Early Administration of Insulin Glargine in Patients With Diabetic Ketoacidosis

In 2014, there were 168,000 hospitalizations for DKA, and the average length of stay was 3.4 days in 2009. The estimated annual direct medical expense and indirect cost is 2.4 billion dollars per year. DKA is a potentially life-threatening condition due to its ability to cause metabolic acidosis, electrolyte imbalances, and dehydration. While DKA treatment protocols differ from institution to institution, the goals of treatment remain the same --- resolution of acidosis, dehydration, and hyperglycemia. Following fluid resuscitation, correction of hyperglycemia with insulin therapy is the mainstay of treatment. Intravenous (IV) insulin infusions with regular insulin are commonly used due to its short half-life of 30 to 60 minutes and resulting titratability. Treatment is then continued with subcutaneous (SC) insulin once the acidosis and anion gaps have cleared and the patient's hemodynamics and electrolytes abnormalities have resolved.

Traditionally, when SC insulin is initiated, the IV insulin infusion is stopped two hours later. However, the timing of SC initiation has becoming more controversial in recent years. The 2019 American Diabetes Association Standards of Care recommend transition of patients from IV to SC insulin requires administration of basal insulin 2-4 h prior to the intravenous insulin being stopped to prevent recurrence of ketoacidosis and rebound hyperglycemia. However, the 2014 Joint British Diabetes Societies Inpatient Care Group recommend continuing a patient's home basal insulin during the initial management of DKA to prevent rebound hyperglycemia and to avoid extending length of stay. Several recent papers have examined early basal insulin administration as adjunct therapies with IV insulin infusions for the treatment of hyperglycemia and DKA.

In 2012, a single-center prospective, randomized controlled trial by Hsia et al. compared IV insulin infusion with or without early administration of insulin glargine (dose = 0.25 U/kg) in 61 hyperglycemic patients with diabetes. Forty-one percent (25/61) of the patients enrolled in the trial were admitted with DKA. Those patients that received early glargine had lower prevalence of rebound hyperglycemia when the insulin infusion was discontinued (experimental group: 33% vs control group: 93.5%; P < 0.001). The total length of IV insulin infusion was similar in the two groups (control group: 35 ± 13h vs experimental group: 42 ± 24h). The mean blood glucose levels within the 12-hour study period were significantly lower in the intervention group, while there were 3 asymptomatic hypoglycemic measurements in the control group and none in the intervention group.

In 2015, Doshi et al. conducted a two-center prospective, randomized controlled trial of 40 patients admitted for DKA. Patients were randomized to receive early insulin glargine (dose = 0.3 U/kg) or no glargine in addition to regular care. Those in the early insulin glargine arm were to receive the glargine subcutaneous injection within 2 hours of diagnosis. Patients in the control group were given insulin glargine once the anion gap closed and the IV insulin infusion was continued for two additional hours. There was no difference in time to anion gap closure, hospital length of stay, ICU admissions, ICU length of stay, and hypoglycemic events.

In 2015, Houshyar et al. conducted a single-center, prospective, randomized controlled trial of 40 patients admitted for DKA. Patients were randomized to receive early insulin glargine (dose = 0.4 U/kg) or no insulin glargine in addition to usual care. Patients in the control group were given insulin glargine once the anion gap closed. There was no difference in duration of acidosis, hospital length of stay or rates of hypoglycemia. There were higher rates of hyperglycemia following discontinuation of the insulin infusion in those that did not receive early glargine (51% vs. 35% of measurements in the experimental group showed a glucose >8.3 mM or >150 mg/dL; p = 0.046).