Congestive Heart Failure, Diabetes Mellitus
Conditions
Keywords
congestive heart failure, diabetes mellitus, hyperglycemia
Brief summary
High glucose as well as fluctuations (rapid swings) in blood glucose can contribute to severe hospital complications and even death.
Detailed description
High glucose as well as fluctuations in blood glucose can contribute to severe hospital complications and even death. Studies also suggest that heart failure patients who have high glucose or diabetes do not live as long as patients with normal glucose. Glucose fluctuations have not been well-studied in patients with heart failure. In this study, we will determine whether better control of blood sugar fluctuations in the hospital improve outcomes. We will enroll 80 patients with severe heart failure and divide them into 2 groups. We will use intravenous (given through the vein) insulin to lower blood sugar levels in group 1, and insulin injections (under the skin) in group 2. We will determine whether intravenous insulin improves blood markers of inflammation, changes in vital signs, and other tests that predict mortality in patients with heart failure.
Interventions
Patients will receive continuous insulin infusion through the vein.
4 injections of insulin/day
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Kathleen Dungan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 and above * Admitted (less than 48 hours) to the with worsening heart failure * Hyperglycemia or diabetes. Hyperglycemia is defined as blood glucose greater than 150 mg/dL on at least 2 occasions separated by at least 4 hours apart, insulin use, or HbA1c \>6.5%.
Exclusion criteria
* Type 1 diabetes * Receiving comfort care measures only * Hospital stay expected to be less than 2 days * Pregnancy * Prisoners * Participation in the study on prior hospitalizations * Acute myocardial infarction within 3 months * End stage renal or liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hospital Length of Stay | participants were followed for the duration of hospital stay, median hospital stay 8 day | Duration of hospitalization |
| Hospital Readmission | 30 days | All-cause hospital readmission within 30 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| High Sensitivity C-reactive Protein (Hs-CRP) | 72 hours | High sensitivity C-reactive Protein (hs-CRP) is a measure of inflammation. hsCRP (range 0-15 mg/L) was performed using Immunlite 1000 assay (Siemens; Erlangen, Germany). |
| Brain Natriuretic Peptide (BNP) | 72 hours | Laboratory analyses were performed by the study institution's Clinical Research Center using standard commercial kits |
| Quality of Life | 30 days | Quality of Life was measured using the Minnesota Living with Heart Failure Questionnaire, which is a 21 question survey that uses a likert scale of 0-5. Each item asks over the past 4 weeks whether they have had a particular symptom of heart failure and to classify the response as no symptoms (0) to having the symptom very much (5). Responses are summed for a total score (0-105). |
| High Frequency Heart Rate Variability | 24 hours | High frequency heart rate variability (HF HRV)is a measure of cardiac autonomic tone. Electrocardiographic measures were obtained using a Bionex system (Mindware, Gahanna, OH). The electrocardiogram was performed in the standard lead II configuration. Software (Mindware, Gahanna, OH) was used to derive HF HRV. HF HRV was calculated using power spectral analysis. |
| Coefficient of Variation (CV) | 24 hours | CV is a measure of glycemic variability |
| Mean Glucose | 24 hours | mean sensor glucose |
| Glycemic Lability Index (GLI) | 24 hours | GLI is a measure of glycemic variability. GLI is the sum of the square of the difference between successive glucose measurements divided by the difference in time between measurements |
| Pre-ejection Period (PEP) | 24 hours | Pre-ejection period (PEP) is the time between the onset of electrical depolarization of the ventricle and the opening of the aortic valve, a measure of sympathetic tone. It is obtained noninvasively using cardiac impedance obtained using a Bionex system (Mindware, Gahanna, OH). PEP is measured in milliseconds; lower values reflect higher sympathetic tone. |
Countries
United States
Participant flow
Recruitment details
Hospitalized patients with type 2 diabetes and heart failure exacerbation were recruited between 2008-2013 from an academic medical center.
Pre-assignment details
Patients were randomized to intravenous or subcutaneous insulin. There were no pre-assignment changes in therapy before randomization. One patient was excluded after consent but prior to randomization due to receipt of corticosteroids which is an exclusion criterion.
