Benefits of Insulin Supplementation for Correction of Hyperglycemia in Patients With Type 2 Diabetes

Benefits of Insulin Supplementation for Correction of Hyperglycemia in Patients With Type 2 Diabetes Treated With Basal Bolus Insulin Regimen

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02408120

Enrollment

226

Registered

2015-04-03

Start date

2015-10-31

Completion date

2019-12-11

Last updated

2023-09-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 2

Keywords

Hyperglycemia, Hypoglycemia

Brief summary

The purpose of this study is to test whether using extra doses of aspart insulin to correct blood sugars before meals improves the care of patients with type 2 diabetes in the hospital who are already receiving the standard of care treatment with glargine and aspart insulin injections to control blood sugar levels. Studies done in the past indicate that blood sugar levels are controlled on the standard treatment of insulin and that most patients do not need the small extra dose of insulin at bedtime. The investigators want to test if there is any benefit to giving patients extra doses of insulin during the day to correct the high blood sugars.

Detailed description

The management of patients with Type 2 diabetes involves treatment with two different types of insulin injections to control blood sugar levels. The doses of the two types of insulins, glargine insulin and aspart insulin are adjusted daily through the hospital stay based on blood sugar levels. Many times, in addition to glargine and aspart insulin at meals, additional small doses of aspart insulin are given to correct high blood sugar levels. It has not been determined if using these extra doses of aspart insulin to correct blood sugars before meals improves care of the patients. Studies done in the past indicate that blood sugar levels are well controlled on the standard treatment of the two insulins and that most patients do not need the small extra dose of insulin at bedtime. This study will test if insulin supplementation improves glycemic control and prevents hypoglycemia in insulin treated patients with type 2 diabetes mellitus.

Interventions

DRUGInsulin glargine

Half of total daily dose (TDD) will be given as insulin glargine and will be given once daily, at the same time of the day. Daily insulin dose will be adjusted as follow: * If the fasting and pre-dinner BG is between 100 - 140 mg/dL in the absence of hypoglycemia the previous day: no change * If the fasting and pre-dinner BG is between 140 - 180 mg/dL in the absence of hypoglycemia: increase basal insulin by 10% every day * If the fasting and pre-dinner BG is \>180 mg/dL in the absence of hypoglycemia the previous day: increase basal insulin dose by 20% every day * If the fasting and pre-dinner BG is between 70 - 99 mg/dL in the absence of hypoglycemia: decrease TDD (basal and prandial) insulin dose by 10% every day * If a patient develops hypoglycemia (BG \<70 mg/dL), the insulin TDD (basal and prandial) should be decreased by 20%.

DRUGInsulin aspart

Half of total daily dose will be given as insulin aspart and in three equally divided doses before each meal. To prevent hypoglycemia, if a subject is not able to eat, the dose of aspart will be held. Daily insulin dose will be adjusted as follow: * If the fasting and pre-dinner BG is between 100 - 140 mg/dL in the absence of hypoglycemia the previous day: no change * If the fasting and pre-dinner BG is between 140 - 180 mg/dL in the absence of hypoglycemia: increase basal insulin by 10% every day * If the fasting and pre-dinner BG is \>180 mg/dL in the absence of hypoglycemia the previous day: increase basal insulin dose by 20% every day * If the fasting and pre-dinner BG is between 70 - 99 mg/dL in the absence of hypoglycemia: decrease TDD (basal and prandial) insulin dose by 10% every day * If a patient develops hypoglycemia (BG \<70 mg/dL), the insulin TDD (basal and prandial) should be decreased by 20%.

DRUGSupplemental insulin aspart

Insulin aspart will be administered following the supplemental insulin scale protocol. For the arm receiving supplemental insulin aspart at BG levels greater than 140 mg/dL, then supplemental insulin scale is as follows: * BG \>141-180 mg/dL; 2-4 units of insulin aspart * BG between 181-220 mg/dL; 3-6 units of insulin aspart * BG between 221-260 mg/dL; 4-8 units of insulin aspart * BG between 261-300 mg/dL; 5-10 units of insulin aspart * BG between 301-350 mg/dL; 6-12 units of insulin aspart * BG between 351-400 mg/dL; 7-14 units of insulin aspart * BG \> 400 mg/dL; 8-16 units of insulin aspart For the arm receiving supplemental insulin aspart at BG levels greater than 260 mg/dL, then supplemental insulin scale is as follows: * BG between 261-300 mg/dL; 5-10 units of insulin aspart * BG between 301-350 mg/dL; 6-12 units of insulin aspart * BG between 351-400 mg/dL; 7-14 units of insulin aspart * BG \> 400 mg/dL; 8-16 units of insulin aspart

