Steroid Induced Hyperglycemia in Stem Cell Transplant

1. Steroid Induced Hyperglycemia in Stem Cell Transplant Kathryn A. Hanavan ANP-BC; BC-ADM Harold Schnitzer Diabetes Health Center September 12, 2013

2. Objectives • Review of steroid, CNI effects on glucose control • Understand how to use insulin to treat steroid induced hyperglycemia • Review place of oral medications

3. Diagnosis of Diabetes • 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 Diabetes Care 2010; 233 (supplement 1)

4. Risk Factors for Diabetes Post Transplant • 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

5. 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

6. Prednisone • Increases hepatic glucose production • Reduces insulin sensitivity • Liver • Muscles • Impairs insulin secretion from the beta cell • Adverse effect on lipids

7. Prednisone Effect on CBG’s • 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

8. Typical Blood Glucose Pattern With Morning Steroid Therapy Glucose Level Breakfast Lunch Dinner

9. Tacrolimus • Deleterious effect on beta cell • Decreases insulin sensitivity • Suppresses basal and meal insulin secretion • Reversible • Worse with prolonged use • Dose dependent

10. Treatment • 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

11. Basal Insulin Choices • 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

12. Bolus Insulin • 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

13. Insulin Action Profiles Aspart, Lispro, Glulisine (4–6 hours) Regular (6–10 hours) NPH (12–20 hours) Detemir (12–24 hours) Glargine (20-26 hours) Plasma insulin levels 24 hours 2 4 6 8 12 14 16 18 20 22 24 0 10 Hours

14. Use of Correction Scale Insulin Alone is Discouraged 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 ACE/ADA Task Force on Inpatient Diabetes. Diabetes Care. 2006;29(8):1955-1962.

15. Therapy for Patients on AM Corticosteroids

16. Typical Blood Glucose Pattern With Morning Steroid Therapy 25% 20% Prandial insulin 15% Glucose Level Basal insulin 15-20% 20-25% Breakfast Lunch Dinner

17. Correction Insulin • 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.

18. Determing Insulin Dose • 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

19. Tapering Prednisone • 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

20. 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

21. Oral Medications • 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

22. Other Meds – less common • 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

23. Lifestyle • Consistent carbohydrate diet vital when onfixed insulin doses • RD consult helpful • Activity • Best at time of peak glucose elevation – mid to late afternoon

24. Tips • 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

25. Thank You