Hyperglycemia, Diabetes Mellitus
Conditions
Keywords
glucocorticoids, hyperglycemia, diabetes mellitus
Brief summary
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
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.
Interventions
DRUGGlargine insulin
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.
DRUGLispro insulin
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.
DRUGNPH Insulin
NPH insulin was given once or twice a day to cover the prednisone or glucocorticoid equivalent in the Glargine/Lispro/NPH Insulin Arm
Sponsors
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Daily Glucose Levels on Days 1-5 After the Initiation of the Treatment Protocol. | 1-5 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Average Glucose >70 and <180 mg/dL | Last Full Day of Protocol for Participant (up to Day 5) | Percent of Participants with Average Daily Glucose \>70 and \<180 mg/dL |
| Daily Insulin Dose/Kg Body Weight | 1-5 days | 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 |
| Glucose Values <70 mg/dL. | 1-5 days | \# participants with glucose values \<70 mg/dL |
Countries
United States
Participant flow
Recruitment details
Participants were identified from admission listing of patients and admitting diagnoses. Admitting physician was contacted to determine eligibility and if s/he were agreeable to our approaching patient regarding the study. Protocol was explained to patient. If s/he agreed to participate, they were asked to sign an informed consent.
Participants by arm
| Arm | Count |
|---|---|
| Glargine/Lispro Insulin Arm The Glargine/Lispro Arm included 0.2 unit/kg/day as insulin glargine 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.
Glargine/Lispro insulin: In both protocols glargine dose was increased by 10% if the fasting glucose value was 141-200 mg/dL and by 20% if the fasting glucose value was more than 200 mg/dL, and decreased by 10% if the fasting FSG was 70-89 mg/dL and by 20% if the fasting FSG was less than 70 mg/dL. | 20 |
| Glargine/Lispro/NPH Insulin Arm The basal and prandial doses of glargine and lispro insulin were similar to those in the Glargine/Lispro Arm. A coverage dose of 0.1 unit/kg/day of 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. | 17 |
| Total | 37 |
Baseline characteristics
| Characteristic | Glargine/Lispro/NPH Insulin Arm | Glargine/Lispro Insulin Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 7 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 13 Participants | 19 Participants |
| Age, Continuous Baseline Participants | 67.1 years STANDARD_DEVIATION 14.3 | 60.8 years STANDARD_DEVIATION 12.9 | 63.7 years STANDARD_DEVIATION 13.7 |
| Region of Enrollment United States | 17 participants | 20 participants | 37 participants |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 20 Participants |
| Sex: Female, Male Male | 8 Participants | 9 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 17 |
| serious Total, serious adverse events | 1 / 20 | 0 / 17 |
Outcome results
Primary
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.
Time frame: 1-5 days
Population: We used t-tests to compare values between the protocols on each day..
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glargine/Lispro Insulin Arm | Average Daily Glucose Levels on Days 1-5 After the Initiation of the Treatment Protocol. | Day 3 (n=20, 17) | 155.1 mg/dL | Standard Deviation 51.8 |
| Glargine/Lispro Insulin Arm | Average Daily Glucose Levels on Days 1-5 After the Initiation of the Treatment Protocol. | Day 2 (n=20, 17) | 160.5 mg/dL | Standard Deviation 45.5 |
| Glargine/Lispro Insulin Arm | Average Daily Glucose Levels on Days 1-5 After the Initiation of the Treatment Protocol. | Day 4 (n=14, 12) | 159.5 mg/dL | Standard Deviation 40.5 |
| Glargine/Lispro Insulin Arm | Average Daily Glucose Levels on Days 1-5 After the Initiation of the Treatment Protocol. | Day 5 (n=10, 7) | 151.7 mg/dL | Standard Deviation 45.5 |
| Glargine/Lispro Insulin Arm | Average Daily Glucose Levels on Days 1-5 After the Initiation of the Treatment Protocol. | Day 1 (n=20, 17) | 181.8 mg/dL | Standard Deviation 40.9 |
| Glargine/Lispro/NPH Insulin Arm | Average Daily Glucose Levels on Days 1-5 After the Initiation of the Treatment Protocol. | Day 5 (n=10, 7) | 132.0 mg/dL | Standard Deviation 33.5 |
