OR25-4 Patients with Diabetes Mellitus Diagnosed with Addison´s Disease Have a Markedly Increased Additional Risk of Death

Program: Abstracts - Orals, Poster Previews, and Posters
Session: OR25-Cushing Syndrome and Primary Adrenal Disorders
Clinical/Translational
Sunday, April 3, 2016: 11:45 AM-1:15 PM
Presentation Start Time: 12:30 PM
BR East (BCEC)
Dimitrios Chantzichristos*1, Anders Persson2, Björn Eliasson3, Mervete Miftaraj2, Stefan Franzén2, Ragnhildur Bergthorsdottir4, Soffia Gudbjörnsdottir3, Ann-Marie Svensson2 and Gudmundur Johannsson1
1Institute of Medicine at Sahlgrenska Academy, University of Gothenburg and The Department of Endocrinology-Diabetes-Metabolism, Sahlgrenska University Hospital, Gothenburg, Sweden, 2National Diabetes Register, Centre of Registers, Gothenburg, Sweden, 3Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, The Department of Endocrinology-Diabetes-Metabolism, Sahlgrenska University Hospital and National Diabetes Register, Centre of Registers, Gothenburg, Sweden, 4Sahlgrenska University Hospital, Gothenburg, Sweden
Background

Increased mortality rate has been observed in both patients with diabetes mellitus (DM) and in patients with Addison’s disease (AD). The excess mortality among patients with DM is up to 3.5 times in patients with type 1 DM (1) (2) and nearly two-fold in patients with AD (3) (4) compared to the background population. Approximately 12% of patients with AD have also type 1 DM (5), whereas the frequency of type 2 DM is not known. Having both DM and AD is therefore a rare combination and difficult to manage due to the contrasting effects of insulin and cortisol on glucose metabolism.

Hypothesis

Our hypothesis was that DM patients diagnosed with AD have an additional increased risk of death.

Study design

In this observational cohort study patients having first DM (type 1 or 2) and then AD were identified using both the Swedish National Diabetes Register (NDR) and the National Inpatient Register between Jan 1st, 1996 and Dec 31th, 2012. For each patient five controls matched for sex, year of birth, type of DM, year when DM was diagnosed and period of time in NDR were selected in NDR. Causes of death data were obtained for both groups during the same time period from the Swedish Register for Cause-Specific Mortality.

Results

A total of 1355 patients were identified; 226 patients having DM (type 1 or 2) and AD and 1129 matched DM controls.  At baseline, patients with DM+AD and patients with DM had a mean (±SD) age of 52.3 (±20.1) and 54.1 (±18.9) years, respectively. Forty seven % in each group were women and 65% had type 1 DM. Mean (±SD) HbA1c at baseline was 7.8% (±3.5%) or 62.0 (±14.7) mmol/mol for the DM+AD group and 7.6% (±3.5%) or 59.6 (±14.7) mmol/mol for the DM controls. 

Overall, 64 out of 226 patients (28%) with DM+AD died, as compared with 112 of 1129 controls (10%). The estimated relative risk increase (hazard ratio) in overall mortality in the DM+AD group was therefore 3.83 (95% confidence interval, 2.80 to 5.24) compared with the DM controls. Type of DM and gender had no significant impact on the relative mortality risk. The most common cause of death in both groups was cardiovascular diseases (33% and 34%, respectively). The second most common cause of death in DM+AD patients was DM and its related complications (23%) and cancer in the DM group (29%). Death from cancer in the DM+AD group occurred in 14% of patients.

Conclusions

The main outcome of this study is that patients with both DM (both type 1 or 2) and AD have an almost 4-fold increased risk of death compared to matched controls with DM, despite similar glycemic control at baseline. This additional risk of death confirms the complex clinical picture in patients with DM and AD and suggests that improvement in management is needed.

(1) Lind M et al. Glycemic Control and Excess Mortality in Type 1 Diabetes. New England Journal of Medicine. 2014;371(21):1972-82. (2) Tancredi M et al. Excess Mortality among Persons with Type 2 Diabetes. New England Journal of Medicine. 2015;373(18):1720-32. (3) Bergthorsdottir R et al. Premature Mortality in Patients with Addison’s Disease: A Population-Based Study. The Journal of Clinical Endocrinology & Metabolism. 2006;91(12):4849-53. (4) Bensing S et al. Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency. Clinical endocrinology. 2008;69(5):697-704. (5) Erichsen MM et al. Clinical, Immunological, and Genetic Features of Autoimmune Primary Adrenal Insufficiency: Observations from a Norwegian Registry. The Journal of Clinical Endocrinology & Metabolism. 2009;94(12):4882-90.

Nothing to Disclose: DC, AP, BE, MM, SF, RB, SG, AMS, GJ

*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting/pr-resources-for-endo