Is depression a risk factor for diabetic foot ulcers? 11-years follow-up of the Nord-Trøndelag Health Study (HUNT) Marjolein M. Iversen a, b, ⁎, Grethe S. Tell c , Birgitte Espehaug a , Kristian Midthjell d , Marit Graue a , Berit Rokne c , Line Iden Berge c , Truls Østbye e a Faculty of Health and Social Sciences, Bergen University College, PO Box 7030, N-5020 Bergen, Norway b Department of Endocrinology, Stavanger University Hospital, PO Box 8100, 4068 Stavanger, Norway c Department of Global Public Health and Primary Care, University of Bergen, PO Box 7800, 5020 Bergen, Norway d The HUNT Research Center, Norwegian University of Science and Technology, Forskningsveien 2, 7600 Levanger, Norway e Duke Global Health Institute, Duke University, Box 90519 Durham, NC 27708, USA abstract article info Article history: Received 13 May 2014 Received in revised form 6 September 2014 Accepted 8 September 2014 Available online xxxx Keywords: Diabetes Depression Risk factor Foot ulcer Cohort study Norway Aim: To prospectively examine whether depressive symptoms increase the risk of diabetes and a diabetic foot ulcer. Methods: The Nord-Trøndelag Health Study (HUNT) is a community-based longitudinal study. The Hospital Anxiety and Depression Scale (HADS-D subscale) assessed depressive symptoms. We followed individuals with complete HADS-D data from HUNT2 (1995–97) and assessed whether they reported diabetes with or without a history of diabetic foot ulcer (DFU) in HUNT3 (2006–08) (n = 36,031). Logistic regression was used to investigate the effect of depressive symptoms on subsequent development of diabetes and of DFU. Results: Unadjusted odds for reporting diabetes at follow-up was higher among individuals who reported a HADS-D score ≥ 8 at baseline (OR 1.30 95% CI, 1.07–1.57) than among those reporting a lower score. After adjusting for age, gender and BMI, this association was no longer significant. The odds of developing a DFU was almost two-fold (OR = 1.95 95% CI, 1.02–3.74) for those reporting a HADS-D score of 8–10, and 3-fold (OR = 3.06 95% CI, 1.24– 7.54) for HADS-D scores ≥ 11, compared to HADS-D scores b 8, after adjusting for age, gender and serum glucose. Conclusions: Symptoms of depression at baseline are associated with an increased risk of a diabetic foot ulcer in a dose response manner during this 11-year follow-up. © 2014 Elsevier Inc. All rights reserved. 1. Introduction Individuals with depression have a moderately increased risk of developing type 2 diabetes (Knol et al., 2006). The reverse is also found (Demakakos, Pierce, & Hardy, 2010; Nouwen et al., 2010; Rotella & Mannucci, 2013), individuals with diabetes have an increased risk of developing depression, suggesting a bidirectional association between the two conditions (Chen, Chan, Chen, Ko, & Li, 2013; Golden et al., 2008; Mezuk, Eaton, Albrecht, & Golden, 2008; Pan et al., 2010). Depression is commonly associated with suboptimal HbA 1c (Lustman et al., 2000) and adverse health outcomes including an increased all-cause and cardiovascular mortality (Dooren, 2013). Individuals with both diabetes and depression are at increased risk of developing clinically relevant micro- and macrovascular complica- tions relative to individuals with diabetes but without depression (Lin et al., 2010). The effect of combined depression and diabetes on the development of complications has been shown to be multiplicative in older Mexican Americans (Black, Markides, & Ray, 2003). Other studies, mostly with relatively short observation periods (Black et al., 2003; Golden et al., 2008; Gonzalez et al., 2010; Lin et al., 2010; Williams et al., 2010) have also found that major depression is an independent risk factor for the development of foot ulcers among persons with diabetes (Gonzalez et al., 2010; Williams et al., 2010). Although depression has been associated with both diabetes and diabetic foot ulcers (DFU), no large community-based cohort studies of European Caucasians have examined the association between depression and these outcomes over an extended time-period. The purpose of this analysis was to examine whether symptoms of depression increases the risk of developing diabetes, and subsequent- ly the risk of developing a DFU during an 11 year follow-up. The HUNT Study (HUNT2) afforded an excellent opportunity to investigate these research questions in a large, population-based sample of Caucasian men and women with and without diabetes at baseline. 2. Subjects: materials and methods 2.1. Study setting and sample The Nord-Trøndelag Health Study (HUNT) is a community-based study including residents of Nord-Trøndelag county aged ≥20 years Journal of Diabetes and Its Complications xxx (2014) xxx–xxx Conflict of Interest: The authors declare that they have no conflict of interests. ⁎ Corresponding author at: Centre of Evidence Based Practice, Bergen University College, PO Box 7030, N-5020 Bergen, Norway. Tel.: +47 55 58 55 18; fax: +47 55 58 77 89. E-mail address: marjolein.iversen@hib.no (M.M. Iversen). http://dx.doi.org/10.1016/j.jdiacomp.2014.09.006 1056-8727/© 2014 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Journal of Diabetes and Its Complications journal homepage: WWW.JDCJOURNAL.COM Please cite this article as: Iversen, M.M., et al., Is depression a risk factor for diabetic foot ulcers? 11-years follow-up of the Nord-Trøndelag Health Study (HUNT), Journal of Diabetes and Its Complications (2014), http://dx.doi.org/10.1016/j.jdiacomp.2014.09.006