The effectiveness of starting long-acting basal insulin during the intravenous (IV) phase of pediatric diabetic ketoacidosis (DKA) is still a topic of debate. We question whether it can improve outcomes without causing additional harm. We performed a systematic review following PRISMA guidelines and a random-effects meta-analysis (PROSPERO: CRD420251155626) of studies involving patients under 18 years with DKA. We defined “early basal” as starting subcutaneous glargine or detemir while IV insulin was still being administered, with a planned overlap of four hours or more. Comparators began basal insulin at or after stopping IV insulin or had less than 4 h of overlap. The main outcome was the time to resolution of DKA/acidosis. Secondary outcomes included the duration of IV insulin, hospital length of stay (LOS), hypoglycemia, and hypokalemia. We assessed the risk of bias using RoB-2 and NOS, and we evaluated the certainty of evidence using GRADE. Eight studies (3 RCTs, 5 cohorts; n = 1325) met our criteria (695 early-basal, 630 comparator). Early basal insulin reduced the time to DKA/acidosis resolution (4 studies; n = 445), showing a mean difference (MD) of − 3.58 h (95% CI − 6.13 to − 1.03; p = 0.006; I2 = 76%). Excluding one heterogeneous study in a sensitivity analysis yielded an MD of − 4.78 h (95% CI − 6.53 to − 3.03; I2 = 31%). The duration of IV insulin showed no significant difference (5 studies; n = 1009), with an MD of − 2.63 h (95% CI − 7.96 to 2.70; p = 0.33; I2 = 92%), although one RCT indicated a benefit (MD of − 12.0 h). Hospital LOS was similar (3 studies; n = 363) with an MD of − 0.17 days (95% CI − 0.53 to 0.19; p = 0.35; I2 = 0%). Safety outcomes were neutral: hypoglycemia (7 studies; n = 1277) showed an odds ratio (OR) of 0.95 (95% CI 0.58–1.56; p = 0.84; I2 = 54%), and hypokalemia (6 studies; n = 731) had an OR of 1.19 (95% CI 0.67–2.11; p = 0.55; I2 = 67%). According to GRADE, the certainty of evidence ranged from high for time to resolution in RCT evidence to moderate for hypoglycemia in RCTs, and low to very low for some observational outcomes due to variability and lack of precision.Conclusions: In pediatric DKA, starting long-acting basal insulin during IV insulin administration with an overlap of four hours or more speeds up metabolic resolution by about 3 to 5 h without raising the risk of hypoglycemia or hypokalemia. The effects on the duration of IV insulin and LOS are inconsistent. These findings support the use of early basal insulin as a safe transition strategy. Further multicenter pragmatic RCTs with standardized definitions for overlap are needed.<Table Float="No" ID="Taba"> <tgroup cols="1"> <colspec align="left" colname="c1" colnum="1" /> <tbody> <row> <entry align="left" colname="c1"> What is Known: • Diabetic ketoacidosis (DKA) in children is a major medical emergency requiring prompt treatment to avoid severe complications, with the standard treatment involving intravenous (IV) insulin administration. • Long-acting basal insulin has been shown in adult populations to hasten recovery from DKA without increasing the risk of hypoglycemia or hypokalemia. </entry> </row> <row> <entry align="left" colname="c1"> What is New: • This meta-analysis emphasizes the effects on the pediatric population, providing high-certainty evidence that early initiation of long-acting basal insulin during IV insulin infusion in pediatric DKA significantly reduces the time to DKA resolution. • The study confirms that early basal insulin does not increase the risk of hypoglycemia or hypokalemia, supporting its safety as a transition strategy in pediatric DKA management. </entry> </row> </tbody> </tgroup> </Table>

Early vs. late initiation of long-acting basal insulin during IV insulin in pediatric diabetic ketoacidosis: a GRADE-assessed systematic review and meta-analysis

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发表日期：

2025年11月26日

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Asim Shah,
Asad Jamal,
Maria Qadri,
Muhammad Jibran Afridi,
Suleman Khan,
Zaryab Bacha,
Adil Nawaz,
Hammad Iftikhar,
Misbah Uddin,
Aizaz Anwar Khalid

摘要

The effectiveness of starting long-acting basal insulin during the intravenous (IV) phase of pediatric diabetic ketoacidosis (DKA) is still a topic of debate. We question whether it can improve outcomes without causing additional harm. We performed a systematic review following PRISMA guidelines and a random-effects meta-analysis (PROSPERO: CRD420251155626) of studies involving patients under 18 years with DKA. We defined “early basal” as starting subcutaneous glargine or detemir while IV insulin was still being administered, with a planned overlap of four hours or more. Comparators began basal insulin at or after stopping IV insulin or had less than 4 h of overlap. The main outcome was the time to resolution of DKA/acidosis. Secondary outcomes included the duration of IV insulin, hospital length of stay (LOS), hypoglycemia, and hypokalemia. We assessed the risk of bias using RoB-2 and NOS, and we evaluated the certainty of evidence using GRADE. Eight studies (3 RCTs, 5 cohorts; n = 1325) met our criteria (695 early-basal, 630 comparator). Early basal insulin reduced the time to DKA/acidosis resolution (4 studies; n = 445), showing a mean difference (MD) of − 3.58 h (95% CI − 6.13 to − 1.03; p = 0.006; I² = 76%). Excluding one heterogeneous study in a sensitivity analysis yielded an MD of − 4.78 h (95% CI − 6.53 to − 3.03; I² = 31%). The duration of IV insulin showed no significant difference (5 studies; n = 1009), with an MD of − 2.63 h (95% CI − 7.96 to 2.70; p = 0.33; I² = 92%), although one RCT indicated a benefit (MD of − 12.0 h). Hospital LOS was similar (3 studies; n = 363) with an MD of − 0.17 days (95% CI − 0.53 to 0.19; p = 0.35; I² = 0%). Safety outcomes were neutral: hypoglycemia (7 studies; n = 1277) showed an odds ratio (OR) of 0.95 (95% CI 0.58–1.56; p = 0.84; I² = 54%), and hypokalemia (6 studies; n = 731) had an OR of 1.19 (95% CI 0.67–2.11; p = 0.55; I² = 67%). According to GRADE, the certainty of evidence ranged from high for time to resolution in RCT evidence to moderate for hypoglycemia in RCTs, and low to very low for some observational outcomes due to variability and lack of precision.

Conclusions: In pediatric DKA, starting long-acting basal insulin during IV insulin administration with an overlap of four hours or more speeds up metabolic resolution by about 3 to 5 h without raising the risk of hypoglycemia or hypokalemia. The effects on the duration of IV insulin and LOS are inconsistent. These findings support the use of early basal insulin as a safe transition strategy. Further multicenter pragmatic RCTs with standardized definitions for overlap are needed.

What is Known:

• Diabetic ketoacidosis (DKA) in children is a major medical emergency requiring prompt treatment to avoid severe complications, with the standard treatment involving intravenous (IV) insulin administration.

• Long-acting basal insulin has been shown in adult populations to hasten recovery from DKA without increasing the risk of hypoglycemia or hypokalemia.

What is New:

• This meta-analysis emphasizes the effects on the pediatric population, providing high-certainty evidence that early initiation of long-acting basal insulin during IV insulin infusion in pediatric DKA significantly reduces the time to DKA resolution.

• The study confirms that early basal insulin does not increase the risk of hypoglycemia or hypokalemia, supporting its safety as a transition strategy in pediatric DKA management.