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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

Plas

ma

insu

lin le

vels 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 GoalsGoals 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