Diabetes Mellitus
Conditions
Keywords
corticosteroid, diabetes, insulin
Brief summary
Despite a significant problem with out-of-control glucose levels in patients with diabetes receiving corticosteroids for a variety of illnesses, there are no published protocols addressing how to adequately treat corticosteroid-induced hyperglycemia. Investigators propose to test a protocol using scheduled dosing of NPH (Neutral protamine Hagedorn) insulin for inpatients with diabetes receiving corticosteroids. NPH insulin action is ideally timed to counteract corticosteroid-induced hyperglycemia, and the dose is added to the patient's usual insulin regimen and timed to correspond to the corticosteroid dosing regimen. Investigators will prospectively enroll eligible consented patients with diabetes who are receiving corticosteroids as part of their treatment in a large county hospital, will randomize them to intervention or control groups, and will monitor their glucose levels during their inpatient stay. The protocol will demonstrate improved control of glucose levels with minimal risk of hypoglycemia, and will provide a practical and readily implementable protocol using NPH insulin as therapy for corticosteroid-induced diabetes.
Detailed description
As above.
Interventions
DRUGNPH
NPH given per study table based on steroid dose and patient weight in kg.
Given at 2 units per 50 mg/dl over 200 mg/dl and increased to 3 units/50 mg/dl over 200 if glucose rises to over 300 mg/dl. Administered qid during study duration.
Sponsors
Eli Lilly and Company
Hennepin Healthcare Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Prior history of diabetes * Able to provide informed consent * Receiving corticosteroids while hospitalized of greater than 10 mg/d prednisone or the equivalent of dexamethasone or methylprednisolone * Expect to be hospitalized for 48 hours
Exclusion criteria
* Renal failure with GFR (glomerular filtration rate) \< 30 ml/min/1.73m2 * ALT (alanine aminotransferase) \> 2 times upper normal for laboratory
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean POC Glucose Level Between Groups | Assessed from enrollment to discharge or enrollment to day five. | Primary outcome measure was mean blood glucose levels measured pre-meal and at bedtime in study patients and controls for the duration of the intervention. Values shown are the overall mean point of care blood glucose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Episodes of Hypoglycemia Between NPH and Control Groups | Glucose levels measured pre-meal, at bedtime, and during symptoms of hypoglycemia in study patients and controls for the duration of the intervention. Values shown represent cumulative episodes of hypoglycemia per group. | Hypoglycemia was defined as point of care glucose less than 70 mg/dL. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Hyperglycemia Defined as Point of Care Glucose 300 - 400 mg/dl | From day 1 (day of enrollment) to day 5 (last day of study participation) or final day of hospitalization if less than 5 days. Point of care glucose was checked before breakfast, lunch, dinner, bed time and during symptoms of hypoglycemia. | Glucose levels measured pre-meal, at bedtime, and during symptoms of hypoglycemia in study patients and controls for the duration of the intervention. Values shown are the overall percentage of glucose measurements 300 - 400 mg/dl. |
| Incidence of Hyperglycemia Defined as Point of Care Glucose > 400 mg/dL | From day 1 (day of enrollment) to day 5 (last day of study participation) or final day of hospitalization if less than 5 days. Point of care glucose was checked before breakfast, lunch, dinner, bed time and during symptoms of hypoglycemia. | Glucose levels measured pre-meal, at bedtime, and during symptoms of hypoglycemia in study patients and controls for the duration of the intervention. Values shown are the overall percentage of glucose measurements \> 400 mg/dL. |
| Difference in Length of Stay Between NPH and Control Group | Measured from the day of admission till the day of discharge | Time difference of hospitalization between the NPH and control groups. |
| Mean Point of Care (POC) Glucose Level in Both Groups. | On day 1 of study enrollment. Point of care glucose was checked before breakfast, lunch, dinner, and bed time. | The overall mean point of care glucose levels in the NPH group and control group on the first day of the study. |
