Current Psychiatry Reports

, Volume 14, Issue 1, pp 8–14 | Cite as

A Review of the Association Between Depression and Insulin Resistance: Pitfalls of Secondary Analyses or a Promising New Approach to Prevention of Type 2 Diabetes?



We review the validity of the evidence for an association between depression and the risk of insulin resistance (IR). We describe the potentially plausible biological and behavioral mechanisms that explain how depression increases the risk of IR and consequent overt diabetes. We have identified gaps in the literature to guide future research. Evidence for bidirectional associations between depression and IR is inconsistent. Results showing positive associations between depression and IR are derived from cross-sectional studies, whereas negative findings are typically reported in cohort studies. On the other hand, tentative trial evidence suggests that the effective treatment of depression can improve IR, and that lifestyle programs improve IR and reduce depressive symptoms. These emerging themes could lead to potential new multidisciplinary approaches to preventing diabetes.


Diabetes Depression Insulin resistance (IR) Hypothalamic-pituitary-adrenal (HPA) axis Homeostatic model assessment (HOMA) Type 2 diabetes Prevention 


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    World Health Organization. The global burden of disease: 2004 Update. WHO Press; 2008.Google Scholar
  2. 2.
    Egede LE, Zheng D, Simpson K. Comorbid depression is associated with increased health care use and expenditures in individuals with diabetes. Diabetes Care. 2002;25(3):464–70.PubMedCrossRefGoogle Scholar
  3. 3.
    Abdul-Ghani MA, Tripathy D, DeFronzo RA. Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diabetes Care. 2006;29(5):1130–9.PubMedCrossRefGoogle Scholar
  4. 4.
    ••Nouwen A, Nefs G, Caramlau I, et al. Prevalence of depression in individuals with impaired glucose metabolism or undiagnosed diabetes. Diabetes Care. 2011;34(3):752–762. This review shows that the prevalence of depression is similar in people with pre-diabetes compared with those with normal fasting plasma glucose and undiagnosed diabetes, but higher in people with known diabetes.PubMedCrossRefGoogle Scholar
  5. 5.
    Knol MJ, Twisk JW, Beekman AT, et al. Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis. Diabetologia. 2006;49(5):837–45.PubMedCrossRefGoogle Scholar
  6. 6.
    Mezuk B, Eaton WW, Albrecht S, Golden SH. Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care. 2008;31(12):2383–90.PubMedCrossRefGoogle Scholar
  7. 7.
    Lawlor DA, Smith GD, Ebrahim S. British Women’s Heart and Health study: association of insulin resistance with depression: cross sectional findings from the British Women’s Heart and Health study. BMJ. 2003;327(7428):1383–4.PubMedCrossRefGoogle Scholar
  8. 8.
    Timonen M, Rajala U, Jokelainen J, et al. Depressive symptoms and insulin resistance in young adult males: results from the Northern Finland 1966 birth cohort. Mol Psychiatry. 2006;11(10):929–33.PubMedCrossRefGoogle Scholar
  9. 9.
    Timonen M, Salmenkaita I, Jokelainen J, et al. Insulin resistance and depressive symptoms in young adult males: findings from Finnish military conscripts. Psychosom Med. 2007;69(8):723–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Adriaanse MC, Dekker JM, Nijpels G, et al. Associations between depressive symptoms and insulin resistance: the Hoorn study. Diabetologia. 2006;49(12):2874–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Pan A, Ye X, Franco OH, et al. Insulin resistance and depressive symptoms in middle-aged and elderly Chinese: findings from the Nutrition and Health of Aging Population in China Study. J Affect Disord. 2008;109(1–2):75–82.PubMedCrossRefGoogle Scholar
  12. 12.
    Holt RI, Phillips DI, Jameson KA, et al. The relationship between depression and diabetes mellitus: findings from the Hertfordshire cohort study. Diabet Med. 2009;26(6):641–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Pearson S, Schmidt M, Patton G, et al. Depression and insulin resistance: cross sectional associations in young adults. Diabetes Care. 2010;33(5):1128–33.PubMedCrossRefGoogle Scholar
  14. 14.
    Golden SH, Lee HB, Schreiner PJ, et al. Depression and type 2 diabetes mellitus: the multiethnic study of atherosclerosis. Psychosom Med. 2007;69(6):529–36.PubMedCrossRefGoogle Scholar
