Reduction of Oxidative Stress and Inflammation by Blunting Daily Acute Glucose Fluctuations in Patients With Type 2 Diabetes

Abstract

OBJECTIVEEvaluate 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.RESEARCH DESIGN AND METHODSA 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.RESULTSHbA1c, 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, HbA1c 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 HbA1c.CONCLUSIONSMAGE 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.

Dipeptidyl peptidase IV inhibitor protects against renal interstitial fibrosis in a mouse model of ureteral obstruction

“…These results agree with other research showing that DPPIV inhibition decreases oxidative stress in various organs. 18,27 Taken together, these results suggest that DPPIV inhibition decreases oxidative stress in the kidney, leading to improved renal function.…”

Rationale, Design, and Baseline Characteristics of a Trial for the Prevention of Diabetic Atherosclerosis Using a DPP-4 Inhibitor: The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A)

“…Based on a 12-week prospective study in 90 Italian type 2 diabetic patients, they showed that the administration of both sitagliptin and vildagliptin resulted in a significant decrease in the IMT. However, their report was a subanalysis of their previous study that was originally planned to evaluate the effects of two DPP-4 inhibitors on oxidative stress and inflammatory markers 31) , and therefore is considered to have several limitations. First of all, it lacks a control group: all the subjects were administered DPP-4 inhibitors, and a conventional treatment group using drugs other than the DPP-4 inhibitor was not planned.…”

In Vitro Study Examining the Activity of Vildagliptin and Sitagliptin against Hyperglycemia-Induced Effects in Human Umbilical Vein Endothelial Cells

“…Moreover, GLP-1 protects endothelial cells from hyperglycemiainduced dysfunction that may be caused by oxidative stress. Vildagliptin is a DPP-4 inhibitor that displays more prolonged DPP-4 enzyme inhibition (acting as a substrate-blocker) compared to sitagliptin (acting, conversely, as a competitive inhibitor), thereby resulting in higher GLP-1 plasma levels upon the former compared to the latter [14][15][16].…”

“…Vildagliptin is a DPP-4 inhibitor that has displayed better antioxidant properties than other compounds in its class [12][13][14], significantly lowering oxidative stress-related markers. Still, to date, available data are poor.…”