Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition.
OBJECTIVE
Evaluate the effects of two dipeptidyl peptidase-IV (DPP-4) inhibitors, sitagliptin and vildagliptin, known to have different efficacy on mean amplitude of glycemic excursions (MAGE), on oxidative stress, and on systemic inflammatory markers in patients with type 2 diabetes.


METHODS
A prospective, randomized, open-label PROBE design (parallel group with a blinded end point) study was performed in 90 patients with type 2 diabetes inadequately controlled by metformin. The study assigned 45 patients to receive sitagliptin (100 mg once daily; sitagliptin group) and 45 patients to receive vildagliptin (50 mg twice daily; vildagliptin group) for 12 weeks. MAGE, evaluated during 48 h of continuous subcutaneous glucose monitoring, allowed an assessment of daily glucose fluctuations at baseline and after 12 weeks in all patients. Assessment of oxidative stress (nitrotyrosine) and systemic levels of inflammatory markers interleukin (IL)-6 and IL-18 was performed at baseline and after 12 weeks in all patients.


RESULTS
HbA(1c), fasting and postprandial glucose, MAGE, and inflammatory and oxidative stress markers were similar between the groups at baseline. After 12 weeks, MAGE (P < 0.01) was lower in the vildagliptin group than in the sitagliptin group. After treatment, HbA(1c) and postprandial glucose evidenced similar changes between the groups (P = NS). Vildagliptin treatment was associated with a stronger decrease in nitrotyrosine (P < 0.01), IL-6 (P < 0.05), and IL-18 (P < 0.05) than sitagliptin treatment. Nitrotyrosine and IL-6 changes significantly correlated with changes in MAGE but not in fasting glucose and HbA(1c).


CONCLUSIONS
MAGE reduction is associated with reduction of oxidative stress and markers of systemic inflammation in type 2 diabetic patients. These effects were greater in the vildagliptin group than in the sitagliptin group.
Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy.
Maria Rosaria
MR
Rizzo
Michelangela
M
Barbieri
Raffaele
R
Marfella
Giuseppe
G
Paolisso
D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D020382:Interleukin-18 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D019518:Postprandial Period; D011446:Prospective Studies; D011719:Pyrazines / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use*; D000077597:Vildagliptin
D000218:Adamantane; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D020382:Interleukin-18; D015850:Interleukin-6; D008687:Metformin; D009570:Nitriles; D011719:Pyrazines; D011759:Pyrrolidines; D000068900:Sitagliptin Phosphate; D014230:Triazoles; D000077597:Vildagliptin