1. The Essentials John MacFadyen, MD FRCPC, MHPE
Canadian Diabetes Association 2013 Clinical Practice Guidelines
The Essentials John MacFadyen, MD FRCPC, MHPE

2. CDA Guidelines - Essentials
Diagnostic Criteria
Diabetes
Pre-Diabetes
Gylycemic Goals
Approach to Glycemic Therapies
Vascular Prevention Strategies
What is not included in the guidelines

3. 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

4. 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

5. A1C Level and Future Risk of Diabetes: Systematic Review
A1C Category (%)
5-year incidence of diabetes
<5 to 9%
9 to 25%
25 to 50%
Script: Zhang et al did a systematic review on A1c level and future risk of diabetes and you as the A1C increased from 6.0 to 6.5%, this covereted to a 5-year incidence of diabetes across 25% -50%.
Zhang X et al. Diabetes Care. 2010;33:

6. 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

7. Please indicate your recommended A1C target for the following patient profiles:
 45 yo female with newly diagnosed DM on Metformin therapy
< >9.0
65 yo male with DM x 15 years, on Metformin and Diamicron MR with history of prev. PCI and stable angina Class II
45 yo female from a group home, DM x 10 years on maximal oral agents
  < >9.0
84 yo male from Nursing home, on Metformin, Diamicron MR and Lantus insulin   < >9.0

8. Speaker’s Notes
This study demonstrated that the older a patient is upon diagnosis of type 2 diabetes, the less he or she is at risk of blindness or renal insufficiency. In addition, the effect of A1C on this risk also decreases with increasing age at diagnosis.

9. OUTCOME (INTENSIVE VS STANDARD) Median A1c (%) 6.4 vs 7.5 6.4 vs 7.0
ACCORD
ADVANCE
VADT
OUTCOME (INTENSIVE VS STANDARD)
Median A1c (%)
6.4 vs 7.5
6.4 vs 7.0
6.9 vs 8.4
CV death (%)
2.6 vs 1.8
4.5 vs 5.2
2.1 vs 1.7
Nonfatal MI
3.6 vs 4.6
2.7 vs 2.8
6.1 vs 6.3
Nonfatal stroke
1.3 vs 1.2
3.8 vs 3.8
2.0 vs 3.1
All-cause mortality
5.0 vs 4.0
8.9 vs 9.6
11.4 vs 10.6
Major hypoglycemia (requiring assistance)
3.1 vs 1.0 %/yr
0.7 vs 0.4 %/yr
3 vs 9 /100 pt-yr
FACILITATOR NOTES
The ACCORD study was stopped early because of a slight increase in CV and All-cause mortality in the intensively treated group as shown in the red. There was one macrovascular outcome in favour of intensive therapy which was non-fatal MI as shown in the green. Both ADVANCE and VADT showed no difference in macrovasular outcomes.

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

11. (depending on level of frailty)
2013
Among frail elderly
Parameter
Target
A1C
≤ 8.5%
FPG or
preprandial glucose
mmol/L
(depending on level of frailty)
AVOID HYPOGLYCEMIA
FPG= fasting plasma glucose

12. A1c Average glucose 6% 7.0 7% 8.6 8% 10.1 9% 11.7 10% 13.3 11% 14.9
12%
16.5
ABG in mmol/L = (1.583 * A1c) – Nathan D, et al. Diab Care 31(8):1473-8, 2008.

13. Individualized Target A1C
Miller’s Rule: if patient > 70 years old
then target A1C = age / 10
eg – age 85 – Target A1C 8.5

14. Individualized Target A1C
MacFadyen’s Corollary – added to Miller’s Rule
If Advanced Vascular Complications
Cognitive Impartment/Poor Self Care
Significant Hypoglycemia
Disease Duration > yrs
then add 0.5 each – max 9.0
Eg Age MI + prev episode hypoglycemic seizure
= Target – 8.5

15. Individualized Target Blood Glucoses
MacFadyen’s Rule
Goal Glucose = Goal A1C -2 /+ 3
Eg. If target A1c is 8.5
most sugars should be between 6.5 – 11.5

16. Self-Monitoring of Blood Glucose (SMBG) What should we tell patients to do?

17. Regular SMBG is Required for:

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

19. 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

20. 1. Modest weight loss CAN make a difference
Goal is to prevent weight gain, promote weight loss and prevent weight re-gain
Weight loss of only 5-10% improves:
Insulin sensitivity
Glycemic control
Blood pressure
Lipid levels

21. Pharmacotherapy in T2DM checklist
2013
CHOOSE initial therapy based on glycemia
START with Metformin +/- others
INDIVIDUALIZE your therapy choice based on characteristics of the patient and the agent
REACH TARGET within 3-6 months of diagnosis

