1. Canadian Diabetes Association 2013 Clinical Practice Guidelines
The Case of Victor

2. Learning Objectives
By the end of this session, participants will be able to:
Understand the major changes within the 2013 CDA clinical practice guidelines
Understand the rationale behind these changes
Apply the recommendations in clinical practice 

3. Faculty for slide deck development
Jonathan Dawrant, BSc, MSc, MD, FRCPC
Zoe Lysy, MDCM, FRCPC
Geetha Mukerji, MD, FACP, FRCPC
Dina Reiss, MD, FACP, FRCPC
Steven Sovran, BSc, MD, MA, FRCPC
Alice Y.Y. Cheng, MD, FRCPC
Peter J. Lin, MD, CCFP
Catherine Yu, MD, FRCPC, MHSc

5. guidelines.diabetes.ca

6. Victor
59 years old
FBS 6.7 mmol/L
A1C 6.2%
Does he have diabetes?

7. Fasting = no caloric intake for at least 8 hours
Diagnosis of Diabetes
2013
FPG ≥7.0 mmol/L
Fasting = no caloric intake for at least 8 hours or
A1C ≥6.5% (in adults)
Using a standardized, validated assay, in the absence of factors that affect the accuracy of the A1C and not for suspected type 1 diabetes
2hPG in a 75-g OGTT ≥11.1 mmol/L
Random PG ≥11.1 mmol/L
Random= any time of the day, without regard to the interval since the last meal
Script:
Diabetes can be diagnosed by many different cut-offs. The biggest change from the previous set of guidelines is that HbA1c > 6.5% is part of diagnostic cut-off if a standardized validated assay is used with absence of other factors that affect A1c and not suspecting Dm. So FBG >7, A1c >6.5%, or 2h PG > 11.1 or random PG >11.1 can be used to used to diagnose diabetes.
Diagnosis of diabetes is based on thresholds of glycemia that are associated with microvascular disease
2hPG = 2-hour plasma glucose; FPG = fasting plasma glucose; OGTT = oral glucose tolerance test; PG = plasma glucose

8. Diagnosis of Prediabetes*
2013
Test
Result
Prediabetes Category
Fasting Plasma Glucose
(mmol/L)
Impaired fasting glucose (IFG)
2-hr Plasma Glucose in a 75-g Oral Glucose Tolerance Test (mmol/L)
7.8 – 11.0
Impaired glucose tolerance (IGT)
Glycated
Hemoglobin
(A1C) (%)
Prediabetes
* Prediabetes = IFG, IGT or A1C %  high risk of developing T2DM

9. Can we delay the onset of his Type 2 Diabetes?

10. Diabetes Prevention Program (DPP)
Years
Benefit of diet and exercise or Metformin on diabetes prevention in at-risk patients
N = 3234 with IFG and IGT, without diabetes 10 20 30 40
1.0
2.0
3.0
4.0
Placebo
Metformin
Lifestyle
Cumulative
incidence of diabetes
(%)
31%
58% P*
< 0.001
*vs placebo
IFG = impaired fasting glucose, IGT = impaired glucose tolerance
In DPP, 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations were randomly assigned to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7% weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body mass index (BMI) was 34; average follow-up was 2.8 years.
Compared to placebo, the lifestyle intervention reduced the incidence of diabetes by 58% (95% CI, 48 to 66%) and metformin reduced the incidence by 31% (95% CI, 17 to 43%); the lifestyle intervention was significantly more effective than metformin.
Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:
Diabetes Prevention Program (DPP) Research Group. N Engl J Med 2002;346:

11. What do you tell him about exercise?

12. Physical Activity Checklist
2013
DO a minimum of 150 minutes of moderate-to vigorous-intensity aerobic exercise per week
INCLUDE resistance exercise ≥ 2 times a week
SET physical activity goals and INVOLVE a multi-disciplinary team
ASSESS patient’s health before prescribing an exercise regimen

13. Pre-exercise Assessment
Assess for conditions that can predispose to injury before prescribing an exercise regimen:
Neuropathy (autonomic and peripheral)
Retinopathy
Coronary artery disease – resting ECG +/- exercise stress test (see CPG Chapter 23)
Peripheral arterial disease

14. Who Should be Screened with ECG?
Age >40 years
Duration of DM >15years +
Age >30 years
End organ damage
Microvascular
Macrovascular
Cardiac risk factors
Baseline resting
ECG
Repeat every 2 years

