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

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

The Case of Victor

Canadian Diabetes Association 2013 Clinical Practice Guidelines


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


www.guidelines.diabetes.ca


guidelines.diabetes.ca


Victor59 years old

FBS 6.7 mmol/LA1C 6.2%

Does he have 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


Can we delay the onset of his Type 2 Diabetes?


Diabetes Prevention Program (DPP)

Diabetes Prevention Program (DPP) Research Group. N Engl J Med 2002;346:393-403.

Years

• Benefit of diet and exercise or Metformin on diabetes prevention in at-risk patients

• N = 3234 with IFG and IGT, without diabetes

00

10

20

30

40

1.0 2.0 3.0 4.0

Placebo

Metformin

Lifestyle

Cumulativeincidence of diabetes(%)

31%

58%

P*< 0.001

< 0.001

*vs placeboIFG = impaired fasting glucose, IGT = impaired glucose tolerance


What do you tell him about exercise?


Physical Activity Checklist

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

2013


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


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

Who Should be Screened with ECG?


Exercise ECG stress testing

If cannot exercise or resting ECG abnormality present:– Pharmacologic stress

echo– Pharmacologic stress

nuclear imaging

Typical or atypical cardiac symptoms

Associated diseases:– PAD– Carotid bruits– TIA– Stroke

Resting ECG abnormalities (e.g. Q waves)

Who Should have Stress Testing and/or Functional Imaging to Screen for CAD?


What do you tell him about his diet?


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 4 9

Grams for 2000 calorie/day diet

225-300 75-100 44-78

BW = body weight


Choose low glycemic index carbohydrates

www.guidelines.diabetes.ca

http://www.guidelines.diabetes.ca/


VictorLost to follow up and shows up 3 years later

FBS 9.0 mmol/LA1C 8.3%

What are the A1C targets for Victor?


Targets Checklist

A1C ≤ 7.0% for MOST people with diabetes

A1C ≤ 6.5% for SOME people with T2DM

A1C 7.1-8.5% in people with specific features

2013

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

Why ≤ 7%?Macro and Microvascular Benefits?


After median 8.5 years post-trial follow-up

Aggregate Endpoint 1997 2007

Any diabetes related endpoint RRR: 12% 9% P: 0.029 0.040

Microvascular disease RRR: 25% 24% P: 0.0099 0.001

Myocardial infarction RRR: 16% 15% P: 0.052 0.014

All-cause mortality RRR: 6% 13% P: 0.44 0.007

Legacy Effect of Earlier Glucose Control

Holman R, et al. N Engl J Med 2008;359.


After median 8.5 years post-trial follow-up

Aggregate Endpoint 1997 2007

Any diabetes related endpoint RRR: 12% 9% P: 0.029 0.040

Microvascular disease RRR: 25% 24% P: 0.0099 0.001

Myocardial infarction RRR: 16% 15% P: 0.052 0.014

All-cause mortality RRR: 6% 13% P: 0.44 0.007

Legacy Effect of Earlier Glucose Control

Holman R, et al. N Engl J Med 2008;359.


Would < 6.5% be good for him?


ADVANCE: Glucose Control

Follow-up (months)

Mean A1C (%)

Standard control 7.3%

Intensive control 6.5%

10.0

9.0

8.0

7.0

6.0

5.0

0.00 6 12 18 24 30 36 42 48 54 60 66

p < 0.001

ADVANCE Collaborative Group. N Engl J Med 2008;358:24.


ADVANCE: Treatment Effect on the Primary Microvascular Outcomes

• New/worsening nephropathy, retinopathy

66

Cumulative incidence (%)

Follow-up (months)

HR 0.86 (0.77-0.97)p = 0.01 Standard

control

Intensive control

25

20

15

10

5

00 6 12 18 24 30 36 42 48 54 60

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.


When would A1C 7.1-8.5%

be acceptable?


Consider A1C 7.1-8.5% if …• 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

2013


Individualizing A1C Targets

which must be balanced against the risk of hypoglycemia

Consider 7.1-8.5% if:

2013


What do you prescribe for his glucose control?

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


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


Victor’s friend passed out because of low sugars

What do you tell Victor about Hypoglycemia?


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


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


Hypoglycemia and Driving

• 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):128-140.

Safe blood glucose (BG) prior to driving

BG ≥ 5.0 mmol/L


“Do I need to poke my fingers 8 times a day?”

What do you tell Victor about SMBG?


Regular SMBG is Required for:


Increased frequency of SMBG may be required:

Daily SMBG is not usually required if patient:


Should Victor get:

Statin ACE-inhibitor or ARB

ASA

for Vascular Protection


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


• ≥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? (regardless of baseline LDL-C)


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.


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)]

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

EUROPA Investigators, Lancet 2003;362(9386):782-788.HOPE study investigators. Lancet. 2000;355:253-59.

ONTARGET study investigators. NEJM. 2008:358:1547-59


Recommendation

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]

2013


X


What is Victor’s BP Target?


Hypertension Checklist

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

2013


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


What is Victor’s LDL target?


If on therapy, target

LDL ≤ 2.0 mmol/L

Increase the statin dose and continue to monitor


Drug ClassGeneric name (Trade name)

Principal effects Other considerations

Bile Acid Sequestrant•Cholestyramine resin (Questran)•Colestipol HCl (Colestid)•Colesevalam (Lodalis)

Lowers LDL-C Gastrointestinal intolerabilityTG elevationColesevelam: A1C lowering effect

Cholesterol Absorption Inhibitor•Ezetimibe (Ezetrol)

Lowers LDL-C Effective in combination with statin

Fibrate•Bezafibrate (Bezalip SR)•Fenofibrate (Lipidil)•Gemfibrozil (Lopid)

Lowers TG Variable LDL-C effectVariable 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-CRaise HDL-C

Dose related deterioration in glycemiaER 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


“Why do you keep testing my urine?”

What do you tell Victor?


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

• 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)

When to Refer…..



“My grandmother went blind from diabetes – I am afraid

of that.”



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


Victor heard that amputations are highest in

people with diabetes



Public Health Agency of Canada (August 2011); using 2008/09 data from the Canadian Chronic Disease Surveillance System (Public Health Agency of Canada).

Patients with DM are 20X More Likely to be Hospitalized for Non-traumatic Limb Amputation


Educate patients on proper foot care – The “DO’s”DO …

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


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


“I get numbness in my toes.”



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


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


What are the options for 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®)

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


What if we do all of the vascular protective steps

for Victor –

What will happen?


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


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

STENO 2 – Microvascular Disease


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


Tools to help us keep track of our patients


Tools to help us keep track of our patients


Back Page:“Cheat Sheet” of Targets and Goals


Back Page:“Cheat Sheet” of Targets and Goals


“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/

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