| Glargine/Lispro/NPH Insulin Arm | Average Daily Glucose Levels on Days 1-5 After the Initiation of the Treatment Protocol. | Day 1 (n=20, 17) | 173.7 mg/dL | Standard Deviation 51.2 |
| Glargine/Lispro/NPH Insulin Arm | Average Daily Glucose Levels on Days 1-5 After the Initiation of the Treatment Protocol. | Day 2 (n=20, 17) | 148.4 mg/dL | Standard Deviation 36.7 |
| Glargine/Lispro/NPH Insulin Arm | Average Daily Glucose Levels on Days 1-5 After the Initiation of the Treatment Protocol. | Day 3 (n=20, 17) | 140.8 mg/dL | Standard Deviation 35.2 |
| Glargine/Lispro/NPH Insulin Arm | Average Daily Glucose Levels on Days 1-5 After the Initiation of the Treatment Protocol. | Day 4 (n=14, 12) | 133.4 mg/dL | Standard Deviation 34 |
p-value: 0.35t-test, 2 sided
Secondary
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
Time frame: 1-5 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glargine/Lispro Insulin Arm | Daily Insulin Dose/Kg Body Weight | Day 2 (n=20, 17) | 0.91 units of insulin/Kg body weight | Standard Deviation 0.28 |
| Glargine/Lispro Insulin Arm | Daily Insulin Dose/Kg Body Weight | Day 4 (n=14, 12) | 1.01 units of insulin/Kg body weight | Standard Deviation 0.5 |
| Glargine/Lispro Insulin Arm | Daily Insulin Dose/Kg Body Weight | Day 3 (n=20, 17) | 0.96 units of insulin/Kg body weight | Standard Deviation 0.35 |
| Glargine/Lispro Insulin Arm | Daily Insulin Dose/Kg Body Weight | Day 5 (n=10, 7) | 1.12 units of insulin/Kg body weight | Standard Deviation 0.7 |
| Glargine/Lispro Insulin Arm | Daily Insulin Dose/Kg Body Weight | Day 1 (n=20, 17) | 0.89 units of insulin/Kg body weight | Standard Deviation 0.25 |
| Glargine/Lispro/NPH Insulin Arm | Daily Insulin Dose/Kg Body Weight | Day 5 (n=10, 7) | 0.65 units of insulin/Kg body weight | Standard Deviation 0.21 |
| Glargine/Lispro/NPH Insulin Arm | Daily Insulin Dose/Kg Body Weight | Day 1 (n=20, 17) | 0.80 units of insulin/Kg body weight | Standard Deviation 0.17 |
| Glargine/Lispro/NPH Insulin Arm | Daily Insulin Dose/Kg Body Weight | Day 2 (n=20, 17) | 0.82 units of insulin/Kg body weight | Standard Deviation 0.18 |
| Glargine/Lispro/NPH Insulin Arm | Daily Insulin Dose/Kg Body Weight | Day 3 (n=20, 17) | 0.77 units of insulin/Kg body weight | Standard Deviation 0.24 |
| Glargine/Lispro/NPH Insulin Arm | Daily Insulin Dose/Kg Body Weight | Day 4 (n=14, 12) | 0.75 units of insulin/Kg body weight | Standard Deviation 0.16 |
Comparison: Daily values for each protocol were compared using t-tests.p-value: 0.06t-test, 2 sided
Secondary
Glucose Values <70 mg/dL.
\# participants with glucose values \<70 mg/dL
Time frame: 1-5 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glargine/Lispro Insulin Arm | Glucose Values <70 mg/dL. | # with glucose values <70 mg/dL | 5 participants |
| Glargine/Lispro Insulin Arm | Glucose Values <70 mg/dL. | # with glucose values <60 mg/dL | 4 participants |
| Glargine/Lispro Insulin Arm | Glucose Values <70 mg/dL. | # with glucose <50 | 1 participants |
| Glargine/Lispro/NPH Insulin Arm | Glucose Values <70 mg/dL. | # with glucose values <70 mg/dL | 4 participants |
| Glargine/Lispro/NPH Insulin Arm | Glucose Values <70 mg/dL. | # with glucose values <60 mg/dL | 2 participants |
| Glargine/Lispro/NPH Insulin Arm | Glucose Values <70 mg/dL. | # with glucose <50 | 0 participants |
p-value: 0.795Chi-squared
Secondary
Percent of Participants With Average Glucose >70 and <180 mg/dL
Percent of Participants with Average Daily Glucose \>70 and \<180 mg/dL
Time frame: Last Full Day of Protocol for Participant (up to Day 5)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glargine/Lispro Insulin Arm | Percent of Participants With Average Glucose >70 and <180 mg/dL | 90 percentage of participants |
| Glargine/Lispro/NPH Insulin Arm | Percent of Participants With Average Glucose >70 and <180 mg/dL | 94 percentage of participants |
p-value: 0.65Chi-squared
Post Hoc
Percent of Glucose Determinations >180 mg/dL
Time frame: 1-5 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glargine/Lispro Insulin Arm | Percent of Glucose Determinations >180 mg/dL | 31.0 Percent of glucose values |
| Glargine/Lispro/NPH Insulin Arm | Percent of Glucose Determinations >180 mg/dL | 24.6 Percent of glucose values |
Comparison: Values in each group were compared by Chi squared.p-value: 0.055Chi-squared