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
8
Hispanic/ Latino
Americans
14
Non-Hispanic Black
15
American Indian/
Native American
18
0
Age > 20 years
2
4
6
8
10
12
14
16
18
20
Pathogenesis of Type 2 Diabetes
Glucose enters
the bloodstream
Insulin Secretion
Defective Insulin
Secretion
Blunted insulin
secretion
Glucose can’t 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
Osler’s 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 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
Prevalence (%)
18
12-month
Lifetime
16
14
12
10
8
6
4
2
0
Male
Female
18-29
30-44
45-64
65+
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
10
8
(%)
6
4
2
0
No Diabetes
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
50
40
30
20
10
0
Normal
fasting
glucose
Impaired
fasting
glucose
Untreated
Diabetes
Treated
diabetes
*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
0
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)
Rate of Diabetes per 1000 person-years
(a) Full Sample
20
18
16
14
12
10
8
6
4
2
0
High
Intermediate
Low
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
1
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
1
2
3
RR
Age, race, sex
3.1
1 + smoking status, ETOH, 2.9
physical activity
2 + BMI
2.3
% Excess
Risk
Ref
6
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 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