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Diabetes and Depression- The Two Headed Monster

Diabetes and Depression- The Two Headed Monster. Roger Chen MB BS (Hons), PhD (Sydney), FRACP Senior Staff Specialist Concord Hospital Clinical Senior Lecturer, University of Sydney. Introduction. Traditional Risk Factors for Diabetes Mellitus Physical

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Diabetes and Depression- The Two Headed Monster

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  1. Diabetes and Depression- The Two Headed Monster Roger Chen MB BS (Hons), PhD (Sydney), FRACP Senior Staff Specialist Concord Hospital Clinical Senior Lecturer, University of Sydney

  2. Introduction • Traditional Risk Factors for Diabetes Mellitus • Physical • Traditional Complications and Co-morbidities • Physical • Traditional Treatments • Pharmacological • Mental Health – • Risk factor for and complication of diabetes

  3. Cerebrovascular disease Retinopathy Blindness Cardiovascular diseaseHypertensionDyslipidaemia Peripheral vascular disease Nephropathy, renal failure Autonomic neuropathyGI, genitourinary & CV symptoms & sexual dysfunction Peripheral neuropathyUlcersCharcot jointsAmputations Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 1999

  4. Case • Mr GS: 52 year old male with a 20 year history of Type 1 Diabetes • Depression: on multiple medications and atypical antipsychotic • Glycaemic control poor till 2002 • Enrolled in clinical trial using new long acting basal insulin • Blood sugar levels improved significantly overall • Punctuated by periods of very high blood glucose levels (usually coinciding with periods of depression)

  5. 52 year old female with Type2 diabetes 12 years Obese, Waist circumference 120 cm, BMI 35 Pain on walking and at rest- generalised, painful knees, hips, back and shoulders Own family- disengaged with sisters, mother recently died not allowed to go to the funeral Son just admitted for alcohol and drug rehab Unable to do much exercise (painful back) Not sleeping, puffed out continually Some weight gain- blames tablets (6kg in 6 months) Blames thyroid (convinced she wants thyroidectomy) HbA1c (10.2%) out of proportion to home monitoring Blood pressure 180/100 mHg Feels miserable

  6. The Global Burden of the 2 “Ds” • Increase in Diabetes well recognised • Increase in Mental Illness not as appreciated • World Health Organization 2007 • Depression prevalence ranges from 2-15% • 60 countries • Greatest proportion of disease burden attributable to non-fatal health outcomes • Depression produces the greatest decrement in health compared with other chronic diseases • Co-morbid state of depression worsens health with diabetes Moussavi et al, Lancet September 8 2007

  7. “Probing Depression and its ties to diabetes • Millions of people face a two-headed beast- diabetes and depression- that gnaws at them from the inside out. • The struggle of coping with diabetes feeds deep sadness. Depression gets in the way of dieting, exercising, and even taking the medicines that can control diabetes. The downward spiral can make the depression unrelenting, increase diabetic complications, and even double the risk of death “ • The Boston Globe Nov 1 2006

  8. Diabetes doubles the odds of comorbid depression elevated depression symptoms in 31% major depressive disorder present in 11% Self-report-based estimates were higher than interview-based estimates, as interviews identify major depressive disorder, but exclude other clinically relevant presentations Depression rates double in patients with diabetes Meta-analysis of 42 studies to estimate the prevalence of depression in adults with diabetes (n=21,351) Diagnostic interview Self-report scale *p<0.001 between methods 60 * 40 34.9 * 31.0 * Depression prevalence (%) 26.1 20 14.2 11.4 9.0 0 (n=7) (n=11) (n=7) (n=14) (n=14) (n=25) Controlled Uncontrolled All studies studies studies Anderson RJ. Diabetes Care 2001;24:1069–78.

  9. Why do patients develop depression ? • Chronic disease • Self management • Generally early • Associated with more complications • Common mechanism • Late onset depression • Microvascular • Associated with brain infarcts (Chemerinski 2000) • MRI white matter signal hyperintensities

  10. Why do patients develop depression ? • Type 1 • GAD antibodies may affect GABA synthesis • ? Reduced GABAergic neurpns in occipital and prefrontal cortices in depression • 2 peaks • Year following diagnosis • 2nd peak 10 years later, in some cases, puberty/adulthood

  11. Management of diabetes may contribute to impaired HRQoL- and an increased risk of depression • Impact of diabetes management on HRQoL: • Demanding self-care regimens1,2 • Significant lifestyle changes • Multiple medications • Treatment dissatisfaction • Perceived treatment inefficacy • Fear of injections • Fear of hypoglycaemia1,2 • 1. Rubin RR. Diabetes Spectrum 2000;13:21. • 2. Barnett AH. Eur J Endocrinol 2004;151(suppl 2):T3–7.

