A One Year Clinical Trial Assessing the Usefulness and Safety of Inhaled Insulin in Diabetics With COPD

Bronchodilator Responsiveness as Determined by the Change in FEV1

Responsiveness was the percent change from the FEV1 value before bronchodilator use to the FEV1 value 30 minutes after bronchodilator use, operationally defined as \[(post-bronchodilator FEV1 minus pre-bronchodilator FEV1 divided by pre-bronchodilator FEV1\] multiplied by 100.

Time frame: Weeks 1, 2, 3, 4, 6, 12, 18, 26, 39, 52

Insulin Dose Responsiveness for FEV1

FEV1 dose responsiveness 10 and 60 minutes after insulin. FEV1 dose-responsiveness to insulin (defined as the difference between the FEV1 value following a dose of insulin and FEV1 value before a dose of insulin, operationally defined as the post-dose FEV1 value minus pre-dose FEV1 value).

Time frame: Baseline, Week 9, Week 51

Insulin Dose Responsiveness for DLco

DLco dose responsivness 10 and 60 minutes after insulin. DLco dose-responsiveness to insulin (defined as the difference between the DLco value following a dose of insulin and DLco value before a dose of insulin, operationally defined as the post-dose DLco value minus pre-dose DLco value).

Time frame: Baseline, Week 9, Week 51

Methacholine PC20

Methacholine challenge testing was conducted at selected sites at visits which did not occur at other sites (Weeks -2.9, -0.9, 11, 50 and 52+5). Methacholine challenge was not analyzed as there was only 1 test performed, which was a baseline test, and no methacholine tests performed in subjects using inhaled insulin.

Time frame: Duration of the study

Mean Weekly Number of Puffs of Short-Acting Bronchodilator Used

All subjects used diary cards to record their daily use of short-acting bronchodilators. Subjects recorded the sum of their short-acting bronchodilator use (puffs of albuterol plus ipratropium plus Combivent®, as applicable) daily, immediately upon arising, and again in the evening or before bed. Mean weekly number of puffs of short-acting bronchodilator used data were collected, but not analyzed.

Time frame: Duration of the study

Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

Non-severe COPD exacerbation = additional therapy (systemic corticosteroids, antibiotics, oxygen) needed for worsening respiratory symptoms and/or lung function, not needing hospitalization \> 24 hours. Crude event rate = total events divided by subject-months. Subject-months=elapsed number of months a subject was in the study in each time interval.

Time frame: 0 to 1 week to > 9 months

Incidence of Severe COPD Exacerbations

Severe COPD exacerbation = a COPD-related hospitalization \> 24 hours. Crude event rate = total events divided by subject-months. Subject-months=elapsed number of months a subject was in the study in each time interval.

Time frame: 0 to 1 week to > 9 months

Baseline Dyspnea Index (BDI) and Transition Dyspnea Index (TDI) Questionnaires

The BDI and TDI measured or quantitated the severity of breathlessness (shortness of breath) in symptomatic subjects. BDI and TDI data were collected, but not analyzed.

Time frame: Duration of the study

Change From Baseline in Glycosylated Hemoglobin (HbA1c)

Change from baseline: mean of (value of observed HbA1c at treatment duration minus baseline value).

Time frame: Baseline, Weeks 6, 12, 26, 39, and 52

Change From Baseline in Fasting Plasma Glucose

Change from baseline: mean of (value of observed fasting plasma glucose in milligrams/deciliters (mg/dL) at treatment duration minus baseline value).

Time frame: Baseline, Weeks 6, 12, 26, 39, 52

Change From Baseline in Body Weight

Change from baseline: mean of (value of observed body weight in kilograms (kg) at treatment duration minus baseline value).

Time frame: Baseline, Weeks 1, 2, 3, 4, 6, 9, 11, 12, 18, 26, 39, 50, 51, 52

Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight)

Intermediate-/long-acting insulin included Insulin NPH, Ultralente, and Insulin Glargine for both groups.

Time frame: Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52

Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight)

Short-acting insulin (mg) for the Inhaled Insulin group was Inhaled Insulin. Short-acting insulin (unit) for the Subcutaneous Insulin group included Insulin Lispro, Insulin Aspart, and Regular Insulin.

Time frame: Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52

Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight)

Intermediate/long-acting insulin included Insulin NPH, Ultralente, and Insulin Glargine for both groups. Dose was adjusted for body weight (units divided by kg).

Time frame: Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52

Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight)

Short-acting insulin (mg) for the Inhaled Insulin group was Inhaled Insulin. Short-acting insulin (unit) for the Subcutaneous Insulin group included Insulin Lispro, Insulin Aspart, and Regular Insulin. Dose was adjusted for body weight (mg divided by kg or units divided by kg).

Time frame: Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52

Lipids

Lipids collected: Total cholesterol, high-density lipoprotein, low-density lipoptrotein, and triglycerides. Lipids data were collected, but not analyzed.

Time frame: Duration of the study

Hypoglycemic Event Rates

A hypoglycemic event was identified by characteristic symptoms; blood glucose levels at 59 mg/dL (3.2 mmol/L) or less with a glucose check; or any glucose measurement 49 mg/dL (2.7 mmol/L) or less, with or without symptoms. Crude event rate=total events divided by subject-months. Subject-months=elapsed number of months a subject was in the study in each time interval.

Time frame: 0 to1 month to > 11 months

Severe Hypoglcyemic Event Rates

An event was severe if the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of \< = 49 mg/dL or the blood glucose was not measured, but the clinical manifestations were reversed by oral carbohydrates, subcutaneous glucagon, or intravenous glucose. Crude event rate=total events/100 subject-months. Subject-months=elapsed number of months a subject was in the study in each time interval.

Time frame: 0 to 1 month to > 11 months