Inpatient Diabetes on Corticosteroids

Despite a significant problem with out-of-control glucose levels in patients with diabetes receiving corticosteroids for a variety of illnesses, there are no published protocols addressing how to adequately treat corticosteroid-induced hyperglycemia. Investigators propose to test a protocol using scheduled dosing of NPH (Neutral protamine Hagedorn) insulin for inpatients with diabetes receiving corticosteroids. NPH insulin action is ideally timed to counteract corticosteroid-induced hyperglycemia, and the dose is added to the patient's usual insulin regimen and timed to correspond to the corticosteroid dosing regimen. Investigators will prospectively enroll eligible consented patients with diabetes who are receiving corticosteroids as part of their treatment in a large county hospital, will randomize them to intervention or control groups, and will monitor their glucose levels during their inpatient stay. The protocol will demonstrate improved control of glucose levels with minimal risk of hypoglycemia, and will provide a practical and readily implementable protocol using NPH insulin as therapy for corticosteroid-induced diabetes.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: NPH; Drug: Correction Factor

Detailed Description

As above.

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Prior history of diabetes
• Able to provide informed consent
• Receiving corticosteroids while hospitalized of greater than 10 mg/d prednisone or the equivalent of dexamethasone or methylprednisolone
• Expect to be hospitalized for 48 hours

Exclusion Criteria:

• Renal failure with GFR (glomerular filtration rate) < 30 ml/min/1.73m2
• ALT (alanine aminotransferase) > 2 times upper normal for laboratory

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NPH with steroid dose; Receive NPH with each corticosteroid dose during the study duration (2-5 days). Low dose corticosteroids High dose corticosteroids Eating and 6a-8p 0.15 units NPH/kg 0.3 units NPH/kg NPO(nothing by mouth) or 8p-6a 0.1 units NPH/kg 0.2 units NPH/kg	Drug: NPH; NPH given per study table based on steroid dose and patient weight in kg.; Other Names: NPH Lilly Insulin; Drug: Correction Factor; Given at 2 units per 50 mg/dl over 200 mg/dl and increased to 3 units/50 mg/dl over 200 if glucose rises to over 300 mg/dl. Administered qid during study duration.; Other Names: Rapid acting regular insulin
Active Comparator: Control - Background and correction insulin; Receive usual care with background insulin and correction factor for duration of study (2-5 days)	Drug: Correction Factor; Given at 2 units per 50 mg/dl over 200 mg/dl and increased to 3 units/50 mg/dl over 200 if glucose rises to over 300 mg/dl. Administered qid during study duration.; Other Names: Rapid acting regular insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean POC Glucose Level Between Groups	Primary outcome measure was mean blood glucose levels measured pre-meal and at bedtime in study patients and controls for the duration of the intervention. Values shown are the overall mean point of care blood glucose.	Assessed from enrollment to discharge or enrollment to day five.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Episodes of Hypoglycemia Between NPH and Control Groups	Hypoglycemia was defined as point of care glucose less than 70 mg/dL.	Glucose levels measured pre-meal, at bedtime, and during symptoms of hypoglycemia in study patients and controls for the duration of the intervention. Values shown represent cumulative episodes of hypoglycemia per group.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Point of Care Glucose Measurements Between 70 - 180 mg/dL	Glucose levels measured pre-meal, at bedtime, and during symptoms of hypoglycemia in study patients and controls for the duration of the intervention. Values shown are the overall percentage of glucose measurements between 70 - 180 mg/dl.	From day 1 (day of enrollment) to day 5 (last day of study participation) or final day of hospitalization if less than 5 days. Point of care glucose was checked before breakfast, lunch, dinner, bed time and during symptoms of hypoglycemia.
Incidence of Hyperglycemia Defined as Point of Care Glucose 180 - 300 mg/dL	Glucose levels measured pre-meal, at bedtime, and during symptoms of hypoglycemia in study patients and controls for the duration of the intervention. Values shown are the overall percentage of glucose measurements 180 - 300 mg/dL.	From day 1 (day of enrollment) to day 5 (last day of study participation) or final day of hospitalization if less than 5 days. Point of care glucose was checked before breakfast, lunch, dinner, bed time and during symptoms of hypoglycemia.
Incidence of Hyperglycemia Defined as Point of Care Glucose 300 - 400 mg/dl	Glucose levels measured pre-meal, at bedtime, and during symptoms of hypoglycemia in study patients and controls for the duration of the intervention. Values shown are the overall percentage of glucose measurements 300 - 400 mg/dl.	From day 1 (day of enrollment) to day 5 (last day of study participation) or final day of hospitalization if less than 5 days. Point of care glucose was checked before breakfast, lunch, dinner, bed time and during symptoms of hypoglycemia.
Incidence of Hyperglycemia Defined as Point of Care Glucose > 400 mg/dL	Glucose levels measured pre-meal, at bedtime, and during symptoms of hypoglycemia in study patients and controls for the duration of the intervention. Values shown are the overall percentage of glucose measurements > 400 mg/dL.	From day 1 (day of enrollment) to day 5 (last day of study participation) or final day of hospitalization if less than 5 days. Point of care glucose was checked before breakfast, lunch, dinner, bed time and during symptoms of hypoglycemia.
Difference in Length of Stay Between NPH and Control Group	Time difference of hospitalization between the NPH and control groups.	Measured from the day of admission till the day of discharge
Mean Point of Care (POC) Glucose Level in Both Groups.	The overall mean point of care glucose levels in the NPH group and control group on the first day of the study.	On day 1 of study enrollment. Point of care glucose was checked before breakfast, lunch, dinner, and bed time.
Mean Point of Care (POC) Glucose Level in Both Groups.	The overall mean point of care glucose levels in the NPH group and control group on the last day of the study.	On day 5 or last day of hospitalization (if less than 5 days) glucose level as measured by point of care glucose before breakfast, lunch, dinner and bed time.
Correlation of C-peptide With Age		plasma C-peptide was measured once at the time of enrollment
Correlation of C-peptide With BMI		Measured once at the time of enrollment
Correlation of C-peptide With eGFR		Measured once at the time of enrollment
Correlation of C-peptide With Serum Creatinine		Measured once at the time of enrollment
Correlation of C-peptide With ALT		Measured once at the time of enrollment
Correlation of C-peptide With Hemoglobin A1c		Measured once at the time of enrollment
Correlation of C-peptide With Duration of Diabetes		Measured once at the time of enrollment
Correlation of C-peptide With Plasma Glucose		Measured the time of enrollment
Correlation of C-peptide With Length of Stay		Measured once at the time of enrollment

Collaborators and Investigators

• Sponsor: Hennepin Healthcare Research Institute
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Lisa Fish, MD, Hennepin County Medical Center, Minneapolis

Publications and helpful links

General Publications

• Khowaja A, Alkhaddo JB, Rana Z, Fish L. Glycemic Control in Hospitalized Patients with Diabetes Receiving Corticosteroids Using a Neutral Protamine Hagedorn Insulin Protocol: A Randomized Clinical Trial. Diabetes Ther. 2018 Aug;9(4):1647-1655. doi: 10.1007/s13300-018-0468-3. Epub 2018 Jun 30.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: September 4, 2013
• First Submitted That Met QC Criteria: October 24, 2013
• First Posted (Estimate): October 28, 2013

Study Record Updates

• Last Update Posted (Actual): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 9, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: diabetes; insulin; corticosteroid
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: MMRF-13-3658