Can Depression Cause Diabetes?

Behavioral Health SymposiumMay 16, 2008

Mercedes R. Carnethon, Ph.D.Assistant Professor of Preventive Medicine

Feinberg School of MedicineNorthwestern University, Chicago, IL

Outline

• Type 2 Diabetes

• Depression and diabetes

• Depression and diabetes risk factors

• Depression as a cause of diabetes

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

Age-Adjusted Prevalence of Diabetes in 2005

18

15

14

8

0 2 4 6 8 10 12 14 16 18 20

American Indian/ Native American

Non-Hispanic Black

Hispanic/ Latino Americans

Non-Hispanic White

Age > 20 years

Overall prevalence~ 10%

Pathogenesis of Type 2 Diabetes

Defective Insulin Secretion

Blunted insulin secretion

Insulin Resistance

Glucose can’t get to cells in the body

Impaired glucose tolerance

Insulin Secretion

Glucose enters the bloodstream

Glucose builds up in blood stream

Type 2 Diabetes

Impaired fasting glucose

Risk Factors for Type 2 DiabetesOsler’s Principles & Practice of Medicine, 1892

• Heredity

• Ethnicity

• Social Class

• Adiposity

• Sedentary life

• Overindulgence

• Defective Assimilation

• Nervous strain

• Worry

• CNS Lesions

• Environment

• Infections

• Liver Disturbances

Adiposity

Multiple Mechanistic Pathways for Diabetes Development

Obesity

DiabetesAutonomic Dysfunction

Insulin Resistance

InflammationEndothelialDysfunction

Depression and Diabetes

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

Estimated Prevalence DSM-IV Major Depressive Disorder in the US, 2005

0

2

4

6

8

10

12

14

16

18

Male Female 18-29 30-44 45-64 65+

12-monthLifetime

Prevalence (%)

Hasin DS. Arch of Gen Psychiatry 2005; 62: 1097

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

Prevalence (%) of Adults with Major Depressive Disorder in Adults, by Diabetes

0

2

4

6

8

10

No Diabetes Diabetes

Egede LE. Diabetes Care 2003; 26: 104Kessler RC. JAMA 2003; 289: 3095

(%)

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

Which comes first—depression or diabetes?

Diabetes

Depression

?

Depressive Illness Preceding Diabetes Onset

• Stress of coping with diabetes results in symptoms of depression

Or

• Depression produces physiologic or behavioral changes that lead to diabetes

Diabetes Depression

Diabetes HPA-axis alterations

Cortisol Secretion

Depressive Symptomatology

Psychological Factors

Confronting the “loss” of healthy function

Changes in self esteem

Complications decrease QOL

Perceived Disability

Coping Difficulties

Rate of Depression* Over 3.1 Years by Baseline Glucose Status

0

10

20

30

40

50

Normalfasting

glucose

Impairedfastingglucose

UntreatedDiabetes

Treateddiabetes

Rat

e p

er 1

000

Per

son

-Yea

rs

Multi-Ethnic Study of Atherosclerosis

*Depression defined as CES-D>16 or initiation of depression meds

40% elevated following

adjustment

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”

Average Ages of Onset for Diabetes and Depression

Type 1 DM5-14

Depression18 - 39

Type 2 DM40-60

Age

10 20 30 40 50 60 700

Depression45 - 64

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

Evidence for Depression Preceding the Onset of Diabetes

Diabetes

Depression

Behavioral Mechanisms Energy Balance

• If depression leads to decreased physical activity levels and increased energy intake. . .

The scale tips and weight gain ensues

Behavioral Pathways for Depression to Precede the Onset of Diabetes

Depressive Symptomatology

Incident Diabetes

Food Intake

PhysicalInactivity

Poor Sleep Habits

Cigarette Smoking

Weight Gain

Insulin Resistance

Multiple Mechanistic Pathways for Diabetes Development

Obesity

DiabetesAutonomic Dysfunction

Insulin Resistance

InflammationEndothelialDysfunction

HPA-axis Dysregulation

Cortisol release

Meta-Analysis of Longitudinal Studies of Depression and Incident Diabetes

Knol MJ et al. Diabetologia 2006; 49: 837

26% elevated risk37% elevated risk

Depressive Symptom Scores Over Time and the 10-Year Risk of Developing Diabetes: in Older Adults

(Age > 65)

Adjusted for age, race, sex, education, marital status, physical activity, smoking, ETOH, BMI, CRP

Od

ds

Rat

io (

95%

CI)

0.5

1

2

3

45

Adjusted

Score > 8 Scores> 5 2 Scores> 8

CES-D Scores OverFollow-Up

Baseline CES-DScore

Carnethon et. Archives Internal Medicine 2007; 167: 802

Association between Depressive Symptoms and Incident Diabetes over 16 years:

NHEFS (n = 6190)

(a) Full Sample

0

2

4

6

8

10

12

14

16

18

20

High Intermediate Low

Rat

e of

Dia

bete

s pe

r 100

0 pe

rson

-yea

rs

Carnethon et al. Am J Epidemiol 2003: 158: 416

General Well Being Depression Subscale

Relative Risk of Incident Diabetes over 16 years by Depressive Symptoms Category and

Education

0.5

1

2

3

4

5

High Intermediate Low

>=HS Educ< HS Educ

General Well-Being Depression Scale

Relative Risk (95% CI)

Carnethon et al. Am J Epidemiol 2003: 158: 416

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

% Excess Risk Explained by Covariates: NHEFS ppt w/ < HS Education

Model Model Terms RR % Excess

Risk

1 Age, race, sex 3.1 Ref

2 1 + smoking status, ETOH, physical activity

2.9 6

3 2 + BMI 2.3 37

“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. . .”

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

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

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

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!

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