Poor Glycemic Control
Conditions
Keywords
Coronary Artery Bypass Graft surgery
Brief summary
Most coronary artery bypass graft surgery (CABG) patients develop high blood sugar while they are in the hospital. No studies have shown what the best insulin regimen is for CABG patients with type 2 diabetes is after going home from the hospital. Patients with high blood sugar and diabetes after cardiac bypass surgery will be followed for 3 months to look at how well their treatment(s) for diabetes work after discharge. Patients with diabetes will be discharged on oral antidiabetic drugs or with insulin glargine injections based on their sugar control. Patients with admission HbA1c \< 7% (a laboratory value that shows the average blood sugar level in the body over 3 months) will be discharged on the same diabetes medications that they used before coming to the hospital. Those with an HbA1c between 7% and 9% will be discharged on insulin glargine at 50%-80% of the dose used in the hospital and oral antidiabetic drugs. Those with an HbA1c \> 9% will be discharged on glargine at 80-100% of the dose used in the hospital in addition to oral antidiabetic drugs or with insulin glargine and insulin glulisine. The primary outcome will be a change in HbA1c at 4 and 12 weeks after discharge.
Detailed description
Hospital discharge represents a critical time for ensuring a safe transition to the outpatient setting and reducing the need for emergency department visits and re-hospitalization. Poor coordination of patient care and education on insulin administration at the time of patient discharge to home may be associated with medical errors that may increase risk of hypoglycemia, hyperglycemia and hospital readmission. No prospective studies have examined the impact of a discharge treatment regimen after cardiac surgery. Therefore, this study aims to determine the efficacy and safety of an HbA1c based treatment algorithm in controlling blood glucose (BG) after discharge. The total duration of the study is 3 months. This study will include diabetic and non-diabetic subjects who participated in the American Diabetes Association (ADA) trial entitled Intensive Insulin Therapy in Patients Undergoing Coronary Artery Bypass Surgery. The ADA study is a two-arm randomized multicenter, open-label controlled trial aimed to determine if intensive insulin control with a BG target of 100-140mg/dl will reduce perioperative complications compared to a conventional BG control with a target of 141-180 mg/dl in hyperglycemic subjects who undergo coronary artery bypass graft surgery (CABG). Treatment recommendations at discharge: * Patients with admission HbA1c \< 7%: * Patients without a history of diabetes not requiring subcutaneous (SC) insulin in the hospital will be discharged on no antidiabetic therapy. * Patients without a history of diabetes requiring SC insulin therapy in the hospital will be discharged on metformin monotherapy. A patient without a history of diabetes who requires SC insulin is likely a newly diagnosed diabetic. The HbA1c value will be important to confirm the diagnosis. If the HbA1c is \>6.5%, he/she will be diagnosed with diabetes. We do not anticipate that a patient without a history of diabetes and with an HbA1c \<6.5% will require insulin treatment or oral agents long-term. Those patients will be discharged on no anti diabetic therapy with repeated testing after discharge to rule out diabetes. * Patients with a history of diabetes will be discharged on their same outpatient antidiabetic regimen (diet, oral antidiabetic agents and/or insulin). * Assure there are no contraindications to oral agents (i.e.Thiazolidinediones (TZDs) and heart failure; metformin and renal failure or heart failure). * Patients with Admission HbA1c between 7% and 9%: * Treatment naïve patients not on any pharmacologic treatment prior to admission will be discharged on metformin monotherapy or a combination of metformin and a single dose of basal (glargine) insulin at 50% of total daily hospital dose. * Patients treated with oral antidiabetic agents or glucagon-like peptide-1 (GLP1) analogs prior to admission will be discharged on pre-admission oral antidiabetic therapy plus a single dose of glargine insulin at 50% of the total daily hospital dose. * Patients treated with combination of oral antidiabetic agents and basal insulin (NPH insulin also known as Neutral Protamine Hagedorn insulin, glargine, detemir) prior to admission will be discharged on pre-admission oral antidiabetic therapy plus a single dose of glargine insulin or with basal bolus insulin regimen at 50% of total daily hospital dose. * Patients not to be treated with oral agents will be discharged on glargine monotherapy or basal bolus at 100% of inpatient total daily dose. * Admission HbA1c ≥ 9% prior to admission: * Discharge on basal bolus regimen at same inpatient total daily insulin dose. * Basal insulin (glargine) once daily, at the same time of the day. * Rapid-acting insulin (glulisine) before meals. * Alternative treatment: If no contraindications to oral agents (i.e., Thiazolidinediones (TZDs) and heart failure; metformin and renal failure) restart oral agents in combination to glargine once daily at 80% of total daily hospital dose.
