Congestive Heart Failure, Diabetes Mellitus
Conditions
Keywords
Heart failure, Hyperglycemia, Hospital, Diabetes Mellitus
Brief summary
Patients with heart failure often have high blood sugar (glucose).
Detailed description
Patients with heart failure often have high blood sugar. High glucose contributes to severe hospital complications and even death. Studies suggest that heart failure patients who have high glucose or diabetes do not live as long as patients with normal glucose. In this study, we will determine whether normalizing blood sugars using intravenous insulin short-term will improve outcomes in patients hospitalized for congestive heart failure. We enrolled patients with severe heart failure and randomly assigned them into 2 groups. We used intravenous (given through the vein) insulin to lower blood sugar levels in group 1, and insulin injections in group 2. We determined whether intravenous insulin improved hospital length of stay, rates of readmission, inflammatory markers, and cardiovascular tests that predict mortality in patients with heart failure.
Interventions
Half of subjects will receive insulin through the intravenous route while the other half will receive 4 injections per day.
Half of subjects will receive insulin through the intravenous route while the other half will receive 4 injections per 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 OSU Ross Heart Hospital 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 | Days | Duration of hospitalization in days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital Readmission | 30 days | All-cause hospital readmission at 30 days after discharge |
| Heart Rate Variability | 72 hours | High frequency (HF) Heart rate variability (HRV). HRV was assessed with a Bionex system (Mindware, Gahanna, OH). The electrocardiogram was performed in the standard lead II configuration and impedance cardiography was performed using a standard tetrapolar arrangement. Measures were performed at baseline and each morning (0800-1000 hour) during and following the intervention for 7 minutes each. Software (Mindware, Gahanna, OH) was used to derive HF HRV. The middle five minutes of the recordings were scored minute by minute and the first suitable1 minute period was used for calculation. Five minute epochs were not feasible due to an unexpectedly high frequency of ectopy. One minute intervals allow calculation of HF (parasympathetic tone) but not low frequency (combination of sympathetic and parasympathetic tone). |
| Change in Quality of Life | 30 day | Change in Quality of Life questionnaire measured from baseline (enrollment) to 30 days following discharge. The questionnaire is a self-administered disease-specific questionnaire for patients with HF, comprising 21 items rated on six-point Likert scales, representing different degrees of impact of HF on health related quality of life, from 0 (none) to 5 (very much). It provides a total score (range 0-105, from best to worst HRQoL), |
| Brain Natriuretic Peptide (BNP) | 72 hours | Brain natriuretic peptide (BNP) was measured at day 3 |
| Cardiac Output | 72 hours | Cardiac output measured using impedance cardiography at 72 hours. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intravenous (IV) Insulin Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap. | 26 |
| Subcutaneous (SQ) Insulin Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was \<11.1 mmol/l or \>11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of \<11.1 mmol/l or \>11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l. | 39 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Intravenous (IV) Insulin | Subcutaneous (SQ) Insulin | Total |
|---|---|---|---|
| Age, Continuous | 61 years STANDARD_DEVIATION 10 | 63 years STANDARD_DEVIATION 12 | 62 years STANDARD_DEVIATION 11 |
| HbA1c | 8.4 Percentage of hemoglobin STANDARD_DEVIATION 2 | 7.7 Percentage of hemoglobin STANDARD_DEVIATION 1.4 | 8.0 Percentage of hemoglobin STANDARD_DEVIATION 1.7 |
| Preserved ejection fraction Preserved Ejection Fraction | 6 participants | 11 participants | 17 participants |
| Preserved ejection fraction Reduced Ejection Fraction | 20 participants | 28 participants | 48 participants |
| Region of Enrollment United States | 26 participants | 39 participants | 65 participants |
| Sex: Female, Male Female | 8 Participants | 13 Participants | 21 Participants |
| Sex: Female, Male Male | 18 Participants | 26 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 | 9 / 26 | 3 / 39 |
| serious Total, serious adverse events | 0 / 26 | 0 / 39 |
Outcome results
Primary
Hospital Length of Stay
Duration of hospitalization in days
Time frame: Days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous (IV) Insulin | Hospital Length of Stay | 7 days |
| Subcutaneous (SQ) Insulin | Hospital Length of Stay | 8 days |
Secondary
Brain Natriuretic Peptide (BNP)
Brain natriuretic peptide (BNP) was measured at day 3
Time frame: 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous (IV) Insulin | Brain Natriuretic Peptide (BNP) | 794 pg/ml |
| Subcutaneous (SQ) Insulin | Brain Natriuretic Peptide (BNP) | 356 pg/ml |
Secondary
Cardiac Output
Cardiac output measured using impedance cardiography at 72 hours.
Time frame: 72 hours
Population: Patients without data due to medical devices, conditions that preclude measurement of PEP such as arrhythmias, or technical problems.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous (IV) Insulin | Cardiac Output | 10.3 liter/min | Standard Deviation 9.3 |
| Subcutaneous (SQ) Insulin | Cardiac Output | 8.6 liter/min | Standard Deviation 3.5 |
Secondary
Change in Quality of Life
Change in Quality of Life questionnaire measured from baseline (enrollment) to 30 days following discharge. The questionnaire is a self-administered disease-specific questionnaire for patients with HF, comprising 21 items rated on six-point Likert scales, representing different degrees of impact of HF on health related quality of life, from 0 (none) to 5 (very much). It provides a total score (range 0-105, from best to worst HRQoL),
Time frame: 30 day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous (IV) Insulin | Change in Quality of Life | -22.4 units on a scale | Standard Deviation 22 |
| Subcutaneous (SQ) Insulin | Change in Quality of Life | -22.6 units on a scale | Standard Deviation 26.3 |
Secondary
Heart Rate Variability
High frequency (HF) Heart rate variability (HRV). HRV was assessed with a Bionex system (Mindware, Gahanna, OH). The electrocardiogram was performed in the standard lead II configuration and impedance cardiography was performed using a standard tetrapolar arrangement. Measures were performed at baseline and each morning (0800-1000 hour) during and following the intervention for 7 minutes each. Software (Mindware, Gahanna, OH) was used to derive HF HRV. The middle five minutes of the recordings were scored minute by minute and the first suitable1 minute period was used for calculation. Five minute epochs were not feasible due to an unexpectedly high frequency of ectopy. One minute intervals allow calculation of HF (parasympathetic tone) but not low frequency (combination of sympathetic and parasympathetic tone).
Time frame: 72 hours
Population: Subjects with medical devices, conditions that preclude measurement of HRV such as arrhythmias, or technical problems could not be analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous (IV) Insulin | Heart Rate Variability | 5.1 ms^2 |
| Subcutaneous (SQ) Insulin | Heart Rate Variability | 20.7 ms^2 |
Secondary
Hospital Readmission
All-cause hospital readmission at 30 days after discharge
Time frame: 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intravenous (IV) Insulin | Hospital Readmission | Readmitted | 7 participants |
| Intravenous (IV) Insulin | Hospital Readmission | Not readmitted | 19 participants |
| Subcutaneous (SQ) Insulin | Hospital Readmission | Readmitted | 15 participants |
| Subcutaneous (SQ) Insulin | Hospital Readmission | Not readmitted | 24 participants |