An overview of potential mechanisms of the depression-diabetes link

Integration of Psychiatry into Primary Health Care Kuwait

26-28 Jan 20141www.kcl.ac.uk

Khalida Ismail

Depression-diabetes link

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Current evidence base

Depression is common in diabetes (10-30%)

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Depression associated with worse biomedical outcomes: 2-3 fold increase in mortality

Depression is under-detected yet highly treatable

Bi directional association

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depression type 2 diabetes

RR 1.10 (1.02-1.19)RR 1.10 (1.02-1.19)

RR 1.54 (1.13-2.09)

Golden et al JAMA 2008

Cause AND consequence= common origins?

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type 2 diabetes

depression

The type 2 diabetes continuum

insulin resistance

impaired glucose tolerance

HPA axisinflammation

early metabolic

programmingtype 2

diabetes

Depression is associated with all stages of the diabetes continuum

odds ratio 1.37-1.60

Pre-diabetes: Mezuk Diabetes Care 2008Diabetes: Anderson et al Diabetes Care 2001 Glyceamic control: Lustman et al Diabetes Care 2000Complications: dr Groot et al Psychosom Med 2001 Mortality: Katon et al Diabetes Care 2005; Ismail et al Diabetes Care 2007

odds ratio 2.1

effect size 0.17

odds ratio 3.1

hazards ratio 2.0-5.0

pre-diabetes diabetes suboptimal glycaemic control

complications mortality

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Common mechanisms for the depression-diabetes link

Psychological processes Biological processes

+/-

Psychological mechanisms

• diabetes specific distress• self-neglect of depression• impulse control• satiety

A cognitive behavioural model of the effect of depression on the t2dm continuum

High blood sugar

Altered cognitions‘Im a failure if I can’t get blood sugars right’

‘Insulin is bad for me’‘My life is not worth living’

Behaviourreduced diabetes self care

unhealthy lifestyles

AffectAnxiety

low mood

Perception of symptoms

blood glucosemedic side effects

fatigue/pain

Limitations of the psychological model

Potential of the psychological model

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Biological mechanisms

• HPA axis• innate inflammation• autonomic nervous system • early life programming• antidepressants• circadian clock • gut hormones and satiety• sleep apnoea• mitochondria

Brotman et al Lancet 2007

Multiple effects of the innate immune response

Innate inflammation as a common pathway

Innate inflammatory

responseDepression

Macrophage theory of depression (Smith 1991)

T2DM is an inflammatory condition (Pickup et al 1998)

Innate inflammatory

response

Insulin resistance

T2DMEarly

metabolic programming

Pooled effect size (95% confidence interval): 0.19 (0.11-0.27)

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Self reported

Diagnostic Interview

0.13 (0.08, 0.21)

0.46 (0.22, 0.71)

Depression is associated with insulin resistance

Kan et al Diabetes Care 2012

Childhood maltreatment is associated with inflammatory markers in adults

• High CRP risk group for cardiovascular disease • (CDC, AHA): CRP>3mg/L0

1020

3040

No Moderate Severe

Childhood maltreatment

hsC

RP

> 3

mg/

L (%

)

Danese et al PNAS 2007

The SOUth London Diabetes Cohort Study

Setting of SOUL-D

Lambeth Southwark Lewisham n= 96/139 surgeries

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Baseline characteristics by Patient Health Questionnaire-9 (≥10 represents depression case)

No depression (n=1278)

Depression (n=182)

Mean age (SD), years 56.2 (11.5) 52.8 (9.5)*

Female (%) 557 (43.6) 94 (51.6)*

Mean body mass index (SD), kg/m2

31.6 (6.3) 32.7 (7.1)*

Mean % HbA1c 7.00 (1.4) 7.10 (1.5)

Median hs C-reactive protein (IQR), mg/l

2.6 (1.1-6.2) 3.4 (1.5-8.9)*

Median white cell count (IQR), x109/L

6.5 (5.3-7.9) 7.1 (5.7-8.6)*

*p<0.05 adjusted for age, gender, marital status, smoking, ethnicity, BMI, antiinflammatory medication

Baseline results from SOUL-D

Innate inflammation as a common pathway

Innate inflammatory

responseDepression

Macrophage theory of depression (Smith 1991)

T2DM is an inflammatory condition (Pickup et al 1998)

Innate inflammatory

response

Insulin resistance

T2DMEarly

metabolic programming

Insulin resistance

Early metabolic

programming

Depression and type 2 diabetes: the search for common origins

innate inflammationinnate inflammation

lifestyleslifestyles

foetal nutritionfoetal nutrition

social adversity

social adversitygenomicsgenomics

Ismail PoS 2013

Final conclusions

• Global epidemic of T2DM has led to increased absolute burden of depression comorbidity

• The notion that depression and T2DM may share common pathways offers new aetiological mechanisms for both conditions

• There is a need for innovative models integrating depression management with diabetes management (similar to diabetes complications)

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