Risk factors associated with mortality among individuals with type 2 diabetes and depression across two cohorts

in European Journal of Endocrinology
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  • 1 Department of Affective Disorders, Aarhus University Hospital – Psychiatry, Aarhus, Denmark
  • | 2 Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  • | 3 DD2, Steno Diabetes Centre Odense, Odense University Hospital, Odense, Denmark
  • | 4 The Department of Clinical Research, University of Southern Denmark, Odense, Denmark
  • | 5 Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
  • | 6 Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark

Correspondence should be addressed to C Rohde; Email: chrroh@rm.dk
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Objective

Depression has been linked to excess mortality in individuals with type 2 diabetes, but it remains unclear what drives this association. We examined if the association depends on unhealthy lifestyle and medical comorbidity.

Methods

We followed a clinically recruited cohort of Danish people with type 2 diabetes (n  = 8175) with fine-grained clinical information and a population-wide register-based cohort of Danish individuals with HbA1c-defined type 2 diabetes (n  = 87 500) representing everyday clinical practice. Antidepressant drug use prior to the onset of type 2 diabetes was used as a proxy for preexisting depression. In both cohorts, we first estimated the association between depression and 5-year mortality following type 2 diabetes, using a Cox proportional hazards model, yielding sex- and age-adjusted mortality rate ratios (MRRs). We subsequently examined how further adjustment for markers of unhealthy lifestyle (smoking, physical inactivity, obesity, alcohol abuse, and marital status) and medical comorbidity affected the association.

Results

Preexisting depression was associated with an approximately 50% increased age- and sex-adjusted all-cause mortality rate in both the clinically recruited- (5-year MRR: 1.46; 95% CI: 1.12–1.90) and the register-based type 2 diabetes cohort (5-year MRR: 1.51; 95% CI: 1.45–1.57). The excess mortality associated with depression almost disappeared when the analyses were adjusted for unhealthy lifestyle and medical comorbidity in both the clinically recruited- (MRR: 1.05; 95% CI: 0.72–1.52) and the register-based type 2 diabetes cohort (MRR: 1.14, 95% CI: 1.09–1.19).

Conclusions

A large fraction of the excess mortality associated with preexisting depression in type 2 diabetes is attributable to the unhealthy lifestyle and medical comorbidity accompanying depression.

Supplementary Materials

 

     European Society of Endocrinology

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  • 1

    Lindekilde N, Scheuer SH, Diaz LJ, Rubin KH, Plana-Ripoll O, Henriksen JE, Lasgaard M, Andersen GS, Pouwer F. Risk of developing type 2 diabetes in individuals with a psychiatric disorder: a nationwide register-based cohort study. Diabetes Care 2022 45 724733. (https://doi.org/10.2337/dc21-1864)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2

    Lindekilde N, Scheuer SH, Rutters F, Knudsen L, Lasgaard M, Rubin KH, Henriksen JE, Kivimäki M, Andersen GS, Pouwer F. Prevalence of type 2 diabetes in psychiatric disorders: an umbrella review with meta-analysis of 245 observational studies from 32 systematic reviews. Diabetologia 2022 65 440456. (https://doi.org/10.1007/s00125-021-05609-x)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3

    Semenkovich K, Brown ME, Svrakic DM, Lustman PJ. Depression in type 2 diabetes mellitus: prevalence, impact, and treatment. Drugs 2015 75 577587. (https://doi.org/10.1007/s40265-015-0347-4)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4

    Rohde C, Schmitz N, Thomsen RW, Østergaard SD. Incident psychopharmacological treatment and psychiatric hospital contact in individuals with newly developed type 2 diabetes – a register-based cohort study. Acta Neuropsychiatrica 2021 33 7284. (https://doi.org/)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5

    Hayashino Y, Okamura S, Tsujii S, Ishii H & Diabetes Distress and Care Registry at Tenri Study Group. The joint association of diabetes distress and depressive symptoms with all-cause mortality in Japanese individuals with type 2 diabetes: a prospective cohort study (Diabetes Distress and Care Registry in Tenri [DDCRT 20]). Diabetologia 2020 63 25952604. (https://doi.org/10.1007/s00125-020-05274-6)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

