1. Kathryn A. Hanavan ANP-BC; BC-ADM Harold Schnitzer Diabetes Health Center September 12, 2013 1

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

3.  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 3 Diabetes Care 2010; 233 (supplement 1)

4.  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 4

5. 5 Potential Consequences of Hyperglycemia 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.  Increases hepatic glucose production  Reduces insulin sensitivity ◦ Liver ◦ Muscles  Impairs insulin secretion from the beta cell  Adverse effect on lipids 6

7.  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 2 nd dose given late afternoon, fastings may be normal 7

8. BreakfastLunchDinner Glucose Level

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

10.  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 10

11.  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 11

12.  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 12

13. 0 2468 10 12141618202224 Plasma insulin 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 Insulin Action Profiles 24 hours 13

14. 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. 14

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16. BreakfastLunchDinner Glucose Level Basal insulin Prandial insulin 20-25% 20% 25% 15% 15-20% 16

17.  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. 17

18.  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 18

19.  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 19

20. 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 20

21.  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 21

22.  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 22

23.  Consistent carbohydrate diet vital when on fixed insulin doses ◦ RD consult helpful  Activity ◦ Best at time of peak glucose elevation – mid to late afternoon 23

24.  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 24

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