Age
    • Sex
    • Serum Cr
    • Race
  • Performs well when the GFR is <60 mL/min


How is a diagnosis of CKD in diabetes made? (CDA)

  • Random urine ACR ≥2.0 mg/mmol and/or eGFR <60 mL/min in at least 2 of 3 samples over a 3-month period


In which circumstance would confirmatory testing be unnecessary for diabetic nephropathy? (CDA)

  • Random urine ACR in overt nephropathy range (>20 mg/mmol)


What are 7 conditions that can cause transient albuminuria? (CDA)

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Once a diagnosis of CKD has been made, what 2 tests should be ordered? (CDA)

  • Urine dipstick
  • Urine microscopy

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What is the only finding on urine dipstick and urine microscopy that would be typical of diabetic nephropathy? (CDA)

  • Proteinuria
  • 20% of people have persistent microscopic hematuria but cause needs to be further investigated


What factors would favour the diagnosis of classical diabetic nephropathy vs an alternative renal diagnosis? (CDA)

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What medication should patients with diabetes and CKD with either hypertension or albuminuria be on? (CDA)

  • ACEi or ARB to delay progression of CKD (Grade A, Level 1A in type 2 diabetes)


According to the CDA guidelines, which medication (ACEi or ARB) is better for cardiorenal protection in diabetes? (CDA)

  • Equal


How should patients with diabetes on an ACEi or ARB be monitored? (CDA)

  • Serum Cr and K levels checked at baseline and within 1 to 2 weeks of initiation or titration of therapy and during times of acute illness


What changes in Cr or K levels would be concerning in patients started on or treated with an ACEi or ARB? (CDA)

  • Hyperkalemia
  • Cr increases by more than 30% from baseline


In patients treated with either an ACEi or ARB with diabetes, how should mild-to-moderate hyperkalemia and severe hyperkalemia be managed? (CDA)

  • Mild-to-moderate stable hyperkalemia
    • Counsel on a low-potassium diet
    • Non-potassium-sparing diuretics (Furosemide) and/or oral sodium bicarbonate 500 to 1300 mg PO BID (if metabolic acidosis) should be considered
    • Consider temporarily holding RAAS blockade
  • Severe hyperkalemia
    • Emergency management strategies
    • Hold or discontinue RAAS blockade


Are ACEi or ARBs safe in pregnant women? (CDA)

  • No – increased risk of congenital malformations


What should patients with diabetes and CKD be counselled on during times of acute illness? (CDA)

  • “Sick Day” medication list – SADMAN
    • Sulfonylureas
    • ACE-inhibitors
    • Diuretics, direct renin inhibitors
    • Metformin
    • Angiotensin receptor blockers
    • NSAIDs


What are the 5 stages of CKD based on renal function? (CDA)

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What are 5 indications to refer a patient with diabetes and CKD to a nephrologist? (CDA)

  • Chronic, progressive loss of kidney function
  • ACR persistently >60 mg/mmol
  • eGFR <30 mL/min
  • Unable to remain on renal-protective therapies due to adverse effects such as hyperkalemia or >30% increase in serum creatinine within 3 months of starting an ACE inhibitor or ARB
  • Unable to achieve target BP


What are the 3 forms of diabetic retinopathy? (CDA)

  1. Macular edema
  2. Non-proliferative diabetic retinopathy à Proliferative diabetic retinopathy
    1. Microaneurysms
    2. Intraretinal hemorrhage
    3. Vascular tortuosity
    4. Vascular malformation
  3. Retinal capillary closure (no treatment options)


How often should screening and evaluation for diabetic retinopathy be performed? (CDA)

  • Type 1 Diabetes
    • Annually starting 5 years after the onset of diabetes
  • Type 2 Diabetes
    • Every 1-2 years starting at the time of diagnosis


What did the Diabetes Control and Complications Trial (DCCT) and the UKPDS demonstrate in regards to the development and progression of retinopathy? (CDA)

  • Reduced with intensive glycemic control (A1c ≤7%)


What is the evidence for BP control to reduce the risk of diabetic retinopathy progression? (CDA)