| Correlation of C-peptide With Age | plasma C-peptide was measured once at the time of enrollment | — |
| Correlation of C-peptide With BMI | Measured once at the time of enrollment | — |
| Percentage of Point of Care Glucose Measurements Between 70 - 180 mg/dL | From day 1 (day of enrollment) to day 5 (last day of study participation) or final day of hospitalization if less than 5 days. Point of care glucose was checked before breakfast, lunch, dinner, bed time and during symptoms of hypoglycemia. | Glucose levels measured pre-meal, at bedtime, and during symptoms of hypoglycemia in study patients and controls for the duration of the intervention. Values shown are the overall percentage of glucose measurements between 70 - 180 mg/dl. |
| Correlation of C-peptide With Serum Creatinine | Measured once at the time of enrollment | — |
| Correlation of C-peptide With ALT | Measured once at the time of enrollment | — |
| Correlation of C-peptide With Hemoglobin A1c | Measured once at the time of enrollment | — |
| Correlation of C-peptide With Duration of Diabetes | Measured once at the time of enrollment | — |
| Correlation of C-peptide With Plasma Glucose | Measured the time of enrollment | — |
| Correlation of C-peptide With Length of Stay | Measured once at the time of enrollment | — |
| Correlation of C-peptide With eGFR | Measured once at the time of enrollment | — |
| Incidence of Hyperglycemia Defined as Point of Care Glucose 180 - 300 mg/dL | From day 1 (day of enrollment) to day 5 (last day of study participation) or final day of hospitalization if less than 5 days. Point of care glucose was checked before breakfast, lunch, dinner, bed time and during symptoms of hypoglycemia. | Glucose levels measured pre-meal, at bedtime, and during symptoms of hypoglycemia in study patients and controls for the duration of the intervention. Values shown are the overall percentage of glucose measurements 180 - 300 mg/dL. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NPH With Corticosteroid Dose Receive NPH with each corticosteroid dose during the study duration (2-5 days).
Low dose corticosteroids High dose corticosteroids Eating and 6a-8p 0.15 units NPH/kg 0.3 units NPH/kg NPO(nothing by mouth) or 8p-6a 0.1 units NPH/kg 0.2 units NPH/kg
NPH: NPH given per study table based on steroid dose and patient weight in kg.
Correction Factor: Given at 2 units per 50 mg/dl over 200 mg/dl and increased to 3 units/50 mg/dl over 200 if glucose rises to over 300 mg/dl. Administered qid during study duration. | 29 |
| Control Receive usual care with background insulin and correction factor for duration of study (2-5 days)
Correction Factor: Given at 2 units per 50 mg/dl over 200 mg/dl and increased to 3 units/50 mg/dl over 200 if glucose rises to over 300 mg/dl. Administered qid during study duration. | 31 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Steroid d/c;discharge<48 hrs. | 15 | 8 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Control | Total | NPH With Corticosteroid Dose |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 15 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 45 Participants | 18 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 31 participants | 60 participants | 29 participants |
| Sex: Female, Male Female | 17 Participants | 32 Participants | 15 Participants |
| Sex: Female, Male Male | 14 Participants | 28 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 31 |
| other Total, other adverse events | 0 / 29 | 0 / 31 |
| serious Total, serious adverse events | 6 / 29 | 0 / 31 |
Outcome results
Primary
Mean POC Glucose Level Between Groups
Primary outcome measure was mean blood glucose levels measured pre-meal and at bedtime in study patients and controls for the duration of the intervention. Values shown are the overall mean point of care blood glucose.
Time frame: Assessed from enrollment to discharge or enrollment to day five.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NPH With Corticosteroid | Mean POC Glucose Level Between Groups | 225 mg/dl | Standard Deviation 87.2 |
| Control | Mean POC Glucose Level Between Groups | 266 mg/dl | Standard Deviation 69.51 |
Secondary
Episodes of Hypoglycemia Between NPH and Control Groups
Hypoglycemia was defined as point of care glucose less than 70 mg/dL.