  15. 15.
    Roos C, Lidfeldt J, Agardh CD, et al. Insulin resistance and self-rated symptoms of depression in Swedish women with risk factors for diabetes: the Women’s Health in the Lund Area study. Metab Clin Exp. 2007;56(6):825–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Shen Q, Bergquist-Beringer S, Sousa VD. Major depressive disorder and insulin resistance in nondiabetic young adults in the United States: the National Health and Nutrition Examination Survey, 1999–2002. Biological Research for Nursing 2010. [Epub ahead of print].Google Scholar
  17. 17.
    Lawlor DA, Ben-Shlomo Y, Ebrahim S, et al. Insulin resistance and depressive symptoms in middle aged men: findings from the Caerphilly prospective cohort study. BMJ. 2005;330(7493):705–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Everson-Rose SA, Meyer PM, Powell LH, et al. Depressive symptoms, insulin resistance, and risk of diabetes in women at midlife. Diabetes Care. 2004;27(12):2856–62.PubMedCrossRefGoogle Scholar
  19. 19.
    Chiba M, Suzuki S, Hinokio Y, et al. Tyrosine hydroxylase gene microsatellite polymorphism associated with insulin resistance in depressive disorder. Metab Clin Exp. 2000;49(9):1145–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Hung YJ, Hsieh CH, Chen YJ, et al. Insulin sensitivity, proinflammatory markers and adiponectin in young males with different subtypes of depressive disorder. Clin Endocrinol. 2007;67(5):784–9.CrossRefGoogle Scholar
  21. 21.
    Okamura F, Tashiro A, Utumi A, et al. Insulin resistance in patients with depression and its changes during the clinical course of depression: minimal model analysis. Metabolism. 2000;49(10):1255–160.PubMedCrossRefGoogle Scholar
  22. 22.
    Kauffman RP, Castracane VD, White DL, et al. Impact of the selective serotonin reuptake inhibitor citalopram on insulin sensitivity, leptin and basal cortisol secretion in depressed and non-depressed euglycemic women of reproductive age. Gynecol Endocrinol. 2005;21(3):129–37.PubMedCrossRefGoogle Scholar
  23. 23.
    Weber-Hamann B, Gilles M, Lederbogen F, et al. Improved insulin sensitivity in 80 nondiabetic patients with MDD after clinical remission in a double-blind, randomized trial of amitriptyline and paroxetine. J Clin Psychiatry. 2006;67(12):1856–61.PubMedCrossRefGoogle Scholar
  24. 24.
    Chen YC, Lin WW, Chen YJ, et al. Antidepressant effects on insulin sensitivity and proinflammatory cytokines in the depressed males. Mediators of Inflammation; 2010. [Epub 2010 May 18].Google Scholar
  25. 25.
    Atlantis E, Lange K, Goldney RD, et al. Specific medical conditions associated with clinically significant depressive symptoms in men. Soc Psychiatry Psychiatr Epidemiol 2010.Google Scholar
  26. 26.
    Barton DA, Dawood T, Lambert EA, et al. Sympathetic activity in major depressive disorder: identifying those at increased cardiac risk? J Hypertens. 2007;25:2117–24.PubMedCrossRefGoogle Scholar
  27. 27.
    Bao AM, Meynen G, Swaab DF. The stress system in depression and neurodegeneration: focus on the human hypothalamus. Brain Res Rev. 2008;57:531–53.PubMedCrossRefGoogle Scholar
  28. 28.
    Pizzi C, Manzoli L, Mancini S, Costa GM. Analysis of potential predictors of depression among coronary heart disease risk factors including heart rate variability, markers of inflammation, and endothelial function. Eur Heart J. 2008;29:1110-a–1117.CrossRefGoogle Scholar
  29. 29.
    Champeri Wand GS, Malhotra SS, et al. Biological basis of depression in adults with diabetes. Curr Diabetes Rep. 2010;10(6):396–405.CrossRefGoogle Scholar
  30. 30.
    Pizzi C, Mancini S, Angeloni L, et al. Effects of selective serotonin reuptake inhibitor therapy on endothelial function and inflammatory markers in patients with coronary heart disease. Clin Pharmacol Ther. 2009;86:527–32.PubMedCrossRefGoogle Scholar
  31. 31.
    Buhl ES, Jensen TK, Jessen N, et al. Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats. Am J Physiol Endocrinol Metab. 2010;298:E920–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Danese A, Pariante CM, Caspi A, et al. Childhood maltreatment predicts adult inflammation in a life-course study. Proc Natl Acad Sci USA. 2007;104(4):1319–24.PubMedCrossRefGoogle Scholar
  33. 33.