15. Who Should have Stress Testing and/or Functional Imaging to Screen for CAD?
Typical or atypical cardiac symptoms
Associated diseases:
PAD
Carotid bruits
TIA
Stroke
Resting ECG abnormalities (e.g. Q waves)
Exercise ECG
stress testing
If cannot exercise or resting ECG abnormality present:
Pharmacologic stress echo
Pharmacologic stress nuclear imaging

16. What do you tell him about his diet?

17. Macronutrient Distribution (% Total Energy)
Carbohydrates
Protein
Fat
% of total energy
45-60%
15-20%
(or 1-1.5g / kg BW)
20-35%
Calories per gram 4 9
Grams for 2000 calorie/day diet
75-100
44-78
Protein: g/kg body weight/day is usual representing 15-20%, but this intake in grams/kg/day should be maintained or increased in energy reduced diets.
BW = body weight

18. Choose low glycemic index carbohydrates

19. Lost to follow up and shows up 3 years later
Victor
Lost to follow up and shows up 3 years later
FBS 9.0 mmol/L
A1C 8.3%
What are the A1C targets for Victor?

20. A1C ≤ 7.0% for MOST people with diabetes
2013
Targets Checklist
A1C ≤ 7.0% for MOST people with diabetes
A1C ≤ 6.5% for SOME people with T2DM
A1C % in people with specific features

21. Why ≤ 7%?
Macro and Microvascular Benefits?

22. Legacy Effect of Earlier Glucose Control
After median 8.5 years post-trial follow-up
Aggregate Endpoint
Any diabetes related endpoint RRR: 12% 9% P:
Microvascular disease RRR: 25% 24% P:
Myocardial infarction RRR: 16% 15% P:
All-cause mortality RRR: 6% 13% P:
N Engl J Med Oct 9;359(15): doi: /NEJMoa Epub 2008 Sep 10.
10-year follow-up of intensive glucose control in type 2 diabetes.
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA.
Source
Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology, and Metabolism, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom.
Abstract
BACKGROUND:
During the United Kingdom Prospective Diabetes Study (UKPDS), patients with type 2 diabetes mellitus who received intensive glucose therapy had a lower risk of microvascular complications than did those receiving conventional dietary therapy. We conducted post-trial monitoring to determine whether this improved glucose control persisted and whether such therapy had a long-term effect on macrovascular outcomes.
METHODS:
Of 5102 patients with newly diagnosed type 2 diabetes, 4209 were randomly assigned to receive either conventional therapy (dietary restriction) or intensive therapy (either sulfonylurea or insulin or, in overweight patients, metformin) for glucose control. In post-trial monitoring, 3277 patients were asked to attend annual UKPDS clinics for 5 years, but no attempts were made to maintain their previously assigned therapies. Annual questionnaires were used to follow patients who were unable to attend the clinics, and all patients in years 6 to 10 were assessed through questionnaires. We examined seven prespecified aggregate clinical outcomes from the UKPDS on an intention-to-treat basis, according to previous randomization categories.
RESULTS:
Between-group differences in glycated hemoglobin levels were lost after the first year. In the sulfonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related end point (9%, P=0.04) and microvascular disease (24%, P=0.001), and risk reductions for myocardial infarction (15%, P=0.01) and death from any cause (13%, P=0.007) emerged over time, as more events occurred. In the metformin group, significant risk reductions persisted for any diabetes-related end point (21%, P=0.01), myocardial infarction (33%, P=0.005), and death from any cause (27%, P=0.002).
CONCLUSIONS:
Despite an early loss of glycemic differences, a continued reduction in microvascular risk and emergent risk reductions for myocardial infarction and death from any cause were observed during 10 years of post-trial follow-up. A continued benefit after metformin therapy was evident among overweight patients. (UKPDS 80; Current Controlled Trials number, ISRCTN )
Holman R, et al. N Engl J Med 2008;359.

