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Diabetes Flashcards

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1
Q

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

A
  • Blindness
  • ESRD
  • Nontraumatic amputation
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2
Q

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

A
  • Cardiovascular disease – 2-4x higher incidence than in people without diabetes
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3
Q

What is the definition of diabetes mellitus? (CDA)

A
  • A metabolic disorder characterized by the presence of hyperglycemia due to defective insulin secretion, defective insulin action or both
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4
Q

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

A
  • 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
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5
Q

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

A
  • Thresholds of glycemia that are associated with microvascular disease, especially retinopathy
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6
Q

What are the diagnostic criteria for diabetes? (CDA)

A

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%

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7
Q

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

A
  • 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
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8
Q

In which patients may A1c be misleading? (CDA)

A
  • 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
Q

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

A
  • Children
  • Adolescents
  • Pregnant women
  • Suspected Type 1 Diabetes
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10
Q

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

A
  • 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
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11
Q

What are the diagnostic criteria for prediabetes? (CDA)

A

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%

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12
Q

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

A
  • FPG 6.1 to 6.9 mmol/L AND A1c 6.0 to 6.4%
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13
Q

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

A

≥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

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14
Q

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

A
  • No current evidence of clinical benefit
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15
Q

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

A
  • 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?
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16
Q

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

A
  • 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
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17
Q

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

A
  • 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
Q

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

A
  • 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
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19
Q

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

A
  • 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
Q

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

A
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21
Q

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

A
  • 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
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22
Q

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

A
  • 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”]
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23
Q

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

A
  • 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

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24
Q

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

A
  • ACCORD
  • ADVANCE
  • VADT
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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)**
148
**How does renal function affect the use of antihyperglycemic medications? (CDA)**
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
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)**
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)**
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)**
236
**Once a diagnosis of CKD has been made, what 2 tests should be ordered? (CDA)**
* Urine dipstick * Urine microscopy
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)**
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** * **S**ulfonylureas * **A**CE-inhibitors * **D**iuretics, direct renin inhibitors * **M**etformin * **A**ngiotensin receptor blockers * **N**SAIDs
246
**What are the 5 stages of CKD based on renal function? (CDA)**
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?**
272
**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)**
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)**
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)**
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)**
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)**
308
**What is the alternative approach to screening and diagnosis of GDM? (CDA)**
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
Primary Care
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