DPP4 Activity, Microvascular Reactivity and Inflammation

NCT ID: NCT03178019

Last Updated: 2017-06-08

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 52 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-02-01
• Study Completion Date: 2016-12-01

Brief Summary

Dipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides involved in inflammation, immunity and vascular function. 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.

Detailed 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.

Conditions

Overweight; Pre Diabetes; Diabetes Mellitus Type 2 Without Complication

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Euglycemia group

Normoglycemic/normotolerant subjects

Laser-Doppler methods

Intervention Type: OTHER

This was a cross-sectional study in which participants were subjected to a screening phase before being eligible to participate in the study. All subjects were submitted to Laser-Doppler methods (assessment of microcirculatory blood flow), bioimpedance analysis (assessment of body composition), venous blood collections (laboratory analysis), and Finometer Pro (assessment of heart rate variability and blood pressure variability).

Prediabetes group

Subjects with prediabetes

Laser-Doppler methods

Intervention Type: OTHER

This was a cross-sectional study in which participants were subjected to a screening phase before being eligible to participate in the study. All subjects were submitted to Laser-Doppler methods (assessment of microcirculatory blood flow), bioimpedance analysis (assessment of body composition), venous blood collections (laboratory analysis), and Finometer Pro (assessment of heart rate variability and blood pressure variability).

Diabetes group

Subjects with type 2 diabetes mellitus

Laser-Doppler methods

Intervention Type: OTHER

This was a cross-sectional study in which participants were subjected to a screening phase before being eligible to participate in the study. All subjects were submitted to Laser-Doppler methods (assessment of microcirculatory blood flow), bioimpedance analysis (assessment of body composition), venous blood collections (laboratory analysis), and Finometer Pro (assessment of heart rate variability and blood pressure variability).

Interventions

Laser-Doppler methods

This was a cross-sectional study in which participants were subjected to a screening phase before being eligible to participate in the study. All subjects were submitted to Laser-Doppler methods (assessment of microcirculatory blood flow), bioimpedance analysis (assessment of body composition), venous blood collections (laboratory analysis), and Finometer Pro (assessment of heart rate variability and blood pressure variability).

Intervention Type: OTHER

Other Intervention Names

Venous blood collections; Bioimpedance analysis; Finometer Pro

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Rio de Janeiro State University

OTHER

Sponsor Role: lead

Responsible Party

Luiz Guilherme Kraemer-Aguiar, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wellington S Silva Júnior, MD

Role: PRINCIPAL_INVESTIGATOR

State University of Rio de Janeiro

Other Identifiers

940.029

Identifier Type: -

Identifier Source: org_study_id