Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes.

Autor:	Rotbain Curovic V; Steno Diabetes Center Copenhagen, Herlev, Denmark., Sørland BA; Steno Diabetes Center Copenhagen, Herlev, Denmark., Hansen TW; Steno Diabetes Center Copenhagen, Herlev, Denmark., Jain SY; Steno Diabetes Center Copenhagen, Herlev, Denmark., Sulek K; Steno Diabetes Center Copenhagen, Herlev, Denmark., Mattila IM; Steno Diabetes Center Copenhagen, Herlev, Denmark., Frimodt-Moller M; Steno Diabetes Center Copenhagen, Herlev, Denmark., Trost K; Steno Diabetes Center Copenhagen, Herlev, Denmark.; Department of Clinical Medicine, University of Copenhagen, København, Denmark., Legido-Quigley C; Steno Diabetes Center Copenhagen, Herlev, Denmark.; King's College London, London, UK., Theilade S; Steno Diabetes Center Copenhagen, Herlev, Denmark.; Department of Clinical Medicine, University of Copenhagen, København, Denmark., Tofte N; Steno Diabetes Center Copenhagen, Herlev, Denmark., Winther SA; Steno Diabetes Center Copenhagen, Herlev, Denmark., Hansen CS; Steno Diabetes Center Copenhagen, Herlev, Denmark., Rossing P; Steno Diabetes Center Copenhagen, Herlev, Denmark.; Department of Clinical Medicine, University of Copenhagen, København, Denmark., Ahluwalia TS; Steno Diabetes Center Copenhagen, Herlev, Denmark tarun.veer.singh.ahluwalia@regionh.dk.; University of Copenhagen Bioinformatics Centre, København, Denmark.; Department of Science and Environment, Roskilde University, Roskilde, Denmark.
Jazyk:	angličtina
Zdroj:	BMJ open diabetes research & care [BMJ Open Diabetes Res Care] 2024 Apr 11; Vol. 12 (2). Date of Electronic Publication: 2024 Apr 11.
DOI:	10.1136/bmjdrc-2023-003973
Abstrakt:	Introduction: Diabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN) share common pathophysiology and pose an additive risk of early mortality. Research Design and Methods: In adults with type 1 diabetes, 49 metabolites previously associated with either DR or DKD were assessed in relation to presence of DSPN. Metabolites overlapping in significance with presence of all three complications were assessed in relation to microvascular burden severity (additive number of complications-ie, presence of DKD±DR±DSPN) using linear regression models. Subsequently, the same metabolites were assessed with progression to endpoints: soft microvascular events (progression in albuminuria grade, ≥30% estimated glomerular filtration rate (eGFR) decline, or any progression in DR grade), hard microvascular events (progression to proliferative DR, chronic kidney failure, or ≥40% eGFR decline), and hard microvascular or macrovascular events (hard microvascular events, cardiovascular events (myocardial infarction, stroke, or arterial interventions), or cardiovascular mortality), using Cox models. All models were adjusted for sex, baseline age, diabetes duration, systolic blood pressure, HbA1c, body mass index, total cholesterol, smoking, and statin treatment. Results: The full cohort investigated consisted of 487 participants. Mean (SD) follow-up was 4.8 (2.9, 5.7) years. Baseline biothesiometry was available in 202 participants, comprising the cross-sectional cohort. Eight metabolites were significantly associated with presence of DR, DKD, and DSPN, and six with additive microvascular burden severity. In the full cohort longitudinal analysis, higher levels of 3,4-dihydroxybutanoic acid (DHBA), 2,4-DHBA, ribonic acid, glycine, and ribitol were associated with development of events in both crude and adjusted models. Adding 3,4-DHBA, ribonic acid, and glycine to a traditional risk factor model improved the discrimination of hard microvascular events. Conclusions: While prospective studies directly assessing the predictive ability of these markers are needed, our results strengthen the role of clinical metabolomics in relation to risk assessment of diabetic complications in chronic type 1 diabetes. Competing Interests: Competing interests: TWH owns shares in Novo Nordisk. NT and SAW are full-time employees of and own shares in Novo Nordisk. CL-Q has served on advisory panels and/or received research support from Pfizer, Novo Nordisk and other companies via the IMI funding scheme. PR has received consultancy and/or speaking fees (to his institution) from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, MSD, Mundipharma, Novo Nordisk, Vifor, and Sanofi Aventis, and holds research grants from AstraZeneca and Novo Nordisk. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu