the study of exenatide action on vessel function in type 2 diabetes and prediabetes

Conditions: Type 2 Diabetes Mellitus

Summary: the purpose of this investigation is to evaluate whether exenatide, a type 2 diabetes medication, will improve the function of the innermost part of the arterial wall called the endothelium after a fat-enriched meal and to determine how this occurs. the results of this study will help to determine and understand a novel action of this group of diabetes medications based on the action of naturally occuring gut substances called incretins. this may have a significant impact on cardiovascular health in patients with early and longstanding diabetes.

two independent, double-blinded, crossover substudies will be conducted to test the effect of exenatide on daylong post-meal and fasting endothelial function. we will measure endothelial function measured by peripheral arterial tonometry (endopat2000, itamar inc.). patients with recent onset (\ 5 years, substudy 1 only) diabetes and impaired sugar tolerance (substudy 2 only) will be studied. the plan is to complete studies in 75 patients (40 in substudy 1 and 35 in substudy 2). in substudy 1 patients will get twice a day a skin injection of exenatide (byetta) or identically looking placebo for 10 days, separated by 14-day period. on the next day after each treatemnt period (day 11), they get just one injection and eat a fat-enriched breakfast. a fatty lunch of similar caloric content will be given 4 hours following the breakfast. endothelial function will be measured just prior to the injection and every 2 hours for total 8 hours. in substudy 2, patients on 3 different days will get infusion of exenatide withg or without a blocking drug exendin-9, and a control test with placebo without exendin-9. endothelial function will be measured before the infusion and 2 hours later during the final 15 minutes of the infusion cocktails. patients will not eat any meal during the test visits.

Eligibility criteria:
inclusion criteria: * us veterans * type 2 diabetes mellitus (t2d) diagnosed within 3 years with good glycemic control on diet, metformin, or sulfonylurea agents or combinations of these agents (hba1c ≤8.0%) * t2d diagnosed ≥ 5 years prior to study enrollment * impaired glucose tolerance exclusion criteria: * t2d not meeting inclusion above criteria for duration of diabetes or hba1c values * known or suspected t1d (early onset age, low body mass index, lack of family history) * tzd use in the prior 3 months * prior regular use of insulin * creatinine \>2.0 mg/dl or other laboratory or clinical evidence of kidney disease * anemia * known active liver disease or hepatic enzyme elevation two-and-a half times above normal * acute bacterial or viral illness or evidence of other active infection in the past 4 weeks * stable or unstable angina or other major illness in the past 6 months * raynaud's disease or any rheumatic disease affecting fingers * current regular use of anti-inflammatory medications or antioxidants, including over the counter medications and high dose salicylates (\>1 g/day); * subjects receiving lipid lowering or anti-hypertension medications must be on stable doses for at least 2 months prior to participation.

Keywords: type 2 diabetes mellitus, impaired glucose tolerance