• David E Kloecker, Kamlesh Khunti, Melanie J Davies, Dario Pitocco, and Francesco Zaccardi.
• Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, United Kingdom; Leicester Real World Evidence Unit, Leicester Diabetes Centre, Leicester General Hospital, United Kingdom. Electronic address: davidekloecker@gmail.com.
• Mayo Clin. Proc. 2021 Jun 1; 96 (6): 1458-1469.

ObjectiveTo assess whether the presence of microvascular complications modifies the effect of intensive glucose reduction on long-term outcomes in patients with type 2 diabetes.Patients And MethodsUsing ACCORD and ACCORDION study data, we investigated the risk of the primary outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) or death in relation to the prerandomization type and extent of microvascular complications. Interaction terms were fitted in survival models to estimate the risk of both outcomes across levels of an overall microvascular disease score (range 0 to 100) and its individual components: diabetic nephropathy, retinopathy, and neuropathy.ResultsDuring a mean follow-up of 7.7 years, 1685 primary outcomes and 1806 deaths occurred in 9405 participants. The outcome-specific microvascular score was ≤30 in 97.9% of subjects for the primary outcome and in 98.5% for death. For participants with scores of 0 and 30, respectively, the 10-year absolute risk difference between intensive glucose control and standard treatment ranged from -0.8% (95% CI, -2.6, 1.1) to -3.0% -7.1, 1.1) for the primary outcome and from -0.5% (-2.1, 1.1) to 0.7% (-4.2, 5.6) for mortality. Retinopathy was associated with the largest effects, with a 10-year absolute risk difference of -6.5% (-11.1 to -2.0) for the primary outcome and -3.9% (-7.8 to 0.1) for mortality.ConclusionThis hypothesis-generating study identifies diabetic retinopathy as predictor of the beneficial effect of intensive glucose control on the risk of cardiovascular disease and possibly death. Further long-term studies are required to confirm these findings.Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

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