23. Legacy Effect of Earlier Glucose Control
After median 8.5 years post-trial follow-up
Aggregate Endpoint
Any diabetes related endpoint RRR: 12% 9% P:
Microvascular disease RRR: 25% 24% P:
Myocardial infarction RRR: 16% 15% P:
All-cause mortality RRR: 6% 13% P:
N Engl J Med Oct 9;359(15): doi: /NEJMoa Epub 2008 Sep 10.
10-year follow-up of intensive glucose control in type 2 diabetes.
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA.
Source
Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology, and Metabolism, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom.
Abstract
BACKGROUND:
During the United Kingdom Prospective Diabetes Study (UKPDS), patients with type 2 diabetes mellitus who received intensive glucose therapy had a lower risk of microvascular complications than did those receiving conventional dietary therapy. We conducted post-trial monitoring to determine whether this improved glucose control persisted and whether such therapy had a long-term effect on macrovascular outcomes.
METHODS:
Of 5102 patients with newly diagnosed type 2 diabetes, 4209 were randomly assigned to receive either conventional therapy (dietary restriction) or intensive therapy (either sulfonylurea or insulin or, in overweight patients, metformin) for glucose control. In post-trial monitoring, 3277 patients were asked to attend annual UKPDS clinics for 5 years, but no attempts were made to maintain their previously assigned therapies. Annual questionnaires were used to follow patients who were unable to attend the clinics, and all patients in years 6 to 10 were assessed through questionnaires. We examined seven prespecified aggregate clinical outcomes from the UKPDS on an intention-to-treat basis, according to previous randomization categories.
RESULTS:
Between-group differences in glycated hemoglobin levels were lost after the first year. In the sulfonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related end point (9%, P=0.04) and microvascular disease (24%, P=0.001), and risk reductions for myocardial infarction (15%, P=0.01) and death from any cause (13%, P=0.007) emerged over time, as more events occurred. In the metformin group, significant risk reductions persisted for any diabetes-related end point (21%, P=0.01), myocardial infarction (33%, P=0.005), and death from any cause (27%, P=0.002).
CONCLUSIONS:
Despite an early loss of glycemic differences, a continued reduction in microvascular risk and emergent risk reductions for myocardial infarction and death from any cause were observed during 10 years of post-trial follow-up. A continued benefit after metformin therapy was evident among overweight patients. (UKPDS 80; Current Controlled Trials number, ISRCTN )
Holman R, et al. N Engl J Med 2008;359.

24. Would < 6.5% be good for him?

25. ADVANCE: Glucose Control
10.0
9.0
Standard control 7.3%
8.0
Mean A1C (%)
7.0
p < 0.001
6.0
Intensive control 6.5%
N Engl J Med Jun 12;358(24): doi: /NEJMoa Epub 2008 Jun 6.
Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.
ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F.
The following toggler user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.
Destroy user interface controlCollaborators (1307)
Abstract
BACKGROUND:
In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain.
METHODS:
We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately.
RESULTS:
After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001).
CONCLUSIONS:
A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT )
Reference(s)
The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. New Engl J Med 2008;358:
5.0
0.0 6 12 18 24 30 36 42 48 54 60 66
Follow-up (months)
ADVANCE Collaborative Group. N Engl J Med 2008;358:24.

26. ADVANCE: Treatment Effect on the Primary Microvascular Outcomes
New/worsening nephropathy, retinopathy 25 20
HR 0.86 ( ) p = 0.01
Standard control 15
Cumulative incidence (%) 10
Intensive control 5
N Engl J Med Jun 12;358(24): doi: /NEJMoa Epub 2008 Jun 6.
Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.
ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F.
The following toggler user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.
Destroy user interface controlCollaborators (1307)
Abstract
BACKGROUND:
In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain.
METHODS:
We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately.
RESULTS:
After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001).
CONCLUSIONS:
A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT )
Reference(s)
The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. New Engl J Med 2008;358: 6 12 18 24 30 36 42 48 54 60 66
Follow-up (months)
Intensive
Standard HR p
Nephropathy/retinopathy (%)
9.4
10.9
0.86
0.01
Nephropathy (%)
4.1
5.2
0.79
0.006
Retinopathy (%)
6.0
6.3
0.95 NS
ADVANCE Collaborative Group. N Engl J Med 2008;358:24.

