Psychoneuroendocrine:  Research Article

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Depressive Symptoms and the Risk of Type 2 Diabetes

CITATION: Sherita Hill Golden, Janice E Williams, Daniel E Ford, Hsin-Chieh Yeh,  et al. (2004, February). Depressive Symptoms and the Risk of Type 2 Diabetes. Diabetes Care, 27(2), 429-435.


We analyzed data on depressive symptoms (including recent fatigue, sleep disturbance, feelings of hopelessness, loss of libido, and increased irritability) in a longitudinal, biracial cohort study of 11,615 initially nondiabetic adults aged 48-67 years, who were subsequently followed for 6 years for the development of type 2 diabetes.

Results: At baseline, depressive symptoms were positively associated with BMI, fasting insulin, systolic blood pressure, caloric intake, physical inactivity, and current smoking (all P < 0.05). In prospective analyses, after adjusting for age, race, sex, and education, individuals in the highest quartile of depressive symptoms had a 63% increased risk of developing diabetes compared with those in the lowest quartile (relative hazard [RH] 1.63, 95% CI 1.31-2.02). This relation persisted after adjustment for stress-associated lifestyle factors (smoking, physical activity, caloric intake, and adiposity) (1.28, 1.02-1.60) and metabolic covariates (fasting insulin and glucose, lipids, blood pressure, and adiposity) (1.38, 1.10-1.73).

Conclusions:  In this cohort, depressive symptoms predicted incident type 2 diabetes. This relation is only partially explained by demographic, metabolic, and lifestyle factors. Possible neuroendocrine mediators of the stress-obesity-diabetes relationship require further evaluation in prospective cohort studies that use an established tool to assess depression and incorporate neurohormonal measurements.  


1. Eaton WW, Armenian H, Gallo J, Pratt L, Ford DE: Depression and risk for onset of type II diabetes: a prospective population-based study. Diabetes Care 19:1097-1102, 1996

2. Kawakami N, Takatsuka N, Shimizu H, Ishibashi H: Depressive symptoms and occurrence of type 2 diabetes among Japanese men. Diabetes Care 22:1071-1076, 1999

3. Padgett DK: Sociodemographic and disease-related correlates of depressive morbidity among diabetic patients in Zagreb, Croatia. J Nerv Ment Dis 181:123-129, 1993

4. Ciechanowski PS, Katon WJ, Russo JE: Depression and diabetes: impact of depressive symptoms on adherence, function, and costs. Arch Intern Med 160:3278-3285, 2000

5. Littlefield CH, Craven JL, Rodin GM, Daneman D, Murray MA, Rydall AC: Relationship of self-efficacy and binging to adherence to diabetes regimen among adolescents. Diabetes Care 15:90-94, 1992

6. DiMatteo MR, Lepper HS, Croghan TW: Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med 160:2101-2107, 2000

7. Marcus MD, Wing RR, Guare J, Blair EH, Jawad A: Lifetime prevalence of major depression and its effect on treatment outcome in obese type II diabetic patients. Diabetes Care 15:253-255, 1992

8. Plotsky PM, Owens MJ, Nemeroff CB:Psychoneuroendocrinology of depression: hypothalamic-pituitary-adrenal axis. Psychiatr Clin North Am 21:293-307, 1998

9. Rubin RT, Phillips JJ, McCracken JT, Sadow TF: Adrenal gland volume in major depression: relationship to basal and stimulated pituitary-adrenal cortical axis function. Biol Psychiatry 40:89-97, 1996

10. Nemeroff CB, Krishnan KR, Reed D, Leder R, Beam C, Dunnick NR: Adrenal gland enlargement in major depression: a computed tomographic study. Arch Gen Psychiatry 49:384-387, 1992

11. Lake CR, Pickar D, Ziegler MG, Lipper S, Slater S, Murphy DL: High plasma norepinephrine levels in patients with major affective disorder. Am J Psychiatry 139:1315-1318, 1982

12. Roy A, Pickar D, De Jong J, Karoum F, Linnoila M: Norepinephrine and its metabolites in cerebrospinal fluid, plasma, and urine: relationship to hypothalamic-pituitary-adrenal axis function in depression. Arch Gen Psychiatry 45:849-857, 1988

13. Maes M, Vandewoude M, Schotte C, Martin M, Blockx P: Positive relationship between the catecholaminergic turnover and the DST results in depression. Psychol Med 20:493-499, 1990

14. Hippisley-Cox J, Fielding K, Pringle M: Depression as a risk factor for ischaemic heart disease in men: population based case-control study [published erratum appears in BMJ 317:185, 1998]. BMJ 316:1714-1719, 1998

