Irbesartan treatment does not influence plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone in participants with type 2 diabetes and microalbuminuria: An IRMA2 sub-study

M. Piazza; N. M. J. Hanssen; F. Persson; J. L. Scheijen; M. P. H. van de Waarenburg; M. M. J. van Greevenbroek; P. Rossing; P. Hovind; C. D. A. Stehouwer; H-H. Parving; C. G. Schalkwijk

doi:10.1111/dme.14405

Irbesartan treatment does not influence plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone in participants with type 2 diabetes and microalbuminuria: An IRMA2 sub-study

M. Piazza, N. M. J. Hanssen, F. Persson, J. L. Scheijen, M. P. H. van de Waarenburg, M. M. J. van Greevenbroek, P. Rossing, P. Hovind, C. D. A. Stehouwer, H-H. Parving, C. G. Schalkwijk^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Aim Angiotensin receptor blockers (ARBs) reduce vascular complications in diabetes independently of blood pressure. Experimental studies suggested that ARBs may restore the detoxifying enzyme glyoxalase 1, thereby lowering dicarbonyls such as methylglyoxal. Human data on the effects of ARBs on plasma dicarbonyl levels are lacking. We investigated, in individuals with type 2 diabetes, whether irbesartan lowered plasma levels of the dicarbonyls methylglyoxal, glyoxal, 3-deoxyglucosone and their derived advanced glycation end products (AGEs), and increasedd-lactate, reflecting greater methylglyoxal flux. Methods We analysed a subset of the Irbesartan in Patients with T2D and Microalbuminuria (IRMA2) study. We measured plasma dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone, free AGEs andd-lactate using ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS) in the treatment arm receiving 300 mg irbesartan (n = 121) and a placebo group (n = 101) at baseline and after 1 and 2 years. Effect of treatment was analysed with repeated measurements ANOVA. Results There was a slight, but significant difference in baseline median methylglyoxal levels [placebo 1119 (907-1509) nmol/l vs. irbesartan 300 mg 1053 (820-1427) nmol/l], but no significant changes were observed in any of the plasma dicarbonyls over time in either group and there was no effect of irbesartan treatment on plasma free AGEs ord-lactate levels at either 1 or 2 years. Conclusion Irbesartan treatment does not change plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone, free AGEs ord-lactate in type 2 diabetes. This indicates that increased dicarbonyls in type 2 diabetes are not targetable by ARBs, and other approaches to lower systemic dicarbonyls are needed in type 2 diabetes. (Clinical Trial Registry No: #NCT00317915).

Original language	English
Article number	14405
Number of pages	7
Journal	Diabetic Medicine
Volume	38
Issue number	9
Early online date	16 Oct 2020
DOIs	https://doi.org/10.1111/dme.14405
Publication status	Published - Sept 2021

Keywords

RENIN-ANGIOTENSIN SYSTEM
GLYCATION END-PRODUCTS
INDIVIDUALS
NEPHROPATHY
PATHOLOGY

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10.1111/dme.14405Licence: CC BY-NC

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Piazza, M., Hanssen, N. M. J., Persson, F., Scheijen, J. L., van de Waarenburg, M. P. H., van Greevenbroek, M. M. J., Rossing, P., Hovind, P., Stehouwer, C. D. A., Parving, H.-H., & Schalkwijk, C. G. (2021). Irbesartan treatment does not influence plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone in participants with type 2 diabetes and microalbuminuria: An IRMA2 sub-study. Diabetic Medicine, 38(9), Article 14405. https://doi.org/10.1111/dme.14405

@article{5dd98af560ff44ecb95e7f9a15f8441b,

title = "Irbesartan treatment does not influence plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone in participants with type 2 diabetes and microalbuminuria: An IRMA2 sub-study",