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

HEALTH_SERVICES_RESEARCH

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Inclusion criteria

1. Subjects admitted to the hospital with acute or chronic medical illnesses or for elective and emergency surgical illness or trauma 2. Known history of Type 2 diabetes mellitus for \>3 months 3. Treated with either diet alone, any combination of oral antidiabetic agents, non-insulin injectables or insulin therapy 4. Blood glucose levels between \>140 mg and \<400 mg/dL without laboratory evidence of diabetic ketoacidosis

Exclusion criteria

1. Hyperglycemia without a history of diabetes 2. Subjects with acute critical illness admitted to the ICU or expected to require ICU admission 3. Subjects receiving continuous insulin infusion 4. Clinically relevant hepatic disease 5. Corticosteroid therapy 6. Serum creatinine ≥ 3.5 mg/dL and/or glomerular filtration rate (GFR) \<30 7. Subjects unable to sign consent 8. Pregnancy

Design outcomes

Primary

Measure	Time frame	Description
Mean Daily BG Levels	5 days (average time of discharge from the hospital)	Blood glucose (BG) will be measured, and mean daily BG levels will be calculated.

Secondary

Measure	Time frame	Description
Mean Blood Glucose Levels at Bedtime	5 days (average time of discharge from the hospital)	The blood glucose levels will be assessed at bedtime using a glucose meter.
Mean Blood Glucose Levels Before Dinner	5 days (average time of discharge from the hospital)	The blood glucose levels will be assessed before dinner using a glucose meter.
Number of Hypoglycemia Events	5 days (average time of discharge from the hospital)	The number of occurrences of hypoglycemia (blood glucose levels \< 70 mg/dL) will be recorded.
Incidence of Hyperglycemia	5 days (average time of discharge from the hospital)	The number of occurrences of hyperglycemia (blood glucose levels \> 260 mg/dL) will be recorded.
Mean Blood Glucose Levels Before Lunch	5 days (average time of discharge from the hospital)	The blood glucose levels will be assessed prior to lunch using a glucose meter.
Average Number of Days of Hospital Stay	5 days (average time of discharge from the hospital)	The average number of days in the hospital for subjects will be calculated.
Mortality	5 days (average time of discharge from the hospital)	The total number of subject deaths during hospital stay will be recorded.
Number of Subjects That Experienced Hospital Complications	5 days (average time of discharge from the hospital)	The total number of subjects in which hospital complications occurred prior to discharge will be recorded. These complications will mainly be cases of nosocomial infections, pneumonia, bacteremia, respiratory failure, and acute kidney injury \[rise of serum creatinine \>0.5 mg/dL (or 50%) of baseline value\]. Nosocomial infections will be diagnosed based on standardized Centers for Disease Control (CDC) criteria.
Mean Daily Dose of Insulin	5 days (average time of discharge from the hospital)	Daily dose of insulin will be recorded
Number of Blood Glucose Readings Within 100-140 mg/dL Range	5 days (average time of discharge from the hospital)	The number of blood glucose readings that are in the target range of 100-140 mg/dL will be recorded.

Countries

United States

Participant flow

Recruitment details

A total of 226 subjects consented from October 2015 to December 2019. Two subjects withdrew or left the hospital prior to randomization.

Participants by arm

Arm	Count
Insulin Aspart for BG > 140 mg/dL Subjects will consist of hospitalized patients with type 2 diabetes and be randomized to receive insulin glargine once daily and insulin aspart divided in three equal doses before meals. Supplemental insulin aspart will be given before meals and at bedtime to subjects with blood glucose (BG) levels \>140 mg/dL.	108
Insulin Aspart for BG > 260 mg/dL Subjects will consist of hospitalized patients with type 2 diabetes and be randomized to receive insulin glargine once daily and insulin aspart divided in three equal doses before meals. Supplemental insulin aspart will be given before meals and at bedtime to subjects with blood glucose (BG) levels \>260 mg/dL.	107
Total	215

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Did not receive insulin	1	2
Overall Study	Discharged same day	1	1
Overall Study	Received Steroids	1	1
Overall Study	Treatment Refusal	1	0
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Insulin Aspart for BG > 140 mg/dL	Insulin Aspart for BG > 260 mg/dL	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	32 Participants	29 Participants	61 Participants
Age, Categorical Between 18 and 65 years	76 Participants	78 Participants	154 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	92 Participants	82 Participants	174 Participants
Race (NIH/OMB) More than one race	1 Participants	3 Participants	4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	15 Participants	22 Participants	37 Participants
Region of Enrollment United States	108 participants	107 participants	215 participants
Sex: Female, Male Female	57 Participants	58 Participants	115 Participants
Sex: Female, Male Male	51 Participants	49 Participants	100 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	1 / 108	0 / 107
other Total, other adverse events	11 / 108	12 / 107
serious Total, serious adverse events	0 / 108	0 / 107