  • UKPDS with target BP <150/85 resulted in significant reduction in retinopathy progression compared to BP <180/105
  • ACCORD and ADVANCE found no difference for aggressive BP lowering <140/80


What medication may be added to statin therapy to slow the progression of established retinopathy? (CDA)

  • Fenofibrate


What are 3 treatment options for patients with sight-threatening diabetic retinopathy? (CDA)

  • Laser therapy (Retinal Photocoagulation)
  • Vitrectomy (Vitreoretinal surgery)
  • Intraocular injection of pharmacological agents (anti-VEGF)
    • Ranibizumab (Lucentis)
    • Bevacizumab (Avastin)


When should screening for peripheral neuropathy be started and how often should it be performed in patients with diabetes? (CDA)

  • Type 1 Diabetes
    • Annually starting 5 years after the onset of diabetes
  • Type 2 Diabetes
    • Annually starting at the time of diagnosis


How should screening for peripheral neuropathy be performed? (CDA)

  • 10-g monofilament
  • 128-Hz tuning fork – vibration at the dorsum of the great toe


What % reduction in baseline pain in considered to be a clinically meaningful response when treating painful peripheral neuropathy? (CDA)

  • 30 to 50%


What are the two classes of first-line agents for painful peripheral neuropathy? (CDA)

  • Anticonvulsants
  • Antidepressants


What are 3 examples of anticonvulsants that can be prescribed for painful peripheral neuropathy? (CDA)

  • Pregabalin (Grade A, Level 1)
    • 75 mg BID titrate up to 300 mg PO BID (max 600 mg/day)
  • Gabapentin (Grade B, Level 2)
    • 300 mg BID titrate up to 600 mg PO QID (max 3600 mg/day)
  • Valproate (Grade B, Level 2)


What are 3 examples of antidepressants that can be prescribed for painful peripheral neuropathy? (CDA)

  • Amitriptyline
    • 10 mg qhs titrate up to 100 mg qhs (max 150 mg/day)
  • Duloxetine
    • 30 mg daily titrate up to 60 mg daily (max 120 mg/day)
  • Venlafaxine
    • 37.5 mg BID titrate up to 150 mg BID (max 300 mg/day)


What is the class of third-line agents for painful peripheral neuropathy? (CDA)

  • Opioids


What are 2 topical agents that can be prescribed for painful peripheral neuropathy? (CDA)

  • Topical nitrate sprays
    • 30 mg spray to legs qhs titrate up to BID
  • Topical capsaicin 0.075% cream applied 3-4 times per day titrate up to 5-6 times per day


What are 8 risk factors for ulceration in persons with diabetes? (CDA)

  • Peripheral neuropathy
  • Previous ulceration or amputation
  • Structural deformity
  • Limited joint mobility
  • PAD
  • Microvascular complications
  • High A1c levels
  • Onychomycosis


How often should foot examinations be performed for patients with diabetes? (CDA)

  • Annually
    • Higher frequency in those at high risk)


What should be examined for in a foot examination for patients with diabetes? (CDA)

  • Skin changes
  • Structural abnormalities (range of motion of ankles and toe joints, callus pattern, bony deformities)
  • Skin temperature
  • Evaluation for neuropathy
  • Evaluation for PAD
  • Ulcerations
  • Evidence of infection


What are 2 noninvasive assessments for PAD in diabetes? (CDA)

  • Ankle-brachial blood pressure index (ABI)
  • Systolic toe pressure by photoplethysmography (PPG)


What diagnosis is difficult to differentiate from osteomyelitis in diabetes? (CDA)

  • Charcot foot


What are 3 things that should be discussed with diabetics at high risk of foot ulceration and amputation? (CDA)

  • Foot care education (counselling to avoid foot trauma)
  • Professionally fitted footwear
  • Early referrals to a healthcare professional trained in foot care management


What are the 3 most frequently encountered pathogens when infection complicates a foot ulcer?

  • Staphylococcus aureus
  • Streptococcus pyogenes (GAS)
  • Streptococcus agalactiae (group B streptococcus)


What % of adult men with diabetes have erectile dysfunction? (CDA)

  • 34 to 45%


What % of men newly diagnosed with diabetes have erectile dysfunction at presentation? (CDA)

  • 1/3


What are the recommended glycemic targets for children and adolescents with type 1 diabetes?

