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Flashcards in Diabetes Deck (316):
1

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

  • Blindness
  • ESRD
  • Nontraumatic amputation

2

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

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

3

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

4

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

5

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

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

6

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)

≥6.5%

7

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

8

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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9

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

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

10

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

11

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

Prediabetes

6.0-6.4%

12

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%

13

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)

TG

≥1.7 mmol/L

HDL

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

BP

SBP ≥130 mm Hg and/or DBP ≥85 mm Hg

FPG

≥5.6 mmol/L

14

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

  • No current evidence of clinical benefit

15

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?

16

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

17

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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18

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

19

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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20

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

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21

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

22

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”]

23

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

24

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

  • ACCORD
  • ADVANCE
  • VADT

25

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

26

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

27

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

28

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

29

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

30

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%

31

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

32

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)

33

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

34

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

35

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

36

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

37

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)

38

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

39

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

40

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

41

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

42

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

43

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

44

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

45

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

46

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

47

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

48

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

49

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

  • 1.0 to 2.0%

50

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

51

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

  • 80-90%

52

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%

53

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

54

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

55

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)

56

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

57

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

58

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

  • 7%

59

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)

60

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)

61

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)

62

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

63

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

64

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

65

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)

66

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

67

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

  • Aspart or Lispro

68

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

  • Determir or Glargine

69

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 ***

70

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)

71

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

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

72

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)

73

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

74

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

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

75

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)

76

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

77

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)

78

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

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

79

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

80

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

  • Hypoglycemia

81

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

82

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)

83

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

  • 20 to 50%

84

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

85

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

  • 3 to 6 months

86

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

  • 3 to 6 months

87

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

88

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

89

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

  • Metformin

90

How does metformin work to treat diabetes? (CDA)

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

91

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

92

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

  • 1.0-1.5%

93

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

  • Negligible

94

How does metformin affect weight? (CDA)

  • Weight neutral

95

What are 4 contraindications to metformin use? (UTD)

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

96

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)

97

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)

98

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

  • Acarbose (Glucobay)

99

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

  • 0.6%

100

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

  • Negligible

101

How does acarbose affect weight? (CDA)

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

102

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

  • DPP-4 inhibitor
  • GLP-1 receptor agonist

103

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

  • Sitagliptin (Januvia)
  • Linagliptin (Trajenta)

104

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

  • 0.7%

105

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

  • Negligible

106

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

  • Weight neutral

107

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

  • Rare cases of pancreatitis

108

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)

109

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

  • Liraglutide (Victoza)

110

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

  • 1.0%

111

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

  • Negligible

112

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

  • Significant weight loss

113

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

  • Parenteral administration

114

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

  • Nausea and vomiting
  • Rare cases of pancreatitis

115

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)

116

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

  • 0.9-1.1%

117

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

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

118

What are 2 types of insulin secretagogues? (CDA)

  • Sulfonylureas
  • Meglitinides

119

What are 2 examples of sulfonylureas? (CDA)

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

120

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

  • 0.8%

121

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

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

122

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

  • Hypoglycemia
  • Weight gain

123

What is an example of a meglitinide? (CDA)

  • Repaglinide (GlucoNorm)

124

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

  • 0.7%

125

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

  • Minimal/moderate risk

126

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

127

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

128

What are 3 examples of SGLT2 inhibitors? (CDA)

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

129

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

  • 0.7-1.0%

130

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

  • Negligible

131

How do SGLT2 inhibitors affect weight? (CDA)

  • Weight loss

132

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

133

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

134

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

135

What are 2 examples of TZDs? (CDA)

  • Pioglitazone (Actos)
  • Rosiglitazone (Avandia)

136

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

  • 0.8%

137

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

  • Negligible

138

How do TZDs affect weight? (CDA)

  • Weight gain

139

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)

140

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

  • 0.5%

141

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

  • Negligible

142

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

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

143

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) =
  5.  
  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%

144

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

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

145

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

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

146

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

147

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

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148

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

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149

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

150

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

151

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

152

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

153

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

154

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

155

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

  • 20%

156

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

157

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

158

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)

159

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

160

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

161

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

162

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

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

163

What are 8 neuroglycopenic symptoms of hypoglycemia? (CDA)

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

164

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

165

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

  • Dementia

166

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

167

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

168

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

169

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

170

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

171

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

172

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

173

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

174

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

175

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

176

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

177

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)

178

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

179

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

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

180

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

181

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

  • Lower glucose levels
    • Case reports of euglycemic DKA

182

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

183

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

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

184

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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185

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

186

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

187

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

  • Central pontine myelinolysis

188

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

189

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

190

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

191

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

  • Only in extreme acidosis of pH ≤ 7.0

192

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

193

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

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194

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

195

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

  • 78%

196

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

197

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

  • 10 to 15 years

198

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

199

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

  • <130/80

200

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

201

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

202

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

203

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

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

204

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

205

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

206

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

  • 65-80%

207

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

  • 1/3

208

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

209

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

  • Every 2 years

210

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)

211

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

212

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)

213

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

  • Yearly

214

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

  • ≤2.0 mmol/L

215

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

216

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

217

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

218

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

219

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

  • Fibrate
    • Reduces the risk of pancreatitis

220

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

  • <1.5 mmol/L

221

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

  • < 130/80 mm Hg

222

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

223

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

  • ACEi or ARB

224

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

225

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

  • Dihydropyridine CCB

226

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

227

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

  • Albuminuria

228

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

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229

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

  • Hypertensive nephropathy
  • Ischemic nephropathy

230

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

231

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

232

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

233

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

234

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

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

235

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

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236

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

  • Urine dipstick
  • Urine microscopy

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237

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

238

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

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239

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)

240

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

  • Equal

241

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

242

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

243

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

244

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

  • No – increased risk of congenital malformations

245

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

246

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

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247

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

248

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)

249

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

250

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%)

251

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

252

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

  • Fenofibrate

253

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)

254

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

255

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

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

256

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

  • 30 to 50%

257

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

  • Anticonvulsants
  • Antidepressants

258

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)

259

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)

260

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

  • Opioids

261

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

262

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

263

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

  • Annually
    • Higher frequency in those at high risk)

264

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

265

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

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

266

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

  • Charcot foot

267

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

268

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

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

269

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

  • 34 to 45%

270

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

  • 1/3

271

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

273

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

274

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

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

275

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

276

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

277

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

  • Cerebral edema

278

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

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279

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)

280

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

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281

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

  • 15 to 30%

282

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

  • 4 to 9%
    • 60 to 70% asymptomatic

283

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

284

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

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285

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%

286

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

Characteristic

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

Yes

Yes

287

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

288

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

  • Every 2 years

289

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

  • FPG

290

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

291

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

  • ≤7.0%

292

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

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

293

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

  • Metformin
  • Glimepiride
  • Insulin

294

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

295

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

  • Annually at time of diagnosis

296

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

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297

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

298

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)

299

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

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

300

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

301

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

302

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

303

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

  • Metformin
  • Glyburide

304

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

  • Thyroiditis = TSH test at 6-8 week postpartum

305

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

306

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

  • 24 to 28 weeks

307

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

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308

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

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309

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

310

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

  • 2 weeks

311

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

  • Metformin
  • Glyburide

312

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

313

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

314

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

  • 75 g OGTT between 6 weeks and 6 months

315

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

316

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