Steroid Induced Hyperglycemia in Stem Cell Transplant Kathryn A. Hanavan ANP-BC; BC-ADM Harold Schnitzer Diabetes Health Center September 12, 2013 1
Dec 26, 2015
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Steroid Induced Hyperglycemia in Stem
Cell Transplant Kathryn A. Hanavan ANP-BC; BC-ADM
Harold Schnitzer Diabetes Health CenterSeptember 12, 2013
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Review of steroid, CNI effects on glucose control
Understand how to use insulin to treat steroid induced hyperglycemia
Review place of oral medications
Objectives
HgbA1c ≥ 6.5% Fasting blood glucose ≥ 126 mg/dl 75 gm glucose tolerance test with a two hour
glucose value 200mg/dl. Random glucose >200 mg/dl with symptoms
Should have two tests positive to make the diagnosis
HbA1c often unreliable in stem cell transplant due to anemia, transfusions
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Diagnosis of Diabetes
Diabetes Care 2010; 233 (supplement 1)
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Insulin resistance: obesity, FH dm, pre diabetes, ethnic minorities
Medications: glucocorticoids, tacrolimus, cyclosporine
Significant illness: “Stress response” related to the release of counter-regulatory hormones
Increases in nutritional intake (e.g. restarting a diet, starting enteral or parenteral nutrition)
Age: beta cell function decline over time◦ Greater risk > 45 yo with substantial increase > 60
Risk Factors for Diabetes Post Transplant
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Potential Consequences of Hyperglycemia
– leukocyte function– Impaired healing– Risk of ischemia– Electrolyte fluxes– Volume depletion
– ↑ risk CVD– DM complications– ↓ survival in solid
organ transplant– Burden for patient
– Complexity– Cost
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Increases hepatic glucose production
Reduces insulin sensitivity◦ Liver◦ Muscles
Impairs insulin secretion from the beta cell
Adverse effect on lipids
Prednisone
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AM dose◦Fasting glucoses often normal◦Mild to moderately increased CBG at lunch ◦Largest increase mid afternoon to early eve◦Rapid decrease after 12 hours
BID dosing◦Will raise glucose more equally at all times◦ If 2nd dose given late afternoon, fastings
may be normal
Prednisone Effect on CBG’s
Typical Blood Glucose Pattern With Morning Steroid Therapy
Breakfast Lunch Dinner
Glucose Level
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Deleterious effect on beta cell◦ Decreases insulin sensitivity◦ Suppresses basal and meal insulin secretion◦ Reversible
Worse with prolonged use
Dose dependent
Tacrolimus
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Insulin is drug of choice
Basal Insulin◦ Suppresses glucose production between meals
and overnight when not eating◦ 50% of daily needs; closer to 40% on steroids
Bolus Insulin ◦ Limits hyperglycemia after meals◦ 50% of daily needs; closer to 60% on steroids
Treatment
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NPH◦Most effective with am steroids◦ Overnight dose– lower than am or none◦ May use NPH alone for mild ↑ glucose
Glargine◦ Give in am in case of peak 4 - 5 hours later◦ Can only give enough so fasting CBG at goal
Need higher meal doses L and D
Basal Insulin Choices
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Best choice is a rapid acting analogue◦ Onset in 10” with peak at 1 hr
May also use R◦ Longer lasting – up to 8 hrs◦ Onset 30” – not as good for corrections
Pen formulations are best◦ Make using insulin simpler and more convenient
Bolus Insulin
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0 2 4 6 8 10 12 14 16 18 20 22 24
Pla
sma in
sulin
levels
Regular (6–10 hours)
NPH (12–20 hours) Detemir (12–24 hours)
Hours
Glargine (20-26 hours)
Aspart, Lispro, Glulisine (4–6 hours)
Insulin Action Profiles
24 hours
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Evidence doesn’t support due to:
Hypoglycemia –”stacking”
Hyperglycemia - is reactive rather than
proactive
◦Often mismatched with changes in insulin sensitivity
◦It does not meet the physiologic needs of the patient
Use of Correction Scale Insulin Alone is Discouraged
ACE/ADA Task Force on Inpatient Diabetes. Diabetes Care. 2006;29(8):1955-1962.
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Therapy for Patients on AM Corticosteroids
B L Dinner HS
Regular/Aspart/ Lispro/Glulisine
15% 20% 25%
NPH 20-25%
15-20%
Or Glargine/Detemirr
40%
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Typical Blood Glucose Pattern With Morning Steroid Therapy
Breakfast Lunch Dinner
Glucose Level
Basal insulin
Prandial insulin
20-25%
20%
25%
15%
15-20%
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Depends on TDD
Use only with meals
Make it simple! ◦ 1u:50 > 150 (< 40u daily)◦ 2u:50 > 150 (40 – 90u daily)
Do not use at hs with am steroids initially
For more fragile pts, might want to start correction at 200.
Correction Insulin
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Weight based approach◦ Start with 0.5u/kg for TDD◦ 0.6u/kg for high dose
For example – 60 kgs at 0.5u/kg ◦ 30u TDD; (0.6u/kg = 36u TDD)◦ 40% basal = 12u NPH – 8u hs; 4u hs◦ 60% bolus = 18u
4uB; 6uL; 8u D
Add correction dosing if pt capable
Titrate q 2 – 3 days
Determing Insulin Dose
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Need to gradually back off on insulin with each decrease unless CBG’s still > 150
Reduce NPH overnight
May need to reduce L and D doses on am dose only
If < 20 – 25u daily, may change to oral
Tapering Prednisone
Glucose Goals
Goals post transplant – no guidelines◦ Start to lose glucose in the urine with CBG 180◦ Try for most glucoses < 180 – 200
Lower is better – low to mid 100’s ADA for diabetes in general
◦ Fasting 70 – 130◦ Postprandial: < 180◦ HbA1c < 7%
Difficult to achieve if high dose steroids
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Can consider when TDD < 20 - 25u insulin Most common – sulfonylureas
◦ Use short acting glipizide with am steroids ◦ Start low dose – 2.5 - 5 mgs◦ Do not use glyburide due to ↑ risk of hypos◦ Long acting formulations will cause fasting hypos
Used with more mild hyperglycemia
More useful with lower prednisone doses
Oral Medications
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Metformin◦ Risk with elevated creatinine and/or LFT’s◦ Need to dc for radio contrast dye◦ Better later post transplant
DPP-IV inhibitors◦ Expensive◦ Very modest benefit
GLP agonists◦ SE nausea, weight loss◦ ? Risk of pancreatitis
Other Meds – less common
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Consistent carbohydrate diet vital when on fixed insulin doses ◦ RD consult helpful
Activity◦ Best at time of peak glucose elevation – mid to
late afternoon
Lifestyle
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Managing diabetes is challenging, particularly in addition to other medical care required post transplant (both patient and provider!)
More of an art than a science
Patients don’t have to be perfect!◦ OK to have treats occasionally◦ Ok to miss testing occasionally
Adjust insulin q 2 – 3 days if > 200
Get endocrine consult if not attaining goals
Tips
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Thank You