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What is the concern with minimizing severe hypoglycemia in children <6 years of age? (CDA)

  • Cognitive impairment


What is the honeymoon period in type 1 diabetes? (CDA)

  • Good glycemic control and low insulin requirements (<0.5 units/kg/day) in the first 2 years after diagnosis


What are 2 methods of intensive diabetes management in type 1 diabetes in children? (CDA)

  • Basal-Bolus regiments
  • Continuous Subcutaneous Insulin Infusion (CSII)


How can hypoglycemia be managed at home with mild or impending hypoglycemia associated with inability or refusal to take oral carbohydrate? (CDA)

  • Mini-doses of glucagon
    • 10 ug per year of age
    • Minimum dose 20 ug and maximum dose 150 ug


How can severe hypoglycemia in an unconscious child >5 years of age be treated at home? (CDA)

  • 1 mg Glucagon SC or IM
    • 0.5 mg Glucagon in children ≤5 years of age


What adverse effect of DKA can occur in children but is rarely seen in adults? (CDA)

  • Cerebral edema


How should DKA in children be assessed and managed? (CDA)

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What % of female adolescents with type 1 diabetes meet the DSM-IV criteria for eating disorders? (CDA)

  • 10% (compared to 4% in age-matched peers without diabetes)


What 3 comorbid conditions should children with type 1 diabetes be screened for and how? (CDA)

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What % of individuals with type 1 diabetes have clinical autoimmune thyroid disease? (CDA)

  • 15 to 30%


What % of children with type 1 diabetes have celiac disease, and what % are asymptomatic? (CDA)

  • 4 to 9%
    • 60 to 70% asymptomatic


What is the controversy regarding Celiac disease screening in patients with type 1 diabetes? (CDA)

  • No evidence that untreated asymptomatic celiac disease is associated with short- or long-term health risks or that a gluten-free diet improves health in these individuals


When should children with type 1 diabetes be screened for diabetes complications? (CDA)

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What % of young adults with type 1 diabetes have no medical follow-up during the transition from pediatric to adult diabetes care services? (CDA)

  • 25 to 65%


How do children with type 1 diabetes typically differ from those with type 2 diabetes? (CDA)


Type 1

Type 2

Body habitus

Not overweight

Recent history of weight loss

Overweight (BMI >85th %ile)

Age at diagnosis

Before puberty

After puberty

Insulin resistance


Acanthosis nigricans, hypertension, dyslipidemia, PCOS

Family history




In which children should screening for type 2 diabetes be performed? (CDA)

  • ≥3 risk factors in nonpubertal or ≥2 risk factors in pubertal children
    • Obesity (BMI ≥95th %ile for age and gender
    • Member of a high-risk ethnic group (e.g. Aboriginal, African, Asian, Hispanic or South Asian descent)
    • Family history of type 2 diabetes and/or exposure to hyperglycemia in utero
    • Signs or symptoms of insulin resistance:
      • Acanthosis nigricans
      • Hypertension
      • Dyslipidemia
      • NAFLD (ALT >3x upper limit of normal or fatty liver on ultrasound)
      • PCOS
  • Impaired fasting glucose or impaired glucose tolerance
  • Use of atypical antipsychotic medications


How often should screening for type 2 diabetes be performed? (CDA)

  • Every 2 years


What test should be used to screen for type 2 diabetes in children? (CDA)

  • FPG


When could an oral GTT (1.75 g/kg; maximum 75 g) be used for screening of type 2 diabetes in children? (CDA)

  • Very obese (BMI ≥99th %ile for age and gender
  • Multiple risk factors


What is the target A1c for most children with type 2 diabetes? (CDA)

  • ≤7.0%


When should insulin therapy be considered in children with type 2 diabetes? (CDA)

  • A1c ≥9.0%
  • Severe metabolic decompensation (e.g. DKA)


What are 3 pharmacologic options for treating children with type 2 diabetes? (CDA)

  • Metformin
  • Glimepiride
  • Insulin


How much physical activity is recommended for children with type 2 diabetes? (CDA)