27. When would A1C 7.1-8.5% be acceptable?

28. Consider A1C 7.1-8.5% if … Limited life expectancy
2013
Limited life expectancy
High level of functional dependency
Extensive coronary artery disease at high risk of ischemic events
Multiple co-morbidities
History of recurrent severe hypoglycemia
Hypoglycemia unawareness
Longstanding diabetes for whom is it difficult to achieve an A1C ≤ 7%, despite effective doses of multiple antihyperglycemic agents, including intensified basal-bolus insulin therapy

29. Individualizing A1C Targets
2013
Consider % if:
which must be balanced against the risk of hypoglycemia

30. What do you prescribe for his glucose control?

31. L I F E S T Y 2013 AT DIAGNOSIS OF TYPE 2 DIABETES
Start lifestyle intervention (nutrition therapy and physical activity) +/- Metformin
A1C <8.5%
A1C 8.5%
Symptomatic hyperglycemia with metabolic decompensation
If not at glycemic target (2-3 mos)
Start metformin immediately
Consider initial combination with another antihyperglycemic agent
Initiate insulin +/-
metformin
Start / Increase metformin
If not at glycemic targets
Add an agent best suited to the individual:
Patient Characteristics
Degree of hyperglycemia
Risk of hypoglycemia
Overweight or obesity
Comorbidities (renal, cardiac, hepatic)
Preferences & access to treatment
Other
Agent Characteristics
BG lowering efficacy and durability
Risk of inducing hypoglycemia
Effect on weight
Contraindications & side-effects
Cost and coverage
Other
May start Metformin at the time of diagnosis
Change to 8.5% as threshold
Start metformin immediately as an option
Concept of individualizing therapy based on patient and agent characteristics
With that in mind, the next figure shows the characteristics of the agents ….
2013
See next page…

32. Make timely adjustments to attain target A1C within 3-6 months
From prior page… L I F E S T Y
Concept of RELATIVE A1c lowering – not absolute
Concept of RELATIVE cost considerations
Change to achieve target within 3-6 months.
If not at glycemic target
Add another agent from a different class
Add/Intensify insulin regimen
2013
Make timely adjustments to attain target A1C within 3-6 months

33. Patient Characteristics Agent Characteristics
AT DIAGNOSIS OF TYPE 2 DIABETES L I F E S T Y
Start lifestyle intervention (nutrition therapy and physical activity) +/- Metformin
A1C < 8.5%
A1C  8.5%
Symptomatic hyperglycemia with metabolic decompensation
If not at glycemic target (2-3 mos)
Start metformin immediately
Consider initial combination with another antihyperglycemic agent
Initiate insulin +/-
metformin
Start / Increase metformin
If not at glycemic targets
Add an agent best suited to the individual:
Patient Characteristics
Degree of hyperglycemia
Risk of hypoglycemia
Overweight or obesity
Comorbidities (renal, cardiac, hepatic)
Preferences & access to treatment
Other
Agent Characteristics
BG lowering efficacy and durability
Risk of inducing hypoglycemia
Effect on weight
Contraindications & side-effects
Cost and coverage
Other
May start Metformin at the time of diagnosis
Change to 8.5% as threshold
Start metformin immediately as an option
Concept of individualizing therapy based on patient and agent characteristics
With that in mind, the next figure shows the characteristics of the agents ….
2013
See next page…

34. 2013 guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca
Copyright © 2013 Canadian Diabetes Association

35. Antihyperglycemic agents and Renal Function
Not recommended / contraindicated
Safe
Caution and/or dose reduction
Repaglinide
Metformin 30 60
Saxagliptin
Linagliptin
Glyburide 50
Thiazolidinediones
GFR (mL/min):
< 15
15-29
30-59
60-89
≥ 90
CKD Stage: 5 4 3 2 1
Gliclazide/Glimepiride 15
Liraglutide
Exenatide
Acarbose 25
Sitagliptin
2.5 mg
50 mg
25 mg
Adapted from: Product Monographs as of March 1, 2013; CDA Guidelines 2008; and Yale JF. J Am Soc Nephrol 2005; 16:S7-S10.

36. Victor’s friend passed out because of low sugars What do you tell Victor about Hypoglycemia?

37. Recognize Risk Factors for Severe Hypoglycemia
Risk factors in Type 1 DM patients
Risk factors in Type 2 DM patients
Adolescence
Elderly
Children unable to detect and/or treat mild hypoglycemia
Poor health literacy, Food insecurity
A1C <6.0%
Increased A1C
Long duration of diabetes
Duration of insulin therapy
Prior episode of severe hypoglycemia
Severe cognitive impairment
Hypoglycemia unawareness
Renal impairment
Autonomic neuropathy
Neuropathy
Severe hypoglycemia refers to hypoglycemia resulting in individuals requiring assistance – typicall with a PG of less than 2.8.
There are many risk factors for severe hypoglycemia in T1DM patients including:
The risk factors for type 2 diabetes
Teaching caregivers to administer glucagon should be undertaken especially in those with risk factors for severe hypoglycemia.

