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Original investigation
Jun Wada
Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences: Okayama Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka Igakubu
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1468-5170
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear.
Methods
Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as cardiovascular event including cardiovascular disease, stroke, and peripheral arterial disease.
Results
During approximately 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+ 1 SD for the glycan index) were: UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24–2.55, P = 0.002) and Calsepa (High-Man [Man2-6]): 1.56 (1.19–2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known factors of CVE improved the outcome prediction (Difference of Harrel’s C-index: 0.028 [95% CI: 0.001–0.055, P = 0.044], net reclassification improvement at 5-year risk increased by 0.368 [0.045–0.692, P = 0.026], and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively).
Conclusions
The urinary excretion of high-mannose glycan may be a valuable marker for predicting CVE in patients with type 2 diabetes, which provide the rationale to explore the mechanism underlying abnormal N-glycosylation in CVE of patients with diabetes.
Trial registration
This study was registered with the University Hospital Medical Information Network in June 26th 2012 (Clinical trial number: UMIN000011525, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013482).
Keywords
cardiovascular event, diabetes, glycans, lectins, lectin microarray, N-glycans, prognosis, urinary biomarkers
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Original investigation
Jun Wada
Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences: Okayama Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka Igakubu
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1468-5170
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 05 Feb, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear.
Methods
Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as cardiovascular event including cardiovascular disease, stroke, and peripheral arterial disease.
Results
During approximately 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+ 1 SD for the glycan index) were: UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24–2.55, P = 0.002) and Calsepa (High-Man [Man2-6]): 1.56 (1.19–2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known factors of CVE improved the outcome prediction (Difference of Harrel’s C-index: 0.028 [95% CI: 0.001–0.055, P = 0.044], net reclassification improvement at 5-year risk increased by 0.368 [0.045–0.692, P = 0.026], and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively).
Conclusions
The urinary excretion of high-mannose glycan may be a valuable marker for predicting CVE in patients with type 2 diabetes, which provide the rationale to explore the mechanism underlying abnormal N-glycosylation in CVE of patients with diabetes.
Trial registration
This study was registered with the University Hospital Medical Information Network in June 26th 2012 (Clinical trial number: UMIN000011525, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013482).
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
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