Guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association The Essentials 5 th Annual CE LHIN CME Canadian

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

The Essentials

5th Annual CE LHIN CME

Canadian Diabetes Association 2013 Clinical Practice Guidelines


Dr. John SigalasEndocrinologistRouge Valley Health SystemToronto

May 15 , 2013


Learning Objectives

By the end of this session, participants will be able to:

1. Understand the major changes within the 2013 CDA clinical practice guidelines

2. Understand the rationale behind these changes

3. Apply the recommendations in clinical practice


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


TIA 2005

Stroke 2006

MI 2003

MI 2004

Bypass 2001

PAD 2002

Ischemic Toes Amputation 2004

Neuropathy 2003

CKD 2002

Retinopathy 2004

ACS 2001Victor59 years oldType 2 Diabetes


Victor59 years oldType 2 Diabetes

TIA 2005

Stroke 2006

PAD 2002Ischemic Toes Amputation 2004

MI 2003

MI 2004

Bypass 2001ACS 2001

Macrovascular

Neuropathy 2003

CKD 2002

Retinopathy 2004

Microvascular

Reorganize his history

He has EVERY complication of DiabetesThat is what we need to avoid


www.guidelines.diabetes.ca


What is new in making the diagnosis of diabetes?


FPG ≥7.0 mmol/LFasting = 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 diabetesor

2hPG in a 75-g OGTT ≥11.1 mmol/Lor

Random PG ≥11.1 mmol/L Random= any time of the day, without regard to the interval since the last meal

2hPG = 2-hour plasma glucose; FPG = fasting plasma glucose; OGTT = oral glucose tolerance test; PG = plasma glucose

Diagnosis of Diabetes 2013


Diagnosis of Prediabetes*

Test Result Prediabetes Category

Fasting Plasma Glucose(mmol/L)

6.1 - 6.9

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)

GlycatedHemoglobin(A1C) (%)

6.0 - 6.4 Prediabetes

* Prediabetes = IFG, IGT or A1C 6.0 - 6.4% high risk of developing T2DM

2013

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

Copyright © 2013 Canadian Diabetes Association

Individualizing A1C Targets

which must be balanced against the risk of hypoglycemia

Consider 7.1-8.5% if:

2013



Diabetes in Canada: Prevalence by Province and Territory

Public Health Agency of Canada. Diabetes in Canada: Facts and figures from a public health perspective. Ottawa, 2011.

NL6.5%

ON 6.0%

QC 5.1%

PE5.6%

NB5.9%

NS 6.1%

MB 5.9%

SK 5.4%

AB 4.9%

BC 5.4%

NT 5.5%

YT 5.4%

NU 4.4%

† Age-standardized to the 1991 Canadian population.

Age-standardized† prevalence of diagnosed DM among individuals ≥ 1 year, 2008/09

NL, NS and ON had the highest prevalence, while NU, AB and QC had the lowest.

< 5.0

5.0 < 5.5

5.5 < 6.0

6.0 < 6.5

≥ 6.5


Copyright © 2013 Canadian Diabetes Association Public Health Agency of Canada. Diabetes in Canada: Facts and figures from a public health perspective. Ottawa, 2011.

Prevalence of diagnosed diabetes among individuals aged ≥ 1 year, by age group and sex, 2008/09

Diabetes in Canada: Prevalence of Diagnosed Diabetes by age and sex

Prevalence increased with age. The sharpest increase occurred after age 40 years. The highest prevalence was in the 75-79 year age group.

Pre

va

len

ce

(%

)

0

10

15

25

30

1-19

5

20

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 CanadaAge group (years)

Females

Males

Total

Overall Prevalence

6.4%

7.2%

6.8%



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).



Guideline Targets Achieved %

of

pat

ien

ts

Leiter LA et al. Can J Diabetes 2013; in press


Self-Monitoring of Blood Glucose (SMBG)

What should we tell patients to do?


Regular SMBG is Required for:


Increased frequency of SMBG may be required:

Daily SMBG is not usually required if patient:


Pharmacotherapy in T2DM checklist

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

2013

Start metformin immediately

Consider initial combination with another antihyperglycemic agent

Start lifestyle intervention (nutrition therapy and physical activity) +/- Metformin

A1C <8.5%Symptomatic hyperglycemia with

metabolic decompensationA1C 8.5%

Initiate insulin +/-metformin

If not at glycemic target (2-3 mos)

Start / Increase metformin

If not at glycemic targets

LIFESTYLE

Add an agent best suited to the individual:

Patient CharacteristicsDegree of hyperglycemiaRisk of hypoglycemiaOverweight or obesityComorbidities (renal, cardiac, hepatic)Preferences & access to treatmentOther

See next page…

AT DIAGNOSIS OF TYPE 2 DIABETES

Agent CharacteristicsBG lowering efficacy and durabilityRisk of inducing hypoglycemiaEffect on weightContraindications & side-effectsCost and coverageOther

