Type 2 diabetic patients with Graves’ disease have more frequent and severe Graves’ orbitopathy R. Le Moli a, *, V. Muscia a , A. Tumminia a , L. Frittitta a , M. Buscema a , F. Palermo a , L. Sciacca a , S. Squatrito a , R. Vigneri a,b a Department of Clinical and Molecular Biomedicine, Endocrinology Unit, Garibaldi-Nesima Medical Center, University of Catania, Via Palermo 636, 95100 Catania, Italy b National Research Council (CNR), Department of Biostructures and Bioimmaging, Catania, Italy Received 24 October 2014; received in revised form 9 January 2015; accepted 18 January 2015 Available online --- KEYWORDS Graves’; Ophthalmopath severity; Diabetes Abstract Background and aims: Due to the worldwide increasing prevalence of diabetes (DM), patients with both diabetes and Graves’ disease (GD) have become more frequent. Sporadic reports indicate that Graves’ orbitopathy (GO), a GD complication that affects orbital soft tissues, can be severe in DM patients. The relationship between these diseases is not well understood. This study aims at evaluating the association of GD and GO with autoimmune and non- autoimmune diabetes (DM) and to assess diabetic features that influence GD and GO prevalence and severity. Methods and results: This retrospective study evaluated GD, GO and DM association in 1211 consecutive GD patients (447 with GO and 77 with DM). A case-control study was carried out to evaluate DM relationship with GO severity by comparing at 1:2 ratio GO patients with or without DM. A strong association was found between GD and T1DM (p Z 0.01) but not T2DM. Instead, the presence of GO was strongly associated with T2DM (p Z 0.01). Moreover, GO was more frequently severe in GD patients with T2DM (11/30 or 36.6%) than in those without T2DM (1/60 or 1.7%, p Z 0.05). T2DM was the strongest risk factor for severe GO (OR Z 34.1 vs. 4.4 p < 0.049 in cigarette smokers). DM duration, obesity and vascular complications, but not metabolic control were significant determinants of GO severity. Conclusions: GD is associated with T1DM but not with T2DM, probably because of the common autoimmune background. GO, in contrast, is more frequent and severe in T2DM, significantly associated with obesity, diabetes duration and diabetic vasculopathy but not metabolic control. ª 2015 Elsevier B.V. All rights reserved. Introduction Diabetes mellitus (DM) [1,2] has been reported to be a risk factor for Graves’ orbitopathy (GO) [3]. GO is a manifes- tation of Graves’ disease (GD) characterized by inflam- mation and expansion of retroocular soft tissues. Proptosis, malfunctioning of the extraocular muscles and optic nerve damage are the major clinical consequences that impair a patient’s quality of life and may be sight-threatening [4e6]. GO severity is the result of a complex interaction between genetic (familiarity, gender, orbit characteristics) and non-genetic factors (smoking, radioiodine treatment, thyroid function) [6]. The mechanisms why diabetes can favor and worsen GO are unclear. One possibility involves the autoimmune background of the disorder. GD, GO and type I diabetes mellitus (T1DM) share an autoimmune nature and, in particular, can share susceptibility as well as involved loci * Corresponding author. Tel.: þ39 095 7598702; fax: þ39 095 472988. E-mail address: rlemoli@unict.it (R. Le Moli). Please cite this article in press as: Le Moli R, et al., Type 2 diabetic patients with Graves’ disease have more frequent and severe Graves’ orbitopathy, Nutrition, Metabolism & Cardiovascular Diseases (2015), http://dx.doi.org/10.1016/j.numecd.2015.01.003 http://dx.doi.org/10.1016/j.numecd.2015.01.003 0939-4753/ª 2015 Elsevier B.V. All rights reserved. Nutrition, Metabolism & Cardiovascular Diseases (2015) xx,1e6 Available online at www.sciencedirect.com Nutrition, Metabolism & Cardiovascular Diseases journal homepage: www.elsevier.com/locate/nmcd