Interventions
DRUGMetformin
Metformin is an oral antidiabetic agent used to control high blood glucose levels and is given in divided doses with meals. During treatment initiation and dose titration, the patient's blood glucose levels will be used to determine the therapeutic response to metformin and identify the minimum effective dose for the patient. Patients without a history of diabetes and admission HbA1c \< 7% requiring SC insulin therapy in the hospital will be discharged on metformin monotherapy. Treatment naïve patients with an HbA1c between 7% and 9% prior to admission will be discharged on metformin monotherapy or a combination of metformin and a single dose of subcutaneous insulin.
DRUGGlargine insulin
Glargine is a recombinant human insulin analog that exhibits a constant glucose-lowering profile over 24 hours and permits once-daily dosing. It is administered subcutaneously once a day at the same time every day. Patients with an HbA1c between 7% and 9% requiring subcutaneous insulin therapy in the hospital will be discharged on oral metformin and a single dose of glargine insulin at 50% of total daily hospital dose. Patients with an HbA1c \> 9% will be discharged on oral metformin and a single dose of glargine insulin at 80% of total daily hospital dose.
DRUGGlulisine
Glulisine is an injectable, recombinant insulin analog. The total daily dose varies between 0.5 to 1 unit/kg/day depending on the levels of blood glucose. Glulisine will be given within 15 minutes before a meal or within 20 minutes after starting a meal.
Sponsors
Emory University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Males or females between the ages of 18 and 80 years undergoing primary coronary artery bypass graft surgery (CABG). 2. Post surgical hyperglycemia (Blood glucose \>140 mg/dl) 3. Patients with and without a history of type 2 diabetes
Exclusion criteria
1. Patients with severely impaired renal function (serum creatinine ≥3.0 mg/dl or a glomerular filtration rate \< 30 ml/min) or clinically significant hepatic failure. 2. Subjects with acute hyperglycemic crises such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic states. 3. Moribund patients and those at imminent risk of death (brain death or cardiac standstill). 4. Patients or next-to-kin with mental conditions rendering the subject or family member unable to understand the nature, scope, and possible consequences of the study. 5. Female subjects who are pregnant or breast-feeding at time of enrollment into the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy, Measured by a Change in HbA1c Levels | One month after hospital discharge | Change in the level of HbA1c in a one month period after discharge from the hospital. The A1c test result is reported as a percentage. Higher percentages indicate higher blood glucose levels in the previous three months. A normal HbA1c level is below 5.7 percent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Readmitted to the Hospital | 3 months after discharge | The number of participants that were readmitted to the hospital 3 months after initial hospital discharge |
| The Number of Participants Experiencing a Hypoglycemic Event | 3 months after discharge | The number of participants that experienced hypoglycemia, defined as blood glucose levels ≤70 mg/dl. |
| The Number of Participants Experiencing a Severe Hypoglycemic Event | 3 months after discharge | The number of participants that experienced severe hypoglycemia, defined as blood glucose levels ≤ 40 mg/dl. |
| Number of Participants Experiencing a Hyperglycemic Event | 3 months after discharge | The number of participants that experienced hyperglycemia, defined as blood glucose levels ≥ 140 mg/dl. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from Emory University Hospital, Emory University Hospital - Midtown, and Grady Memorial Hospital, in Atlanta, Georgia, from October 2012 to February 2014. Study arms for results are presented to precisely reflect the medication used post-hospital discharge, as prescribed by the participant's provider.