2013

If not at glycemic target

From prior page…

• Add another agent from a different class

• Add/Intensify insulin regimen

Make timely adjustments to attain target A1C within 3-6 months 2013

LIFESTYLE

Start metformin immediately

Consider initial combination with another antihyperglycemic agent

Start lifestyle intervention (nutrition therapy and physical activity) +/- Metformin

A1C < 8.5%Symptomatic hyperglycemia with

metabolic decompensationA1C 8.5%

Initiate insulin +/-metformin

If not at glycemic target (2-3 mos)

Start / Increase metformin

If not at glycemic targets

LIFESTYLE

Add an agent best suited to the individual:

Patient CharacteristicsDegree of hyperglycemiaRisk of hypoglycemiaOverweight or obesityComorbidities (renal, cardiac, hepatic)Preferences & access to treatmentOther

See next page…

AT DIAGNOSIS OF TYPE 2 DIABETES

Agent CharacteristicsBG lowering efficacy and durabilityRisk of inducing hypoglycemiaEffect on weightContraindications & side-effectsCost and coverageOther

2013

2013

Adapted from: Product Monographs as of March 1, 2013; CDA Guidelines 2008; and Yale JF. J Am Soc Nephrol 2005; 16:S7-S10.

Antihyperglycemic agents and Renal Function

Not recommended / contraindicated SafeCaution and/or dose reduction

Repaglinide

Metformin 30 60

Saxagliptin

Linagliptin

Glyburide 30 50

Thiazolidinediones 30

GFR (mL/min): < 15 15-29 30-59 60-89 ≥ 90

CKD Stage: 5 4 3 2 1

Gliclazide/Glimepiride 15 30

Liraglutide 50

Exenatide 30 50

Acarbose 25

Sitagliptin 50

5015 2.5 mg

15

30 50 mg25 mg


Wh

at are th

e o

ptio

ns fo

r In

sulin

?


Insulin Type (trade name) Onset Peak Duration

Bolus (prandial) Insulins

Rapid-acting insulin analogues (clear):• Insulin aspart (NovoRapid®)• Insulin glulisine (Apidra™)• Insulin lispro (Humalog®)

10 - 15 min10 - 15 min10 - 15 min

1 - 1.5 h1 - 1.5 h1 - 2 h

3 - 5 h3 - 5 h

3.5 - 4.75 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 16 - 24 h)

Types of Insulin


Insulin Type (trade name) Time action profile

Premixed Insulins

Premixed regular insulin – NPH (cloudy):• 30% insulin regular/ 70% insulin NPH (Humulin® 30/70)• 30% insulin regular/ 70% insulin NPH (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®)

Types of Insulin (continued)


Ser

um

Insu

lin L

evel

Time

Analogue Bolus: Apidra, Humalog, NovoRapid

Human Basal: Humulin-N, Novolin ge NPH

Analogue Basal: Lantus, Levemir

Human Bolus: Humulin-R, Novolin ge Toronto


Time

Ser

um

Insu

lin L

evel

Human Premixed: Humulin 30/70, Novolin ge 30/70

Analogue Premixed: Humalog Mix25, NovoMix 30


Wh

at ab

ou

t H

ypo

glycem

ia?


1.D

evelopment of neurogenic

or neuroglycopenic sym

ptoms

2.Low

blood glucose (<4

mm

ol/L if on insulin or secretagogue)

3.R

esponse to carbohydrate load Neurogenic

(autonomic)Neuroglycopenic

Trembling Difficulty Concentrating

Palpitations Confusion

Sweating Weakness

Anxiety Drowsiness

Hunger Vision Changes

Nausea Difficulty Speaking

Dizziness

Defin

itio

n

of

Hyp

og

lycem

ia


Steps to Address Hypoglycemia

1. Recognize autonomic or neuroglycopenic symptoms

2. Confirm if possible (blood glucose <4.0 mmol/L)

3. Treat with “fast sugar” (simple carbohydrate) (15 g) to relieve symptoms

4. Retest in 15 minutes to ensure the BG >4.0 mmol/L and retreat (see above) if needed

5. Eat usual snack or meal due at that time of day or a snack with 15 g carbohydrate plus protein


Macrovascular Disease

Vascular Protection:Who and When?


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


• ≥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.

2013Who Should Receive Statins?


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

2013



JPAD = Japanese Primary Prevention of Atherosclerosis with Aspirin for DiabetesPOPADAD = Prevention of Progression of Arterial Disease and DiabetesPPP = Primary Prevention ProjectETDRS = Early Treatment Diabetic Retinopathy StudyPHS = Physicians’ Health StudyWHS = Women’s Health Study

De Beradis G, et al. BMJ 2009; 339:b4531.