  12. Community I live in is intolerant of diabetes Family and friends pressurise me about my diabetes Diabetes causes worries about financial future Worry about not being able to carry out family responsibilities in the future Constantly afraid of diabetes worsening Diabetes ‘prevents me doing what I want’ ‘Burned out’ because of diabetes ‘Stressed’ because of diabetes Proportion of patients (%) Diabetes causes psychological distressDiabetes, Attitudes, Wishes and Needs (DAWN) survey A large (n=5,104) international survey designed to identify a set of attitudes, wishes and needs among diabetic patients and care providers in order to investigate how diabetes management could be improved1,2 1. The DAWN Study. Pract Diabetes Int 2002;19:22–4. 2. Skovlund S, et al. Diabetes Spectrum 2005;18:136–142.

  13. Evaluating diabetes-specific HRQoL along three major, interrelated dimensions Psychological/emotional Physical • Long-term complications: • vision loss, kidney damage, • heart disease, amputation • Short-term complications: • fatigue, sleep disturbance, • infections, weight gain • Symptoms: • glucose control (HbA1c), hypo-/hyperglycaemia & lifestyle changes • Depression • Anger • Fear • Persistent fatigue • Exhaustion • Helplessness • Chronic frustration Social • Changes in daily habits • Relationships with family/friends suffer • Social life affected Polonsky WH. Diabetes Spectrum 2000;13:36–41.

  14. Depression negatively impacts diabetes management and progression • Significant association between depression and hyperglycaemia1 • Improvements in depressive symptoms predict improvements in glycaemic control2,3 • Improvements in glycaemic control are correlated with improvements in depressive symptoms4,5 • Poorer self management where diabetes and depression co-exist • Lustman PJ, et al. Diabetes Care 2000;23:434–2. • Lustman PJ, et al. Psychsom Med 1997;59:241–50. • Lustman PJ, et al. Ann Intern Med 1998;129:613–21. • Mazze RS, et al. Diabetes Care 1984;7:360–6. • Testa MA, et al. JAMA 1998;280:1490–6.

  15. Depression as risk factor for Type 2 diabetes • Thomas Willis 1684 “ Grief or sadness could bring on diabetes” • Meta-analysis of 9 studies1 • 37% increased risk of developing Type2 diabetes • Increased HPA axis, increased catecholamines, CRP, TNF-alpha, IL-6 • Impaired omega 3 polyunsaturated fatty acid metabolism • Increased inactivity, tobacco • ? Genes • Problems • Undetected / undiagnosed diabetes • Method of diagnosis • Baseline risk • Follow-up duration • Multiple ways of assessing depression Knol et al; Diabetologia 49;837-845, 2006

  16. Depression 40% more likley to precede than follow onset of Type 2 diabetes (Mezuk 2008) • Mechanisms • Lifestyle: sedentary, social withdrawal, poor motivation • Socioeconomic- increase in depression and diabetes • Environmental stress (Catecholamines, Cortisol) • Hippocampal glucose transporters inhibited by Cortisol • Inflammatory markers: TNF, CRP, IL-6

  17. Hypothalamic-Pituitary: Cortisol Sympathetic-Adrenal-Medullary: Catecholamines: Adrenaline and Noradrenaline Endocrine Response to Stress

  18. Chronic Stress • Link with chronic disease- heart, lung, diabetes, infections, malignancy • Makes self care difficult • Diabetes: Par Excellence • Need for blood glucose monitoring, healthy food, physical activity • Shift work • Travel

  19. Depression and heart disease A ‘chicken vs egg’ debate: Depression as a significant risk factor for development of heart disease1,2 Comorbid depression confers a poorer prognosis in heart disease1 1. Jiang et al. CNS Drugs 2002;16:111–27. 2. NHFA and CSANZ. Reducing risk in heart disease 2007 (Updated 2008).

