Background

Diabetic ketoacidosis (DKA) is a diagnosis commonly encountered in the emergency department (ED), with the numbers of patients presenting in DKA rising. The increasing number of DKA patients has led to a concomitant rise in cost, with a substantial part of the cost related to intensive care unit (ICU) stay. Treatment of DKA involves correcting acidosis/electrolyte derangements, hypovolemia, and hyperglycemia; these patients often require an intravenous (IV) insulin drip and are subsequently transitioned to subcutaneous insulin after closure of the anion gap (AG). Insulin glargine is a long acting insulin with an onset of action at approximately two hours. Starting a patient on insulin glargine early in their DKA course may decrease the amount of time the patient requires IV insulin and could thus reduce the amount of time spent in the ICU.

Clinical Question

In patients presenting to the ED with DKA, does co-administration of insulin glargine decrease the time to resolution of DKA as determined by time to closure of the AG?

Population

Patients in DKA >age 18 presenting to the ED in two large hospitals in Houston, Texas

Intervention

Administration of insulin glargine 0.3units/kg within 2 hours of diagnosing DKA, in addition to the usual care protocol

Control

Usual Care Protocol - 2L crystalloid bolus followed by continuous IV fluid infusion at a rate chosen by the provider, IV insulin 0.1units/kg/hr

Outcomes

Primary: Time to closure of anion gap (AG ≤12)
Secondary: Hospital length of stay (LOS), ICU LOS, rate of ICU admission, incidence of hypoglycemia (≤60 during the 24 hours after AG closure)

Design

Prospective, randomized, single-blinded trial

Excluded

  • Patients age <18
  • Required IV inotropes/vasopressors
  • Pregnant
  • Unwilling to consent
  • End-stage renal disease
  • Transferred from an outside hospital
  • Required emergent surgery

Primary Results

  • No difference in primary outcome (time to AG closure 10.2 hours in experimental group vs 10.6 hours in control group)
  • No difference in secondary outcomes (hospital LOS, ICU LOS, ICU admission rate, hypoglycemic episodes)

Strengths

  • Study design (prospective, randomized trial)
  • No patients lost to follow-up

Limitations

  • Convenience sample
  • Small sample size (40 patients)

Other Issues

It is unclear if the primary and secondary endpoints are clinically relevant; ie. even if the difference between time to closure of AG and/or LOS for the groups was statistically significant, how would that translate into a clinically significant endpoint?

Author's Conclusions

“Coadministration of glargine in combination with an insulin infusion in the acute management of DKA is feasible. Further study is needed to determine the true efficacy in terms of TCAG and hospital LOS.”

Our Conclusions

Based on the findings of this one small study, it does not appear beneficial to co-administer insulin glargine with IV insulin in the acute management of DKA. While the pharmacokinetics and pharmacodynamics of administering insulin glargine in DKA make intuitive sense, large studies are needed to determine if this is the case. Additionally, the primary outcome (time to closure of AG) chosen by the authors is difficult to interpret for clinical impact, even if the findings were statistically significant.

Bottom Line

While the idea of co administering insulin glargine in acute DKA makes sense, larger studies with more clinically relevant endpoints are needed to determine if doing so would be advantageous .