Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jul 4;23(1):235.
doi: 10.1186/s12933-024-02316-w.

Protein glycation products associate with progression of kidney disease and incident cardiovascular events in individuals with type 1 diabetes

Krishna Adeshara  1   2   3 , Daniel Gordin  3   4   5 , Anni A Antikainen  1   2   3 , Valma Harjutsalo  1   2   3 , Niina Sandholm  1   2   3 , Markku J Lehto  1   2   3 , Per-Henrik Groop  6   7   8   9   10 ; FinnDiane Study Group
Affiliations

Protein glycation products associate with progression of kidney disease and incident cardiovascular events in individuals with type 1 diabetes

Krishna Adeshara et al. Cardiovasc Diabetol. .

Abstract

Background: Despite improved glycemic treatment, the impact of glycation on pathological consequences may persist and contribute to adverse clinical outcomes in diabetes. In the present study we investigated the association between serum protein glycation products and progression of kidney disease as well as incident major adverse cardiovascular events (MACE) in type 1 diabetes.

Methods: Fructosamine, advanced glycation end products (AGEs), and methylglyoxal-modified hydro-imidazolone (MG-H1) were measured from baseline serum samples in the FinnDiane study (n = 575). Kidney disease progression was defined as steep eGFR decline (> 3 mL/min/1.73 m2/year) or progression of albuminuria (from lower to higher stage of albuminuria). MACE was defined as acute myocardial infarction, coronary revascularization, cerebrovascular event (stroke), and cardiovascular death.

Results: Fructosamine was independently associated with steep eGFR decline (OR 2.15 [95% CI 1.16-4.01], p = 0.016) in the fully adjusted model (age, sex, baseline eGFR). AGEs were associated with steep eGFR decline (OR 1.58 per 1 unit of SD [95% CI 1.07-2.32], p = 0.02), progression to end-stage kidney disease (ESKD) (HR 2.09 per 1 unit of SD [95% CI 1.43-3.05], p < 0.001), and pooled progression (to any stage of albuminuria) (HR 2.72 per 1 unit of SD [95% CI 2.04-3.62], p < 0.001). AGEs (HR 1.57 per 1 unit of SD [95% CI 1.23-2.00], p < 0.001) and MG-H1 (HR 4.99 [95% CI 0.98-25.55], p = 0.054) were associated with incident MACE. MG-H1 was also associated with pooled progression (HR 4.19 [95% CI 1.11-15.89], p = 0.035). Most AGEs and MG-H1 associations were no more significant after adjusting for baseline eGFR.

Conclusions: Overall, these findings suggest that protein glycation products are an important risk factor for target organ damage in type 1 diabetes. The data provide further support to investigate a potential causal role of serum protein glycation in the progression of diabetes complications.

Keywords: Advanced glycation end products; Diabetic kidney disease; Fructosamine; MACE; MG-H1; Type 1 diabetes.

PubMed Disclaimer

Conflict of interest statement

P-H.G. has received investigator-initiated research grants from Eli Lilly and Roche, lecture fees from Astellas, Astra Zeneca, Bayer, Boehringer-Ingelheim, Eli Lilly, Elo Water, Medscape, MSD, Mundipharma, Novartis, Novo Nordisk, PeerVoice, Sanofi and SCIARC. He is an advisory board member for AbbVie, Astellas, Bayer, Boehringer-Ingelheim, Eli Lilly, Janssen, Medscape, MSD, Mundipharma, Nestlé, Novartis, Novo Nordisk, and Sanofi. D..G. has received lecture or advisory meeting honorariums from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Fresenius, GE Healthcare, Novo Nordisk, and, Ratiopharm. All other authors declared that they had no conflict of interest.

Figures

Fig. 1
Fig. 1
Kaplan–Meier plot for progression of diabetes kidney disease (A), and incident major adverse cardiovascular event (MACE; B). Individuals were stratified by quartiles of advanced glycation end products (AGEs) at baseline
See this image and copyright information in PMC

References

    1. Ortiz F, Harjutsalo V, Helantera I, Lempinen M, Forsblom C, Groop PH. Long-term mortality after kidney transplantation in a nationwide cohort of patients with type 1 diabetes in Finland. Diabetes Care. 2019;42(1):55–61. doi: 10.2337/dc18-1029. - DOI - PubMed
    1. Harjutsalo V, Thomas MC, Forsblom C, Groop PH, Group FS. Risk of coronary artery disease and stroke according to sex and presence of diabetic nephropathy in type 1 diabetes. Diabetes Obes Metab. 2018;20(12):2759–67. doi: 10.1111/dom.13456. - DOI - PubMed
    1. Jansson Sigfrids F, Groop PH, Harjutsalo V. Incidence rate patterns, cumulative incidence, and time trends for moderate and severe albuminuria in individuals diagnosed with type 1 diabetes aged 0–14 years: a population-based retrospective cohort study. Lancet Diabetes Endocrinol. 2022;10(7):489–98. doi: 10.1016/S2213-8587(22)00099-7. - DOI - PubMed
    1. Armbruster DA. Fructosamine: structure, analysis, and clinical usefulness. Clin Chem. 1987;33(12):2153–63. doi: 10.1093/clinchem/33.12.2153. - DOI - PubMed
    1. Dobler D, Ahmed N, Song LJ, Eboigbodin KE, Thornalley PJ. Increased dicarbonyl metabolism in endothelial cells in hyperglycemia induces anoikis and impairs angiogenesis by RGD and GFOGER motif modification. Diabetes. 2006;55:1961–9. doi: 10.2337/db05-1634. - DOI - PubMed

Publication types

MeSH terms