Transcript TYPE 2 DIABETES MELLITUS: REVIEW OF Clinical Practice

TYPE 2 DIABETES MELLITUS
REVIEW OF Clinical Practice Guidelines
WEEK 2: Therapy
UHN AIMGP CLINIC
SEMINAR SERIES 2007
Updates Dr. K. Tzanetos
T2DM: References
Canadian Diabetes Association (CDA): 2003
Clinical Practice Guidelines for the Prevention
and Management of diabetes in Canada.
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Can J Diabetes 2003; 27 (Suppl 2).
http://www.diabetes.ca/cpg2003
American Diabetes Association (ADA): Clinical
Practice Recommendations 2006.
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Diabetes Care 2006; 29 (Suppl 1).
T2DM: Therapy
WEEK 2 OBJECTIVES:
Develop familiarity with the indications, goals and therapy
progression of treatment:
1) Non-pharmacologic therapy
2) Pharmacologic therapy for glycemia
- Oral agents: monotherapy and combination
- Insulin: monotherapy and in combination with OHAs
3) Therapy for nephropathy (if time permits)
4) Therapy for neuropathy (if time permits)
Note: HTN, CAD, and Dyslipidemia will be discussed in
future seminars…
T2DM: Therapy – Take a minute to discuss…
CASE:
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Recall Mrs. X, our 58 yo woman with recently diagnosed Type
2 DM
She has completed her diabetes education course and has
learned how to self-monitor her blood glucose
She has returned to clinic in follow-up…
‘You explain that overall metabolic control (of both
glycemia and lipids) will be important to
her future
health’
How can glycemic control be measured, and what are the
CDA recommended target values for each test?
T2DM: Therapy
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RCTs have provided compelling evidence
that long-term complications of DM can be
reduced with tight glycemic control (DM1:
DCCT, DM2: UKPDS)
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HbA1c levels >7% are associated with
markedly increased risk of both micro and
macrovascular complications (regardless of
underlying therapy)
TYPE 2 DIABETES MELLITUS: Therapy
Table 1. Targets for Glucose control in DM (CDA)
Ideal
Optimal
Suboptimal
Inadequate
< 0.06
<0.07
0.07-0.084
>0.084
FPG or
pre-P
(mmol/L)
4-6
4-7
7.1-10
>10
2-hr post-P
(mmol/L)
5-8
5-10
10.1-14
>14
HbA1C (%)
Ideal = Normal, nondiabetic
Optimal = Minimal long-term complications, difficult to achieve
Suboptimal = May not prevent complications, but is attainable for the majority of patients
Inadequate = Markedly risk of long-term complications
T2DM: Therapy
CASE:
 Mrs. X. has an HbA1c of 0.95!!
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Here are the BG levels from her record book for the last
few days:
FBG
Lunch
Dinner
M
10
14
16
T
9.5
14
15.2
W
12
12
18
T2DM: Therapy – Take a minute to discuss…
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Given the CDA goals, how would you characterize
her glycemic control ?
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How would you begin to lower her blood glucose
levels ?
T2DM: Therapy
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Mrs. X.’s glycemic control is INADEQUATE
according to the CDA guidelines for both HbA1c
and FBG (or post-prandial)
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The first step in improved glycemic control is to
initiate non-pharmacologic therapy
T2DM: Therapy – Take a minute to discuss…
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What are the major components of nonpharmacologic therapy?
Exercise
Diet
Weight
loss
T2DM: Nutritional approaches (CDA)
Individualized counseling by registered dietician
 Weight reduction to target (0.25-1 kg/week)
 for all patients with BMI > 25
 loss of 5% body weight can have significant
health benefits
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T2DM: Nutritional approaches (CDA)
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Balanced diet from the 4
food groups with:
 fat <30% of caloric
intake (saturated fats
<10%)
 carbohydrates 50-55%
 protein 15-20%
 sucrose containing
foods up to a maximum
of 10% of calories (< 10
g/d of sugar alcohols)
T2DM: Physical activity and Diabetes
(CDA)
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Accumulate at least
150 minutes (up to > 4
hrs) of moderate
intensity aerobic
exercise each week
(spread over at least 3
non-consecutive days)
Encourage to perform
resistance exercise
training 3x/wk
T2DM: Physical Activity And Exercise (CDA)
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Consider the need for a pre-emptive EST in
patients at high risk of occlusive vascular disease,
neuropathy or microvascular disease (or previously
sedentary)
NB: Exercise may induce short-term hypoglycemia
Emphasize:
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Proper foot care
Avoidance of exercise at times of poor metabolic control
or extreme heat or cold
The need to take rapid-acting CHO if pre-exercise BG <5
Insulin injections at a site remote from the exercising
limb
T2DM: Therapy
CASE:
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Mrs. X. has followed your advice
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She has improved her diet and now walks 1.5
kms/d (She has lost 4 kg)
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However, her SMBG levels have not markedly
improved and she has developed symptoms of
sensory peripheral neuropathy
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Her electrolytes, creatinine and liver function
tests and enzymes are normal
T2DM: Therapy – Take a minute to discuss…
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How can we further improve Mrs. X.’s
glycemic control ?
