DPP4 Activity, Microvascular Reactivity and Inflammation
Condition: Overweight; Pre Diabetes; Diabetes Mellitus Type 2 Without Complication
MeSH terms: Diabetes Mellitus; Overweight; Prediabetic State; Diabetes Mellitus, Type 2
Study type: Observational

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.
    

Intervention name(s): Laser-Doppler methods
Intervention type(s): Other
Intervention description(s): 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).
Other intervention name(s): Venous blood collections; Bioimpedance analysis; Finometer Pro
Observational model: Other
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Men and women aged between 18 and 50 years, BMI ≥ 25.0 kg/m², with different degrees of
        glucose tolerance, and living in the state of Rio de Janeiro (Brazil).