Effect of Dipeptidyl-Peptidase 4 Inhibitors on Circulating Oxidative Stress Biomarkers in Patients with Type 2 Diabetes Mellitus

Abstract

Pre-clinical studies suggested potential cardiovascular benefits of dipeptidyl peptidase-4 inhibitors (DPP4i), however, clinical trials showed neither beneficial nor detrimental effects in patients with type 2 diabetes mellitus (T2DM). We examined the effects of DPP4i on several circulating oxidative stress markers in a cohort of 32 T2DM patients (21 males and 11 post-menopausal females), who were already on routine antidiabetic treatment. Propensity score matching was used to adjust demographic and clinical characteristics between patients who received and who did not receive DPP4i. Whole-blood reactive oxygen species (ROS), plasma advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), carbonyl residues, as well as ferric reducing ability of plasma (FRAP) and leukocyte DNA oxidative damage (Fpg sites), were evaluated. With the exception of Fpg sites, that showed a borderline increase in DPP4i users compared to non-users (p = 0.0507), none of the biomarkers measured was affected by DPP4i treatment. An inverse correlation between estimated glomerular filtration rate and AGEs (p < 0.0001) and Fpg sites (p < 0.05) was also observed. This study does not show any major effect of DPP4i on oxidative stress, assessed by several circulating biomarkers of oxidative damage, in propensity score-matched cohorts of T2DM patients.

Plasma Nitrate Levels Are Related to Metabolic Syndrome and Are Not Altered by Treatment with DPP-4 Inhibitor Linagliptin: A Randomised, Placebo-Controlled Trial in Patients with Early Type 2 Diabetes Mellitus

“…While animal studies have demonstrated the anti-inflammatory and antioxidant effects of DPP-4 inhibitors, these favourable effects have not been confirmed in humans. Consistent with the findings of earlier studies, the present investigation did not show major effects of DPP-4 inhibitors on oxidative stress and inflammatory status in patients with T2DM [51,52]. However, 12 weeks of linagliptin treatment decreased malondialdehyde-modified LDL, a marker of oxidative stress, but not systemic inflammation [53].…”

Significance of Serum Oxidative and Antioxidative Status in Congenital Central Hypoventilation Syndrome (CCHS) Patients

“…TBARS are markers of lipid peroxidation, and they were determined as reported in our previous work [ 25 ]. Briefly, the serum sample (100 µL) was deproteinized by adding 100 µL of trichloroacetic acid (Merck KGaA, Darmstadt, DA, Germany) (1:1 v / v ), and 160 µL of the resulting supernatant was added to 32 µL of thiobarbituric acid (0.12 M) (Merck KGaA, Darmstadt, DA, Germany) in 0.26 M Tris, before heating at 100 °C for 15 min.…”

“…Assays based on Benzie and Strain’s method were used to determine FRAP [ 28 ]. As previously described [ 25 ], serum samples (10 μL) were added to 90 μL of distilled water. A FRAP solution (300 mM acetate buffer (pH 3.6), 10 mM 2,4,6-tripyridyl-S-triazine (TPTZ) in 40 mM HCl, and 20 mM FeCl 3 ·6H 2 O (10:1:1)) was freshly prepared incubated for 30 min at 37 °C.…”

Anti-Diabetic Therapy, Heart Failure and Oxidative Stress: An Update

“…A recent observational study that assessed several biomarkers of oxidative damage in propensity-score-matched cohorts, including ROS, plasma advanced glycation end products, advanced oxidation protein products, carbonyl residues and the ferric-reducing ability of plasma and leukocyte DNA oxidative damage in Fpg sites, does not suggest any major effect of DPP4 on oxidative stress in humans [ 106 ].…”