22. 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…

23. 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

25. Consider weight effects when selecting antihyperglycemic medications
Weight Gain
Weight Effect (kg)
Insulin
+4.5 to 5.0
Thiazolidenediones (TZDs)
+4.2 to 4.8
Sulfonylureas
+1.6 to 2.6
Meglitinides
+ 0.7 to 1.8
Weight Neutral or Decrease Weight
Metformin
-4.6 to 0.4
α-Glucosidase inhibitors
+0.0 to 0.2
Dipeptidyl peptidase-4 (DPP-4) inhibitors
+0.0 to 0.4
Glucagon-like peptide-1 (GLP-1) receptor agonists
-1.3 to 3.0
Anti-Diabetes and Anti-Obesity Medications: Effects on Weight in People With Diabetes
Priscilla Hollander, MD
Abstract
In Brief
Choosing medications for people with diabetes involves consideration of a number of factors, including effects on weight. Improvements in glucose control are often linked to weight gain, but this does not have to be the inevitable result of diabetes treatment. Adding a drug that either promotes weight-loss or is weight neutral to one that promotes weight gain and providing medical nutrition therapy can be considered.
Hollander, P. Diabetes Spectrum 2007; 20(3):

26. 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.

27. Measure Lipids at Diagnosis
Repeat yearly if treatment not started
Repeat q3-6mos if on treatment
Fasting (8-hr) profile:
Total cholesterol, triglycerides, HDL-C, LDL-C or
Non-fasting profile:
ApoB
Non-HDL-C

28. Who Should Receive Statins?
2013
≥40 yrs old or
Macrovascular disease or
Microvascular disease or
DM >15 yrs duration and age >30 yrs or
Warrant 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.
guidelines.diabetes.ca | BANTING ( ) | diabetes.ca
Copyright © 2013 Canadian Diabetes Association

29. If on therapy, target LDL ≤2.0 mmol/L

30. Second line agents : Only if LDL-C target not reached with statin
Bile acid sequestrants
Cholesterol absorption inhibitors
Fibrates
Nicotinic acid

31. If Triglycerides > 10.0 mmol/L …
2013
If Triglycerides > 10.0 mmol/L …
Use a FIBRATE to reduce the risk of pancreatitis
Optimize glycemic control
Implement lifestyle interventions
Weight loss
Optimal dietary strategies
Reduce alcohol

32. Who Should Receive ACEi or ARB Therapy?
2013
Who Should Receive ACEi or ARB Therapy?
≥55 years of age or
Macrovascular disease or
Microvascular disease
At doses that have shown vascular protection (ramipril 10 mg daily, perindopril 8 mg daily, telmisartan 80 mg daily)
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

33. 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

34. ADA 2013
Hypertension/Blood Pressure Control has been revised to suggest that the systolic blood pressure goal for many people with diabetes and hypertension should be <140 mmHg, but that lower systolic targets (such as <130 mmHg) may be appropriate for certain individuals, such as younger patients, if it can be achieved without undue treatment burden.

