Investigators propose to examine the effect of 12 weeks of Linagliptin, a diabetes drug, treatment on inflammation as well as vascular and mitochondrial function in diabetic patients. Investigators hypothesize that Linagliptin will reduce the proinflammatory state, improve endothelial function, increase the blood flow at the muscle microcirculation level and improve mitochondrial function. In this study, investigators will perform tests that evaluate the function of small and large blood vessels by employing ultrasound and laser doppler techniques. In addition MRI scans that evaluate the mitochondrial function of the lower extremity muscles at rest and during exercise will also be employed. Forty subjects with Type 2 diabetes will be studied for twelve weeks and half of them will be randomly assigned to receive linagliptin while the other half will receive placebo. All tests will be performed at the beginning and the end of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
45
The endothelial function of the micro-circulation will be assessed by measuring the hyperemic response of the vessels in the superficial skin of the forearm after the iontophoresis of acetylcholine. The endothelium independent vasodilation will be assessed by the iontophoresis of sodium nitroprusside. Laser Doppler perfusion imaging will be used to measure relative changes in flow velocity.Visible and NIR Medical Hyperspectral Imaging (MHSI) data will be collected with a HyperMed OxyView MHSI System (HyperMed, Inc., Watertown, MA). MHSI images will be obtained from same forearm area where the iontophoresis of acetylcholine and sodium nitroprusside will be performed, before and after the iontophoresis test.
Use ultrasound to measure brachial artery flow mediated vasodilation (FMD, endothelium-dependent vasodilation) and nitroglycerin induced dilation (NID, endothelium-independent vasodilation).
Phosphorus-31 MRI data will be obtained during an exercise protocol. Muscle oxygenation will be measured using the blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI) technique after induced hyperemia.
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Phosphocreatine (PCR) Recovery Time After Exhaustive or up to 6 Minutes of Leg Exercise.
Change in the time to phosphocreatine recovery between the baseline visit and post-treatment visit following the graded exercise test.
Time frame: Baseline and 12 weeks
Change in Muscle Oxygenation Recovery Time
Change in muscle oxygenation after ischemia inducing occlusion for 4 minutes.
Time frame: Baseline and 12 weeks
Changes in Vascular Reactivity in the Micro- and Macro-circulation.
Change in markers of macro- and microvascular function from the baseline visit to the post-treatment visit between the two groups.
Time frame: Baseline and 12 weeks
Changes in SDF1-α and Substance P
Time frame: Baseline and 12 weeks
Changes in Circulating Endothelial Progenitor Cell Phenotypes
The measurements of the various EPC phenotypes were performed at the Beth Israel Deaconess Flow Cytometry Core Facility. Immunofluorescent cell staining was performed on peripheral blood with the use of the fluorescent conjugated antibodies. 1.000.000 events per sample were acquired using a FACS LSR II analyzer (Becton Dickinson, Franklin Lakes, NJ, USA) and the results were analyzed using the Beckman Coulter Kaluza analysis software (Beckman Coulter Inc., Brea, CA, USA).
Time frame: Baseline and 12 weeks
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