The Management of Glucocorticoid-Induced Hyperglycemia in Hospitalized Patients

Study Overview
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Brief Summary
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The investigators hypothesize that includes patient weight and glucocorticoid dose can be used to safely initiate insulin treatment in diabetic/hyperglycemic patients who are to be treated with pharmacological doses of glucocorticoids.

Detailed Description
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The target fasting serum glucose (FSG) and pre-meal SG was 90-140 mg/dL, and the random SG was less than 180 mg/dL, taking into consideration the ADA/AACE target glucose levels in non-ICU patients (15). The Glargine/Lispro Protocol included 0.2 unit/kg/day as insulin glargine once daily if the dose was between 40-80 units, or twice daily if the dose was less than 40 or more than 80 units; plus 0.2 unit/kg/day as lispro divided between three meals for all insulin-naïve patients. A coverage dose of 0.1 unit/kg/day of lispro for each 10 mg of prednisone or its equivalent was divided between 3 meals. The maximum starting coverage dose was 0.4 units/kg per day. The prandial dose of lispro was increased by 10% if the pre-lunch, pre-dinner, or bedtime SG was between 141-200 mg/dL, and by 20% if the pre-lunch, pre-dinner or bedtime SG is >200 mg/dL. The prandial dose of lispro was decreased by 10% if the pre-lunch, pre-dinner, or bedtime SG is between 70-89 mg/dL, and by 20% if the pre-lunch, pre-dinner or bedtime SG was less than 70 mg/dL. The Glargine/Lispro/NPH Protocol included 0.2 unit/kg/day as insulin glargine as per G/L; plus 0.2 unit/kg/day as lispro divided between three meals for all the insulin-naïve patients. A coverage dose of 0.1 unit/kg/day of Neutral Protamine Hagedorn (NPH) for each 10 mg of prednisone or its equivalent was given twice daily with the administration of the glucocorticoid. The maximum starting coverage dose was 0.4 units/kg per day. The NPH dose was increased by 10% if the pre-lunch, pre-dinner, or bedtime SG is between 141-200 mg/dL, and by 20% if the pre-lunch, pre-dinner or bedtime SG was greater than 200 mg/dL. The NPH dose was decreased by 10% if the pre-lunch, pre-dinner, or bedtime SG was between 70-89 mg/dL, and by 20% if the pre-lunch, pre-dinner or bedtime SG was less than 70 mg/dL. In both protocols glargine dose was increased by 10% if the fasting glucose value is 141-200 mg/dL and by 20% if the fasting glucose value was more than 200 mg/dL, and decreased by 10% if the FSG was 70-89 mg/dL and by 20% if the FSG was less than 70 mg/dL. If the patient had an outpatient regimen which includes a total daily dose of insulin (TDI) that exceeded 0.4 unit/kg/day, then the same TDI was continued with 50% given as glargine once daily if the dose was between 40-80 units, or twice daily if the dose was less than 40 or more than 80 units; and 50% given as lispro divided between three meals. The patient was still randomly assigned to either one of the two protocols as described previously. If the patient were on a TDI less than 0.4 unit/kg/day in addition to oral antidiabetic medications as an outpatient, then all the oral antidiabetic medications were discontinued and the patient was started on 0.5 unit/kg/day divided as 50% glargine given once daily if the dose was between 40-80 units, or twice daily if the dose was less than 40 or more than 80 units; and 50% lispro divided between three meals. The patient was randomly assigned to either one of the two protocols based upon even and odd hospital numbers.

Official Title
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The Management of Glucocorticoid-Induced Hyperglycemia in Hospitalized Patients

Conditions
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Hyperglycemia, Diabetes Mellitus