Time frame: Glucose levels measured pre-meal, at bedtime, and during symptoms of hypoglycemia in study patients and controls for the duration of the intervention. Values shown represent cumulative episodes of hypoglycemia per group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPH With Corticosteroid | Episodes of Hypoglycemia Between NPH and Control Groups | 6 Hypoglycemic episodes. |
| Control | Episodes of Hypoglycemia Between NPH and Control Groups | 0 Hypoglycemic episodes. |
Other Pre-specified
Correlation of C-peptide With Age
Time frame: plasma C-peptide was measured once at the time of enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPH With Corticosteroid | Correlation of C-peptide With Age | 0.197 correlation coefficient |
| Control | Correlation of C-peptide With Age | -0.226 correlation coefficient |
Other Pre-specified
Correlation of C-peptide With ALT
Time frame: Measured once at the time of enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPH With Corticosteroid | Correlation of C-peptide With ALT | -0.358 correlation coefficient |
| Control | Correlation of C-peptide With ALT | 0.436 correlation coefficient |
Other Pre-specified
Correlation of C-peptide With BMI
Time frame: Measured once at the time of enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPH With Corticosteroid | Correlation of C-peptide With BMI | 0.095 correlation coefficient |
| Control | Correlation of C-peptide With BMI | 0.305 correlation coefficient |
Other Pre-specified
Correlation of C-peptide With Duration of Diabetes
Time frame: Measured once at the time of enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPH With Corticosteroid | Correlation of C-peptide With Duration of Diabetes | -0.320 correlation coefficient |
| Control | Correlation of C-peptide With Duration of Diabetes | -0.380 correlation coefficient |
Other Pre-specified
Correlation of C-peptide With eGFR
Time frame: Measured once at the time of enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPH With Corticosteroid | Correlation of C-peptide With eGFR | -0.272 correlation coefficient |
| Control | Correlation of C-peptide With eGFR | -0.063 correlation coefficient |
Other Pre-specified
Correlation of C-peptide With Hemoglobin A1c
Time frame: Measured once at the time of enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPH With Corticosteroid | Correlation of C-peptide With Hemoglobin A1c | -0.325 correlation coefficient |
| Control | Correlation of C-peptide With Hemoglobin A1c | -0.251 correlation coefficient |
Other Pre-specified
Correlation of C-peptide With Length of Stay
Time frame: Measured once at the time of enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPH With Corticosteroid | Correlation of C-peptide With Length of Stay | -0.068 correlation coefficient |
| Control | Correlation of C-peptide With Length of Stay | -0.002 correlation coefficient |
Other Pre-specified
Correlation of C-peptide With Plasma Glucose
Time frame: Measured the time of enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPH With Corticosteroid | Correlation of C-peptide With Plasma Glucose | 0.171 correlation coefficient |
| Control | Correlation of C-peptide With Plasma Glucose | -0.053 correlation coefficient |
Other Pre-specified
Correlation of C-peptide With Serum Creatinine
Time frame: Measured once at the time of enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPH With Corticosteroid | Correlation of C-peptide With Serum Creatinine | 0.328 correlation coefficient |
| Control | Correlation of C-peptide With Serum Creatinine | -0.026 correlation coefficient |
Other Pre-specified
Difference in Length of Stay Between NPH and Control Group
Time difference of hospitalization between the NPH and control groups.
Time frame: Measured from the day of admission till the day of discharge
Population: Difference in mean length of stay between NPH group and usual care group
| Arm | Measure | Value (MEAN) |
|---|---|---|
| NPH With Corticosteroid | Difference in Length of Stay Between NPH and Control Group | 5.21 Days |
| Control | Difference in Length of Stay Between NPH and Control Group | 5.23 Days |
Other Pre-specified
Incidence of Hyperglycemia Defined as Point of Care Glucose 180 - 300 mg/dL
Glucose levels measured pre-meal, at bedtime, and during symptoms of hypoglycemia in study patients and controls for the duration of the intervention. Values shown are the overall percentage of glucose measurements 180 - 300 mg/dL.
Time frame: From day 1 (day of enrollment) to day 5 (last day of study participation) or final day of hospitalization if less than 5 days. Point of care glucose was checked before breakfast, lunch, dinner, bed time and during symptoms of hypoglycemia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPH With Corticosteroid | Incidence of Hyperglycemia Defined as Point of Care Glucose 180 - 300 mg/dL | 42.1 Percentage of total measurements |
| Control | Incidence of Hyperglycemia Defined as Point of Care Glucose 180 - 300 mg/dL | 45.3 Percentage of total measurements |
Other Pre-specified
Incidence of Hyperglycemia Defined as Point of Care Glucose 300 - 400 mg/dl
Glucose levels measured pre-meal, at bedtime, and during symptoms of hypoglycemia in study patients and controls for the duration of the intervention. Values shown are the overall percentage of glucose measurements 300 - 400 mg/dl.
