title: Bipolar disorder and diabetes mellitus: evidence for disease-modifying effects and treatment implications.
abstract: BACKGROUND
  Bipolar disorder refers to a group of chronic psychiatric disorders of mood and energy levels. While dramatic psychiatric symptoms dominate the acute phase of the diseases, the chronic course is often determined by an increasing burden of co-occurring medical conditions. High rates of diabetes mellitus in patients with bipolar disorder are particularly striking, yet unexplained. Treatment and lifestyle factors could play a significant role, and some studies also suggest shared pathophysiology and risk factors.
  
  
  OBJECTIVE
  In this systematic literature review, we explored data around the relationship between bipolar disorder and diabetes mellitus in recently published population-based cohort studies with special focus on the elderly.
  
  
  METHODS
  A systematic search in the PubMed database for the combined terms "bipolar disorder" AND "elderly" AND "diabetes" in papers published between January 2009 and December 2015 revealed 117 publications; 7 studies were large cohort studies, and therefore, were included in our review.
  
  
  RESULTS
  We found that age- and gender- adjusted risk for diabetes mellitus was increased in patients with bipolar disorder and vice versa (odds ratio range between 1.7 and 3.2).
  
  
  CONCLUSIONS
  Our results in large population-based cohort studies are consistent with the results of smaller studies and chart reviews. Even though it is likely that heterogeneous risk factors may play a role in diabetes mellitus and in bipolar disorder, growing evidence from cell culture experiments and animal studies suggests shared disease mechanisms. Furthermore, disease-modifying effects of bipolar disorder and diabetes mellitus on each other appear to be substantial, impacting both treatment response and outcomes.
  
  
  CONCLUSIONS
  The risk of diabetes mellitus in patients with bipolar disorder is increased. Our findings add to the growing literature on this topic. Increasing evidence for shared disease mechanisms suggests new disease models that could explain the results of our study. A better understanding of the complex relationship between bipolar disorder and diabetes mellitus could lead to novel therapeutic approaches and improved outcomes.
authors.affiliation: David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA, 90095, USA.
authors.forename: Ellen F
authors.initials: EF
authors.lastname: Charles
authors.affiliation: Center for Global Health, Division of Translational Informatics, Department of Internal Medicine, University of New Mexico Health Sciences Center, University of New Mexico, MSC10 5550, Albuquerque, NM, 87131, USA.
authors.forename: Christophe G
authors.initials: CG
authors.lastname: Lambert
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, University of California, 695 Charles E. Young Drive South, Box 951761, Los Angeles, CA, 90095, USA. Berit.Kerner@uni-wh.de.|Fakultät für Gesundheit, Private Universität Witten/Herdecke, Alfred-Herrhausen-Straße 50, 58448, Witten, Germany. Berit.Kerner@uni-wh.de.
authors.forename: Berit
authors.initials: B
authors.lastname: Kerner
keywords: Bipolar disorder; Cohort studies; Diabetes; Epidemiology; Evidence; Pathophysiology