Early use of neutral Protamine Hagedorn (NPH) insulin in the management of diabetic ketoacidosis: an open-label randomized controlled trial in a resource-limited setting.

OBJECTIVE

Regular insulin infusion and intravenous fluids are the cornerstones of managing diabetic ketoacidosis (DKA). To shorten the time taken to resolve DKA in known diabetic patients, the concomitant administration of glargine with regular insulin infusion has been tried, with promising results. This study primarily aimed to assess whether the addition of Neutral Protamine Hagedorn (NPH) insulin to continuous insulin infusion (CII) hastens the resolution of DKA. The secondary objectives were to compare the time to rebound hyperglycemia, frequency of hypoglycemia and duration of hospital stay between the early NPH insulin and control groups.

RESULTS

An open-label, randomised controlled trial (CTRI ref/2022/08/044760, dated August 8, 2022) of 50 adult participants with DKA was conducted from August 2022 to June 2023. In the intervention arm, 25 participants received 0.25 IU/kg subcutaneous NPH insulin in 2 divided doses, along with a continuous insulin infusion from the time of randomization until the primary outcome was achieved. The control arm (n = 25) received the standard of care. The time to resolution of DKA was significantly shorter in the intervention arm [Intervention (I): 20 (16-32) hours vs. Standard (S): 38.5 (27-48) hours] in those with severe DKA (p = 0.01). Rebound hyperglycemia was delayed in the intervention arm [I: 7.9 ± 2.7 h vs. S: 5.9 ± 2.2 h]. There was no significant difference in the duration of hospital stay or frequency of hypoglycemia. However, the small sample size restricts the generalizability of the results and, larger studies are needed for confirmation of these findings.

TRIAL REGISTRATION: This trial was prospectively registered in the Clinical Trials Registry India (CTRI)-CTRI/2022/08/044760 on August 8, 2022.