Time frame: From day 1 (day of enrollment) to day 5 (last day of study participation) or final day of hospitalization if less than 5 days. Point of care glucose was checked before breakfast, lunch, dinner, bed time and during symptoms of hypoglycemia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPH With Corticosteroid | Incidence of Hyperglycemia Defined as Point of Care Glucose 300 - 400 mg/dl | 16.9 Percentage of total measurements |
| Control | Incidence of Hyperglycemia Defined as Point of Care Glucose 300 - 400 mg/dl | 27.0 Percentage of total measurements |
Other Pre-specified
Incidence of Hyperglycemia Defined as Point of Care Glucose > 400 mg/dL
Glucose levels measured pre-meal, at bedtime, and during symptoms of hypoglycemia in study patients and controls for the duration of the intervention. Values shown are the overall percentage of glucose measurements \> 400 mg/dL.
Time frame: From day 1 (day of enrollment) to day 5 (last day of study participation) or final day of hospitalization if less than 5 days. Point of care glucose was checked before breakfast, lunch, dinner, bed time and during symptoms of hypoglycemia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPH With Corticosteroid | Incidence of Hyperglycemia Defined as Point of Care Glucose > 400 mg/dL | 5.9 Percentage of total measurements |
| Control | Incidence of Hyperglycemia Defined as Point of Care Glucose > 400 mg/dL | 8.5 Percentage of total measurements |
Other Pre-specified
Mean Point of Care (POC) Glucose Level in Both Groups.
The overall mean point of care glucose levels in the NPH group and control group on the first day of the study.
Time frame: On day 1 of study enrollment. Point of care glucose was checked before breakfast, lunch, dinner, and bed time.
Population: Point of care glucose checked before breakfast, lunch, dinner, and bed time on day 1 of study enrollment. The numbers indicated below show the mean point of care (POC) glucose readings in the two groups on the first day of the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| NPH With Corticosteroid | Mean Point of Care (POC) Glucose Level in Both Groups. | 246.9 mg/dL (mean values) |
| Control | Mean Point of Care (POC) Glucose Level in Both Groups. | 280.9 mg/dL (mean values) |
Other Pre-specified
Mean Point of Care (POC) Glucose Level in Both Groups.
The overall mean point of care glucose levels in the NPH group and control group on the last day of the study.
Time frame: On day 5 or last day of hospitalization (if less than 5 days) glucose level as measured by point of care glucose before breakfast, lunch, dinner and bed time.
Population: Point of care glucose checked before breakfast, lunch, dinner, and bed time on day 5 of study enrollment. The numbers indicated below show the mean point of care (POC) glucose readings in the two groups on the last day of the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| NPH With Corticosteroid | Mean Point of Care (POC) Glucose Level in Both Groups. | 197.3 mg/dL (mean values) |
| Control | Mean Point of Care (POC) Glucose Level in Both Groups. | 253.5 mg/dL (mean values) |
Other Pre-specified
Percentage of Point of Care Glucose Measurements Between 70 - 180 mg/dL
Glucose levels measured pre-meal, at bedtime, and during symptoms of hypoglycemia in study patients and controls for the duration of the intervention. Values shown are the overall percentage of glucose measurements between 70 - 180 mg/dl.
Time frame: From day 1 (day of enrollment) to day 5 (last day of study participation) or final day of hospitalization if less than 5 days. Point of care glucose was checked before breakfast, lunch, dinner, bed time and during symptoms of hypoglycemia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPH With Corticosteroid | Percentage of Point of Care Glucose Measurements Between 70 - 180 mg/dL | 33.1 Percentage of total measurements of gluc |
| Control | Percentage of Point of Care Glucose Measurements Between 70 - 180 mg/dL | 19.2 Percentage of total measurements of gluc |