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Association of blood glucose control and pancreatic reserve with diabetic retinopathy in the Veterans Affairs Diabetes Trial (VADT)

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Abstract

Aims/hypothesis

The aim of this study was to test the hypothesis that intensive glycaemic control (INT) and higher plasma C-peptide levels in patients with poorly controlled diabetes would be associated with better eye outcomes.

Methods

The incidence and progression of diabetic retinopathy (DR) was assessed by grading seven-field stereoscopic fundus photographs at baseline and 5 years later in 858 of 1,791 participants in the Veterans Affairs Diabetes Trial (VADT).

Results

After adjustment for all covariates, risk of progression (but not incidence) of DR increased by 30% for each 1% increase in baseline HbA1c (OR 1.3; 95% CI 1.123, 1.503; p = 0.0004). Neither assignment to INT nor age was independently associated with DR in the entire cohort. However, INT showed a biphasic interaction with age. The incidence of DR was decreased in INT participants ≤55 years of age (OR 0.49; 95% CI 0.24, 1.0) but increased in those ≥70 years old (OR 2.88; 95% CI 1.0, 8.24) (p = 0.0043). The incidence of DR was reduced by 67.2% with each 1 pmol/ml increment in baseline C-peptide (OR 0.328; 95% CI 0.155, 0.7; p = 0.0037). Baseline C-peptide was also an independent inverse risk factor for the progression of DR, with a reduction of 47% with each 1 pmol/ml increase in C-peptide (OR 0.53; 95% CI 0.305, 0.921; p = 0.0244).

Conclusions/interpretation

Poor glucose control at baseline was associated with an increased risk of progression of DR. INT was associated with a decreased incidence of DR in younger patients but with an increased risk of DR in older patients. Higher C-peptide at baseline was associated with reduced incidence and progression of DR.

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Abbreviations

ACCORD:

Action to Control Cardiovascular Risk in Diabetes

ADVANCE:

Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation

DR:

Diabetic retinopathy

eGFR:

Estimated GFR

ETDRS:

Early Treatment Diabetic Retinopathy Study

HDL-C:

HDL cholesterol

INT:

Intensive glycaemic control

LDL-C:

LDL cholesterol

PAI-1:

Plasminogen activator inhibitor-1

STD:

Standard glycaemic therapy

TC:

Total cholesterol

UKPDS:

UK Prospective Diabetic Study

VADT:

Veterans Affairs Diabetes Trial

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Funding

The study was sponsored by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development. There was also generous support from the National Eye Institute. Medications and financial support were provided by Sanofi-Aventis, GlaxoSmithKline, Novo Nordisk, Roche, Kos Pharmaceuticals, Merck and Amylin. These companies had no role in the design of the study, in the accrual or analysis of the data, or in the preparation or approval of the manuscript.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

All authors vouch for the accuracy and completeness of the data and the analysis. NA is the guarantor of this work and, as such, had full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NA, LA, NVE, PR, RK and GDB contributed to the conception and design of the data analysis for this paper. They all were involved in drafting and revising the manuscript critically for important intellectual content, and all gave final approval of the version to be published. In addition, GDB performed the statistical analysis and provided the figures and tables.

Author information

Authors and Affiliations

  1. Endocrinology Section, Edward Hines, Jr VA Hospital, Building 1, Room D139, Hines, IL, 60141, USA

    Nasrin Azad, Lily Agrawal & Nicholas V. Emanuele

  2. Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA

    Ronald Klein

  3. Cooperative Studies Program Coordinating Center, Hines, IL, USA

    Gideon D. Bahn

  4. Endocrinology Section, Carl T. Hayden VA Medical Center, Phoenix, AZ, USA

    Peter Reaven

Authors
  1. Nasrin Azad
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  2. Lily Agrawal
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  3. Nicholas V. Emanuele
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  4. Ronald Klein
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  5. Gideon D. Bahn
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  6. Peter Reaven
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and The VADT Study Group

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Correspondence to Nasrin Azad.

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Azad, N., Agrawal, L., Emanuele, N.V. et al. Association of blood glucose control and pancreatic reserve with diabetic retinopathy in the Veterans Affairs Diabetes Trial (VADT). Diabetologia 57, 1124–1131 (2014). https://doi.org/10.1007/s00125-014-3199-7

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