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Article

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

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Medical Center Groningen, Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, 9713 Groningen, The Netherlands
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Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, 9713 Groningen, The Netherlands
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Department of Biomedical Photoacustic Imaging (BMPI), University of Twente, 7522 Enschede, The Netherlands
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Faculty of Medicine, Clinical and Experimental Sciences, University of Southampton, SO17 1BJ Southamptonc, UK
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Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, University of Groningen, 9713 Groningen, The Netherlands
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Medical Center Groningen, Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, 9713 Groningen, The Netherlands
*
Author to whom correspondence should be addressed.
Academic Editor: Mario Allegra
Antioxidants 2021, 10(10), 1548; https://doi.org/10.3390/antiox10101548
Received: 25 August 2021 / Revised: 23 September 2021 / Accepted: 24 September 2021 / Published: 29 September 2021
The depletion of nitrate and nitrite, stable nitric oxide (NO) end-products, promotes adipose tissue dysfunction and insulin resistance (IR). Dipeptidyl peptidase-4 (DPP-4) inhibitors have the potentially beneficial side effect of increasing NO availability. In this study, nitrate and nitrite levels and the effects of DPP-4 inhibitor linagliptin were investigated in relation to metabolic syndrome (MetS) markers. Treatment-naive patients with early type 2 diabetes mellitus (T2DM) (n = 40, median age 63 IQR (55–67) years, 63% male, mean HbA1c 45 ± 4.4 mmol/mol) were randomized (1:1) to linagliptin (5 mg/day) or placebo. MetS-related markers (body mass index (BMI), triglycerides, HOMA-IR, gamma-glutamyltransferase (GGT), C-reactive protein (CRP), and adiponectin), plasma levels of nitrate, nitrite, total free thiols (TFT) and vegetable intake were estimated at baseline and after 4 and 26 weeks of treatment. Plasma nitrate, but not nitrite, correlated positively with vegetable intake (r = 0.38, p = 0.018) and was inversely associated with HOMA-IR (r = −0.44, p = 0.006), BMI (r = −0.35, p = 0.028), GGT (r = −0.37, p = 0.019) and CRP (r = −0.34, p = 0.034). The relationship between nitrate and HOMA-IR remained significant after adjusting for BMI, CRP, vegetable intake and GGT. With stable vegetable intake, nitrate and nitrite, TFT, adipokines and CRP did not change after 26 weeks of linagliptin treatment. While plasma nitrate is inversely associated with MetS, linagliptin treatment does not significantly influence nitrate and nitrite concentrations, oxidative stress, adipose tissue function and systemic inflammation. View Full-Text
Keywords: diabetes; inflammation; linagliptin; metabolic syndrome; nitrate; nitric oxide; oxidative stress; vegetable intake diabetes; inflammation; linagliptin; metabolic syndrome; nitrate; nitric oxide; oxidative stress; vegetable intake
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MDPI and ACS Style

Reijrink, M.; De Boer, S.A.; Van Roon, A.M.; Slart, R.H.J.A.; Fernandez, B.O.; Feelisch, M.; Heerspink, H.J.L.; Van Goor, H.; Hillebrands, J.-L.; Mulder, D.J. 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. Antioxidants 2021, 10, 1548. https://doi.org/10.3390/antiox10101548

AMA Style

Reijrink M, De Boer SA, Van Roon AM, Slart RHJA, Fernandez BO, Feelisch M, Heerspink HJL, Van Goor H, Hillebrands J-L, Mulder DJ. 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. Antioxidants. 2021; 10(10):1548. https://doi.org/10.3390/antiox10101548

Chicago/Turabian Style

Reijrink, Melanie, Stefanie A. De Boer, Anniek M. Van Roon, Riemer H.J.A. Slart, Bernadette O. Fernandez, Martin Feelisch, Hiddo J.L. Heerspink, Harry Van Goor, Jan-Luuk Hillebrands, and Douwe J. Mulder. 2021. "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" Antioxidants 10, no. 10: 1548. https://doi.org/10.3390/antiox10101548

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