    Farooqi A, Khunti K, Abner S, Gillies C, Morriss R, Seidu S. Comorbid depression and risk of cardiac events and cardiac mortality in people with diabetes: a systematic review and meta-analysis. Diabetes Research and Clinical Practice 2019 156 107816. (https://doi.org/10.1016/j.diabres.2019.107816)

    • Search Google Scholar
    • Export Citation
  • 7

    Naicker K, Johnson JA, Skogen JC, Manuel D, Øverland S, Sivertsen B, Colman I. Type 2 diabetes and comorbid symptoms of depression and anxiety: longitudinal associations with mortality risk. Diabetes Care 2017 40 352358. (https://doi.org/10.2337/dc16-2018)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    van Dooren FE, Nefs G, Schram MT, Verhey FR, Denollet J, Pouwer F. Depression and risk of mortality in people with diabetes mellitus: a systematic review and meta-analysis. PLoS ONE 2013 8 e57058. (https://doi.org/10.1371/journal.pone.0057058)

    • Search Google Scholar
    • Export Citation
  • 9

    Majd M, Saunders EFH, Engeland CG. Inflammation and the dimensions of depression: a review. Frontiers in Neuroendocrinology 2020 56 100800. (https://doi.org/10.1016/j.yfrne.2019.100800)

    • Search Google Scholar
    • Export Citation
  • 10

    Krass I, Schieback P, Dhippayom T. Adherence to diabetes medication: a systematic review. Diabetic Medicine 2015 32 725737. (https://doi.org/10.1111/dme.12651)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. New England Journal of Medicine 2008 358 580591. (https://doi.org/10.1056/NEJMoa0706245)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Svensson E, Baggesen LM, Johnsen SP, Pedersen L, Nørrelund H, Buhl ES, Haase CL, Thomsen RW. Early glycemic control and magnitude of HbA(1c) reduction predict cardiovascular events and mortality: population-based cohort study of 24,752 metformin initiators. Diabetes Care 2017 40 800807. (https://doi.org/10.2337/dc16-2271)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Rohde C, Knudsen JS, Schmitz N, Østergaard SD, Thomsen RW. The impact of hospital-diagnosed depression or use of antidepressants on treatment initiation, adherence and HbA(1c)/LDL target achievement in newly diagnosed type 2 diabetes. Diabetologia 2021 64 361374. (https://doi.org/)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Hoogendoorn CJ, Schechter CB, Llabre MM, Walker EA, Gonzalez JS. Distress and type 2 diabetes self-care: putting the pieces together. Annals of Behavioral Medicine 2021 55 938948. (https://doi.org/10.1093/abm/kaaa070)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Shrestha M, Ng A, Al-Ghareeb A, Alenazi F, Gray R. Association between subthreshold depression and self-care behaviors in people with type 2 diabetes: a systematic review of observational studies. Systematic Reviews 2020 9 45. (https://doi.org/10.1186/s13643-020-01302-z)

    • Search Google Scholar
    • Export Citation
  • 16

    Van Buren DJ, Wilfley DE, Marcus MD, Anderson B, Abramson NW, Berkowitz R, Ievers-Landis C, Trief P, Yasuda P & Hirst K et al.Depressive symptoms and glycemic control in youth with type 2 diabetes participating in the TODAY clinical trial. Diabetes Research and Clinical Practice 2018 135 8587. (https://doi.org/10.1016/j.diabres.2017.11.008)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Ismail K, Moulton CD, Winkley K, Pickup JC, Thomas SM, Sherwood RA, Stahl D, Amiel SA. The association of depressive symptoms and diabetes distress with glycaemic control and diabetes complications over 2 years in newly diagnosed type 2 diabetes: a prospective cohort study. Diabetologia 2017 60 20922102. (https://doi.org/10.1007/s00125-017-4367-3)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    Steffen A, Nübel J, Jacobi F, Bätzing J, Holstiege J. Mental and somatic comorbidity of depression: a comprehensive cross-sectional analysis of 202 diagnosis groups using German nationwide ambulatory claims data. BMC Psychiatry 2020 20 142. (https://doi.org/10.1186/s12888-020-02546-8)

    • Search Google Scholar
    • Export Citation
  • 19

    Koyanagi A, Kohler-Forsberg O, Benros ME, Munk Laursen T, Haro JM, Nordentoft M, Hjorthoj C. Mortality in unipolar depression preceding and following chronic somatic diseases. Acta Psychiatrica Scandinavica 2018 138 500508. (https://doi.org/10.1111/acps.12899)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20

    Schuch FB, Vancampfort D, Firth J, Rosenbaum S, Ward PB, Silva ES, Hallgren M, Ponce De Leon A, Dunn AL & Deslandes AC et al.Physical activity and incident depression: a meta-analysis of prospective cohort studies. American Journal of Psychiatry 2018 175 631648. (https://doi.org/10.1176/appi.ajp.2018.17111194)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Weinberger AH, Kashan RS, Shpigel DM, Esan H, Taha F, Lee CJ, Funk AP, Goodwin RD. Depression and cigarette smoking behavior: a critical review of population-based studies. American Journal of Drug and Alcohol Abuse 2017 43 416431. (https://doi.org/10.3109/00952990.2016.1171327)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22

    Bonnet F, Irving K, Terra JL, Nony P, Berthezène F, Moulin P. Anxiety and depression are associated with unhealthy lifestyle in patients at risk of cardiovascular disease. Atherosclerosis 2005 178 339344. (https://doi.org/10.1016/j.atherosclerosis.2004.08.035)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23

    Zhang YB, Pan XF, Chen J, Cao A, Xia L, Zhang Y, Wang J, Li H, Liu G, Pan A. Combined lifestyle factors, all-cause mortality and cardiovascular disease: a systematic review and meta-analysis of prospective cohort studies. Journal of Epidemiology and Community Health 2021 75 9299. (https://doi.org/10.1136/jech-2020-214050)

    • Search Google Scholar
    • Export Citation
  • 24

    Katon WJ, Rutter C, Simon G, Lin EH, Ludman E, Ciechanowski P, Kinder L, Young B, Von Korff M. The association of comorbid depression with mortality in patients with type 2 diabetes. Diabetes Care 2005 28 26682672. (https://doi.org/10.2337/diacare.28.11.2668)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Zhang X, Norris SL, Gregg EW, Cheng YJ, Beckles G, Kahn HS. Depressive symptoms and mortality among persons with and without diabetes. American Journal of Epidemiology 2005 161 652660. (https://doi.org/10.1093/aje/kwi089)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    Egede LE, Nietert PJ, Zheng D. Depression and all-cause and coronary heart disease mortality among adults with and without diabetes. Diabetes Care 2005 28 13391345. (https://doi.org/10.2337/diacare.28.6.1339)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    Wu CS, Hsu LY, Wang SH. Association of depression and diabetes complications and mortality: a population-based cohort study. Epidemiology and Psychiatric Sciences 2020 29 e96. (https://doi.org/10.1017/S2045796020000049)

    • Search Google Scholar
    • Export Citation
  • 28

    Jung I, Kwon H, Park SE, Han KD, Park YG, Kim YH, Rhee EJ, Lee WY. Increased risk of cardiovascular disease and mortality in patients with diabetes and coexisting depression: a nationwide population-based cohort study. Diabetes and Metabolism Journal 2021 45 379389. (https://doi.org/10.4093/dmj.2020.0008)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Christensen DH, Nicolaisen SK, Berencsi K, Beck-Nielsen H, Rungby J, Friborg S, Brandslund I, Christiansen JS, Vaag A & Sørensen HT et al.Danish Centre for Strategic Research in Type 2 Diabetes (DD2) project cohort of newly diagnosed patients with type 2 diabetes: a cohort profile. BMJ Open 2018 8 e017273. (https://doi.org/10.1136/bmjopen-2017-017273)

    • Search Google Scholar
    • Export Citation
  • 30

    Thomsen RW, Friborg S, Nielsen JS, Schroll H, Johnsen SP. The Danish Centre for Strategic Research in Type 2 Diabetes (DD2): organization of diabetes care in Denmark and supplementary data sources for data collection among DD2 study participants. Clinical Epidemiology 2012 4 1519. (https://doi.org/10.2147/CLEP.S30082)

