Hyperglycemia Steroid-induced, Insulin Resistance, Diabetes
Conditions
Keywords
steroid, prednisone, methylprednisolone, hyperglycemia, insulin, hypoglycemia
Brief summary
Glucocorticoids are known to cause an increase in insulin resistance, leading to hyperglycemia, in both diabetic and non-diabetic patients. In both the inpatient and outpatient setting, steroids are used for their anti-inflammatory property to treat a variety of conditions. There is a paucity of information regarding the best way to treat steroid-induced hyperglycemia. In this study we will compare (1) the addition of NPH insulin, an intermediate-acting insulin, given at the time of steroid administration to the patient's standard basal/bolus insulin to (2) modification of the standard basal-bolus insulin regimen which will consist primarily increasing the prandial doses at lunch and supper in order to determine which regimen is superior for glycemic control.
Detailed description
Inpatients who will receive single daily doses of prednisone or methylprednisolone for treatment of their underlying condition and who become hyperglycemic will be eligible. Subjects will be randomized in a 1:1 fashion to one of two arms: (1) to their standard basal bolus insulin the addition of NPH insulin given at the time of the steroid adminstration, adjusting the dose based on the dose of steroid; (2) an increase in the basal and prandial bolus insulin doses based on the dose of steroid. Glycemic control and the incidence of hypoglycemia will be assessed over the first 3 days after initiating these insulin regimens.
Interventions
DRUGNPH Insulin
Intermediate acting insulin
DRUGglargine
basal insulin
DRUGInsulin Aspart
prandial insulin
Sponsors
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients receiving single dose steroids who become hyperglycemic will be randomized to two treatment arms in a parallel design: (1) NPH added to basal/bolus insulin; (2) increase in doses of basal and bolus insulin
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients receiving once daily dosing of methylprednisolone or prednisone in a dose of 10 mg/day or greater * Hyperglycemic (Glucose level \> 126 mg/dL) * Diabetic and nondiabetic patients * Expected duration of hospital stay and time on steroids \>= 3 days * Patient of appropriate caregiver able to give Informed Consent
Exclusion criteria
* Patients with 2 or more doses of methylprednisolone/prednisone per day * Steroids other than methylprednisolone or prednisone * Pregnancy * estimated glomerular filtration rate (eGFR) \< 45 ml/min/1.73m2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycemic Control | 3 days | mean of 4 glucose levels per day (premeal and bedtime) for each group for first 3 days after intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Glucose Values Within Therapeutic Range | 3 days | Percentage of the glucose values (premeal and bedtime for 3 days) within the therapeutic target of 80 - 180 mg/dL |
| Percentage of Glucose Values Within the Hypoglycemic Range | 3 days | Percentage of the glucose values (premeal and bedtime for 3 days) less than 70 mg/dL and 54 mg/dL |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NPH Insulin NPH will be given at the time of steroid administration to the patient in addition to standard basal/bolus insulin the patient may be receiving in the following doses:
Prednisone Dose (mg/day) - NPH dose (U=Units): 10-20 mg/day - 1.2U (units)/mg; 21-40 mg/day - 0.6U/mg; 41-60 mg/day - 0.45U/mg; 61-80 mg/day - 0.3U/mg; \>80 mg/day - no additional NPH. Note that the amounts of NPH are added to each other for the various prednisone doses. For example, a dose of 75 mg/day of prednisone would come out to be (1.2U x 20mg = 24U) + (0.6U x 20mg = 12U) + (0.45U x 20mg = 9U) + 0.3U x 15 mg = 4.5U) for a total of 24 + 12 + 9 + 4.5 = 49.5U of NPH for 75 mg of prednisone.
NPH Insulin: Intermediate acting insulin
glargine: basal insulin
Insulin Aspart: prandial insulin | 2 |
| Basal/Bolus Insulin Basal insulin (glargine) and Bolus insulin (insulin aspart) will be increased (doses given in U \[units\]/kg) according to the Prednisone dose (mg/day) as follows:
Prednisone Dose (mg/day) - doses of insulin (U/kg): Prednisone 0 mg - Glargine 0.25U/kg, Bkfst Aspart 0.08U/kg, Lunch Aspart 0.08U/kg, Dinner Aspart - 0.08U/kg; Prednisone 10-20 mg - Glargine 0.25U/kg, Bkfst Aspart 0.1U/kg, Lunch Aspart 0.15U/kg, Dinner Aspart - 0.2U/kg; Prednisone 21-40 mg - Glargine 0.25U/kg, Bkfst Aspart 0.1U/kg, Lunch Aspart 0.2U/kg, Dinner Aspart - 0.25U/kg; Prednisone 41-60 mg - Glargine 0.30U/kg, Bkfst Aspart 0.15U/kg, Lunch Aspart 0.25U/kg, Dinner Aspart - 0.30U/kg; Prednisone 61-80 mg - Glargine 0.30U/kg, Bkfst Aspart 0.15U/kg, Lunch Aspart 0.30U/kg, Dinner Aspart - 0.35U/kg; Prednisone \>80 mg - Glargine 0.30U/kg, Bkfst Aspart 0.15U/kg, Lunch Aspart 0.35U/kg, Dinner Aspart - 0.40U/kg.
glargine: basal insulin
Insulin Aspart: prandial insulin | 1 |
| Total | 3 |
Baseline characteristics
| Characteristic | Basal/Bolus Insulin | Total | NPH Insulin |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 3 Participants | 2 Participants |
| Age, Continuous | 36 years STANDARD_DEVIATION 0 | 50.3 years STANDARD_DEVIATION 10.2 | 57.5 years STANDARD_DEVIATION 1.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Initial Glucose | 80 mg/dL STANDARD_DEVIATION 0 | 189 mg/dL STANDARD_DEVIATION 77.4 | 244 mg/dL STANDARD_DEVIATION 4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment United States | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 1 |
| other Total, other adverse events | 0 / 2 | 0 / 1 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 |
Outcome results
Primary
Glycemic Control
mean of 4 glucose levels per day (premeal and bedtime) for each group for first 3 days after intervention
Time frame: 3 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NPH Insulin | Glycemic Control | 284.3 mg/dL | Standard Deviation 81 |
| Basal/Bolus Insulin | Glycemic Control | 184.3 mg/dL | Standard Deviation 61.8 |
Secondary
Percentage of Glucose Values Within the Hypoglycemic Range
Percentage of the glucose values (premeal and bedtime for 3 days) less than 70 mg/dL and 54 mg/dL
Time frame: 3 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| NPH Insulin | Percentage of Glucose Values Within the Hypoglycemic Range | 0 Percentage of glucose values < 70 mg/dL |
| Basal/Bolus Insulin | Percentage of Glucose Values Within the Hypoglycemic Range | 0 Percentage of glucose values < 70 mg/dL |
Secondary
Percentage of Glucose Values Within Therapeutic Range
Percentage of the glucose values (premeal and bedtime for 3 days) within the therapeutic target of 80 - 180 mg/dL
Time frame: 3 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| NPH Insulin | Percentage of Glucose Values Within Therapeutic Range | 4.2 percentage of glucose values in range |
| Basal/Bolus Insulin | Percentage of Glucose Values Within Therapeutic Range | 50 percentage of glucose values in range |