Early Basal Insulin Administration in Adult Diabetic Ketoacidosis Management

Study Overview
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Brief Summary
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Early Basal Insulin Administration in Adult Diabetic Ketoacidosis Management

Detailed Description
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The transition from IV Insulin Infusion (IVII) to Subcutaneous Long-acting insulin injections in Diabetic Ketoacidosis (DKA) management frequently results in rebound hyperglycemia, particularly if there are high insulin requirements that can adversely affect the DKA recovery, increase Length Of Stay (LOS), morbidity, and mortality. Investigators propose a prospective, open-label, intervention, non-randomized, controlled study to test the hypothesis that an insulin glargine dose of 0.4 Units/kg early administered (within four hours) of IVII initiation in DKA management in adult would be effective and safe in shortening the time to anion gap closure comparing to the standard practice.

Official Title
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Early Basal Insulin Administration in Adult Diabetic Ketoacidosis Management

Conditions
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Diabetic Ketoacidosis, Type 1 Diabetes, Type 2 Diabetes

Intervention / Treatment
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* Drug: Early Glargine
* Drug: Late Glargine
* Other: IV insulin infusion
* Other: IV fluid and electrolytes replacement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old Meet DKA definition (BG ≥ 250 mg/dl, Anion Gap > 12 mEq/L, and positive Ketones in serum or urine) Having the capacity to sign Informed consent Exclusion Criteria: IV insulin infusion was initiated for more than 4 hours. Persistent hypotension (SBP<80 mmHg despite receiving 1000cc normal saline). Require Vasopressor Acute Coronary Syndrome Pregnant End-stage renal disease Unwilling to consent to participate in the trial Currently under police custody Transferred from another hospital Require emergent surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early Glargine<br>All consecutive adult patients getting admitted to Medical ICU and meet the inclusion criteria and accepted to receive insulin glargine early as per the protocol. They will receive insulin glargine 0.4 unit/kg within 4 hours from initiating the IV Insulin Infusion, as per the Cleveland Clinic DKA protocol. | Drug: Early Glargine<br>* A dose of insulin glargine, 0.4 unit/kg, will be given within 4 hours from initiating the IV Insulin Infusion<br>* Other names: lantus;Other: IV insulin infusion<br>* Continuous weight based IV insulin infusion as per Cleveland Clinic DKA Protocol<br>Other: IV fluid and electrolytes replacement<br>* The IV fluid and electrolytes replacement will be left to the treating physician's discretion. IV fluid to contain dextrose to keep Target Blood Glucose 150 - 200 mg/dl during the DKA management and 140 - 180 mg/dl after DKA resolution.<br>|
| Active Comparator: Standard practice (Late Glargine)<br>Retrospective, prespecified and matched sample of consecutive adults who admitted to the same Medical ICU with a diagnosis of DKA in the period between January 1st 2019 till the Institutional Review Board (IRB) approval date and didn't receive basal insulin before Anion Gap closure. | Drug: Late Glargine<br>* A historical retrospective control group for the adult patients admitted to the same ICU with a diagnosis of DKA and received insulin glargine after anion gap closure.<br>* Other names: lantus;Other: IV insulin infusion<br>* Continuous weight based IV insulin infusion as per Cleveland Clinic DKA Protocol<br>Other: IV fluid and electrolytes replacement<br>* The IV fluid and electrolytes replacement will be left to the treating physician's discretion. IV fluid to contain dextrose to keep Target Blood Glucose 150 - 200 mg/dl during the DKA management and 140 - 180 mg/dl after DKA resolution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Anion Gap Closure | Measured in hours from starting insulin infusion till anion gap ≤ 12 milliequivalent/Liter (mEq/L) | Participants monitored from hospital admission to discharge, an average of 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital Length of Stay | The time, in days, from the patient admission to the hospital till discharge | Participants monitored from hospital admission to discharge, an average of 5 days | 
| ICU Length of Stay | The time, in hours, from the patient admission to the ICU till transfer to regular nursing floor | Participants monitored from hospital admission to discharge, an average of 5 days | 
| Total IV Insulin Infusion Dose | the total amount of insulin infusion, by International Unit, has been received by the patient during the DKA treatment | Participants monitored from hospital admission to discharge, an average of 5 days | 
| Incidence of Transitional Failure | Defined as the recurrence of DKA (BG ≥ 250 mg/dl, Anion Gap > 12 milliequivalent/Liter (mEq/L), and positive Ketones in serum or urine) after initial IV insulin infusion (IVII) discontinuation within 24 hours and requiring re-initiating the IVII | up to 24 hours after IVII discontinuation | 
| Incidence of Hyperglycemia | Incidence of hyperglycemia (> 180 mg/dL) after IVII discontinuation | up to 24 hours after initial Insulin Glargine dose | 
| Incidence of Hypoglycemia | Incidence of hypoglycemia (defined as ≤ 70 mg/dL, <54 mg/dL, <40 mg/dl) after IVII discontinuation | up to 24 hours after initial Insulin Glargine dose |