  20. Among patients with diabetes, depression is strongly associated with mortality 2.30-fold increase in mortality (p<0.0001) 1.67-fold increase in mortality (p=0.002) Patient mortality (%) 13.6%(n=48) 11.9%(n=59) 8.3%(n=275) Without depression(n=3303) Minor depression(n=354) Major depression(n=497) Katon WJ et al. Diabetes Care 2005;28:2668–72.

  21. Impact of diabetes in patients with depression • 10 000 participants in National Health and Nutrition Examination Survey • First study to compare effects of depression on mortality in subjects with and without diabetes • Over 8 years of follow-up and after adjustment for confounders, subjects with both co-morbidities had • 1.3 fold increased risk of death vs diabetes itself • 2 fold increased risk of death vs depression itself • 2.5 fold increased risk of death vs neither Egede et al, Diabetes Care 28:1339-1345, 2005 Adriaanse 2008 Li 2009

  22. Depression increased CV mortality post-MI and in stable CHD Post-MI1 Stable CHD (adjusted for age)3 HR: 5.74, p = 0.0006 n=186 baseline; n=7 endpoint n=768 baseline; n=36 endpoint Adapted from Whooley et al.3 Adapted from Frasure-Smith et al.1 1. Frasure-Smith et al. JAMA 1993;270:1819–25. 2. Frasure-Smith et al. Circulation 1995;91:999–1005. 3. Whooley et al. JAMA 2008;300:2379–88.

  23. Acute mental stress and heart attacks Natural disasters and stressful events are associated with a spike in rates of MI and lethal cardiac arrhythmias Earthquakes: e.g. Los Angeles 19941 September 11, 20012 Bushfire disasters3 World Cup soccer matches4 1. Leor et al. N Eng J Med 1996;334:413–19. 2. Feng et al. Clin Cardiol 2006;29:13–17. 3. Kolbe & Gilchrist. NSW Public Health Bull 2009;20:19–23. 4. Wilbert-Lampen et al. N Eng J Med 2008;358:475–83. Adapted from Leor et al.1

  24. Depressive illness is a risk factor for development of heart disease 13 studies prospectively followed > 40,000 patients with major depressive disorder Depression was a significant independent risk factor for development of coronary heart disease Comparable to the risk associated with smoking 1. Jiang et al. CNS Drugs 2002;16:111–27.

  25. How does stress trigger MI and sudden death? Most commonly occurs in patients with pre-existing coronary artery narrowing Sympathetic nervous system activation – lethal arrhythmias1 BP surge – rupture of plaques leading to thrombosis1 Adrenaline secretion leading to1 Platelet activation Low potassium levels- causing cardiac arrhythmias Sympathetic activation and augmented adrenaline secretion during panic attacks can increase cardiac risk2 At rest Panic attack Adapted from Esler et al.1 1. Esler et al. Stress Health 2008;24:196–202. 2. Esler et al. Ann NY AcadSci2004;1018:505–14.

  26. GENERAL Age (rate  >45) Ethnicity Family History History Gestational Diabetes Hypertension (>140/90) Smoking Obesity (esp. central) Dyslipidaemias (HDL, TG) Diet Inactivity Mental Health Population Depression Schizophrenia Risk Factors for Diabetes

  27. Complication Screening in diabetes • Physical • CV • Eyes • Feet • Kidneys • Neuropathy • Psychological • Depression • Multiple Depression Questionnaires

  28. AHA recommendation: Routine depression screening post-MI AHA recommendation 2008: “Routine screening for depression in patients with CHD…”1 Recommended screening tools: PHQ-2 for rapid, initial assessment “During the past month, have you often been bothered by feeling down, depressed, or hopeless?” “During the past month, have you often been bothered by little interest or pleasure in doing things?” PHQ-9 for more detailed assessment 1. Lichtman et al. Circulation 2008;118:1768–75. 2. Stafford et al. Gen Hosp Psychiatry 2007;29:417–24. 3. McManus et al. Am J Cardiol2005;96:1076–81

  29. What to do • Screen for depression • Typical clinical features • Multiple complications, poor metabolic control • Refer if uncomfortable • Treatment options • Cognitive Behavioural Therapy • Pharmacological Therapy: TCA, SSRI • Combinations

  30. Thank You

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