Summary: In a small open-label trial in a resource-limited setting, adding early subcutaneous NPH insulin to a continuous insulin infusion shortened time to resolution of severe diabetic ketoacidosis and delayed rebound hyperglycaemia, without a significant difference in hypoglycaemia or hospital stay.
PICO Summary
| Element | Detail |
|---|---|
| Population | 50 adults with diabetic ketoacidosis; open-label RCT in a resource-limited setting, India. |
| Intervention | Early subcutaneous NPH insulin 0.25 IU/kg in two divided doses plus continuous insulin infusion (n=25). |
| Comparison | Standard continuous insulin infusion alone (n=25). |
| Outcome | In severe DKA, time to resolution was shorter with early NPH (20 vs 38.5 hours; p=0.01). Rebound hyperglycaemia was delayed (7.9 vs 5.9 hours). There was no significant difference in length of hospital stay or in the frequency of hypoglycaemia between groups. |
Early NPH insulin in DKA
Open-label RCT · DKA · severe subgroup
In severe DKA, early NPH roughly halved time to resolution (20 vs 38.5 h) and delayed rebound hyperglycaemia, with no significant increase in hypoglycaemia or length of stay.
Expert Commentary
This is a pragmatic and resource-conscious trial testing a physiologically sensible idea, that adding intermediate-acting basal insulin early, while the patient is still ketoacidotic, provides a depot that suppresses lipolysis and ketogenesis and overlaps the eventual transition off intravenous insulin. The signal is encouraging where it matters most, in severe DKA, where resolution was roughly halved, and rebound hyperglycaemia after stopping the infusion was delayed, which fits the rationale neatly. An important correction to a common misreading is warranted here: in this trial the early-NPH group did not have a statistically significant excess of hypoglycaemia, nor a different length of stay, so the strategy looks safe within the limits of the data rather than safety-compromising. Those limits are real, however, namely a small single-centre sample of 50, an open-label design, and benefit demonstrated mainly in the severe subgroup, so confirmation in larger trials is needed before routine adoption. Can I use this with my patients? Cautiously and selectively. In settings where prolonged infusions are hard to sustain, early NPH is a reasonable, inexpensive adjunct with intensified glucose monitoring, while in well-resourced units the standard practice of overlapping basal insulin shortly before stopping the infusion remains appropriate.
References
Baby N, Wyawahare M, Naik D, Ramasamy N. 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. BMC Res Notes. 2025;18(1):471. doi:10.1186/s13104-025-07508-5