Depression and type 2 diabetes - Integration of Psychiatry into

An overview of potential mechanisms of the depression-diabetes link Khalida Ismail Integration of Psychiatry into Primary Health Care Kuwait 26-28 Jan 2014 www.kcl.ac.uk

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Depression-diabetes link

depression

type 2 diabetes

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Current evidence base Depression is common in diabetes (10-30%) Depression associated with worse biomedical outcomes: 2-3 fold increase in mortality

Depression is under-detected yet highly treatable

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Bi directional association

depression

RR 1.10 (1.02-1.19) RR 1.54 (1.13-2.09)

type 2 diabetes

Golden et al JAMA 2008 www.kcl.ac.uk

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Cause AND consequence= common origins?

depression

type 2 diabetes

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The type 2 diabetes continuum early metabolic programming

HPA axis inflammation

insulin resistance

impaired glucose tolerance

type 2 diabetes

Depression is associated with all stages of the diabetes continuum odds ratio 1.37-1.60

odds ratio 2.1

pre-diabetes

diabetes

effect size 0.17

odds ratio 3.1

complications suboptimal glycaemic control

hazards ratio 2.0-5.0

mortality

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

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Common mechanisms for the depression-diabetes link

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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 Altered cognitions ‘Im a failure if I can’t get blood sugars right’ ‘Insulin is bad for me’ ‘My life is not worth living’

Perception of symptoms blood glucose medic side effects fatigue/pain

Affect Anxiety low mood

Behaviour reduced diabetes self care unhealthy lifestyles

High blood sugar

Limitations of the psychological model Glycaemic control

• Cross-sectional studies: pooled effect size 0.17 (Lustman, Diabetes Care 2000) • Prospective studies: limited number and unconvincing

Treatment of depression in diabetes

• Depression improves • Inconsistent findings that glycaemic control also improves (Katon et al Arch Gen Psychiatry 2004; Katon et al NEJM 2010)

Treatment of depression in cardiovascular disease

• Depression improves • No evidence from SADHEART (Glassman JAMA 2002) or ENRICHD (JAMA 2003) that cardiac outcomes and mortality improves

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 ENVIRONMENTAL THREATS/TOXINS: excessive adiposity, chronic psychosocial stressors eg smoking MACROPHAGES: pro-inflammatory (IL-6, IL-1, TNF-) and anti-inflammatory cytokines (adiponectin) ‘sickness behaviors’

ACUTE-PHASE RESPONSE: blood proteins (C-reactive protein (CRP), serum amyloid A) and triglycerides CELL DAMAGE: Pancreatic -cell apoptosis, insulin resistance, reduced insulin secretion, endothelial dysfunction, central effects on neuroglia DISEASE: type 2 diabetes, arthrosclerosis, depression, cognitive impairment

Innate inflammation as a common pathway T2DM is an inflammatory condition (Pickup et al 1998) Early metabolic programming

Innate inflammatory response

Insulin resistance

T2DM

Macrophage theory of depression (Smith 1991) Innate inflammatory response

Depression

Depression is associated with insulin resistance 1 2 3 4 5 6 7 8 9 10

Diagnostic Interview

11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

Self reported

0.46 (0.22, 0.71)

0.13 (0.08, 0.21)

Kan et al Diabetes Care 2012

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

Childhood maltreatment is associated with inflammatory markers in adults

30 20 10 0

hsCRP > 3 mg/L (%)

40

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

No

Moderate

Severe

Childhood maltreatment

Danese et al PNAS 2007

The SOUth London Diabetes Cohort Study

Setting of SOUL-D

Lambeth Southwark Lewisham

n= 96/139 surgeries

Baseline results from SOUL-D 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