abstract = "Aim Angiotensin receptor blockers (ARBs) reduce vascular complications in diabetes independently of blood pressure. Experimental studies suggested that ARBs may restore the detoxifying enzyme glyoxalase 1, thereby lowering dicarbonyls such as methylglyoxal. Human data on the effects of ARBs on plasma dicarbonyl levels are lacking. We investigated, in individuals with type 2 diabetes, whether irbesartan lowered plasma levels of the dicarbonyls methylglyoxal, glyoxal, 3-deoxyglucosone and their derived advanced glycation end products (AGEs), and increasedd-lactate, reflecting greater methylglyoxal flux. Methods We analysed a subset of the Irbesartan in Patients with T2D and Microalbuminuria (IRMA2) study. We measured plasma dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone, free AGEs andd-lactate using ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS) in the treatment arm receiving 300 mg irbesartan (n = 121) and a placebo group (n = 101) at baseline and after 1 and 2 years. Effect of treatment was analysed with repeated measurements ANOVA. Results There was a slight, but significant difference in baseline median methylglyoxal levels [placebo 1119 (907-1509) nmol/l vs. irbesartan 300 mg 1053 (820-1427) nmol/l], but no significant changes were observed in any of the plasma dicarbonyls over time in either group and there was no effect of irbesartan treatment on plasma free AGEs ord-lactate levels at either 1 or 2 years. Conclusion Irbesartan treatment does not change plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone, free AGEs ord-lactate in type 2 diabetes. This indicates that increased dicarbonyls in type 2 diabetes are not targetable by ARBs, and other approaches to lower systemic dicarbonyls are needed in type 2 diabetes. (Clinical Trial Registry No: #NCT00317915).",

keywords = "RENIN-ANGIOTENSIN SYSTEM, GLYCATION END-PRODUCTS, INDIVIDUALS, NEPHROPATHY, PATHOLOGY",

author = "M. Piazza and Hanssen, {N. M. J.} and F. Persson and Scheijen, {J. L.} and {van de Waarenburg}, {M. P. H.} and {van Greevenbroek}, {M. M. J.} and P. Rossing and P. Hovind and Stehouwer, {C. D. A.} and H-H. Parving and Schalkwijk, {C. G.}",

note = "Funding Information: FP reports having received research grants from AstraZeneca, Novo Nordisk and Novartis and lecture fees from Novartis, Eli Lilly, MSD, AstraZeneca, Sanofi, Novo Nordisk and Boehringer Ingelheim and having served as a consultant for Astra Zeneca, Bayer, Amgen, Novo Nordisk and MSD. PR has received consultancy and/or speaking fees (to his institution) from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Sanofi Aventis, and Vifor. Research grants from AbbVie, AstraZeneca and Novo Nordisk. Funding Information: N.M.J.H. is supported by a Dr E. Dekker grant by the Dutch Heart Foundation (2017T039) and a junior post‐doc grant from the Dutch Diabetes Foundation (2017.85.005). Publisher Copyright: {\textcopyright} 2020 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK",

year = "2021",

month = sep,

doi = "10.1111/dme.14405",

language = "English",

volume = "38",

journal = "Diabetic Medicine",

issn = "0742-3071",

publisher = "Wiley",

number = "9",

}

Piazza, M, Hanssen, NMJ, Persson, F, Scheijen, JL, van de Waarenburg, MPH, van Greevenbroek, MMJ, Rossing, P, Hovind, P, Stehouwer, CDA, Parving, H-H & Schalkwijk, CG 2021, 'Irbesartan treatment does not influence plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone in participants with type 2 diabetes and microalbuminuria: An IRMA2 sub-study', Diabetic Medicine, vol. 38, no. 9, 14405. https://doi.org/10.1111/dme.14405

Irbesartan treatment does not influence plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone in participants with type 2 diabetes and microalbuminuria: An IRMA2 sub-study. / Piazza, M.; Hanssen, N. M. J.; Persson, F. et al.
In: Diabetic Medicine, Vol. 38, No. 9, 14405, 09.2021.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Irbesartan treatment does not influence plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone in participants with type 2 diabetes and microalbuminuria

T2 - An IRMA2 sub-study

AU - Piazza, M.

AU - Hanssen, N. M. J.

AU - Persson, F.

AU - Scheijen, J. L.

AU - van de Waarenburg, M. P. H.

AU - van Greevenbroek, M. M. J.

AU - Rossing, P.

AU - Hovind, P.

AU - Stehouwer, C. D. A.

AU - Parving, H-H.

AU - Schalkwijk, C. G.

N1 - Funding Information: FP reports having received research grants from AstraZeneca, Novo Nordisk and Novartis and lecture fees from Novartis, Eli Lilly, MSD, AstraZeneca, Sanofi, Novo Nordisk and Boehringer Ingelheim and having served as a consultant for Astra Zeneca, Bayer, Amgen, Novo Nordisk and MSD. PR has received consultancy and/or speaking fees (to his institution) from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Sanofi Aventis, and Vifor. Research grants from AbbVie, AstraZeneca and Novo Nordisk. Funding Information: N.M.J.H. is supported by a Dr E. Dekker grant by the Dutch Heart Foundation (2017T039) and a junior post‐doc grant from the Dutch Diabetes Foundation (2017.85.005). Publisher Copyright: © 2020 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK

