Effect of Glycemic Variability on Autonomic Tone in Hospitalized Patients With Type 2 Diabetes

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