1. The Essentials 5th Annual CE LHIN CME
Canadian Diabetes Association 2013 Clinical Practice Guidelines
The Essentials 5th Annual CE LHIN CME

2. Dr. John Sigalas Endocrinologist Rouge Valley Health System Toronto
May 15 , 2013

3. 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 

4. 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. Victor
59 years old
Type 2 Diabetes
TIA 2005
Stroke 2006
MI 2003
MI 2004
Bypass 2001
PAD 2002
Ischemic Toes Amputation 2004
Neuropathy 2003
CKD 2002
Retinopathy 2004
ACS 2001

6. Reorganize his history
Victor
59 years old
Type 2 Diabetes
He has EVERY complication of Diabetes
That is what we need to avoid
TIA 2005
Stroke 2006
PAD 2002
Ischemic Toes Amputation 2004
MI 2003
MI 2004
Bypass 2001
ACS 2001
Macrovascular
Neuropathy 2003
CKD 2002
Retinopathy 2004
Microvascular
Neuropathy 2002

9. What is new in making the diagnosis of diabetes?

10. 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

11. 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

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

13. Diabetes in Canada: Prevalence by Province and Territory
Age-standardized† prevalence of diagnosed DM among individuals ≥ 1 year, 2008/09
< 5.0
5.0 < 5.5
5.5 < 6.0
6.0 < 6.5
≥ 6.5 YT
5.4% NT
5.5% NU
4.4% NL
6.5% BC
5.4% AB
4.9% MB
5.9%
Source: Public Health Agency of Canada (September 2011); using 2008/09 data from the Canadian Chronic Disease Surveillance System (Public Health Agency of Canada). PE
5.6% SK
5.4% QC
5.1% ON
6.0% NS
6.1% NB
5.9%
† Age-standardized to the 1991 Canadian population.
NL, NS and ON had the highest prevalence, while NU, AB and QC had the lowest.
Public Health Agency of Canada. Diabetes in Canada: Facts and figures from a public health perspective. Ottawa, 2011. 13

14. Diabetes in Canada: Prevalence of Diagnosed Diabetes by age and sex
Prevalence of diagnosed diabetes among individuals aged ≥ 1 year, by age group and sex, 2008/09
Overall Prevalence 30
6.4%
Females 25
7.2%
Males 20
Total
6.8%
Prevalence (%) 15 10
Source: Public Health Agency of Canada (July 2011); using 2008/09 data from the Canadian Chronic Disease Surveillance System (Public Health Agency of Canada). 5
Age group (years)
1-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
≥85
Canada
Prevalence increased with age. The sharpest increase occurred after age 40 years. The highest prevalence was in the year age group.
Public Health Agency of Canada. Diabetes in Canada: Facts and figures from a public health perspective. Ottawa, 2011. 14

15. Patients with DM are more likely to be hospitalized for many conditions
Public Health Agency of Canada (August 2011); using 2008/09 data from the Canadian Chronic Disease Surveillance System (Public Health Agency of Canada).

16. Guideline Targets Achieved
% of patients
ABSTRACT
Objective: To gain insight into the current management of patients with type 2 diabetes mellitus (T2DM)
by Canadian primary care physicians.
Methods: 479 primary care physicians from across Canada submitted data on 5123 T2DM patients whom
they had seen on a single day on or around World Diabetes Day, November 14th, 2012.
Results: Mean A1C was 7.4%, LDL-C 2.1 mmol/L and blood pressure 128/75 mmHg. A1C≤7.0% was
met by 50%, LDL-C ≤2.0 mmol/L by 57%, BP <130/80 mmHg by 36% and the composite triple target by
13% of patients. Diet counselling had been offered to 38% of patients. Of the 87% prescribed
antihyperglycemic agents, 18% were on 1 non-insulin antihyperglycemic agent (NIAHA) (85% of which
was metformin), 15% 2 NIAHAs, 6% ≥3 NIAHAs, 19% insulin only and 42% insulin+≥1 NIAHA(s).
Amongst the 81% prescribed lipid-lowering therapy, 88% were on monotherapy (97% of which was a
statin). Amongst the 83% prescribed antihypertensive agents, 39%, 34% and 21% and 6% received 1, 2,
3 and >3 drugs, respectively, with 59% prescribed angiotensin-converting enzyme inhibitors and 35%
angiotensin II receptor blockers.
Conclusion: The DM-SCAN survey highlights the persistent treatment gap associated with the treatment
of T2DM and the challenges faced by primary care physicians to gain glycemic control and global
vascular protection in these patients. It also reveals a higher use of insulin therapy in primary care
practices relative to previous surveys. Practical strategies aimed at more effectively managing T2DM
patients are urgently needed.
Leiter LA et al. Can J Diabetes 2013; in press 16

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

18. Regular SMBG is Required for:

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

20. 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

21. 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…

22. 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

23. 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…

24. 2013

25. 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.