    • Search Google Scholar
    • Export Citation
  • 31

    Pedersen CB The Danish civil registration system. Scandinavian Journal of Public Health 2011 39 (7 S upplement) 2225. (https://doi.org/10.1177/1403494810387965)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32

    Grann AF, Erichsen R, Nielsen AG, Frøslev T, Thomsen RW. Existing data sources for clinical epidemiology: the Clinical Laboratory Information System (LABKA) Research Database at Aarhus University, Denmark. Clinical Epidemiology 2011 3 133138. (https://doi.org/10.2147/CLEP.S17901)

    • Search Google Scholar
    • Export Citation
  • 33

    Kildemoes HW, Sørensen HT, Hallas J. The Danish national prescription registry. Scandinavian Journal of Public Health 2011 39 (7 S upplement) 3841. (https://doi.org/10.1177/1403494810394717)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34

    Lynge E, Sandegaard JL, Rebolj M. The Danish national patient register. Scandinavian Journal of Public Health 2011 39 (7 S upplement) 3033. (https://doi.org/10.1177/1403494811401482)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35

    Musliner KL, Liu X, Gasse C, Christensen KS, Wimberley T, Munk-Olsen T. Incidence of medically treated depression in Denmark among individuals 15–44 years old: a comprehensive overview based on population registers. Acta Psychiatrica Scandinavica 2019 139 548557. (https://doi.org/10.1111/acps.13028)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36

    Thygesen SK, Christiansen CF, Christensen S, Lash TL, Sørensen HT. The predictive value of ICD-10 diagnostic coding used to assess Charlson comorbidity index conditions in the population-based Danish National Registry of patients. BMC Medical Research Methodology 2011 11 83. (https://doi.org/10.1186/1471-2288-11-83)

    • Search Google Scholar
    • Export Citation
  • 37

    Lash TL, Fox MP, Fink AK. Applying Quantitative Bias Analysis to Epidemiologic Data. Springer Publishing Company, Incorporated, 2009.

  • 38

    Reeves GC, Alhurani AS, Frazier SK, Watkins JF, Lennie TA, Moser DK. The association of comorbid diabetes mellitus and symptoms of depression with all-cause mortality and cardiac rehospitalization in patients with heart failure. BMJ Open Diabetes Research and Care 2015 3 e000077. (https://doi.org/10.1136/bmjdrc-2014-000077)

    • Search Google Scholar
    • Export Citation
  • 39

    Belvederi Murri M, Folesani F, Zerbinati L, Nanni MG, Ounalli H, Caruso R, Grassi L. Physical activity promotes health and reduces cardiovascular mortality in depressed populations: a literature overview. International Journal of Environmental Research and Public Health 2020 17 5545. (https://doi.org/10.3390/ijerph17155545)

    • Search Google Scholar
    • Export Citation
  • 40

    Pirie K, Peto R, Reeves GK, Green J, Beral V. The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK. Lancet 2013 381 133141. (https://doi.org/10.1016/S0140-6736(1261720-6)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41

    Machado MO, Veronese N, Sanches M, Stubbs B, Koyanagi A, Thompson T, Tzoulaki I, Solmi M, Vancampfort D & Schuch FB et al.The association of depression and all-cause and cause-specific mortality: an umbrella review of systematic reviews and meta-analyses. BMC Medicine 2018 16 112. (https://doi.org/10.1186/s12916-018-1101-z)

    • Search Google Scholar
    • Export Citation
  • 42

    Yuan S, Larsson SC. An atlas on risk factors for type 2 diabetes: a wide-angled Mendelian randomisation study. Diabetologia 2020 63 23592371. (https://doi.org/10.1007/s00125-020-05253-x)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43

    Xuan L, Zhao Z, Jia X, Hou Y, Wang T, Li M, Lu J, Xu Y, Chen Y & Qi L et al.Type 2 diabetes is causally associated with depression: a Mendelian randomization analysis. Frontiers of Medicine 2018 12 678687. (https://doi.org/10.1007/s11684-018-0671-7)

    • Crossref
    • Search Google Scholar
    • Export Citation