38. Steps to Address Hypoglycemia
Recognize autonomic or neuroglycopenic symptoms
Confirm if possible (blood glucose <4.0 mmol/L)
Treat with “fast sugar” (simple carbohydrate) (15 g) to relieve symptoms
Retest in 15 minutes to ensure the BG >4.0 mmol/L and retreat (see above) if needed
Eat usual snack or meal due at that time of day or a snack with 15 g carbohydrate plus protein
Teaching patients to recognize and treat hypoglycemia can be done in 3 steps
1) It is important to teach patients to recognize the common autonomic and neuroglycopenic symptoms associated with hypoglycemia including: Trembling, Palpitations, Sweating, Anxiety, Hunger, Nausea, Tingling which are common autonomic symptoms and Difficulty concentrating, Confusion, Weakness, Vision change, and Headache are common neuroglycopenic symptoms.

39. Hypoglycemia and Driving
Safe blood glucose (BG) prior to driving
BG ≥ 5.0 mmol/L
If BG <5.0 mmol/L prior to driving:
Take 15 g carbohydrate
Re-check in 15 minutes
When BG >5 mmol/L for at least 45 minutes  safe to drive
Need to re-check BG every 4 hours of continuous driving and carry simple carbohydrate snacks
Iain S. Begg et al . Canadian Journal of Diabetes. 2003;27(2):

40. “Do I need to poke my fingers 8 times a day
“Do I need to poke my fingers 8 times a day?” What do you tell Victor about SMBG?

41. Regular SMBG is Required for:

42. Increased frequency of SMBG may be required:
Daily SMBG is not usually required if patient:

43. Should Victor get: Statin ACE-inhibitor or ARB ASA for Vascular Protection

44. Vascular Protection Checklist
2013
A • A1C – optimal glycemic control (usually ≤7%)
B • BP – optimal blood pressure control (<130/80)
C • Cholesterol – LDL ≤2.0 mmol/L if decided to treat
D • Drugs to protect the heart
A – ACEi or ARB │ S – Statin │ A – ASA if indicated
E • Exercise / Eating healthily – regular physical activity, achieve and maintain healthy body weight
S • Smoking cessation

45. Who Should Receive Statins? (regardless of baseline LDL-C)
2013
≥40 yrs old or
Macrovascular disease or
Microvascular disease or
DM >15 yrs duration and age >30 years or
Warrants therapy based on the 2012 Canadian Cardiovascular Society lipid guidelines
Among women with childbearing potential, statins should only be used in the presence of proper preconception counseling & reliable contraception. Stop statins prior to conception.

46. What if baseline LDL-C ≤2.0 mmol/L?
Within CARDS and HPS, the subgroups that started with lower baseline LDL-C still benefited to the same degree as the whole population
If the patient qualifies for statin therapy based on the algorithm, use the statin regardless of the baseline LDL-C and then target an LDL reduction of ≥50%
HPS Lancet 2002;360:7-22
Colhoun HM, et al. Lancet 2004;364:685.

47. Macrovascular disease or Microvascular disease
2013
Who Should Receive ACEi or ARB Therapy? (regardless of baseline blood pressure)
≥55 years of age or
Macrovascular disease or
Microvascular disease
At doses that have shown vascular protection [perindopril 8 mg daily (EUROPA), ramipril 10 mg daily (HOPE), telmisartan 80 mg daily (ONTARGET)]
ACE inhiibitor or ARB therapy should be offered to people with diabetes age ≥55 years, or in the presence of macrovasular disease or microvascular disease. This recommendation is regardless of blood pressure. It is important that the ACEi or ARB be titrated to the doses that have been shown to provide vascular protection since low dose ACE-inhibitor or ARB may not result in any benefit (DIABHYCAR study). These vascular protection benefits have been shown to be present irrespective of baseline blood pressure. Since it is not proven that low dose ACEi or ARB confers the same vascular protection, it is recommended that the ACEi or ARB dose be increased to the vascular protective doses (peripdopril 8mg, ramipril 10 mg, telmisartan 80 mg daily). Given that not all ACEi or ARB have conducted “vascular protection” type of studies and of those that have, not all have been positive, it is justified to titrate to doses shown to have vascular protection.
Among women with childbearing potential, ACEi or ARB should only be used in the presence of proper preconception counseling & reliable contraception. Stop ACEi or ARB either prior to conception or immediately upon detection of pregnancy
EUROPA Investigators, Lancet 2003;362(9386):
HOPE study investigators. Lancet. 2000;355:
ONTARGET study investigators. NEJM. 2008:358:

