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Can Depression Cause Diabetes?

Can Depression Cause Diabetes?. Behavioral Health Symposium May 16, 2008 Mercedes R. Carnethon, Ph.D. Assistant Professor of Preventive Medicine Feinberg School of Medicine Northwestern University, Chicago, IL. Outline. Type 2 Diabetes Depression and diabetes

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Can Depression Cause Diabetes?

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  1. Can Depression Cause Diabetes? Behavioral Health Symposium May 16, 2008 Mercedes R. Carnethon, Ph.D. Assistant Professor of Preventive Medicine Feinberg School of Medicine Northwestern University, Chicago, IL

  2. Outline • Type 2 Diabetes • Depression and diabetes • Depression and diabetes risk factors • Depression as a cause of diabetes

  3. Epidemiology of Type 2 Diabetes • Non-insulin dependent diabetes • 90-95% of all diagnosed cases • 21 million adults (10%) have T2DM • Average age of onset: > 40 years • Typically overweight or obese • Higher Prevalence in non-white minorities • Roughly equal by sex

  4. Age-Adjusted Prevalence of Diabetes in 2005 Overall prevalence ~ 10% Non-Hispanic White Hispanic/ Latino Americans Non-Hispanic Black American Indian/ Native American Age > 20 years

  5. Glucose enters the bloodstream Insulin Secretion Defective Insulin Secretion Blunted insulin secretion Insulin Resistance Glucose can’t get to cells in the body Impaired glucose tolerance Type 2 Diabetes Glucose builds up in blood stream Impaired fasting glucose Pathogenesis of Type 2 Diabetes

  6. Heredity Ethnicity Social Class Adiposity Sedentary life Overindulgence Defective Assimilation Nervous strain Worry CNS Lesions Environment Infections Liver Disturbances Risk Factors for Type 2 DiabetesOsler’s Principles & Practice of Medicine, 1892 Adiposity

  7. Obesity Insulin Resistance Autonomic Dysfunction Endothelial Dysfunction Inflammation Multiple Mechanistic Pathways for Diabetes Development Diabetes

  8. Depression and Diabetes

  9. Major Depressive Disorder (MDD) • Combination of somatic and mood symptoms • Symptoms persist for at least 2 weeks • Mood represents a change from person’s normal mood • Not due to bereavement • Diagnosed by a structured clinical interview • Diagnostic Interview Schedule (DIS) • Structured Clinical Interview for Depression (SCID) Adapted from: DSM-IV

  10. Estimated Prevalence DSM-IV Major Depressive Disorder in the US, 2005 Prevalence (%) Hasin DS. Arch of Gen Psychiatry 2005; 62: 1097

  11. Depression and Diabetes • Persons with diabetes up to three times more likely to suffer depression • Rate varies based on self-reported symptoms or diagnosed major depressive disorder

  12. Prevalence (%) of Adults with Major Depressive Disorder in Adults, by Diabetes (%) Egede LE. Diabetes Care 2003; 26: 104 Kessler RC. JAMA 2003; 289: 3095

  13. Depression and Diabetes: Mechanisms • Cross-sectional • Common neuroendocrine basis underlying both disorders • Depression and diabetes share somatic symptoms (e.g., fatigue) • Temporal • Stress of coping with diabetes leads to symptoms of depression • Depression leads to physiologic or behavioral changes that lead to diabetes

  14. Which comes first—depression or diabetes? ? Diabetes Depression

  15. Stress of coping with diabetes results in symptoms of depression Or Depression produces physiologic or behavioral changes that lead to diabetes Depressive Illness Preceding Diabetes Onset

  16. HPA-axis alterations Cortisol Secretion Diabetes Psychological Factors Confronting the “loss” of healthy function Changes in self esteem Complications decrease QOL Perceived Disability Coping Difficulties Depressive Symptomatology Diabetes Depression

  17. Rate of Depression* Over 3.1 Years by Baseline Glucose Status Multi-Ethnic Study of Atherosclerosis 40% elevated following adjustment Rate per 1000 Person-Years *Depression defined as CES-D>16 or initiation of depression meds

  18. Shared Symptoms of Diabetes and Depression • DSM-IV excludes illness as criteria for defining major depressive disorder • Mood disorder due to a general medical condition • Diabetes and depression share symptoms (e.g., decreased energy, weight changes) “A prominent and persistent disturbance in mood that is judged to be due to the direct physiological effects of a general medical condition”