PY - 2021/9

Y1 - 2021/9

N2 - Aim Angiotensin receptor blockers (ARBs) reduce vascular complications in diabetes independently of blood pressure. Experimental studies suggested that ARBs may restore the detoxifying enzyme glyoxalase 1, thereby lowering dicarbonyls such as methylglyoxal. Human data on the effects of ARBs on plasma dicarbonyl levels are lacking. We investigated, in individuals with type 2 diabetes, whether irbesartan lowered plasma levels of the dicarbonyls methylglyoxal, glyoxal, 3-deoxyglucosone and their derived advanced glycation end products (AGEs), and increasedd-lactate, reflecting greater methylglyoxal flux. Methods We analysed a subset of the Irbesartan in Patients with T2D and Microalbuminuria (IRMA2) study. We measured plasma dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone, free AGEs andd-lactate using ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS) in the treatment arm receiving 300 mg irbesartan (n = 121) and a placebo group (n = 101) at baseline and after 1 and 2 years. Effect of treatment was analysed with repeated measurements ANOVA. Results There was a slight, but significant difference in baseline median methylglyoxal levels [placebo 1119 (907-1509) nmol/l vs. irbesartan 300 mg 1053 (820-1427) nmol/l], but no significant changes were observed in any of the plasma dicarbonyls over time in either group and there was no effect of irbesartan treatment on plasma free AGEs ord-lactate levels at either 1 or 2 years. Conclusion Irbesartan treatment does not change plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone, free AGEs ord-lactate in type 2 diabetes. This indicates that increased dicarbonyls in type 2 diabetes are not targetable by ARBs, and other approaches to lower systemic dicarbonyls are needed in type 2 diabetes. (Clinical Trial Registry No: #NCT00317915).

AB - Aim Angiotensin receptor blockers (ARBs) reduce vascular complications in diabetes independently of blood pressure. Experimental studies suggested that ARBs may restore the detoxifying enzyme glyoxalase 1, thereby lowering dicarbonyls such as methylglyoxal. Human data on the effects of ARBs on plasma dicarbonyl levels are lacking. We investigated, in individuals with type 2 diabetes, whether irbesartan lowered plasma levels of the dicarbonyls methylglyoxal, glyoxal, 3-deoxyglucosone and their derived advanced glycation end products (AGEs), and increasedd-lactate, reflecting greater methylglyoxal flux. Methods We analysed a subset of the Irbesartan in Patients with T2D and Microalbuminuria (IRMA2) study. We measured plasma dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone, free AGEs andd-lactate using ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS) in the treatment arm receiving 300 mg irbesartan (n = 121) and a placebo group (n = 101) at baseline and after 1 and 2 years. Effect of treatment was analysed with repeated measurements ANOVA. Results There was a slight, but significant difference in baseline median methylglyoxal levels [placebo 1119 (907-1509) nmol/l vs. irbesartan 300 mg 1053 (820-1427) nmol/l], but no significant changes were observed in any of the plasma dicarbonyls over time in either group and there was no effect of irbesartan treatment on plasma free AGEs ord-lactate levels at either 1 or 2 years. Conclusion Irbesartan treatment does not change plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone, free AGEs ord-lactate in type 2 diabetes. This indicates that increased dicarbonyls in type 2 diabetes are not targetable by ARBs, and other approaches to lower systemic dicarbonyls are needed in type 2 diabetes. (Clinical Trial Registry No: #NCT00317915).

KW - RENIN-ANGIOTENSIN SYSTEM

KW - GLYCATION END-PRODUCTS

KW - INDIVIDUALS

KW - NEPHROPATHY

KW - PATHOLOGY

U2 - 10.1111/dme.14405

DO - 10.1111/dme.14405

M3 - Article

C2 - 32961617

SN - 0742-3071

VL - 38

JO - Diabetic Medicine

JF - Diabetic Medicine

IS - 9

M1 - 14405

ER -

Piazza M, Hanssen NMJ, Persson F, Scheijen JL, van de Waarenburg MPH, van Greevenbroek MMJ et al. Irbesartan treatment does not influence plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone in participants with type 2 diabetes and microalbuminuria: An IRMA2 sub-study. Diabetic Medicine. 2021 Sept;38(9):14405. Epub 2020 Oct 16. doi: 10.1111/dme.14405

Irbesartan treatment does not influence plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone in participants with type 2 diabetes and microalbuminuria: An IRMA2 sub-study

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