Post-Transplant Glucocorticoid Induced Diabetes
Conditions
Keywords
glucocorticoid, diabetes mellitus, post-transplant, insulin
Brief summary
No consensus guidelines exist for management of post-transplant glucocorticoid induced hyperglycemia, but most published reviews recommend insulin as first line therapy. A variety of insulin regimens have been proposed, including mealtime short-acting regular or analog insulin, once daily neutral protamine hagedorn (NPH) insulin, pre-mixed insulin, or basal insulin alone such as glargine or detemir. However, no randomized trial has ever examined different insulin regimens to determine which most effectively controls post-transplant steroid-induced hyperglycemia. Consequently, the proposed study intends to examine three commonly used insulin regimens used for managing post-transplant once-daily glucocorticoid-induced hyperglycemia to determine which is most effective: * Group 1: Intermediate-acting (NPH) insulin at breakfast * Group 2: Short-acting insulin (regular or aspart) before meals * Group 3: Insulin glargine at breakfast Question/Hypothesis: Among three commonly used insulin regimens, which is most effective for managing post-transplant once-daily glucocorticoid-induced hyperglycemia?
Interventions
DRUGRegular human insulin or Insulin Aspart
DRUGInsulin glargine
Sponsors
Vancouver General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Have undergone bone marrow, liver, lung, or renal transplant. 2. Be using once daily oral glucocorticoid therapy (total daily dose of Prednisone ≥10 mg, Hydrocortisone ≥40 mg, Dexamethasone ≥1.5 mg) administered in the morning and expected to continue for at least 2 weeks. 3. Have pre-existing or newly diagnosed diabetes mellitus established by any of the criteria listed below: 1. Fasting plasma glucose ≥7.0 mmol/L (repeated x 1) 2. Any plasma glucose ≥11.0 mmol/L 4. Have at least three pre-meal inpatient capillary blood glucose (CBG) readings ≥ 7.8 mmol/L 5. Be eating meals by mouth
Exclusion criteria
1. Heart, Pancreas, Islet cell transplant recipients 2. Previous use of Basal-Bolus or Pre-Mixed Insulin regimen 3. Diabetes mellitus type I 4. NPO (not eating meals by mouth) 5. Receiving enteral (tube feeds) or parenteral (TPN) nutrition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood glucose - inpatient | Time (days) from enrollment to described treatment range, an expected average of 7 days | Mean time from baseline to achieve at least 80% of pre-meal capillary blood glucose values within 5.0 - 7.8 mmol/L over a 48 hour period during hospitalization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post prandial blood glucose - inpatient | Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days | Mean inpatient two-hour post-lunch capillary blood glucose (mmol/L) from enrollment to discharge from hospital |
| Length of inpatient hospital stay | Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days | Length of stay in hospital (days) from enrollment to discharge from hospital |
| Blood glucose | Enrollment to 3 months | Mean fasting blood glucose (mmol/L) from enrollment to 3 months |
| Hemoglobin A1C | Enrollment to 3 months | Mean hemoglobin A1C (%) from enrollment to 3 months |
| Post prandial blood glucose | Enrollment to 3 months | Mean two-hour post-lunch capillary blood glucose (mmol/L) from enrollment to 3 months |
| Hypoglycemic episodes | Enrollment to 3 months | Hypoglycemic episodes defined as: (1) Mild - any measured CBG 3.0-4.0 mmol/L; (2) Severe - any episode of hypoglycemia with a measured CBG \< 3.0 mmol/L, OR which the subject is not able to recognize and treat without the direct (substantial) intervention of a professional caregiver, nurse or physician (e.g. intravenous dextrose or intramuscular glucagon) |
| Blood glucose - inpatient | Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days | Mean inpatient capillary blood glucose (mmol/L) from enrollment to discharge from hospital |
| Cardiovascular events | Enrollment to 3 months | New cardiovascular events defined as: myocardial infarction, new or worsened congestive heart failure, stroke, and cardiac arrhythmia. |
| Post-transplant infections or new antibiotic use | Enrollment to 3 months | Post-transplant infections or new antibiotic use from enrollment to 3 months. |
| Transplant graft failure | Enrollment to 3 months | Transplant graft failure (as specified by subject's medical transplant physician) from enrollment to 3 months. |
| New acute renal failure | Enrollment to 3 months | New acute renal failure is defined according to Acute Kidney Network Guidelines: rapid time course and decreased kidney function according to an absolute Creatinine (Cr) rise greater than 26 μmol/L, greater than 2-fold increase in serum Cr from baseline, or urine output less than 0.5 mL/kg/hr for greater than 6 hours |
| Mortality | Enrollment to 3 months | Overall subject mortality from baseline to 3 months. |
| Glycemic treatment failure | Enrollment to 3 months | Hypoglycemic treatment failure: subject experiences ≥3 hypoglycemic episodes (≤ 4.0 mmol/L) over any 5 day period or a single severe hypoglycemic event (as previously defined), they will be withdrawn from study and managed at discretion of attending physician, or hospital endocrine consult service. Hyperglycemic treatment failure: Severe hyperglycemia defined as CBG \>20 mmol/L. If subject experiences ≥3 severe hyperglycemic measures over the course of 48 hours they will be withdrawn from the study and managed at discretion of attending physician, or hospital endocrine consult service. |
Countries
Canada
Outcome results
None listed