15. The ARIC Investigators: The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. Am J Epidemiol 129:687-702, 1989

16. Appels A, Hoppener P, Mulder P: A questionnaire to assess premonitory symptoms of myocardial infarction. Int J Cardiol 17:15-24, 1987

17. Kopp MS, Falger PR, Appels A, Szedmak S: Depressive symptomatology and vital exhaustion are differentially related to behavioral risk factors for coronary artery disease. Psychosom Med 60:752-758, 1998

18. Crum RM, Cooper-Patrick L, Ford DE: Depressive symptoms among general medical patients: prevalence and one-year outcome. Psychosom Med 56:109-117, 1994

19. National Heart, Lung, and Blood Institute: ARIC Manuals of Operation. No. 1-12. Chapel Hill, NC, ARIC Coordinating Center, School of Public Health, University of North Carolina, 1987

20. Baecke JA, Burema J, Frijters JE: A short questionnaire for the measurement of habitual physical activity in epidemiological studies. Am J Clin Nutr 36:936-942, 1982

21. Willett WC, Sampson L, Stampfer MJ, Rosner B, Bain C, Witschi J, Hennekens CH, Speizer FE: Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 122:51-65, 1985

22. Cox DR: Regression models and life tables. J R State Soc Ser (B) 34:187-220, 1972

23. Cronbach LJ: Coefficient [alpha] and the internal structure of tests. Psychometrika 16:297-334, 1951

24. Reuterberg SE, Gustafsson JE: Confirmatory factor analysis and reliability: testing measurement model assumptions. Educ Psychol Meas 52:795-811, 1992

25. Appels A, Mulder P: Excess fatigue as a precursor of myocardial infarction. Eur Heart J 9:758-764, 1988

26. van Diest R, Appels A: Vital exhaustion and depression: a conceptual study. J Psychosom Res 35:535-544, 1991

27. Nicolson NA, van Diesl R: Salivary cortisol patterns in vital exhaustion. J Psychosom Res 49:335-342, 2000

28. Anderson RJ, Freedland KE, Clouse RE, Lustman PJ: The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care 24:1069-1078, 2001

29. Carnethon MR, Kinder LS, Fair JM, Stafford RS, Fortmann SP: Symptoms of depression as a risk factor for incident diabetes: findings from the National Health and Nutrition Examination Epidemiologic Follow-Up Study, 1971-1992. Am J Epidemiol 158:416-423, 2003

30. Haire-Joshu D, Heady S, Thomas L, Schechtman K, Fisher EB Jr: Depressive symptomatology and smoking among persons with diabetes. Res Nurs Health 17:273-282, 1994

31. Manson JE, Ajani UA, Liu S, Nathan DM, Hennekens CH: A prospective study of cigarette smoking and the incidence of diabetes mellitus among U.S. male physicians. Am J Med 109:538-542, 2000

32. Roy A, Roy M: Depressive symptoms in African-American type 1 diabetics. Depress Anxiety 13:28-31, 2001

33. Fisher L, Chesla CA, Mullan JT, Skaff MM, Kanter RA: Contributors to depression in Latino and European-American patients with type 2 diabetes. Diabetes Care 24:1751-1757, 2001

34. Lloyd CE, Wing RR, Orchard TJ: Waist to hip ratio and psychosocial factors in adults with insulin-dependent diabetes mellitus: the Pittsburgh Epidemiology of Diabetes Complications study. Metabolism 45:268-272, 1996

35. Miyaoka Y, Miyaoka H, Motomiya T, Kitamura S, Asai M: Impact ol sociodemographic and diabetes-related characteristics on depressive state among noninsulin-dependent diabetic patients. Psychiatry Clin Neurosci 51:203-206, 1997

36. Sachs GS, Guille C: Weight gain associated with use of psychotropic medications. J Clin Psychiatry 60 (Suppl. 21): 16-19, 1999

37. Fava M: Weight gain and antidepressants. J Clin Psychiatry 61 (Suppl. 11):37-41, 2000

38. Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ: Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 156:1686-1696, 1999

39. Pasquali R, Cantobelli S, Casimirri F, Capelli M, Bortoluzzi L, Flamia R, Labate AM, Barbara L: The hypothalamic-pituitary-adrenal axis in obese women with different patterns of body fat distribution. J Clin Endocrinol Metab 77:341-346, 1993

40. Marin P, Darin N, Amemiya T, Andersson B, Jern S, Bjorntorp P: Cortisol secretion in relation to body fat distribution in obese premenopausal women. Metabolism 41:882-886, 1992