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Insulin Resistance and Proliferative Retinopathy: A Cross-Sectional, Case-Control Study in 115 Patients with Type 2 Diabetes

Clinical Research Center for Rare Diseases Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research (A.P., I.I., B.D.D., G.R., P.R.), Ranica (Bergamo), Italy; Units of Ophtalmology (M.F.), Diabetology (R.T.), and Nephrology (G.R., P.R.), Azienda Ospedaliera, Ospedali Riuniti, 24125 Bergamo, Italy; Section Information Services, University Hospital Saint George (B.D.D.), Plovdiv, 4000 Bulgaria; and Department of Clinical and Experimental Medicine, University of Padova (M.V., A.T.), Padova, 35100 Italy

Address all correspondence and requests for reprints to: Dr. Piero Ruggenenti, Mario Negri Institute for Pharmacological Research, Negri Bergamo Laboratories, Via Gavazzeni 11, 24125 Bergamo, Italy. E-mail: manuelap{at}marionegri.it.

In this cross-sectional, case-control study we explored the association of proliferative diabetic retinopathy (PDR) with insulin resistance (IR) in type 2 diabetics with serum creatinine less than 2.0 mg/dl. For each PDR case, one reference case with background diabetic retinopathy (BDR) and two controls without retinopathy were identified. IR was evaluated by hyperinsulinemic euglycemic clamp; retinopathy was evaluated by indirect ophthalmoscopy and photography. Patients were matched by age, gender, and body mass index. PDR patients (n = 28) had higher IR and low-density lipoprotein cholesterol and triglyceride levels than BDR patients (n = 29), but comparable levels of glycosylated hemoglobin. Compared with patients without retinopathy (n = 58), those with PDR had higher IR, low-density lipoprotein cholesterol, and albuminuria (P < 0.05); those with BDR had higher glycosylated hemoglobin (P < 0.05), but comparable IR. At multivariate regression analysis, IR was the only independent marker of PDR among patients with retinopathy (P = 0.016). IR also retained its independent predictive value at multiple comparison among all groups (by Kruskal-Wallis test, P = 0.019). In type 2 diabetes, IR is an independent specific marker of proliferative retinopathy that may characterize patients at increased risk for blindness who may benefit most from early screening and therapeutic intervention. Longitudinal studies are needed to evaluate the role of IR in the pathogenesis of proliferative retinopathy.

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