Participants by arm
| Arm | Count |
|---|---|
| Control, Non-diabetic, no Treatment Participants who did not have coronary artery bypass graft surgery (CABG), with no history of diabetes and with HbA1C \<7%, who did not require subcutaneous insulin in the hospital and were discharged with no antidiabetic therapy. | 84 |
| Non-diabetic, Metformin Participants without a history of diabetes and with HbA1C \<7%, who were discharged on oral metformin following CABG surgery. | 3 |
| Non-diabetic, Insulin Participants without a history of diabetes and with HbA1C\< 7% and persistent hyperglycemia requiring subcutaneous insulin therapy in the hospital who were discharged without oral diabetes medication, following CABG surgery. | 4 |
| Diabetic, HbA1C <7%, Metformin Participants with a history of diabetes and with HbA1C \<7% who were discharged on oral metformin, following CABG surgery. | 21 |
| Diabetic, HbA1C <7%, Metformin and Insulin Glargine Participants with a history of diabetes and with HbA1C \<7% who were discharged on metformin and insulin glargine, following CABG surgery. | 2 |
| Diabetic, HbA1C <7%, Insulin Glargine Participants with a history of diabetes and with HbA1C \<7% who were discharged on glargine insulin (a long-acting basal insulin analogue), following CABG surgery. | 4 |
| Diabetic, HbA1C 7%- 9%, Metformin Participants with a history of diabetes and with HbA1C between 7% and 9% who were discharged on oral metformin, following CABG surgery. | 14 |
| Diabetic, HbA1C 7%-9%, Metformin and Insulin Glargine Participants with a history of diabetes and with HbA1C between 7% and 9% who were discharged on oral metformin plus a single dose of glargine insulin or with basal bolus insulin regimen at 50% of total daily hospital dose, following CABG surgery. | 7 |
| Diabetic, HbA1C 7%-9%, Insulin Glargine Participants with a history of diabetes and with HbA1C between 7% and 9% who were discharged on glargine insulin (a long-acting basal insulin analogue), following CABG surgery. | 20 |
| Diabetic, HbA1C >9%, Metformin and Insulin Glargine Participants with a history of diabetes and with HbA1C \>9% who were discharged on oral metformin and glargine insulin to be taken daily at the same time of day or a basal bolus insulin regimen, following CABG surgery. | 4 |
| Diabetic, HbA1C >9%, Insulin Glulisine Participants with a history of diabetes and with HbA1C \>9% who were discharged on glulisine, a rapid-acting insulin to be taken before meals, following CABG. | 12 |
| Total | 175 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Death | 3 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 22 | 0 | 0 | 2 | 1 | 1 | 1 | 1 | 7 | 0 | 2 |
Baseline characteristics
| Characteristic | Control, Non-diabetic, no Treatment | Non-diabetic, Metformin | Non-diabetic, Insulin | Diabetic, HbA1C <7%, Metformin | Diabetic, HbA1C <7%, Metformin and Insulin Glargine | Diabetic, HbA1C <7%, Insulin Glargine | Diabetic, HbA1C 7%- 9%, Metformin | Diabetic, HbA1C 7%-9%, Metformin and Insulin Glargine | Diabetic, HbA1C 7%-9%, Insulin Glargine | Diabetic, HbA1C >9%, Metformin and Insulin Glargine | Diabetic, HbA1C >9%, Insulin Glulisine | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 43 Participants | 3 Participants | 3 Participants | 10 Participants | 2 Participants | 3 Participants | 9 Participants | 5 Participants | 12 Participants | 0 Participants | 1 Participants | 91 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 0 Participants | 1 Participants | 11 Participants | 0 Participants | 1 Participants | 5 Participants | 2 Participants | 8 Participants | 4 Participants | 11 Participants | 84 Participants |
| Region of Enrollment United States | 84 Participants | 3 Participants | 4 Participants | 21 Participants | 2 Participants | 4 Participants | 14 Participants | 7 Participants | 20 Participants | 4 Participants | 12 Participants | 175 Participants |
| Sex: Female, Male Female | 23 Participants | 0 Participants | 1 Participants | 6 Participants | 1 Participants | 1 Participants | 5 Participants | 1 Participants | 5 Participants | 3 Participants | 3 Participants | 49 Participants |
| Sex: Female, Male Male | 61 Participants | 3 Participants | 3 Participants | 15 Participants | 1 Participants | 3 Participants | 9 Participants | 6 Participants | 15 Participants | 1 Participants | 9 Participants | 126 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 84 | 0 / 3 | 1 / 4 | 0 / 21 | 0 / 2 | 0 / 4 | 1 / 12 | 0 / 7 | 2 / 20 | 0 / 4 | 1 / 12 |
| other Total, other adverse events | 6 / 84 | 1 / 3 | 0 / 4 | 1 / 21 | 0 / 2 | 1 / 4 | 0 / 14 | 0 / 7 | 0 / 20 | 2 / 4 | 3 / 12 |
| serious Total, serious adverse events | 1 / 84 | 0 / 3 | 0 / 4 | 0 / 21 | 0 / 2 | 0 / 4 | 2 / 14 | 0 / 7 | 0 / 20 | 1 / 4 | 0 / 12 |
Outcome results
Primary
Efficacy, Measured by a Change in HbA1c Levels
Change in the level of HbA1c in a one month period after discharge from the hospital. The A1c test result is reported as a percentage. Higher percentages indicate higher blood glucose levels in the previous three months. A normal HbA1c level is below 5.7 percent.
