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
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