Use of NPH Versus Basal Bolus Insulin for Steroid Induced Hyperglycemia

Study Overview
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Brief Summary
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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
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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.

Official Title
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Use of Neutral Protamine Hagedorn (NPH) Versus Basal Bolus Insulin for Steroid Induced Hyperglycemia

Conditions
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Hyperglycemia Steroid-induced, Insulin Resistance, Diabetes

Intervention / Treatment
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* Drug: NPH Insulin
* Drug: glargine
* Drug: Insulin Aspart


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NPH Insulin<br>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. | Drug: NPH Insulin<br>* Intermediate acting insulin<br>* Other names: Novolin N;Drug: glargine<br>* basal insulin<br>* Other names: Basaglar;Drug: Insulin Aspart<br>* prandial insulin<br>* Other names: Novolog;|
| Active Comparator: Basal/Bolus Insulin<br>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. | Drug: glargine<br>* basal insulin<br>* Other names: Basaglar;Drug: Insulin Aspart<br>* prandial insulin<br>* Other names: Novolog;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic Control | mean of 4 glucose levels per day (premeal and bedtime) for each group for first 3 days after intervention | 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 3 days | 
| 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 | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyperglycemia, insulin, steroid, prednisone, methylprednisolone, hypoglycemia