35. No. of events/No. in group
ASA
Control/placebo
RR (95% CI)
RR (95% CI)
Major CV events
ASA for 1⁰ Prevention in Diabetes Meta analysis of 6 studies (n = 10,117)
JPAD
POPADAD
WHS
PPP
ETDRS
Total
68/1262
105/638
58/514
20/519
350/1856
601/4789
86/1277
108/638
62/513
22/512
379/1855
657/4795
0.80 ( )
0.97 ( )
0.90 ( )
0.90 ( )
0.90 ( )
0.90 ( )
Myocardial infarction
JPAD
POPADAD
WHS
PPP
ETDRS
PHS
Total
28/1262
90/638
36/514
5/519
241/1856
11/275
395/5064
14/1277
82/638
24/513
10/512
283/1855
26/258
439/5053
0.87 ( )
1.10 ( )
1.48 ( )
0.49 ( )
0.82 ( )
0.40 ( )
0.86 ( )
No overall benefit for:
Major CV events MI
Stroke
CV mortality
All-cause mortality
Stroke
JPAD
POPADAD
WHS
PPP
ETDRS
Total
12/1262
37/638
15/514
9/519
92/1856
181/4789
32/1277
50/638
31/513
10/512
78/1855
201/4795
0.89 ( )
0.74 ( )
0.46 ( )
0.89 ( )
1.17 ( )
0.83 ( )
Death from CV causes
This meta-analysis examined whether ASA is beneficial for patients with diabetes who have no clinical evidence of CVD. Of 6 eligible studies included in the meta-analysis of over 10,000 participants, there is no statistically significant reduction in the risk of Major CV events, MI, stroke, CV mortality or all-cause mortality when ASA was compared with placebo for primary prevention among patients with diabetes.
Of 157 studies in the literature searches, six were eligible (10,117 participants). When ASA was compared with placebo, there was no statistically significant reduction in the risk of major CV events (five studies, 9,584 participants; RR 0.90; 95% CI ), CV mortality (four studies, 8,557 participants; RR 0.94; 95% CI ), or all-cause mortality (four studies, 8,557 participants; RR 0.93; 95% CI ).
Significant heterogeneity was found in the analyses for MI (I2 = 62.2%; p = 0.02) and stroke (I2 = 52.5%; p = 0.08). ASA significantly reduced the risk of MI in men (RR 0.57; 95% CI ) but not in women (RR 1.08; 95% CI ; p for interaction = 0.056). Evidence relating to harms was inconsistent.
These authors concluded that a clear benefit of ASA in the primary prevention of major CV events in people with diabetes remains unproved, that sex may be an important effect modifier, and that toxicity is to be explored further.
The analysis shows ASA has benefit for men in prevention of MI but not for stroke prevention, but no benefit in women for either MI or stroke prevention
Reference:
De Berardis G, Sacco M, Strippoli GF, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials. BMJ 2009; 339:b4531.
JPAD
POPADAD
PPP
ETDRS
Total
1/1262
43/638
10/519
244/1856
298/4275
10/1277
35/638
8/512
275/1855
328/4282
0.10 ( )
1.23 ( )
1.23 ( )
0.87 ( )
0.94 ( )
JPAD = Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes
POPADAD = Prevention of Progression of Arterial Disease and Diabetes
PPP = Primary Prevention Project
ETDRS = Early Treatment Diabetic Retinopathy Study
PHS = Physicians’ Health Study
WHS = Women’s Health Study
De Beradis G, et al. BMJ 2009; 339:b4531.
All-cause mortality
JPAD
POPADAD
PPP
ETDRS
Total
34/1262
94/638
25/519
340/1856
493/4275
38/1277
101/638
20/512
366/1855
525/4282
0.90 ( )
0.93 ( )
1.23 ( )
0.91 ( )
0.93 ( ) 2
0.03
0.125
0.5 1 8
Favors ASA
Favors control/placebo

37. 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

38. 2013
CKD in diabetes
ACR ≥ 2.0 mg/mmol
and/or
eGFR < 60 mL/min

39. Reducing progression of diabetic nephropathy
Optimal glycemic control
Optimal blood pressure control
ACE-inhibitor or Angiotensin receptor blocker (ARB)

40. Counsel all Patients About Sick Day Medication List
2013

41. Bariatric Surgery is Appropriate in Select Refractory Cases
2013
Bariatric Surgery is Appropriate in Select Refractory Cases
Class III (BMI ≥ 40 kg/m2), or class II (BMI kg/m2) obesity with comorbidities
Assessment by interdisciplinary team
Medical, surgical, psychiatric, and nutritional
Laparoscopic Roux-en-Y gastric bypass or biliopancreatic diversion with duodenal switch
Long-term medical follow up
Be aware of any provincial regulations with respect to bariatric surgery

42. What isn’t in the CDA Guidelines but still important to consider

43. Exenatide: 68% of 3-Year Completers Both Lost Weight and Had Reduced HbA1c15
10% 6% 10 5
CITATION Klonoff DC, Buse JB, Nielsen LL, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin. 2008;24:
SEE pg 280 Figure 3-B (for slide data and background information)
DISCUSSION
Two hundred seventeen patients in the 3-year completer population were analyzed by body weight change and HbA1c change to reach the following conclusions.
The majority of patients experienced reduction in both HbA1c and body weight:
68% of patients experienced reduction in HbA1c and body weight
16% of patients experienced increased HbA1c and decreased body weight
10% of patients experienced decreased HbA1c and increased body weight
6% of patients experienced increased HbA1c and body weight
SLIDE BACKGROUND
Patients with type 2 diabetes mellitus treated with metformin (MET) and/or sulphonylurea (SFU) were randomized to receive placebo or exenatide in the original placebo-controlled, double- blind, Phase 3, randomized trials and received exenatide in the subsequent open-label extension.
At the time of this analysis, all patients (N=217) had received 3 years of exposure to exenatide. -5
Weight Change from Baseline (kg)
-10
-15
-20
-25
68%
16%
-30 -5 -4 -3 -2 -1 1 2 3 4 5
HbA1c Change from Baseline (%)
N=217
Adapted from Klonoff DC, et al. Curr Med Res Opin 2008;24: 43

44. What is not included in the CDA Guidelines
Ensure that evidence for glycemic benefit with incretin agents
Consider adding back oral agents to patients on insulin if no previous exposure
Identify “super-responders”

45. “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)

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