48. Recommendation
2013
ASA should not be routinely used for the primary prevention of cardiovascular disease in people with diabetes [Grade B, Level 2]
ASA may be used in the presence of additional cardiovascular risk factors [Grade D, Consensus]

49. X

50. What is Victor’s BP Target?

51. Hypertension Checklist
2013
ASSESS for hypertension (≥ 130/80 mmHg)
TREAT to target < 130/80 mmHg
USE multiple antihypertensive medications if needed to achieve target (often necessary)
USE initial combination therapy if systolic blood pressure > 20 mmHg or diastolic blood pressure > 10 mmHg above target

52. Summary of Pharmacotherapy for Hypertension in Patients with Diabetes
Threshold equal or over 130/80 mmHg and Target below 130/80 mmHg
Combination of 2 first line drugs may be considered as initial therapy if the blood pressure is >20 mmHg systolic or >10 mmHg diastolic above target
With Nephropathy, CVD or CV risk factors
ACE Inhibitor or ARB
Diabetes
Without
the above
1. ACE Inhibitor or ARB or
2. Thiazide diuretic or DHP-CCB
> 2-drug combinations
1. Persons with diabetes mellitus should be treated to attain systolic blood pressure of lower than130 mmHg (Grade C) and diastolic blood pressure of less than 80 mmHg (Grade A). (These target blood pressure levels are the same as the blood pressure treatment thresholds.) Combination therapy using two first-line agents may also be considered as initial treatment of hypertension (Grade B) if the SBP is 20 mmHg above the target or if DBP is 10 mmHg above the target. However caution should be exercised in patients in whom a substantial fall in blood pressure is more likely or poorly tolerated (e.g. elderly patients, patients with autonomic neuropathy).
2. For persons with cardiovascular or kidney disease, including microalbuminuria or with cardiovascular risk factors in addition to diabetes and hypertension, an ACE inhibitor or an ARB is recommended as initial therapy (Grade A).
3. For persons with diabetes and hypertension not included in the above recommendation, appropriate choices include (in alphabetical order): ACE inhibitors (Grade A), angiotensin receptor blockers (Grade B), dihydropyridine CCBs (Grade A) and thiazide/thiazide-like diuretics (Grade A).
4. If target blood pressures are not achieved with standard-dose monotherapy, additional antihypertensive therapy should be used. For persons in whom combination therapy with an ACE inhibitor is being considered, a dihydropyridine CCB is preferable to hydrochlorothiazide (Grade A).
Monitor serum potassium and creatinine carefully in patients with CKD prescribed an ACEI or ARB
Combinations of an ACEI with an ARB are specifically not recommended in the absence of proteinuria
More than 3 drugs may be needed to reach target values
If Creatinine over 150 µmol/L or creatinine clearance below 30 ml/min ( 0.5 ml/sec), a loop diuretic should be substituted for a thiazide diuretic if control of volume is desired 52

53. What is Victor’s LDL target?

54. If on therapy, target LDL ≤ 2.0 mmol/L
Increase the statin dose and continue to monitor

55. Gastrointestinal intolerability TG elevation
Drug Class
Generic name (Trade name)
Principal effects
Other considerations
Bile Acid Sequestrant
Cholestyramine resin (Questran)
Colestipol HCl (Colestid)
Colesevalam (Lodalis)
Lowers LDL-C
Gastrointestinal intolerability
TG elevation
Colesevelam: A1C lowering effect
Cholesterol Absorption Inhibitor
Ezetimibe (Ezetrol)
Effective in combination with statin
Fibrate
Bezafibrate (Bezalip SR)
Fenofibrate (Lipidil)
Gemfibrozil (Lopid)
Lowers TG
Variable LDL-C effect
Variable HDL-C effect
May creatinine + homocysteine (but long term fenofibrate use has favorable renal effects)
Do not combine gemfibrozil + statin
Nicotinic Acid
ER Niacin (Niaspan, Niaspan FCT)
IR Niacin (non-prescription)
LA (“no-flush”) Niacin – not recommended
Lower TG + LDL-C
Raise HDL-C
Dose related deterioration in glycemia
ER Niacin more tolerable than IR
Long-acting niacin should NOT be used
ER = extended release; IR = immediate release; LA=long acting; TG=triglycerides; FCT=film coated tablet; SR=sustained release

56. “Why do you keep testing my urine?” What do you tell Victor?

