Effect of Glycemic Variability on Autonomic Tone in Hospitalized Patients With Type 2 Diabetes
Condition: Type 2 Diabetes; Inpatient
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Intravenous insulin; Subcutaneous Insulin
Intervention description: 24 hr IV insulin administered according to hospital guideline; basal bolus insulin using carb counting technique and insulin analogues
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: hospital; diabetes; glycemic variability; autonomic tone

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
    

Eligibility criteria:

        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