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What agents are available and how would
you choose one from among them?
T2DM: Therapy
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Oral Hypoglycemic Agents (OHAs) are the next
step in management
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The 5 main classes of OHAs are:
• Alpha-glucosidase inhibitors (acarbose)
• Biguanides (metformin)
• Sulfonylureas (glyburide)
• Meglitinides (repaglinide)
• Thiazolidinediones (rosiglitazone)
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Each has a unique mechanism of action
T2DM: Therapy
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Secretagogues:
 Sulfonylureas and meglitinides stimulate
pancreatic insulin release
Insulin Sensitizers:
 Biguanides decrease hepatic glucose production
and enhance insulin-mediated glucose uptake
 Thiazolidinediones decrease insulin resistance
Absorption Inhibitors:
 Alpha-glucosidase inhibitors slow absorption of
starch and sucrose in the gut
T2DM: Therapy – Take a minute to discuss…
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How would you choose one medication from
among the OHAs?
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Vary your choice according to your patient’s
individual characteristics
T2DM: Pharmacologic Therapy
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With significant hyperglycemia (FPG > 10) →
initiation of metformin and/or a sulfonylurea
should be considered
Metformin is associated with both decreased
weight gain and hypoglycemic events
Metformin is contraindicated however in the
presence of significant renal or hepatic
insufficiency
• typically used in
combination
• GI SEs
• contraindicated in
persons with renal
or hepatic dysfunction
• less weight gain
• GI SEs
• risks of hypoglycemia
and weight gain
• use with caution in the
elderly
• contraindicated in
hepatic dysfunction
• used in combination
with insulin – may
increase edema and
CHF
T2DM: Therapy – Take a minute to discuss…
CASE:
 You choose metformin for Mrs. X. and
maximize the dose to 1 g po bid
 Unfortunately, she still has not achieved
her target glucose goals
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What is the next step?
T2DM: Pharmacologic Therapy
1.
Add agents from different classes and maximize
the doses (glyburide, acarbose and/or
rosiglitazone)
2.
Consider adding an insulin HS dose to the OHAs
3.
Switch to multi-injection insulin therapy alone or
with concomitant oral acarbose, biguanide or
thiazolidinedione therapy
T2DM: Insulin Therapy
T2DM Complications: Nephropathy
CASE:
 Mrs. X. was noted to have trace proteinuria on
dipstick by the family MD (You obtain a subsequent
albumin:creatinine ratio of 3.0 on a random daytime
urine)
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Over the next 3 months two further ACRs of 2.8
and 2.7 are obtained (a 24-hr urine collection
confirms microalbuminuria at 225 mg/d)
T2DM Complications: Nephropathy – Take a
minute to discuss…
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How would you minimize any further progression
of Mrs. X.’s nephropathy?
T2DM Complications: Nephropathy
T2DM Complications: Nephropathy
1) ACE-I/ARB
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adjust dose to obtain target BP if the patient is hypertensive
2) Intensify glucose control
3) Consider dietary protein restriction
•
controversial
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mentioned in CDA guidelines
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ADA guidelines suggest 10% of calories should be protein
with overt nephropathy [0.8 g/kg/d] with a reduction to 0.6
g/kg/d with further decline in creatinine clearance
4) Referral to nephrology with greater than 50% decrease in
creatinine clearance
T2DM Complications: Neuropathy
CASE:
 During follow-up, you confirm that Mrs. X. has mild
to moderate stocking-glove sensory neuropathy with
decreased vibration at the great toes and midfoot,
and a loss of sensitivity to 10 gm monofilament at
the great toes
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She also complains of a constant prickly, painful
sensation over the same distribution which keeps
her awake at night
T2DM Complications: Neuropathy – Take a
minute to discuss…
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What are the therapeutic options for her neuropathy ?
T2DM: Complications: Neuropathy
Treatment
1) Intensify glucose control
2) Low dose tricyclic antidepressant or carbamazepine
3) Topical capsaicin ointment
T2DM: Week Two Objectives
We have reviewed:
1) Non-pharmacologic therapy
2) Pharmacologic therapy for glycemia
- Oral agents: monotherapy and combination
- Insulin: monotherapy and in combination with
OHAs
3) Therapy for nephropathy
4) Therapy for neuropathy