ASA for 1⁰Prevention in DiabetesMeta analysis of 6 studies(n = 10,117)

No overall benefit for: • Major CV events • MI• Stroke• CV mortality• All-cause mortality

0.03 0.125 0.5 12

8Favors ASA Favors control/placebo

JPADPOPADADWHSPPPETDRSTotal

68/1262105/63858/51420/519

350/1856601/4789

86/1277108/63862/51322/512

379/1855657/4795

0.80 (0.59-1.09)0.97 (0.76-1.24)0.90 (0.63-1.29)0.90 (0.50-1.62)0.90 (0.78-1.04)0.90 (0.81-1.00)

Major CV events

No. of events/No. in group

ASA Control/placebo RR (95% CI) RR (95% CI)

JPADPOPADADWHSPPPETDRSPHSTotal

28/126290/63836/5145/519

241/185611/275

395/5064

14/127782/63824/51310/512

283/185526/258

439/5053

0.87 (0.40-1.87)1.10 (0.83-1.45)1.48 (0.88-2.49)0.49 (0.17-1.43)0.82 (0.69-0.98)0.40 (0.20-0.79)0.86 (0.61-1.21)

Myocardial infarction

JPADPOPADADWHSPPPETDRSTotal

12/126237/63815/5149/519

92/1856181/4789

32/127750/63831/51310/51278/1855

201/4795

0.89 (0.54-1.46)0.74 (0.49-1.12)0.46 (0.25-0.85)0.89 (0.36-2.17)1.17 (0.87-1.58)0.83 (0.60-1.14)

Stroke

JPADPOPADADPPPETDRSTotal

1/126243/63810/519

244/1856298/4275

10/127735/6388/512

275/1855328/4282

0.10 (0.01-0.79)1.23 (0.80-1.89)1.23 (0.49-3.10)0.87 (0.73-1.04)0.94 (0.72-1.23)

Death from CV causes

JPADPOPADADPPPETDRSTotal

34/126294/63825/519

340/1856493/4275

38/1277101/63820/512

366/1855525/4282

0.90 (0.57-1.14)0.93 (0.72-1.21)1.23 (0.69-2.19)0.91 (0.78-1.06)0.93 (0.82-1.05)

All-cause mortality


Summary of Pharmacotherapy for Hypertension in Patients with Diabetes

Threshold equal or over 130/80 mmHg and Target below 130/80 mmHg

With Nephropathy, CVD or CV risk factors

ACE Inhibitor or ARB

Diabetes

Withoutthe above

1. ACE Inhibitor or ARB or

2. Thiazide diureticor DHP-CCB

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

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

> 2-drug combinations


Vascular Protection Checklist

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

2013


What if we did all the right things?

How much could we protect our patients?


Gaede et al. NEJM. 2003: 348;383-393

STENO-2: Intensive Group Achieved Targets


Intensive Group had Improved CV Outcomes

12 24 36 48 60 72 84 960

10

20

30

40

50

60P = 0.007

Conventional therapy

Intensive therapy

Months of Follow-upRRR= relative risk reduction

53 % RRRAny CV event

NNT = 5

Gaede et al. NEJM. 2003: 348;383-393

guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca

STENO 2 Extended Follow-up: Effect of a multi- factorial vascular protective strategy on total mortality

60

50

40

30

20

10Tota

l mor

talit

y (%

)

3

Years of follow-up

0 1 2 4 5 6 7 8 9 10 11 12 13

Conventional therapy

Intensive therapy

END OF TRIAL

HR = 0.54 (0.32-0.88)p = 0.015HR = 0.54 (0.32-0.88)p = 0.015

Gaede et al. N Engl J Med. 2008; 358(6):580-91.


Gaede et al. NEJM. 2003: 348;383-393

STENO 2 – Microvascular Disease


What about Microvascular Disease?

• Nephropathy• Retinopathy• Neuropathy


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

2013

Counsel all Patients About

Sick Day Medication

List

2013


Retinopathy Checklist

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

2013


Delaying Retinopathy

1. Glycemic control: target A1C ≤7%

2. Blood pressure control: target BP <130/80

3. Lipid-lowering therapy: fibrates have been

shown to decrease progression and may be

considered 2013


Neuropathy Checklist

PREVENT with blood glucose control

SCREEN with monofilament or tuning fork

TREAT pain symptoms with anticonvulsants or antidepressants

2013


4. 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.

2013Recommendation 4

Why diagnose and treat GDM?

• Macrosomia• Shoulder dystocia

and nerve injury• Neonatal

hypoglycemia• Preterm delivery• Hyperbilirubinemia

• Caesarian section• Offspring obesity (?)• Offspring diabetes (?)


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

2013


2013 GDM diagnosis: Two approaches 2013


8. 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].

9. Detemir [Grade C, Level 2] or glargine [Grade C, Level 3 ] may

be used in women with pregestational diabetes as

an alternative to NPH.

Recommendation 8-9: Management in Pregnancy for pre-gestational diabetes

2013

2013


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


“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)


CDA Clinical Practice Guidelines

www.guidelines.diabetes.ca – for professionals

1-800-BANTING (226-8464)

www.diabetes.ca – for patients

http://guidelines.diabetes.ca/

http://diabetes.ca/

guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca

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Guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association The Essentials 5 th Annual CE LHIN CME Canadian