Prospective study of inflammatory biomarkers and risk of diabetic retinopathy in the diabetes control and complications trial

Rajeev H. Muni, Radha P. Kohly, Eudocia Q. Lee, Joann E. Manson, Richard David Semba, Debra A. Schaumberg

Research output: Contribution to journalArticle

Abstract

Importance: This study demonstrates that increasing quintiles of baseline high-sensitivity C-reactive protein (hsCRP) level may be associated with higher risk of incident clinically significant macular edema, the leading cause of vision loss in working-aged individuals in North America. Objective: To determine whether baseline levels of hsCRP and intercellular adhesion molecule 1 (ICAM-1) predict development and progression of diabetic retinopathy (DR), clinically significant macular edema (CSME), retinal hard exudates, and proliferative DR in the Diabetes Control and Complications Trial (DCCT) cohort. Design: The DCCT was a large multicenter randomized controlled clinical trial. Setting: Twenty-nine medical centers in the United States and Canada. Participants: The DCCT population consisted of 1441 subjects with type 1 diabetes mellitus aged 13 to 39 years at study entry. Intervention: We measured levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 in stored baseline blood samples. Main Outcome Measures: We assessed the association of levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 with incident DR end points ascertained from grading of standardized 7-field stereoscopic retinal color photographs taken at baseline and every 6 months during follow-up. Results: After adjustment for randomized treatment assignment and other factors, we observed a statistically significant association between hsCRP and risk of CSME, with a relative risk (RR) for the top vs bottom quintile of 1.83 (95% CI, 0.94-3.55; P for trend=.01). Similarly, for the development of retinal hard exudates, the RR for the top vs bottom quintile of hsCRP level was 1.78 (95% CI, 0.98-3.25; P for trend=.004), whereas for ICAM-1 level, the RR comparing the top vs bottom quintiles was 1.50 (95% CI, 0.84-2.68; P for trend=.05). There were no statistically significant associations between baseline VCAM-1 or tumor necrosis factor α receptor 1 levels and risk of any of the DR end points. Conclusions and Relevance: After adjusting for known risk factors, increasing quintiles of baseline hsCRP level may be associated with higher risk of incident CSME and macular hard exudate in the DCCT cohort. Circulating levels of ICAM-1 may also be associated with the development of retinal hard exudates.

Original languageEnglish (US)
Pages (from-to)514-521
Number of pages8
JournalJAMA Ophthalmology
Volume131
Issue number4
DOIs
StatePublished - Apr 2013

Fingerprint

Diabetic Retinopathy
Diabetes Complications
C-Reactive Protein
Biomarkers
Intercellular Adhesion Molecule-1
Prospective Studies
Macular Edema
Exudates and Transudates
Vascular Cell Adhesion Molecule-1
Tumor Necrosis Factor Receptors
North America
Type 1 Diabetes Mellitus
Canada
Randomized Controlled Trials
Color
Outcome Assessment (Health Care)
Population

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Prospective study of inflammatory biomarkers and risk of diabetic retinopathy in the diabetes control and complications trial. / Muni, Rajeev H.; Kohly, Radha P.; Lee, Eudocia Q.; Manson, Joann E.; Semba, Richard David; Schaumberg, Debra A.

In: JAMA Ophthalmology, Vol. 131, No. 4, 04.2013, p. 514-521.

Research output: Contribution to journalArticle

Muni, Rajeev H. ; Kohly, Radha P. ; Lee, Eudocia Q. ; Manson, Joann E. ; Semba, Richard David ; Schaumberg, Debra A. / Prospective study of inflammatory biomarkers and risk of diabetic retinopathy in the diabetes control and complications trial. In: JAMA Ophthalmology. 2013 ; Vol. 131, No. 4. pp. 514-521.
@article{8f1bd1dd22c240a991f923022a86ccc9,
title = "Prospective study of inflammatory biomarkers and risk of diabetic retinopathy in the diabetes control and complications trial",
abstract = "Importance: This study demonstrates that increasing quintiles of baseline high-sensitivity C-reactive protein (hsCRP) level may be associated with higher risk of incident clinically significant macular edema, the leading cause of vision loss in working-aged individuals in North America. Objective: To determine whether baseline levels of hsCRP and intercellular adhesion molecule 1 (ICAM-1) predict development and progression of diabetic retinopathy (DR), clinically significant macular edema (CSME), retinal hard exudates, and proliferative DR in the Diabetes Control and Complications Trial (DCCT) cohort. Design: The DCCT was a large multicenter randomized controlled clinical trial. Setting: Twenty-nine medical centers in the United States and Canada. Participants: The DCCT population consisted of 1441 subjects with type 1 diabetes mellitus aged 13 to 39 years at study entry. Intervention: We measured levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 in stored baseline blood samples. Main Outcome Measures: We assessed the association of levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 with incident DR end points ascertained from grading of standardized 7-field stereoscopic retinal color photographs taken at baseline and every 6 months during follow-up. Results: After adjustment for randomized treatment assignment and other factors, we observed a statistically significant association between hsCRP and risk of CSME, with a relative risk (RR) for the top vs bottom quintile of 1.83 (95{\%} CI, 0.94-3.55; P for trend=.01). Similarly, for the development of retinal hard exudates, the RR for the top vs bottom quintile of hsCRP level was 1.78 (95{\%} CI, 0.98-3.25; P for trend=.004), whereas for ICAM-1 level, the RR comparing the top vs bottom quintiles was 1.50 (95{\%} CI, 0.84-2.68; P for trend=.05). There were no statistically significant associations between baseline VCAM-1 or tumor necrosis factor α receptor 1 levels and risk of any of the DR end points. Conclusions and Relevance: After adjusting for known risk factors, increasing quintiles of baseline hsCRP level may be associated with higher risk of incident CSME and macular hard exudate in the DCCT cohort. Circulating levels of ICAM-1 may also be associated with the development of retinal hard exudates.",
author = "Muni, {Rajeev H.} and Kohly, {Radha P.} and Lee, {Eudocia Q.} and Manson, {Joann E.} and Semba, {Richard David} and Schaumberg, {Debra A.}",
year = "2013",
month = "4",
doi = "10.1001/jamaophthalmol.2013.2299",
language = "English (US)",
volume = "131",
pages = "514--521",
journal = "JAMA Ophthalmology",
issn = "2168-6165",
publisher = "American Medical Association",
number = "4",

