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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin glargine
* Drug: Insulin aspart
* Drug: Supplemental insulin aspart


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects admitted to the hospital with acute or chronic medical illnesses or for elective and emergency surgical illness or trauma Known history of Type 2 diabetes mellitus for >3 months Treated with either diet alone, any combination of oral antidiabetic agents, non-insulin injectables or insulin therapy Blood glucose levels between >140 mg and <400 mg/dL without laboratory evidence of diabetic ketoacidosis Exclusion Criteria: Hyperglycemia without a history of diabetes Subjects with acute critical illness admitted to the ICU or expected to require ICU admission Subjects receiving continuous insulin infusion Clinically relevant hepatic disease Corticosteroid therapy Serum creatinine ≥ 3.5 mg/dL and/or glomerular filtration rate (GFR) <30 Subjects unable to sign consent Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Insulin Aspart for BG > 140 mg/dL<br>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. | Drug: Insulin glargine<br>* 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%.<br>* Other names: Lantus (glargine);Drug: Insulin aspart<br>* 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%.<br>* Other names: Novolog;Drug: Supplemental insulin aspart<br>* 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<br>* Other names: Novolog;|
| Active Comparator: Insulin Aspart for BG > 260 mg/dL<br>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. | Drug: Insulin glargine<br>* 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%.<br>* Other names: Lantus (glargine);Drug: Insulin aspart<br>* 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%.<br>* Other names: Novolog;Drug: Supplemental insulin aspart<br>* 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<br>* Other names: Novolog;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Blood Glucose Levels Before Lunch | The blood glucose levels will be assessed prior to lunch using a glucose meter. | 5 days (average time of discharge from the hospital) | 
| Mean Blood Glucose Levels at Bedtime | The blood glucose levels will be assessed at bedtime using a glucose meter. | 5 days (average time of discharge from the hospital) | 
| Mean Blood Glucose Levels Before Dinner | The blood glucose levels will be assessed before dinner using a glucose meter. | 5 days (average time of discharge from the hospital) | 
| Number of Hypoglycemia Events | The number of occurrences of hypoglycemia (blood glucose levels < 70 mg/dL) will be recorded. | 5 days (average time of discharge from the hospital) | 
| Incidence of Hyperglycemia | The number of occurrences of hyperglycemia (blood glucose levels > 260 mg/dL) will be recorded. | 5 days (average time of discharge from the hospital) | 
| Number of Blood Glucose Readings Within 100-140 mg/dL Range | The number of blood glucose readings that are in the target range of 100-140 mg/dL will be recorded. | 5 days (average time of discharge from the hospital) | 
| Average Number of Days of Hospital Stay | The average number of days in the hospital for subjects will be calculated. | 5 days (average time of discharge from the hospital) | 
| Mortality | The total number of subject deaths during hospital stay will be recorded. | 5 days (average time of discharge from the hospital) | 
| Number of Subjects That Experienced Hospital Complications | 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. | 5 days (average time of discharge from the hospital) | 
| Mean Daily Dose of Insulin | Daily dose of insulin will be recorded | 5 days (average time of discharge from the hospital) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperglycemia, Hypoglycemia