26. What are the options for Insulin?

27. 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)

28. 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®)

29. 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

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

31. What about Hypoglycemia?

32. Definition of Hypoglycemia
Development of neurogenic or neuroglycopenic symptoms
Low blood glucose (<4 mmol/L if on insulin or secretagogue)
Response to carbohydrate load
Neurogenic (autonomic)
Neuroglycopenic
Trembling
Difficulty Concentrating
Palpitations
Confusion
Sweating
Weakness
Anxiety
Drowsiness
Hunger
Vision Changes
Nausea
Difficulty Speaking
Dizziness
The CDA defines hypoglycemia as the development of autonomic (trembling, palpitations, sweating, anxiety, hunger, nausea, tingling) or neuroglycopenic (difficulty concentrating, confusion, weakness, drowsiness, vision changes, difficulty speaking, headache, dizziness) symptoms, a low plasma glucose, and symptoms responding to the administration of a carbohydrate. In mild to moderate hypoglycemia, blood glucose is <4 mmol/L, autonomic and/or neuroglycopenic symptoms are present, but the patient is able to self-treat. However, patients who maintain a higher blood glucose level may experience hypoglycemia at levels >4.0 mmol/L. Severe hypoglycemia indicates the patient is unable to treat the reaction without outside assistance. He/she may or may not be conscious. 32

33. 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.

34. Macrovascular Disease Vascular Protection: Who and When?

35. 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 – regular physical activity, healthy diet, achieve and maintain healthy body weight
S • Smoking cessation

36. Who Should Receive Statins?
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.

37. 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

39. 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

40. 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 40

41. 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 – regular physical activity, healthy diet, achieve and maintain healthy body weight
S • Smoking cessation

42. What if we did all the right things
What if we did all the right things? How much could we protect our patients?

43. 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;

44. 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;

45. STENO 2 Extended Follow-up: Effect of a multi- factorial vascular protective strategy on total mortality 60 50 40 30 20 10
Total mortality (%) 3
Years of follow-up 1 2 4 5 6 7 8 9 11 12 13
Conventional therapy
Intensive therapy
END OF TRIAL
HR = 0.54 ( )
p = 0.015
Effect of a multifactorial intervention on mortality in type 2 diabetes.
Gaede P, Lund-Andersen H, Parving HH, Pedersen O.
Steno Diabetes Center, Copenhagen, Denmark.
PMID: [PubMed - indexed for MEDLINE]
Intensified multifactorial intervention—with tight glucose regulation and the use of renin-angiotensin system blockers, ASA, and lipid-lowering agents—has been shown to reduce the risk of nonfatal CVD among patients with type 2 diabetes and microalbuminuria. The STENO 2 trial evaluated whether this approach would have an effect on the rates of death from any cause and from CV causes.
In the STENO 2 Study, 160 patients with type 2 diabetes and persistent microalbuminuria were randomly assigned to receive either intensive therapy or conventional therapy; the mean treatment period was 7.8 years. Patients were subsequently followed observationally for a mean of 5.5 years, until December The primary endpoint at 13.3 years of follow-up was the time to death from any cause.
Twenty-four patients in the intensive-therapy group died, as compared with 40 in the conventional-therapy group (HR 0.54; 95% CI 0.32 to 0.89; p = 0.02). Intensive therapy was associated with a lower risk of death from CV causes (HR 0.43; 95% CI 0.19 to 0.94; p = 0.04) and of CV events (HR 0.41; 95% CI 0.25 to 0.67; p < 0.001). One patient in the intensive-therapy group had progression to end-stage renal disease, as compared with six patients in the conventional-therapy group (p = 0.04). Fewer patients in the intensive-therapy group required retinal photocoagulation (RR 0.45; 95% CI 0.23 to 0.86; p = 0.02). Few major side effects were reported.
In at-risk patients with type 2 diabetes, intensive intervention with multiple drug combinations and behavior modification had sustained beneficial effects with respect to vascular complications and on rates of death from any cause and from CV causes.
Gaede et al. N Engl J Med. 2008; 358(6):

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

47. What about Microvascular Disease?
Nephropathy
Retinopathy
Neuropathy

48. 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

49. Counsel all Patients About Sick Day Medication List
2013

50. 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

51. 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

52. 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

53. 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.

54. Why diagnose and treat GDM?
Macrosomia
Shoulder dystocia and nerve injury
Neonatal hypoglycemia
Preterm delivery
Hyperbilirubinemia
Caesarian section
Offspring obesity (?)
Offspring diabetes (?)

55. Need a PRECONCEPTION checklist for women with pre-existing diabetes
2013
Need a PRECONCEPTION checklist for women with pre-existing diabetes
1. Attain a preconception A1C of ≤ 7.0% (if safe)
2. Assess for and manage any complications
3. Switch to insulin if on oral agents
4. Folic Acid 5 mg/d: 3 mo pre-conception to 12 weeks post-conception
5. Discontinue potential embryopathic meds:
Ace-inhibitors/ARB (prior to or upon detection of pregnancy)
Statin therapy
Script:

56. 2013 GDM diagnosis: Two approaches

57. Recommendation 8-9: Management in Pregnancy for pre-gestational diabetes
Women with pregestational diabetes may use aspart or lispro in pregnancy instead of regular insulin to improve glycemic control and reduce hypoglycemia [Grade C level 2 for aspart , Grade C, Level 3 for lispro].
Detemir [Grade C, Level 2] or glargine [Grade C, Level 3 ] may be used in women with pregestational diabetes as an alternative to NPH.
2013
2013

58. What about insulin analogues and oral agents among patients with GDM?
May use rapid-acting analog insulin for postprandial glucose control – no difference in perinatal outcomes
May use glyburide or metformin for women who are non-adherent to or who refuse insulin
Likely safe BUT it is OFF- Label  no long-term data, need discussion with patient

59. “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)

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