}

TY - JOUR

T1 - Prospective study of inflammatory biomarkers and risk of diabetic retinopathy in the diabetes control and complications trial

AU - Muni, Rajeev H.

AU - Kohly, Radha P.

AU - Lee, Eudocia Q.

AU - Manson, Joann E.

AU - Semba, Richard David

AU - Schaumberg, Debra A.

PY - 2013/4

Y1 - 2013/4

N2 - Importance: This study demonstrates that increasing quintiles of baseline high-sensitivity C-reactive protein (hsCRP) level may be associated with higher risk of incident clinically significant macular edema, the leading cause of vision loss in working-aged individuals in North America. Objective: To determine whether baseline levels of hsCRP and intercellular adhesion molecule 1 (ICAM-1) predict development and progression of diabetic retinopathy (DR), clinically significant macular edema (CSME), retinal hard exudates, and proliferative DR in the Diabetes Control and Complications Trial (DCCT) cohort. Design: The DCCT was a large multicenter randomized controlled clinical trial. Setting: Twenty-nine medical centers in the United States and Canada. Participants: The DCCT population consisted of 1441 subjects with type 1 diabetes mellitus aged 13 to 39 years at study entry. Intervention: We measured levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 in stored baseline blood samples. Main Outcome Measures: We assessed the association of levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 with incident DR end points ascertained from grading of standardized 7-field stereoscopic retinal color photographs taken at baseline and every 6 months during follow-up. Results: After adjustment for randomized treatment assignment and other factors, we observed a statistically significant association between hsCRP and risk of CSME, with a relative risk (RR) for the top vs bottom quintile of 1.83 (95% CI, 0.94-3.55; P for trend=.01). Similarly, for the development of retinal hard exudates, the RR for the top vs bottom quintile of hsCRP level was 1.78 (95% CI, 0.98-3.25; P for trend=.004), whereas for ICAM-1 level, the RR comparing the top vs bottom quintiles was 1.50 (95% CI, 0.84-2.68; P for trend=.05). There were no statistically significant associations between baseline VCAM-1 or tumor necrosis factor α receptor 1 levels and risk of any of the DR end points. Conclusions and Relevance: After adjusting for known risk factors, increasing quintiles of baseline hsCRP level may be associated with higher risk of incident CSME and macular hard exudate in the DCCT cohort. Circulating levels of ICAM-1 may also be associated with the development of retinal hard exudates.

AB - Importance: This study demonstrates that increasing quintiles of baseline high-sensitivity C-reactive protein (hsCRP) level may be associated with higher risk of incident clinically significant macular edema, the leading cause of vision loss in working-aged individuals in North America. Objective: To determine whether baseline levels of hsCRP and intercellular adhesion molecule 1 (ICAM-1) predict development and progression of diabetic retinopathy (DR), clinically significant macular edema (CSME), retinal hard exudates, and proliferative DR in the Diabetes Control and Complications Trial (DCCT) cohort. Design: The DCCT was a large multicenter randomized controlled clinical trial. Setting: Twenty-nine medical centers in the United States and Canada. Participants: The DCCT population consisted of 1441 subjects with type 1 diabetes mellitus aged 13 to 39 years at study entry. Intervention: We measured levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 in stored baseline blood samples. Main Outcome Measures: We assessed the association of levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 with incident DR end points ascertained from grading of standardized 7-field stereoscopic retinal color photographs taken at baseline and every 6 months during follow-up. Results: After adjustment for randomized treatment assignment and other factors, we observed a statistically significant association between hsCRP and risk of CSME, with a relative risk (RR) for the top vs bottom quintile of 1.83 (95% CI, 0.94-3.55; P for trend=.01). Similarly, for the development of retinal hard exudates, the RR for the top vs bottom quintile of hsCRP level was 1.78 (95% CI, 0.98-3.25; P for trend=.004), whereas for ICAM-1 level, the RR comparing the top vs bottom quintiles was 1.50 (95% CI, 0.84-2.68; P for trend=.05). There were no statistically significant associations between baseline VCAM-1 or tumor necrosis factor α receptor 1 levels and risk of any of the DR end points. Conclusions and Relevance: After adjusting for known risk factors, increasing quintiles of baseline hsCRP level may be associated with higher risk of incident CSME and macular hard exudate in the DCCT cohort. Circulating levels of ICAM-1 may also be associated with the development of retinal hard exudates.

UR - http://www.scopus.com/inward/record.url?scp=84876260169&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876260169&partnerID=8YFLogxK

U2 - 10.1001/jamaophthalmol.2013.2299

DO - 10.1001/jamaophthalmol.2013.2299

M3 - Article

C2 - 23392399

AN - SCOPUS:84876260169

VL - 131

SP - 514

EP - 521

JO - JAMA Ophthalmology

JF - JAMA Ophthalmology

SN - 2168-6165

IS - 4

ER -