Time frame: One month after hospital discharge
Population: This analysis includes participants who had blood drawn one month after hospital discharge. Most patients that completed the discharge part did so over the phone. The diabetic, HbA1C \<7%, metformin and insulin glargine is not included in this table as no participants in this group had blood drawn for this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control, Non-diabetic, no Treatment | Efficacy, Measured by a Change in HbA1c Levels | 5.09 percent of glycosylated hemoglobin | Standard Deviation 0.43 |
| Non-diabetic, Metformin | Efficacy, Measured by a Change in HbA1c Levels | 5.2 percent of glycosylated hemoglobin | Standard Deviation 0 |
| Non-diabetic, Insulin | Efficacy, Measured by a Change in HbA1c Levels | 5.5 percent of glycosylated hemoglobin | Standard Deviation 0.5 |
| Diabetic, HbA1C <7%, Metformin | Efficacy, Measured by a Change in HbA1c Levels | 5.8 percent of glycosylated hemoglobin | Standard Deviation 0.5 |
| Diabetic, HbA1C <7%, Insulin Glargine | Efficacy, Measured by a Change in HbA1c Levels | 6.9 percent of glycosylated hemoglobin | Standard Deviation 1.6 |
| Diabetic, HbA1C 7%- 9%, Metformin | Efficacy, Measured by a Change in HbA1c Levels | 6.1 percent of glycosylated hemoglobin | Standard Deviation 2.6 |
| Diabetic, HbA1C 7%-9%, Metformin and Insulin Glargine | Efficacy, Measured by a Change in HbA1c Levels | 6.3 percent of glycosylated hemoglobin | Standard Deviation 0.89 |
| Diabetic, HbA1C 7%-9%, Insulin Glargine | Efficacy, Measured by a Change in HbA1c Levels | 6.6 percent of glycosylated hemoglobin | Standard Deviation 0.7 |
| Diabetic, HbA1C >9%, Metformin and Insulin Glargine | Efficacy, Measured by a Change in HbA1c Levels | 8.6 percent of glycosylated hemoglobin | Standard Deviation 1.9 |
| Diabetic, HbA1C >9%, Insulin Glulisine | Efficacy, Measured by a Change in HbA1c Levels | 6.9 percent of glycosylated hemoglobin | Standard Deviation 0.4 |
Secondary
Number of Participants Experiencing a Hyperglycemic Event
The number of participants that experienced hyperglycemia, defined as blood glucose levels ≥ 140 mg/dl.
Time frame: 3 months after discharge
Population: Participants who completed the Month 3 study visit, in person or by phone.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control, Non-diabetic, no Treatment | Number of Participants Experiencing a Hyperglycemic Event | 0 Participants |
| Non-diabetic, Metformin | Number of Participants Experiencing a Hyperglycemic Event | 0 Participants |
| Non-diabetic, Insulin | Number of Participants Experiencing a Hyperglycemic Event | 2 Participants |
| Diabetic, HbA1C <7%, Metformin | Number of Participants Experiencing a Hyperglycemic Event | 0 Participants |
| Diabetic, HbA1C <7%, Insulin Glargine | Number of Participants Experiencing a Hyperglycemic Event | 1 Participants |
| Diabetic, HbA1C 7%- 9%, Metformin | Number of Participants Experiencing a Hyperglycemic Event | 1 Participants |
| Diabetic, HbA1C 7%-9%, Metformin and Insulin Glargine | Number of Participants Experiencing a Hyperglycemic Event | 3 Participants |
| Diabetic, HbA1C 7%-9%, Insulin Glargine | Number of Participants Experiencing a Hyperglycemic Event | 1 Participants |
| Diabetic, HbA1C >9%, Metformin and Insulin Glargine | Number of Participants Experiencing a Hyperglycemic Event | 3 Participants |
| Diabetic, HbA1C >9%, Insulin Glulisine | Number of Participants Experiencing a Hyperglycemic Event | 3 Participants |
| Diabetic, HbA1C >9%, Insulin Glulisine | Number of Participants Experiencing a Hyperglycemic Event | 2 Participants |
Secondary
Number of Participants Readmitted to the Hospital
The number of participants that were readmitted to the hospital 3 months after initial hospital discharge
Time frame: 3 months after discharge
Population: This analysis includes participants who completed the month 3 study visit either in person or by phone.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control, Non-diabetic, no Treatment | Number of Participants Readmitted to the Hospital | 11 participants |
| Non-diabetic, Metformin | Number of Participants Readmitted to the Hospital | 0 participants |
| Non-diabetic, Insulin | Number of Participants Readmitted to the Hospital | 0 participants |
| Diabetic, HbA1C <7%, Metformin | Number of Participants Readmitted to the Hospital | 1 participants |
| Diabetic, HbA1C <7%, Insulin Glargine | Number of Participants Readmitted to the Hospital | 0 participants |
| Diabetic, HbA1C 7%- 9%, Metformin | Number of Participants Readmitted to the Hospital | 0 participants |
| Diabetic, HbA1C 7%-9%, Metformin and Insulin Glargine | Number of Participants Readmitted to the Hospital | 1 participants |
| Diabetic, HbA1C 7%-9%, Insulin Glargine | Number of Participants Readmitted to the Hospital | 0 participants |
| Diabetic, HbA1C >9%, Metformin and Insulin Glargine | Number of Participants Readmitted to the Hospital | 0 participants |
| Diabetic, HbA1C >9%, Insulin Glulisine | Number of Participants Readmitted to the Hospital | 0 participants |
| Diabetic, HbA1C >9%, Insulin Glulisine | Number of Participants Readmitted to the Hospital | 0 participants |
Secondary
The Number of Participants Experiencing a Hypoglycemic Event
The number of participants that experienced hypoglycemia, defined as blood glucose levels ≤70 mg/dl.