57. Chronic Kidney Disease (CKD) Checklist
2013
Chronic Kidney Disease (CKD) Checklist
SCREEN regularly with random urine albumin creatinine ratio (ACR) and serum creatinine for estimated glomerular filtration rate (eGFR)
DIAGNOSE with repeat confirmed ACR ≥ 2.0 mg/mmol and/or eGFR < 60 mL/min
DELAY onset and/or progression with glycemic and blood pressure control and ACE inhibitor or angiotensin receptor blocker (ARB)
PREVENT complications with “sick day management” counselling and referral when appropriate
Use same check marks as Geetha

58. Counsel all Patients About Sick Day Medication List
2013

59. When to Refer….. 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 a >30% increase in serum Cr within 3 months of starting ACEi or ARB
Unable to achieve target BP (could be referred to any specialist in hypertension)
guidelines.diabetes.ca | BANTING ( ) | diabetes.ca
Copyright © 2013 Canadian Diabetes Association

60. “My grandmother went blind from diabetes – I am afraid of that
“My grandmother went blind from diabetes – I am afraid of that.” What do you tell Victor?

61. Retinopathy Checklist
2013
SCREEN regularly
DELAY onset and progression with glycemic and blood pressure control ± fibrate
TREAT established disease with laser photocoagulation, intra-ocular injection of medications or vitreoretinal surgery
Use same check marks as Geetha

62. Delaying Retinopathy Glycemic control: target A1C ≤7%
Blood pressure control: target BP <130/80
Lipid-lowering therapy: fibrates have been shown to decrease progression and may be considered
2013

63. Victor heard that amputations are highest in people with diabetes What do you tell Victor?

64. Patients with DM are 20X More Likely to be Hospitalized for Non-traumatic Limb Amputation
Public Health Agency of Canada (August 2011); using 2008/09 data from the Canadian Chronic Disease Surveillance System (Public Health Agency of Canada).

65. Educate patients on proper foot care – The “DO’s”
Check your feet every day for cuts, cracks, bruises, blisters, sores, infections, unusual markings
Use a mirror to see the bottom of your feet if you can not lift them up
Check the colour of your legs & feet – seek help if there is swelling, warmth or redness
Wash and dry your feet every day, especially between the toes
Apply a good skin lotion every day on your heels and soles. Wipe off excess.
Change your socks every day
Trim your nails straight across
Clean a cut or scratch with mild soap and water and cover with dry dressing
Wear good supportive shoes or professionally fitted shoes with low heels (under 5cm)
Buy shoes in the late afternoon since your feet swell by then
Avoid extreme cold and heat (including the sun)
See a foot care specialist if you need advice or treatment

66. Educate patients on proper foot care – The “DON’Ts”
DO NOT …
Cut your own corns or callouses
Treat your own in-growing toenails or slivers with a razor or scissors. See your doctor or foot care specialist
Use over-the-counter medications to treat corns and warts
Apply heat with a hot water bottle or electric blanket – may cause burns unknowingly
Soak your feet
Take very hot baths
Use lotion between your toes
Walk barefoot inside or outside
Wear tight socks, garter or elastics or knee highs
Wear over-the-counter insoles – may cause blisters if not right for your feet
Sit for long periods of time
Smoke

67. “I get numbness in my toes.” What do you tell Victor?

68. Sensorimotor poly- or mono-neuropathy Increased risk for:
40-50% of people with DM will have detectable neuropathy within 10 years
Sensorimotor poly- or mono-neuropathy
Increased risk for:
Foot ulceration and amputation
Neuropathic pain
Significant morbidity
Usage of health care resources

69. PREVENT with blood glucose control
Neuropathy Checklist
2013
PREVENT with blood glucose control
SCREEN with monofilament or tuning fork
TREAT pain symptoms with anticonvulsants or antidepressants
Use Geetha’s check marks

70. Recommendation 4
2013
The following agents may be used alone or in combination for relief of painful peripheral neuropathy:
Anticonvulsants (pregabalin [Grade A, Level 1], gabapentin‡, valproate‡) [Grade B, Level 2]
Antidepressants (amitriptyline‡, duloxetine, venlafaxine‡) [Grade B, Level 2]
Opioid analgesics (tapentadol ER, oxycodone ER, tramadol) [Grade B, Level 2]
Topical nitrate spray [Grade B, Level 2]
‡This drug is not currently approved by Health Canada for the management of neuropathic pain associated with diabetic peripheral neuropathy.

