A Study of Postprandial Hyperglycemia in Participants With Type 2 Diabetes

Study Overview
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Brief Summary
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This Study is looking at whether high blood glucose levels after a meal affect arterial stiffness more or less than low blood glucose levels, and whether certain cardiovascular markers influence the outcome of this.

Official Title
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The Effect of Postprandial Hyperglycemia on the Arterial Stiffness in Patients With Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Lispro


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are diagnosed with T2DM (according to the American Diabetes Association classification [American Diabetes Association 2006]) and on insulin therapy for at least 6 months. Have not smoked in the last 12 hours prior to the study visit. Have albuminuria but normal kidney function or normal UAER [UAER < 20 micrograms per minute (mcg/min) or < 30 milligrams/24 hours (mg/24h), respectively]. Participants with or without albuminuria but normal kidney function will be matched for age and body mass index (BMI). Participants have been judged by the investigator to be reliable to keep appointments for clinic visits and all tests and examinations required by the protocol. Each participant must understand the nature of the study and must sign an informed consent document (ICD). Healthy participants are eligible to be included in the study only if they meet all of the following criteria: Healthy participants 45 to 70 years of age, matched for age and BMI, who have not smoked in the last 12 hours prior to the study. Normal glucose tolerance and normal UAER (UAER between < 20 μg/min in the overnight urine collection or < 30 mg/24h in the 24-h urine collection). Healthy participants have been judged by the investigator to be reliable to keep appointments for clinic visits and all tests and examinations required by the protocol. Each healthy participant must understand the nature of the study and must sign an ICD. Exclusion Criteria: Participants/healthy participants will be excluded from the study if they meet any of the following criteria: Have had a cardiovascular event [stroke, myocardial infarction (MI), coronary artery procedure (by-pass surgery or angioplasty), limb amputation due to ischemia, peripheral vascular disease] or coronary heart disease confirmed by exercise test or scintigraphy. Have arrhythmias. Have an acute infection. Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Are unwilling or unable to comply with the use of a data collection device to directly record data from the participant.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T2DM, albuminuria but normal kidney function<br> | Drug: Lispro<br>* Dosage based on participants with type 2 diabetes mellitus (T2DM) normal morning insulin dose and energy content of participant's normal breakfast. Subcutaneous injection given on one occasion. Administered once on low post prandial day.<br>* Other names: LY275585;|
| No Intervention: Healthy participants<br> | |
| Experimental: T2DM, normal urinary albumin excretion rate (UAER)<br> | Drug: Lispro<br>* Dosage based on participants with type 2 diabetes mellitus (T2DM) normal morning insulin dose and energy content of participant's normal breakfast. Subcutaneous injection given on one occasion. Administered once on low post prandial day.<br>* Other names: LY275585;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial Pulse Wave Velocity (PWV) in Type 2 Diabetes Mellitus (T2DM) Participants at 30 Minutes (Mins) Pre-Breakfast | The PWV measured arterial stiffness in the aortic and brachial arteries of T2DM participants. The Least Square (LS) mean was estimated from a mixed-effect analysis of covariance (ANCOVA) model that was adjusted for age, body mass index (BMI), visit, group, condition, group by condition, and random participant. | 30 mins (pre-breakfast) | 
| Postprandial Pulse Wave Velocity (PWV) in Type 2 Diabetes Mellitus (T2DM) Participants at 60 Minutes (Mins) Post-Breakfast | The PWV measured arterial stiffness in the aortic and brachial arteries of T2DM participants. The Least Square (LS) mean was estimated from a mixed-effect analysis of covariance (ANCOVA) model that was adjusted for age, body mass index (BMI), visit, group, condition, group by condition, and random participant. | 60 mins (post-breakfast) | 
| Postprandial Pulse Wave Velocity (PWV) in Type 2 Diabetes Mellitus (T2DM) Participants at 120 Minutes (Mins) Post-Breakfast | The PWV measured arterial stiffness in the aortic and brachial arteries of T2DM participants. The Least Square (LS) mean was estimated from a mixed-effect analysis of covariance (ANCOVA) model that was adjusted for age, body mass index (BMI), visit, group, condition, group by condition, and random participant. | 120 mins (post-breakfast) | 
| Postprandial Pulse Wave Velocity (PWV) in Type 2 Diabetes Mellitus (T2DM) Participants at 180 Minutes (Mins) Post-Breakfast | The PWV measured arterial stiffness in the aortic and brachial arteries of T2DM participants. The Least Square (LS) mean was estimated from a mixed-effect analysis of covariance (ANCOVA) model that was adjusted for age, body mass index (BMI), visit, group, condition, group by condition, and random participant. | 180 mins (post-breakfast) | 
| Postprandial Pulse Wave Velocity (PWV) in Type 2 Diabetes Mellitus (T2DM) Participants at 240 Minutes (Mins) Post-Breakfast | The PWV measured arterial stiffness in the aortic and brachial arteries of T2DM participants. The Least Square (LS) mean was estimated from a mixed-effect analysis of covariance (ANCOVA) model that was adjusted for age, body mass index (BMI), visit, group, condition, group by condition, and random participant. | 240 mins (post-breakfast) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pulse Wave Amplitude (PWA) | The PWA measured systemic arterial stiffness (augmentation index). PWA was reported as a percentage of systolic peak and calculated as the difference between second and first systolic peak in an ascending aortic pulse pressure waveform divided by the first systolic peak then multiplied by 100. The change in PWA from baseline [30-minute (min) pre-breakfast] is reported. | 30 mins (pre-breakfast), 60, 120, 180 and 240 mins (post-breakfast) | 
| Change in Peripheral Artery Tonometry (PAT) | The PAT device is a pneumatic plethysmograph that applies uniform pressure to the surface of each finger tip and measures digital pulse amplitude. The PAT was reported as a percentage of pulse amplitude and expressed as the ratio of post deflation to baseline pulse amplitude in hyperemic finger divided by the same ratio in the contralateral finger that served as a control. The change in PAT from baseline [30-minute (min) pre-breakfast] is reported. | 30 mins (pre-breakfast), 120 and 240 mins (post-breakfast) | 
| Change in QT Interval on Electrocardiogram (ECG) | QT interval is a measure of time from the beginning of the QRS complex to the end of the T wave on an ECG during which contraction of the ventricles occurs. Changes in QT interval from baseline [30-minute (min) pre-breakfast] are reported. | 30 mins (pre-breakfast), 60, 120, 180 and 240 mins (post-breakfast) | 
| Change in Blood Glucose (BG) | Changes in BG from the baseline [30-minute (min) pre-breakfast] are reported. | 30 mins (pre-breakfast), 50, 110 ,170, and 230 mins (post-breakfast) | 
| Change in Postprandial Pulse Wave Velocity (PWV) | The PWV measured arterial stiffness in the aortic and brachial arteries of healthy participants and T2DM participants. Changes in PWV from baseline [30-minute (min) pre-breakfast] are reported. | 30 mins (pre-breakfast), 60, 120, 180 and 240 mins (post-breakfast) |