DPP4 Activity, Microvascular Reactivity and Inflammation
Keywords
Abstract
Description
Dipeptidyl peptidase 4 (DPP4), also known as adenosine deaminase binding protein or cluster of differentiation 26 (CD26), is a serine exopeptidase able to inactivate various oligopeptides composed of proline, hydroxyproline, or alanine as the penultimate residue. In recent years, DPP4 has received attention due to its ability to rapidly inactivate the main incretins secreted by the gastrointestinal tract: glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). As its own name already says, incretins enhance insulin secretion in a glucose-dependent fashion, but also suppress or modulate glucagon secretion. Since it was demonstrated that type 2 diabetes mellitus (T2D) have incretin deficiency and hyperglucagonemia on its physiopathology, gliptins emerged as a new class of drugs for the treatment of this disease, acting through the inhibition of DPP4 and consequently ameliorating these defects.
DPP4 not only inactivate incretins but also a number of cytokines, chemokines, and neuropeptides involved in inflammation, immunity and vascular function. Furthermore, evidence from in vitro and in vivo studies, including clinical ones in T2D, suggested that gliptins' inhibition of DPP4 was associated with reduction of inflammatory biomarkers and also attenuation of endothelial dysfunction and atherogenesis, possibly through regulation of the DPP4 substrates.
There is a paucity of studies that associate the constitutive levels of DPP4 activity (i.e., outside the context of pharmacological inhibition of the enzyme) with markers of inflammation and endothelial function, specially tested on skin microcirculation. We hypothesized that constitutive levels of DPP4 activity might be directly associated to inflammation and inversely correlated with skin blood flux and one or more components of vasomotion (suggesting an association with endothelial disfunction) even in the absence of diabetes. Our aim was to investigate the associations between constitutive levels of DPP4 activity and inflammatory biomarkers, skin microvascular reactivity, gut peptides, insulin resistance indexes, heart rate and blood pressure variability, and measures of adiposity in subjects with different grades of glucose tolerance.
Dates
| Last Verified: | 05/31/2017 |
| First Submitted: | 06/02/2017 |
| Estimated Enrollment Submitted: | 06/02/2017 |
| First Posted: | 06/05/2017 |
| Last Update Submitted: | 06/05/2017 |
| Last Update Posted: | 06/07/2017 |
| Actual Study Start Date: | 01/31/2014 |
| Estimated Primary Completion Date: | 11/30/2015 |
| Estimated Study Completion Date: | 11/30/2016 |
Condition or disease
Intervention/treatment
Other: Laser-Doppler methods
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Euglycemia group Normoglycemic/normotolerant subjects | |
| Prediabetes group Subjects with prediabetes | |
| Diabetes group Subjects with type 2 diabetes mellitus |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Sampling method | Non-Probability Sample |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - BMI ≥ 25.0 kg/m² - Any degree of glucose tolerance Exclusion Criteria: - BMI < 25.0 kg/m² - Uncontrolled chronic diseases, such as arterial hypertension - Smoking - Severe alcoholism - Moderate to severe chronic kidney disease, heart failure, chronic lung disease, and chronic liver disease - Fasting serum triglycerides > 400 mg/dl - Fasting serum cholesterol > 300 mg/dl - Pregnancy and breastfeeding - Women in the climacteric period - Individuals who undergo bariatric surgery - Acute disease at the time of sampling - Initiation of statin or change in its dose within 60 days - Use of aspirin and/or fluconazole within 10 days prior to the exams |
Outcome
Primary Outcome Measures
1. Intergroup analysis of the associations between DPP4 activity and skin microvascular reactivity [63 minutes]
2. Intergroup analysis of the associations between DPP4 activity and markers of inflammation [63 minutes]
Secondary Outcome Measures
1. Intergroup analysis of the associations between DPP4 activity and biochemical parameters [63 minutes]
2. Intergroup analysis of the associations between DPP4 activity and insulin resistance indexes, heart rate and blood pressure variability, and measures of adiposity [Baseline evaluation]