71. What are the options for Insulin?

72. Insulin Type (trade name)
Types of Insulin
Insulin Type (trade name)
Onset
Peak
Duration
Bolus (prandial) Insulins
Rapid-acting insulin analogues (clear):
Insulin aspart (NovoRapid®)
Insulin glulisine (Apidra™)
Insulin lispro (Humalog®)
min h
1 - 2 h
3 - 5 h h
Short-acting insulins (clear):
Insulin regular (Humulin®-R)
Insulin regular (Novolin®geToronto)
30 min
2 - 3 h
6.5 h
Basal Insulins
Intermediate-acting insulins (cloudy):
Insulin NPH (Humulin®-N)
Insulin NPH (Novolin®ge NPH)
1 - 3 h
5 - 8 h
Up to 18 h
Long-acting basal insulin analogues (clear)
Insulin detemir (Levemir®)
Insulin glargine (Lantus®)
90 min
Not applicable
Up to 24 h
(glargine 24 h,
detemir h)

73. Insulin Type (trade name)
Types of Insulin (continued)
Insulin Type (trade name)
Time action profile
Premixed Insulins
Premixed regular insulin – NPH (cloudy):
30% insulin regular/ 70% insulin NPH
(Humulin® 30/70)
(Novolin®ge 30/70)
40% insulin regular/ 60% insulin NPH
(Novolin®ge 40/60)
50% insulin regular/ 50% insulin NPH
(Novolin®ge 50/50)
A single vial or cartridge contains a fixed ratio of insulin
(% of rapid-acting or short-acting insulin to % of intermediate-acting insulin)
Premixed insulin analogues (cloudy):
30% Insulin aspart/70% insulin aspart protamine
crystals (NovoMix® 30)
25% insulin lispro / 75% insulin lispro protamine
(Humalog® Mix25®)
50% insulin lispro / 50% insulin lispro protamine
(Humalog® Mix50®)

74. Analogue Basal: Lantus, Levemir
Serum Insulin Level
Time
Analogue Bolus: Apidra, Humalog, NovoRapid
Human Basal: Humulin-N, Novolin ge NPH
Analogue Basal: Lantus, Levemir
Human Bolus: Humulin-R, Novolin ge Toronto

75. Serum Insulin Level Time
Human Premixed: Humulin 30/70, Novolin ge 30/70
Analogue Premixed: Humalog Mix25, NovoMix 30

76. What if we do all of the vascular protective steps for Victor – What will happen?

77. STENO-2: Intensive Group Achieved Targets
Patients in the intensive arm significantly achieved targets for glycemia (A1c<6.5%), cholesterol < 175 mg/dL, SBP < 130 and DBP < 80 compared to the conventional arm in the study.
Gaede et al. NEJM. 2003: 348;

78. Intensive Group had Improved CV Outcomes60
P = 0.007 50
53 % RRR
Any CV event
NNT = 5
Conventional therapy 40
Intensive therapy 30 20
Intensive Therapy Resulted in Improved Combined CV OutcomesSignificantly fewer primary endpoints (a composite of CV death, non-fatal stroke or MI, revascularization, or amputation) occurred in the Intensive treatment group. 10 12 24 36 48 60 72 84 96
Months of Follow-up
RRR= relative risk reduction
Gaede et al. NEJM. 2003: 348;

79. STENO 2 – Microvascular Disease
Gaede et al. NEJM. 2003: 348;

80. How can we keep track of all the parameters for Victor?

81. Tools to help us keep track of our patients

82. Tools to help us keep track of our patients

83. Back Page:
“Cheat Sheet” of Targets and Goals

84. Back Page:
“Cheat Sheet” of Targets and Goals

85. “Neither evidence nor clinical judgment alone is sufficient
“Neither evidence nor clinical judgment alone is sufficient. Evidence without judgment can be applied by a technician. Judgment without evidence can be applied by a friend. But the integration of evidence and judgment is what the healthcare provider does in order to dispense the best clinical care.”
(Hertzel Gerstein, 2012)

86. CDA Clinical Practice Guidelines
– for professionals
1-800-BANTING ( )
– for patients