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
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
Overall prevalence
~ 10%

Non-Hispanic White
Hispanic/ Latino
Americans
Non-Hispanic Black
American Indian/
Native American

Age > 20 years

Pathogenesis of Type 2 Diabetes

Glucose enters
the bloodstream

Insulin Secretion
Defective Insulin
Secretion

Blunted insulin
secretion

Glucose cant get

to cells in the body

Impaired glucose
tolerance

Glucose builds up
in blood stream

Impaired
fasting glucose

Insulin Resistance

Type 2
Diabetes

Risk Factors for Type 2 Diabetes

Oslers Principles & Practice of Medicine, 1892

Heredity

Nervous strain

Ethnicity

Worry

Social Class

CNS Lesions

Adiposity
Adiposity

Environment

Sedentary life

Infections

Overindulgence

Liver Disturbances

Defective Assimilation

Multiple Mechanistic Pathways for

Diabetes Development
Obesity

Insulin
Resistance

Diabetes

Inflammation

Autonomic
Dysfunction

Endothelial
Dysfunction

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 persons 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
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

(%)

Egede LE. Diabetes Care 2003; 26: 104

Kessler 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?

?
Depression

Diabetes

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
Diabetes

Depression
HPA-axis
alterations

Psychological Factors
Confronting the loss of healthy function
Changes in self esteem
Complications decrease QOL
Perceived Disability
Coping Difficulties
Depressive Symptomatology

Cortisol
Secretion

Rate of Depression* Over 3.1 Years by

Baseline Glucose Status
Rate per 1000 Person-Years

Multi-Ethnic Study of Atherosclerosis

40% elevated
following
adjustment

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

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
Depression
18 - 39

Depression
45 - 64
Type 2 DM
40-60

Type 1 DM
5-14

10

20

30

Age

40

50

60

70

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

Food
Intake

Physical
Inactivity

Poor Sleep
Habits

Weight
Gain

Cigarette
Smoking

Insulin
Resistance
Incident Diabetes

Multiple Mechanistic Pathways for

Diabetes Development
Obesity

Insulin
Resistance

Diabetes

Autonomic
Dysfunction
HPA-axis
Dysregulation

Inflammation

Endothelial
Dysfunction

Cortisol release

Meta-Analysis of Longitudinal Studies of

Depression and Incident Diabetes

26% elevated risk

37% elevated risk

Knol MJ et al. Diabetologia 2006; 49: 837

Odds Ratio (95% CI)

Depressive Symptom Scores Over Time and the 10Year Risk of Developing Diabetes: in Older Adults (Age
> 65)
5
4

Adjusted for age, race,

sex, education, marital
status, physical
activity, smoking,
ETOH, BMI, CRP

3
2

1
Adjusted
0.5
Score > 8
Baseline CES-D
Score

Scores> 5

2 Scores> 8

CES-D Scores Over

Follow-Up

Carnethon et. Archives Internal Medicine 2007; 167: 802

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

Relative Risk of Incident Diabetes over 16

years by Depressive Symptoms Category and
Education
Relative Risk
5
(95% CI)
4

>=HS Educ
< HS Educ

3
2

0.5

High

Intermediate

Low

General Well-Being Depression Scale

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

3.1

Ref

Age, race, sex

1 + smoking status, ETOH, 2.9

physical activity

2 + BMI

37

2.3

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 sociodemographic 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