Participants by arm
| Arm | Count |
|---|---|
| Intravenous Insulin Patients received intravenous insulin according to the hospital nursing run algorithm with a target glucose of 100-150 mg/dl. | 26 |
| Subcutaneous Insulin Patients received basal and bolus insulin, approximately 5 injections of insulin/day | 39 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Transfer to ICU prior to intervention | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Subcutaneous Insulin | Intravenous Insulin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 16 Participants | 8 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 18 Participants | 41 Participants |
| Age Continuous | 61.3 years STANDARD_DEVIATION 12.4 | 61 years STANDARD_DEVIATION 9.6 | 61 years STANDARD_DEVIATION 9.6 |
| Region of Enrollment United States | 39 participants | 26 participants | 65 participants |
| Sex: Female, Male Female | 13 Participants | 8 Participants | 21 Participants |
| Sex: Female, Male Male | 26 Participants | 18 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 26 | 4 / 39 |
| serious Total, serious adverse events | 16 / 26 | 21 / 39 |
Outcome results
Primary
Hospital Length of Stay
Duration of hospitalization
Time frame: participants were followed for the duration of hospital stay, median hospital stay 8 day
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous Insulin | Hospital Length of Stay | 7 days |
| Subcutaneous Insulin | Hospital Length of Stay | 8 days |
Primary
Hospital Readmission
All-cause hospital readmission within 30 days
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intravenous Insulin | Hospital Readmission | 7 participants |
| Subcutaneous Insulin | Hospital Readmission | 15 participants |
Secondary
Brain Natriuretic Peptide (BNP)
Laboratory analyses were performed by the study institution's Clinical Research Center using standard commercial kits
Time frame: 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous Insulin | Brain Natriuretic Peptide (BNP) | 360 pg/ml |
| Subcutaneous Insulin | Brain Natriuretic Peptide (BNP) | 299 pg/ml |
Secondary
Coefficient of Variation (CV)
CV is a measure of glycemic variability
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Insulin | Coefficient of Variation (CV) | 24.5 percentage (mean glucose/SD) | Standard Deviation 10.2 |
| Subcutaneous Insulin | Coefficient of Variation (CV) | 18.6 percentage (mean glucose/SD) | Standard Deviation 8.5 |
Secondary
Glycemic Lability Index (GLI)
GLI is a measure of glycemic variability. GLI is the sum of the square of the difference between successive glucose measurements divided by the difference in time between measurements
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous Insulin | Glycemic Lability Index (GLI) | 0.83 (mg/dl)^2/hr*day-1 |
| Subcutaneous Insulin | Glycemic Lability Index (GLI) | 0.66 (mg/dl)^2/hr*day-1 |
Secondary
High Frequency Heart Rate Variability
High frequency heart rate variability (HF HRV)is a measure of cardiac autonomic tone. Electrocardiographic measures were obtained using a Bionex system (Mindware, Gahanna, OH). The electrocardiogram was performed in the standard lead II configuration. Software (Mindware, Gahanna, OH) was used to derive HF HRV. HF HRV was calculated using power spectral analysis.
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous Insulin | High Frequency Heart Rate Variability | 15.5 ms^2 |
| Subcutaneous Insulin | High Frequency Heart Rate Variability | 13.9 ms^2 |
Secondary
High Sensitivity C-reactive Protein (Hs-CRP)
High sensitivity C-reactive Protein (hs-CRP) is a measure of inflammation. hsCRP (range 0-15 mg/L) was performed using Immunlite 1000 assay (Siemens; Erlangen, Germany).
Time frame: 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous Insulin | High Sensitivity C-reactive Protein (Hs-CRP) | 10.5 mg/dl |
| Subcutaneous Insulin | High Sensitivity C-reactive Protein (Hs-CRP) | 15.9 mg/dl |
Secondary
Mean Glucose
mean sensor glucose
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Insulin | Mean Glucose | 139 mg/dl | Standard Deviation 23 |
| Subcutaneous Insulin | Mean Glucose | 169 mg/dl | Standard Deviation 49 |
Secondary
Pre-ejection Period (PEP)
Pre-ejection period (PEP) is the time between the onset of electrical depolarization of the ventricle and the opening of the aortic valve, a measure of sympathetic tone. It is obtained noninvasively using cardiac impedance obtained using a Bionex system (Mindware, Gahanna, OH). PEP is measured in milliseconds; lower values reflect higher sympathetic tone.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Insulin | Pre-ejection Period (PEP) | 120 ms | Standard Deviation 24 |
| Subcutaneous Insulin | Pre-ejection Period (PEP) | 117 ms | Standard Deviation 20 |
Secondary
Quality of Life
Quality of Life was measured using the Minnesota Living with Heart Failure Questionnaire, which is a 21 question survey that uses a likert scale of 0-5. Each item asks over the past 4 weeks whether they have had a particular symptom of heart failure and to classify the response as no symptoms (0) to having the symptom very much (5). Responses are summed for a total score (0-105).
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous Insulin | Quality of Life | 50.5 units on a scale |
| Subcutaneous Insulin | Quality of Life | 45 units on a scale |