Epidemiologic and clinical studies have established that Major Depression (MD) often co-occurs with medical conditions in later life, including Type 2 Diabetes Mellitus (T2DM). The relationship between MD and T2DM is likely bi-directional. Indeed, there is consistent evidence from population-based cohort studies that MD is associated with increased risk of and mortality from T2DM, and that T2DM is associated with onset and recurrence of MD. However, prospective studies cannot definitively distinguish whether MD is a unique risk factor for T2DM, or if this phenomenon is due to a common factor shared by both MD and T2DM such as genetic liability or environmental context. The goal of this study is to utilize a large, population-based sample to prospectively investigate the dynamic roles of the contextual environment, familial genetic risk, and their interplay on the development of comorbid T2DM and MD. Data come from Swedish national multi-generational inpatient, outpatient, and pharmacy registries, which have been linked to a nationally-representative sample of primary care centers in Sweden representing over 1 million individuals, collected since 2001. These data have been geocoded to neighborhood-level physical and social contextual environment data. This research utilizes multi-level longitudinal and structural equation modeling to investigate the specific aims, which are to: 1) investigate the association between contextual environmental characteristics (e.g., neighborhood socioeconomic deprivation, crime, proximity to parks or fast food restaurants, social disorganization) and comorbid T2DM and MD;2) examine the familial genetic contributions to the comorbidity between T2DM and MD;and 3) examine the interplay between genetic risk and the contextual environment on development of T2DM and MD. Genetically-informative designs provide a unique opportunity for exploring competing etiologic models of the relationships between the contextual environment and genetic risk for comorbid T2DM-MD. Using family designs we can estimate an individual's genetic liability for T2DM and MD, and thus conduct a more direct and unbiased examination of the contextual environmental factors that contribute to this comorbidity. This application aims to explicitly incorporate contextual environmental factors into our understanding of how genetic liability is expressed and moderated by the environment, and the findings will provide insight into the broad etiologic mechanisms of how environmental context influences risk of T2DM and MD. Public health significance: The research plan addresses the intersection of two common and debilitating health conditions, T2DM and MD, that are leading sources of healthcare costs and public health burden in the US and globally. Understanding the dynamic roles that genetic risk, environmental context, and their interaction play in development of comorbid T2DM and MD will inform innovative programs that reflect this complexity in order to more effectively promote public health and guide clinical care.

Public Health Relevance

The goal of this study is to utilize a large, population-based sample to prospectively investigate the dynamic roles of the contextual environment, familial genetic risk, and their interplay on the development of comorbid type 2 diabetes and depression. The aims are to: 1) investigate the association between contextual environmental characteristics and comorbid diabetes and depression;2) examine the genetic contributions to the comorbidity between diabetes and depression;and 3) examine the interplay between genetic risk and the contextual environment on development of diabetes and depression. Understanding the dynamic roles that genetic risk, environmental context, and their interaction play in development of comorbid diabetes and depression will inform innovative programs that reflect this complexity in order to more effectively promote public health and guide clinical care.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DK096375-02
Application #
8638003
Study Section
Special Emphasis Panel (ZRG1-SSPS-H (09))
Program Officer
Savage, Peter J
Project Start
2013-03-18
Project End
2015-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
2
Fiscal Year
2014
Total Cost
$191,044
Indirect Cost
$35,372
Name
Virginia Commonwealth University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Engeda, J; Mezuk, B; Ratliff, S et al. (2013) Association between duration and quality of sleep and the risk of pre-diabetes: evidence from NHANES. Diabet Med 30:676-80
Mezuk, Briana; Chaikiat, Asa; Li, Xinjun et al. (2013) Depression, neighborhood deprivation and risk of type 2 diabetes. Health Place 23:63-9
Mezuk, Briana; Chen, Yiping; Yu, Canqing et al. (2013) Depression, anxiety, and prevalent diabetes in the Chinese population: findings from the China Kadoorie Biobank of 0.5 million people. J Psychosom Res 75:511-7