Time frame: 3 months after discharge
Population: This analysis includes participants who completed the month 3 study visit either in person or by phone.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control, Non-diabetic, no Treatment | The Number of Participants Experiencing a Hypoglycemic Event | 1 Participants |
| Non-diabetic, Metformin | The Number of Participants Experiencing a Hypoglycemic Event | 0 Participants |
| Non-diabetic, Insulin | The Number of Participants Experiencing a Hypoglycemic Event | 1 Participants |
| Diabetic, HbA1C <7%, Metformin | The Number of Participants Experiencing a Hypoglycemic Event | 0 Participants |
| Diabetic, HbA1C <7%, Insulin Glargine | The Number of Participants Experiencing a Hypoglycemic Event | 0 Participants |
| Diabetic, HbA1C 7%- 9%, Metformin | The Number of Participants Experiencing a Hypoglycemic Event | 0 Participants |
| Diabetic, HbA1C 7%-9%, Metformin and Insulin Glargine | The Number of Participants Experiencing a Hypoglycemic Event | 0 Participants |
| Diabetic, HbA1C 7%-9%, Insulin Glargine | The Number of Participants Experiencing a Hypoglycemic Event | 1 Participants |
| Diabetic, HbA1C >9%, Metformin and Insulin Glargine | The Number of Participants Experiencing a Hypoglycemic Event | 2 Participants |
| Diabetic, HbA1C >9%, Insulin Glulisine | The Number of Participants Experiencing a Hypoglycemic Event | 0 Participants |
| Diabetic, HbA1C >9%, Insulin Glulisine | The Number of Participants Experiencing a Hypoglycemic Event | 1 Participants |
Secondary
The Number of Participants Experiencing a Severe Hypoglycemic Event
The number of participants that experienced severe hypoglycemia, defined as blood glucose levels ≤ 40 mg/dl.
Time frame: 3 months after discharge
Population: Participants who completed the Month 3 study visit in person or by phone.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control, Non-diabetic, no Treatment | The Number of Participants Experiencing a Severe Hypoglycemic Event | 0 Participants |
| Non-diabetic, Metformin | The Number of Participants Experiencing a Severe Hypoglycemic Event | 0 Participants |
| Non-diabetic, Insulin | The Number of Participants Experiencing a Severe Hypoglycemic Event | 0 Participants |
| Diabetic, HbA1C <7%, Metformin | The Number of Participants Experiencing a Severe Hypoglycemic Event | 0 Participants |
| Diabetic, HbA1C <7%, Insulin Glargine | The Number of Participants Experiencing a Severe Hypoglycemic Event | 0 Participants |
| Diabetic, HbA1C 7%- 9%, Metformin | The Number of Participants Experiencing a Severe Hypoglycemic Event | 0 Participants |
| Diabetic, HbA1C 7%-9%, Metformin and Insulin Glargine | The Number of Participants Experiencing a Severe Hypoglycemic Event | 0 Participants |
| Diabetic, HbA1C 7%-9%, Insulin Glargine | The Number of Participants Experiencing a Severe Hypoglycemic Event | 0 Participants |
| Diabetic, HbA1C >9%, Metformin and Insulin Glargine | The Number of Participants Experiencing a Severe Hypoglycemic Event | 0 Participants |
| Diabetic, HbA1C >9%, Insulin Glulisine | The Number of Participants Experiencing a Severe Hypoglycemic Event | 0 Participants |
| Diabetic, HbA1C >9%, Insulin Glulisine | The Number of Participants Experiencing a Severe Hypoglycemic Event | 0 Participants |