Intervention / Treatment
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* Drug: Glargine insulin
* Drug: Lispro insulin
* Drug: NPH Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admission for Chronic Obstructive Pulmonary Disease (COPD) exacerbation. Treatment with pharmacological doses of glucocorticoids (GCs) ≥10 mg of prednisone or its equivalent if they are not on maintenance dose of GCs in the outpatient settings. Treatment with pharmacological doses of GCs ≥10 mg of prednisone or its equivalent above their maintenance dose of GCs in the outpatient settings. Have either a previous diagnosis of diabetes mellitus which has been treated with diet or medications, hemoglobin A1c ≥6.5%, or confirmed inpatient hyperglycemia defined as a fasting laboratory glucose or finger stick reading ≥126 mg/dL or random glucose reading ≥200 mg/dL on two or more determinations. Exclusion Criteria: Unwilling to sign informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glargine/Lispro Insulin Arm<br>Drug: Glargine insulin was administered per above. Drug: Lispro insulin 0.2 unit/kg/day was administered per above. A coverage dose of 0.1 unit/kg/day of lispro for each 10 mg of prednisone or its equivalent was divided between 3 meals. The maximum starting coverage dose was 0.4 units/kg per day. The prandial dose of lispro was increased by 10% if the pre-lunch, pre-dinner, or bedtime SG was between 141-200 mg/dL, and by 20% if the pre-lunch, pre-dinner or bedtime SG is >200 mg/dL. The prandial dose of lispro was decreased by 10% if the pre-lunch, pre-dinner, or bedtime SG is between 70-89 mg/dL, and by 20% if the pre-lunch, pre-dinner or bedtime SG was less than 70 mg/dL. Drug: prednisone or equivalent dose was determined by severity of exacerbation and clinician's judgement. | Drug: Glargine insulin<br>* In both protocols glargine dose was increased by 10% if the FSG value was 141-200 mg/dL and by 20% if the FSG value was more than 200 mg/dL, and decreased by 10% if the FSG was 70-89 mg/dL and by 20% if the FSG was less than 70 mg/dL.<br>Drug: Lispro insulin<br>* In both protocols lispro insulin was given to cover meals. Additional lispro insulin was Lispro insulin was administered before meals to cover the prednisone or glucocorticoid equivalent in the Glargine/Lispro Insulin Arm.<br>|
| Experimental: Glargine/Lispro/NPH Insulin Arm<br>Drugs Glargine and Lispro insulin included similar starting doses of glargine and lispro. Drug: A coverage dose of NPH insulin 0.1 unit/kg/day for each 10 mg of prednisone or its equivalent was given twice daily with the administration of the glucocorticoid. Maximum starting coverage dose was 0.4 units/kg per day. NPH dose was increased by 10% if the pre-lunch, pre-dinner, or bedtime SG is between 141-200 mg/dL, and by 20% if the pre-lunch, pre-dinner or bedtime SG was greater than 200 mg/dL. It was decreased by 10% if the pre-lunch, pre-dinner, or bedtime SG was between 70-89 mg/dL, and by 20% if the pre-lunch, pre-dinner or bedtime SG was less than 70 mg/dL. Drug: the dose of prednisone or equivalent glucocorticoid was determined by severity of exacerbation and clinician's judgement. | Drug: Glargine insulin<br>* In both protocols glargine dose was increased by 10% if the FSG value was 141-200 mg/dL and by 20% if the FSG value was more than 200 mg/dL, and decreased by 10% if the FSG was 70-89 mg/dL and by 20% if the FSG was less than 70 mg/dL.<br>Drug: Lispro insulin<br>* In both protocols lispro insulin was given to cover meals. Additional lispro insulin was Lispro insulin was administered before meals to cover the prednisone or glucocorticoid equivalent in the Glargine/Lispro Insulin Arm.<br>Drug: NPH Insulin<br>* NPH insulin was given once or twice a day to cover the prednisone or glucocorticoid equivalent in the Glargine/Lispro/NPH Insulin Arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Daily Glucose Levels on Days 1-5 After the Initiation of the Treatment Protocol. | Most patients had 4 and all patients had at least 2 readings each day. Average daily glucose values were determined for each participant, then averaged for each Arm. | 1-5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With Average Glucose >70 and <180 mg/dL | Percent of Participants with Average Daily Glucose >70 and <180 mg/dL | Last Full Day of Protocol for Participant (up to Day 5) | 
| Daily Insulin Dose/Kg Body Weight | Total daily dose of insulin required based on weight and glucocorticoid dosage to achieve average daily finger stick glucose (FSG) levels of 90-140 mg/dL | 1-5 days | 
| Glucose Values <70 mg/dL. | # participants with glucose values <70 mg/dL | 1-5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glucocorticoids, hyperglycemia, diabetes mellitus