Kathryn A. Hanavan ANP-BC; BC-ADM
Harold Schnitzer Diabetes Health Center
September 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
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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
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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
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–
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 leukocyte function
Impaired healing
Risk of ischemia
Electrolyte fluxes
Volume depletion
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↑ risk CVD
DM complications
↓ survival in solid
organ transplant
Burden for patient
– Complexity
– Cost
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Increases hepatic glucose production
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Reduces insulin sensitivity
◦ Liver
◦ Muscles
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Impairs insulin secretion from the beta cell
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Adverse effect on lipids
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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
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Glucose
Level
Breakfast
Lunch
Dinner
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Deleterious effect on beta cell
◦ Decreases insulin sensitivity
◦ Suppresses basal and meal insulin secretion
◦ Reversible
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Worse with prolonged use
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Dose dependent
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Insulin is drug of choice
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Basal Insulin
◦ Suppresses glucose production between meals
and overnight when not eating
◦ 50% of daily needs; closer to 40% on steroids
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Bolus Insulin
◦ Limits hyperglycemia after meals
◦ 50% of daily needs; closer to 60% on steroids
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NPH
◦ Most effective with am steroids
◦ Overnight dose– lower than am or none
◦ May use NPH alone for mild ↑ glucose
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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
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Best choice is a rapid acting analogue
◦ Onset in 10” with peak at 1 hr
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May also use R
◦ Longer lasting – up to 8 hrs
◦ Onset 30” – not as good for corrections
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Pen formulations are best
◦ Make using insulin simpler and more convenient
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Insulin Action Profiles
Aspart, Lispro, Glulisine (4–6 hours)
Plasma insulin levels
Regular (6–10 hours)
NPH (12–20 hours)
Detemir (12–24 hours)
Glargine (20-26 hours)
0
2
4
6
8
10
12
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18
20 hours
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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
ACE/ADA Task Force on Inpatient Diabetes. Diabetes Care. 2006;29(8):19551962.
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B
L
Regular/Aspart/
Lispro/Glulisine
15% 20%
NPH
2025%
40%
Or
Glargine/Detemir
r
Dinner
HS
25%
1520%
15
25%
20%
Prandial insulin
15%
Glucose
Level
Basal insulin
15-20%
20-25%
Breakfast
Lunch
Dinner
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Depends on TDD
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Use only with meals
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Make it simple!
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Do not use at hs with am steroids initially
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For more fragile pts, might want to start
correction at 200.
◦ 1u:50 > 150 (< 40u daily)
◦ 2u:50 > 150 (40 – 90u daily)
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Weight based approach
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For example – 60 kgs at 0.5u/kg
◦ Start with 0.5u/kg for TDD
◦ 0.6u/kg for high dose
◦ 30u TDD; (0.6u/kg = 36u TDD)
◦ 40% basal = 12u NPH – 8u hs; 4u hs
◦ 60% bolus = 18u
 4uB; 6uL; 8u D
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Add correction dosing if pt capable
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Titrate q 2 – 3 days
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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
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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
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ADA for diabetes in general
◦ Fasting 70 – 130
◦ Postprandial: < 180
◦ HbA1c < 7%
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Difficult to achieve if high dose steroids
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0
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Can consider when TDD < 20 - 25u insulin
Most common – sulfonylureas
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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
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Used with more mild hyperglycemia
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More useful with lower prednisone doses
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Metformin
◦ Risk with elevated creatinine and/or LFT’s
◦ Need to dc for radio contrast dye
◦ Better later post transplant
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DPP-IV inhibitors
◦ Expensive
◦ Very modest benefit
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GLP agonists
◦ SE nausea, weight loss
◦ ? Risk of pancreatitis
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Consistent carbohydrate diet vital when on
fixed insulin doses
◦ RD consult helpful
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Activity
◦ Best at time of peak glucose elevation – mid to late
afternoon
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Managing diabetes is challenging, particularly in
addition to other medical care required post
transplant (both patient and provider!)
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More of an art than a science
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Patients don’t have to be perfect!
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Adjust insulin q 2 – 3 days if > 200
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Get endocrine consult if not attaining goals
◦ OK to have treats occasionally
◦ Ok to miss testing occasionally
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