  • Same as general population
  • 60 minutes daily of moderate-to-vigorous physical activity
  • Limiting sedentary screen time to no more than 2 hours per day


When should children with type 2 diabetes start screening for microvascular complications of diabetes? (CDA)

  • Annually at time of diagnosis


How should children with type 2 diabetes be screened for diabetes complications and comorbidities? (CDA)

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For women with pregestational diabetes, what are the benefits of attaining a preconception A1c ≤7.0%? (CDA)

  • Spontaneous abortion
  • Congenital anomalies
  • Preeclampsia
  • Progression of retinopathy of pregnancy


For women with pregestational diabetes, what supplements are recommended? (CDA)

  • 5 mg Folic acid at least 3 months preconception and continuing until at least 12 weeks postconception
  • Continue with multivitamin containing 0.4 to 1.0 mg folic acid from 12 weeks postconception to 6 weeks postpartum (or as long as breastfeeding continue)


What medication should women discontinue with pregestational diabetes? (CDA)

  • ACEi and ARBs prior to conception or upon detection of pregnancy
  • Statins


What should women with type 2 diabetes consider doing with their diabetes medications when planning a pregnancy? (CDA)

  • Switch from noninsulin antihyperglycemic agents to insulin


What are the target glucose values for women with pregestational diabetes when pregnant? (CDA)

  • Fasting PG = <5.3 mmol/L
  • 1-hour postprandial = <7.8 mmol/L
  • 2-hour postprandial = <6.7 mmol/L


What is the target maternal blood glucose level for women intrapartum to minimize the risk of neonatal hypoglycemia? (CDA)

  • 4.0 to 7.0 mmol/L


What oral antihyperglycemic medications are safe during breastfeeding? (CDA)

  • Metformin
  • Glyburide


What screening should women with type 1 diabetes in pregnancy be screened for postpartum? (CDA)

  • Thyroiditis = TSH test at 6-8 week postpartum


What are 9 risk factors for GDM? (CDA)

  • Previous diagnosis of GDM
  • Prediabetes
  • Member of a high-risk population (Aboriginal, Hispanic, South Asian, Asian, African)
  • Age 35 years
  • BMI 30
  • PCOS, acanthosis nigricans
  • Corticosteroid use
  • History of macrosomic infant
  • Current fetal macrosomia or polyhydramnios


When should all pregnant women be screened for GDM? (CDA)

  • 24 to 28 weeks


What is the preferred approach to screening and diagnosis of GDM? (CDA)

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What is the alternative approach to screening and diagnosis of GDM? (CDA)

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What are the target glucose values for women with GDM? (CDA)

  • Fasting PG = <5.3 mmol/L
  • 1-hour postprandial = <7.8 mmol/L
  • 2-hour postprandial = <6.7 mmol/L


How long should women with GDM be trialed on nutritional therapy alone before starting insulin therapy? (CDA)

  • 2 weeks


What oral agents can be used for GDM in women who are nonadherent to or refuse to use insulin? (CDA)

  • Metformin
  • Glyburide


What is the evidence comparing metformin to insulin in GDM? (TFP)

  • Metformin results in 1kg less maternal weight gain
  • Less severe neonatal hypoglycaemia for 1 in 22 babies
  • Earlier delivery by about 1 day
  • Other clinical outcomes unchanged
  • Long-term safety reassuring


Why should women with GDM be encouraged to breastfeed immediately after delivery and to continue at least 3 months postpartum? (CDA)

  • Avoids neonatal hypoglycemia
  • Prevent childhood obesity
  • Reduce risk of maternal hyperglycemia


When should women be screened for prediabetes and diabetes postpartum? (CDA)

  • 75 g OGTT between 6 weeks and 6 months


What are the recommended glycemic targets in the frail elderly with diabetes? (CDA)

  • A1c ≤8.5% and fasting plasma glucose or preprandial PG 5.0 – 12.0 mmol/L


Which medications should be used with caution in elderly people with type 2 diabetes? (CDA)

  • Sulphonylureas – risk of hypoglycemia
    • Gliclazide and Gliclazide MR preferred over Glyburide
  • Thiazolidinediones – risk of fractures and heart failure