Rapid Reduction of HbA_1c and Early Worsening of Diabetic Retinopathy: A Real-world Population-Based Study in Subjects With Type 2 Diabetes

OBJECTIVE Early worsening of diabetic retinopathy (EWDR) due to the rapid decrease of blood glucose levels is a concern in diabetes treatment. The aim of the current study is to evaluate whether this is an important issue in subjects with type 2 diabetes with mild or moderate nonproliferative DR (NPDR), who represent the vast majority of subjects with DR attended in primary care. RESEARCH DESIGN AND METHODS This is a retrospective nested case-control study of subjects with type 2 diabetes and previous mild or moderate NPDR. Using the SIDIAP ("Sistema d'informacio pel Desenvolupament de la Recerca a Atencio Primaria") database, we selected 1,150 individuals with EWDR and 1,150 matched control subjects (DR without EWDR). The main variable analyzed was the magnitude of the reduction of HbA(1c) in the previous 12 months. The reduction of HbA(1c) was categorized as rapid (>1.5% reduction in <12 months) or very rapid (>2% in <6 months). RESULTS We did not find any significant difference in HbA(1c) reduction between case and control subjects (0.13 +/- 1.21 vs. 0.21 +/- 1.18; P = 0.12). HbA(1c) reduction did not show significant association with worsening of DR, neither in the unadjusted analyses nor in adjusted statistical models that included the main confounding variables: duration of diabetes, baseline HbA(1c), presence of hypertension, and antidiabetic drugs. In addition, when stratification by baseline HbA(1c) was performed, we did not find that those patients with higher levels of HbA(1c) presented a higher risk to EWDR. CONCLUSIONS Our results suggest that the rapid reduction of HbA(1c) is not associated with progression of mild or moderate NPDR.