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Urinary peptidome and diabetic retinopathy in the DIRECT-Protect 1 and 2 trials

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@article{1f634aa1a3aa44baac81d37e1f3e74be,
title = "Urinary peptidome and diabetic retinopathy in the DIRECT-Protect 1 and 2 trials",
abstract = "BACKGROUND: Given the association of diabetic retinopathy (DR) and kidney disease, we investigated the urinary peptidome to presence and deterioration of DR in a post hoc analysis of trials investigating the effect of candesartan on progression of DR in type 1 and type 2 diabetes, respectively.METHODS: Baseline urinary peptidomic analysis was performed on a random selection of 783 and 792 subjects in two randomized controlled trials, DIRECT-Protect 1 and 2, respectively. End points were two-step (RET2) and three-step (RET3) change in Early Treatment of Diabetic Retinopathy Study protocol (ETDRS) defined level. Peptide levels were correlated to baseline EDTRS level in a discovery set of 2/3 of the participants from DIRECT-Protect 1. The identified peptides were then validated cross-sectionally in the remaining 1/3 from DIRECT-Protect 1. Thereafter, peptides identified in the discovery set were assessed in the entire DIRECT-Protect 1 and 2 cohorts and significant peptides were tested longitudinally.RESULTS: Follow-up ranged 4.0-4.7 years. 24 peptides were associated with baseline DR in the discovery set. COL3A1 (seq: NTG~) and COL4A1 (seq: DGA~) were associated with baseline DR in the validation set (Rho: -.223, p < 0.001 and Rho: -.141, p = 0.024). Neither was significantly associated with end points. Assessing the 24 identified peptides in the entire cohorts, several collagen peptides were associated with baseline DR and end points; however, there was no overlap across diabetes types.CONCLUSIONS: We identified several urinary peptides (mainly collagen) associated with the presence of DR, however they could not be conclusively associated with worsening of DR.",
keywords = "clinical diabetes, clinical trials, nephropathy, peptidomics, retinopathy",
author = "{Rotbain Curovic}, Viktor and Pedro Magalh{\~a}es and Tianlin He and Hansen, {Tine W} and Harald Mischak and Peter Rossing and {DIRECT Programme Study Group}",
note = "{\textcopyright} 2021 Diabetes UK.",
year = "2021",
month = jul,
day = "6",
doi = "10.1111/dme.14634",
language = "English",
pages = "e14634",
journal = "Diabetic Medicine",
issn = "1464-5491",
publisher = "Wiley-Blackwell Publishing Ltd",

}

RIS

TY - JOUR

T1 - Urinary peptidome and diabetic retinopathy in the DIRECT-Protect 1 and 2 trials

AU - Rotbain Curovic, Viktor

AU - Magalhães, Pedro

AU - He, Tianlin

AU - Hansen, Tine W

AU - Mischak, Harald

AU - Rossing, Peter

AU - DIRECT Programme Study Group

N1 - © 2021 Diabetes UK.

PY - 2021/7/6

Y1 - 2021/7/6

N2 - BACKGROUND: Given the association of diabetic retinopathy (DR) and kidney disease, we investigated the urinary peptidome to presence and deterioration of DR in a post hoc analysis of trials investigating the effect of candesartan on progression of DR in type 1 and type 2 diabetes, respectively.METHODS: Baseline urinary peptidomic analysis was performed on a random selection of 783 and 792 subjects in two randomized controlled trials, DIRECT-Protect 1 and 2, respectively. End points were two-step (RET2) and three-step (RET3) change in Early Treatment of Diabetic Retinopathy Study protocol (ETDRS) defined level. Peptide levels were correlated to baseline EDTRS level in a discovery set of 2/3 of the participants from DIRECT-Protect 1. The identified peptides were then validated cross-sectionally in the remaining 1/3 from DIRECT-Protect 1. Thereafter, peptides identified in the discovery set were assessed in the entire DIRECT-Protect 1 and 2 cohorts and significant peptides were tested longitudinally.RESULTS: Follow-up ranged 4.0-4.7 years. 24 peptides were associated with baseline DR in the discovery set. COL3A1 (seq: NTG~) and COL4A1 (seq: DGA~) were associated with baseline DR in the validation set (Rho: -.223, p < 0.001 and Rho: -.141, p = 0.024). Neither was significantly associated with end points. Assessing the 24 identified peptides in the entire cohorts, several collagen peptides were associated with baseline DR and end points; however, there was no overlap across diabetes types.CONCLUSIONS: We identified several urinary peptides (mainly collagen) associated with the presence of DR, however they could not be conclusively associated with worsening of DR.

AB - BACKGROUND: Given the association of diabetic retinopathy (DR) and kidney disease, we investigated the urinary peptidome to presence and deterioration of DR in a post hoc analysis of trials investigating the effect of candesartan on progression of DR in type 1 and type 2 diabetes, respectively.METHODS: Baseline urinary peptidomic analysis was performed on a random selection of 783 and 792 subjects in two randomized controlled trials, DIRECT-Protect 1 and 2, respectively. End points were two-step (RET2) and three-step (RET3) change in Early Treatment of Diabetic Retinopathy Study protocol (ETDRS) defined level. Peptide levels were correlated to baseline EDTRS level in a discovery set of 2/3 of the participants from DIRECT-Protect 1. The identified peptides were then validated cross-sectionally in the remaining 1/3 from DIRECT-Protect 1. Thereafter, peptides identified in the discovery set were assessed in the entire DIRECT-Protect 1 and 2 cohorts and significant peptides were tested longitudinally.RESULTS: Follow-up ranged 4.0-4.7 years. 24 peptides were associated with baseline DR in the discovery set. COL3A1 (seq: NTG~) and COL4A1 (seq: DGA~) were associated with baseline DR in the validation set (Rho: -.223, p < 0.001 and Rho: -.141, p = 0.024). Neither was significantly associated with end points. Assessing the 24 identified peptides in the entire cohorts, several collagen peptides were associated with baseline DR and end points; however, there was no overlap across diabetes types.CONCLUSIONS: We identified several urinary peptides (mainly collagen) associated with the presence of DR, however they could not be conclusively associated with worsening of DR.

KW - clinical diabetes

KW - clinical trials

KW - nephropathy

KW - peptidomics

KW - retinopathy

UR - http://www.scopus.com/inward/record.url?scp=85111133359&partnerID=8YFLogxK

U2 - 10.1111/dme.14634

DO - 10.1111/dme.14634

M3 - Journal article

C2 - 34228837

SP - e14634

JO - Diabetic Medicine

JF - Diabetic Medicine

SN - 1464-5491

M1 - e14634

ER -

ID: 66900669