Inpatient, Type 2 Diabetes
Conditions
Keywords
hospital, diabetes, glycemic variability, autonomic tone
Brief summary
Glycemic variability has been associated with mortality in hospitalized patients with hyperglycemia. However, it is unknown how modulation of glycemic variability would impact outcomes. One possibility is that glycemic variability could impact autonomic tone. In particular, heart rate variability (HRV) measurement is a sensitive marker for measuring autonomic tone, and aberrations in HRV have been associated with mortality. The current randomized pilot study will compare the effects of continuous intravenous (IV) insulin and subcutaneous basal bolus insulin on glycemic variability and autonomic tone in hospitalized non-critically ill patients with diabetes. Non-critically ill patients who are hyperglycemic or are requiring at least 20 units of insulin per day will be included. Patients with conditions that preclude accurate HRV readings (such as atrial fibrillation or paced rhythms) will be excluded. Patients randomized to intravenous insulin will receive the therapy for 24 hours according to our standard hospital guideline. Patients randomized to subcutaneous (SQ) insulin will receive basal bolus therapy using insulin analogues. All therapies will begin between 8 and 10 AM. Patients will undergo repeated heart rate variability recordings during the 24 hour period. Blood draws will be collected at baseline and at 24 hours for measurement of catecholamines, insulin, and c-peptide. Glycemic variability will be measured using a continuous subcutaneous glucose monitor and reported as coefficient of variation. The primary outcome measure is low frequency-to-high frequency power spectrum ratio of heart rate variability. 1. Glycemic variability is associated with unfavorable changes in autonomic tone, as assessed by low frequency (LF)/high frequency (HF) HRV ratio, independent of changes in overall glycemia. 2. Short-term increases in glycemic variability, followed by more prolonged glycemic stability are observed in generalized hospitalized patients treated with intravenous insulin compared to standardized basal bolus therapy. LF/HF HRV differs among subjects receiving intravenous compared to subcutaneous insulin. 3. Glycemic variability differs among subjects receiving intravenous compared to subcutaneous insulin
Interventions
24 hr IV insulin administered according to hospital guideline
basal bolus insulin using carb counting technique and insulin analogues
Sponsors
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 to a general medicine or medicine subspecialty service * Insulin use (\>20 units/day) or hyperglycemia. Hyperglycemia is defined as glucose greater than 180 mg/dL on at least 2 occasions separated by at least 4 hours apart.
Exclusion criteria
* Type 1 diabetes * Hospital stay expected less than 48 hours * Inability to consent * Pregnancy * Prisoners * Previous participation * Autonomic neuropathy * Conditions that preclude accurate heart rate variability monitoring: atrial fibrillation, frequent ectopy, congestive heart failure, paced heart rhythms * Conditions which require lower dose insulin algorithms: end stage renal or liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between Heart Rate Variability Between Intravenous and Subcutaneous Group | 6 hour | difference in mean low frequency/high frequency heart rate variability (LF/HF HRV)at 6 hour. 2 patients were excluded who did not have usable LF/HF HRV data at 6 hours. These patients remained in the study as they did have other measures. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from medical wards of the Ohio State University Wexner Medical Center from 9/1/11 to 5/31/12
Pre-assignment details
Basal insulin was held prior to initiation of IV insulin and all non-insulin diabetes medications were held for the study. 42 patients signed consent. However, 9 subjects were removed due to protocol violation (new arrhythmia 2\], new altered mental status \[1\], initiation of IV insulin \[2\], early hospital discharge \[2\], or sensor failure \[2\].
Participants by arm
| Arm | Count |
|---|---|
| Subcutaneous Insulin Among patients receiving subcutaneous insulin, basal and prandial insulin were administered in approximately equal total daily doses with correction dosing. Daily adjustments were based upon 10-20% of the total daily dose. | 16 |
| Intravenous Insulin IV insulin was started at 0500 hours the morning following consent. Patients continued to receive prandial and correction insulin until the IV insulin was started, after which only the prandial component was continued. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which was adapted from a published protocol and has a target glucose of 6.1-8.3 mmol/l. All floor nurses are trained in its use. Patients were transitioned from the infusion at 1700 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap. | 17 |
| Total | 33 |
Baseline characteristics
| Characteristic | Intravenous Insulin | Subcutaneous Insulin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 13 Participants | 28 Participants |
| Age Continuous | 54 years STANDARD_DEVIATION 11 | 55 years STANDARD_DEVIATION 11 | 54 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 17 participants | 16 participants | 33 participants |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 12 Participants |
| Sex: Female, Male Male | 9 Participants | 12 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 16 | 1 / 17 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 |
Outcome results
Primary
Difference Between Heart Rate Variability Between Intravenous and Subcutaneous Group
difference in mean low frequency/high frequency heart rate variability (LF/HF HRV)at 6 hour. 2 patients were excluded who did not have usable LF/HF HRV data at 6 hours. These patients remained in the study as they did have other measures.
Time frame: 6 hour
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Subcutaneous Insulin | Difference Between Heart Rate Variability Between Intravenous and Subcutaneous Group | 1.0 none (ratio) |
| Intravenous Insulin | Difference Between Heart Rate Variability Between Intravenous and Subcutaneous Group | 2.6 none (ratio) |
Comparison: Since this was a pilot study no formal power analysis was possible. It was hypothesized that IV insulin would be associated with lower LF/HF HRV.p-value: 0.05Wilcoxon (Mann-Whitney)