  19. Depression 18 - 39 Depression 45 - 64 Type 2 DM 40-60 Type 1 DM 5-14 30 20 40 0 10 50 60 70 Age Average Ages of Onset for Diabetes and Depression

  20. Plausibility of Diabetes leading to Depression • Evidence suggests that it is the burden of treatment leading to depression • Inconsistent with the definition of MDD • Average ages for developing both conditions not consistent with a causal model • More longitudinal observational studies needed

  21. Evidence for Depression Preceding the Onset of Diabetes Diabetes Depression

  22. Behavioral Mechanisms Energy Balance • If depression leads to decreased physical activity levels and increased energy intake. . . The scale tips and weight gain ensues

  23. Behavioral Pathways for Depression to Precede the Onset of Diabetes Depressive Symptomatology Physical Inactivity Poor Sleep Habits Cigarette Smoking Food Intake Weight Gain Insulin Resistance Incident Diabetes

  24. Obesity Insulin Resistance Autonomic Dysfunction Endothelial Dysfunction Inflammation Multiple Mechanistic Pathways for Diabetes Development Diabetes HPA-axis Dysregulation Cortisol release

  25. Meta-Analysis of Longitudinal Studies of Depression and Incident Diabetes 26% elevated risk 37% elevated risk Knol MJ et al. Diabetologia 2006; 49: 837

  26. 5 4 Adjusted for age, race, sex, education, marital status, physical activity, smoking, ETOH, BMI, CRP 3 2 Odds Ratio (95% CI) 1 Adjusted 0.5 Score > 8 2 Scores > Scores > 8 5 Baseline CES-D Score CES-D Scores Over Follow-Up Depressive Symptom Scores Over Time and the 10-Year Risk of Developing Diabetes: in Older Adults (Age > 65) Carnethon et. Archives Internal Medicine 2007; 167: 802

  27. Association between Depressive Symptoms and Incident Diabetes over 16 years: NHEFS (n = 6190) General Well Being Depression Subscale Carnethon et al. Am J Epidemiol 2003: 158: 416

  28. Relative Risk (95% CI) 5 4 >=HS Educ 3 < HS Educ 2 1 0.5 High Intermediate Low General Well-Being Depression Scale Relative Risk of Incident Diabetes over 16 years by Depressive Symptoms Category and Education Carnethon et al. Am J Epidemiol 2003: 158: 416

  29. Role of Covariates Mediating the Relationship between Depression and Diabetes • What percent of the association between depressive symptoms and diabetes is attributable to a behavioral characteristic(s) or physiologic factor? • Percent of excess risk explained by the addition of covariates to the model • % Excess Risk = (RR1 – RR2)/(RR1 – 1) • RR1 = Unadjusted or minimally adjusted relative risk • RR2 = Relative risk adjusted for covariates of interest

  30. % Excess Risk Explained by Covariates: NHEFS ppt w/ < HS Education “6% of the association between depressive symptoms and diabetes is explained by smoking status, alcohol intake, and physical activity. . . An additional 37% explained by BMI. . .”

  31. Summary of Previous Findings: Depression and Incident Diabetes • Depression consistently associated with the development of diabetes • Traditional risk factors (e.g., BMI, physical activity) for diabetes mediate the association • Few studies investigating physiological factors mediating the association • Evidence of heterogeneity of effect by socio-demographic characteristics

  32. Summary Conclusions about Temporal Relationship • Weight of evidence suggests that depression precedes the onset of diabetes • Important in middle-aged and elderly • Present in men and women • Effect may be restricted to population subgroups with fewer socioeconomic resources • Both behavioral and mechanistic pathways could explain the association

  33. Future Research Needed • Longitudinal evaluation of development of depressive symptoms in type 2 diabetes • Rigorous definitions of depressive symptoms and diabetes • Studies investigating biological mechanisms mediating assoc between depression and incident diabetes • Experimental trials to treat depression and evaluate risk of diabetes development

  34. Clinical Implications: Emphasis on Health Behaviors • Move attention away from pharmacologic intervention and towards health behaviors • What pill has positive effects on mood, body weight, sleep quantity and quality, lowers blood pressure, lipids, blood glucose, the risk of heart disease, certain cancers, improves functional ability, overall quality of life, arthritis, and extends life? • Evidence for the exercise prescription!

  35. Public Health Implications • Large population at risk for the joint comorbidities of depression and diabetes • Prevalence of diabetes is rising with obesity epidemic • Large proportion of undiagnosed depression • Suggests a need for cross-screening in persons with depression or diabetes • May be particularly important in at-risk subgroups

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