    Ismail K, Sloggett A, De Stavola B. Do common mental disorders increase cigarette smoking? Results from five waves of a population-based panel cohort study. Am J Epidemiol. 2000;152(7):651–7.PubMedCrossRefGoogle Scholar
  34. 34.
    •Luppino FS, de Wit LM, Bouvy PF, et al. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry. 2010;67:220–229. This systematic review showed for the first time bidirectional associations between obesity and depression, and provides support for the hypothesis that lifestyle behaviors (unhealthy eating and physical inactivity) mediate the association between depression and diabetes.PubMedCrossRefGoogle Scholar
  35. 35.
    Patton GC, Carlin JB, Coffey C, et al. Depression, anxiety, and smoking initiation: a prospective study over 3 years. Am J Public Health. 1998;88:1518–22.PubMedCrossRefGoogle Scholar
  36. 36.
    van Gool CH, Kempen GIJM, Penninx BWJH, et al. Relationship between changes in depressive symptoms and unhealthy lifestyles in late middle aged and older persons: results from the Longitudinal Aging Study Amsterdam. Age Ageing. 2003;32:81–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Patten SB, Williams JVA, Lavorato DH, Eliasziw M: A longitudinal community study of major depression and physical activity. General Hospital Psychiatry; 2009;31:571–575.Google Scholar
  38. 38.
    Matza LS, Revicki DA, Davidson JR, Stewart JW. Depression with atypical features in the National Comorbidity Survey: classification, description, and consequences. Arch Gen Psychiatry. 2003;60:817–26.PubMedCrossRefGoogle Scholar
  39. 39.
    Di Marzo V. The endocannabinoid system in obesity and type 2 diabetes. Diabetologia. 2008;51:1356–67.PubMedCrossRefGoogle Scholar
  40. 40.
    Drewnowski A. The real contribution of added sugars and fats to obesity. Epidemiol Rev. 2007;29:160–71.PubMedCrossRefGoogle Scholar
  41. 41.
    Alberti KG, Zimmet P, Shaw J. International Diabetes Federation: a consensus on type 2 diabetes prevention. Diabet Med. 2007;24:451–63.PubMedCrossRefGoogle Scholar
  42. 42.
    The Diabetes Prevention Program. Design and methods for a clinical trial in the prevention of type 2 diabetes. Diabetes Care. 1999;22:623–34.CrossRefGoogle Scholar
  43. 43.
    Gonzalez JS, Peyrot M, McCarl LA, et al. Depression and diabetes treatment nonadherence: a meta-analysis. Diabetes Care. 2008;31:2398–403.PubMedCrossRefGoogle Scholar
  44. 44.
    Gilbody S, Bower P, Fletcher J, et al. Collaborative care for depression: a cumulative meta-analysis and review of longer-term outcomes. Arch Intern Med. 2006;166:2314–21.PubMedCrossRefGoogle Scholar
  45. 45.
    Roy-Byrne P, Craske MG, Sullivan G, et al. Delivery of evidence-based treatment for multiple anxiety disorders in primary care: a randomized controlled trial. JAMA. 2010;303:1921–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Gilbody S, Bower P, Whitty P. Costs and consequences of enhanced primary care for depression: systematic review of randomised economic evaluations. Br J Psychiatry. 2006;189:297–308.PubMedCrossRefGoogle Scholar
  47. 47.
    Katon WJ, Lin EH, Von Korff M, et al. Collaborative care for patients with depression and chronic illnesses. N Engl J Med. 2010;363(27):2611–20.PubMedCrossRefGoogle Scholar
  48. 48.
    Simon GE, Rohde P, Ludman EJ, et al. Association between change in depression and change in weight among women enrolled in weight loss treatment. Gen Hosp Psychiatry. 2010;32:583–9.PubMedCrossRefGoogle Scholar
  49. 49.
    •Ye Z, Chen L, Yang Z, et al. Metabolic effects of fluoxetine in adults with type 2 diabetes mellitus: a meta-analysis of randomized placebo-controlled trials. PLoS One. 2011;6:e21551. This systematic review shows significant treatment effects of fluoxetine on reducing weight, triglyceride, and glycated hemoglobin levels in obese people with type 2 diabetes mellitus, which should be taken into account in the pharmacologic management of depression in individuals with excess body weight and diabetes.PubMedCrossRefGoogle Scholar
  50. 50.
    Atlantis E, Goldney RD, Wittert GA. Obesity and depression or anxiety. BMJ. 2009;339:b3868.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.School of MedicineKing’s College LondonLondonUK
  2. 2.School of Medicine, Faculty of Health SciencesUniversity of AdelaideAdelaideAustralia
  3. 3.Institute of PsychiatryKing’s College LondonLondonUK

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