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
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
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.
1548
Reijrink, Melanie
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De Boer, Stefanie A
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Van Roon, Anniek M
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Slart, Riemer H J A
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Fernandez, Bernadette O
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Feelisch, Martin
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Heerspink, Hiddo J L
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Van Goor, Harry
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Hillebrands, Jan-Luuk
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Mulder, Douwe J
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29 September 2021
Reijrink, Melanie
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De Boer, Stefanie A
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Van Roon, Anniek M
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Slart, Riemer H J A
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Fernandez, Bernadette O
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Feelisch, Martin
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Heerspink, Hiddo J L
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Van Goor, Harry
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Hillebrands, Jan-Luuk
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Mulder, Douwe J
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Reijrink, Melanie, De Boer, Stefanie A, Van Roon, Anniek M, Slart, Riemer H J A, Fernandez, Bernadette O, Feelisch, Martin, Heerspink, Hiddo J L, Van Goor, Harry, Hillebrands, Jan-Luuk and Mulder, Douwe J
(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 (10), .
(doi:10.3390/antiox10101548).
Abstract
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.
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antioxidants-10-01548-v2
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Accepted/In Press date: 24 September 2021
Published date: 29 September 2021
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Local EPrints ID: 456294
URI: http://eprints.soton.ac.uk/id/eprint/456294
ISSN: 2076-3921
PURE UUID: 3e33d35c-9e9c-487d-8c37-b19503b9f5e1
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Date deposited: 27 Apr 2022 01:26
Last modified: 17 Mar 2024 03:31
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Author:
Melanie Reijrink
Author:
Stefanie A De Boer
Author:
Anniek M Van Roon
Author:
Riemer H J A Slart
Author:
Bernadette O Fernandez
Author:
Hiddo J L Heerspink
Author:
Harry Van Goor
Author:
Jan-Luuk Hillebrands
Author:
Douwe J Mulder
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