Man suffering from depressionIntroduction
Diabetes and depression: the link
Diabetes and depression: the risk
Diabetes and depression: the consequences
Diabetes and depression: practical management




The prevalence of diabetes is increasing as increased life expectancy leads to an ageing population.1 Due to an inter-play between metabolic dysfunction, vascular disease, the ageing process and age-related disorders, diabetes can be a disabling disease in old age.2 In addition, psychological complications, such as depression are common in older people with diabetes. Unlike in other chronic conditions, good diabetes management relies heavily on a patient’s selfcare abilities. The presence of depression may make patients more lethargic and less compliant in undertaking these self-care responsibilities, resulting in long-term complications and increasing healthcare costs.3,4 Although depression is common in older people with diabetes, it remains underdiagnosed and therefore often untreated.5 This article reviews the relationship between diabetes and depression and its impact on clinical practice.


Diabetes and depression: the link

Diabetes and depression are inter-related. Changes in the brain: structural, functional and neurochemical may increase the risk of depression in people with diabetes.6 Hyperglycaemia can contribute towards low mood through reducing hippocampal integrity, neurogenesis and neuroplasticity leading to hippocampal atrophy.7 For patients, an awareness of their diagnosis, along with its associated complications, and the burden of treatment may lead to them feeling helpless, which may result in depression. Also, the increased rate of obesity associated with depression, and the resulting insulin resistance, may increase the risk of incident diabetes.8 Disturbed sleep patterns are often seen in people with depression,9 altered circadian rhythm along with poor sleep quality are associated with insulin resistance and therefore an increased risk of diabetes.10

Alternatively, diabetes and depression may be linked through changes in biological, behavioural, neurohormonal and immuno-inflammatory pathways.11 Foetal over-exposure to cortisol, secondary to maternal stress, and low birth weight have been associated with hypothalamic-pituitaryadrenal axis programming and elevated cortisol reactivity possibly predisposing that individual to future metabolic disorders.12


Diabetes and depression: the risk

Diabetes increases the risk of depression. A metaanalysis of 16 studies that examined the risk of depression in those with diabetes showed that both relative risk (RR) and hazard ratio (HR) were significant at 1.27 {95 % confidence interval (CI) 1.17 to 1.38} and 1.23 (1.08 to 1.40).13 In the Health, Ageing, and Body Composition Study, older people (70–79 years old) with diabetes showed an increased incidence of depression compared to those without diabetes (23.5% versus 19.0%, HR 1.31, 95% CI 1.07 to 1.61).14

Conversely, depression increases the risk of diabetes by 65%. In a prospective study of 4,803 adults aged 55 years or older, the incidence rate of diabetes was higher among depressed subjects (19.70 per 1,000 person-years) relative to nondepressed subjects (12.36 per 1,000 person-years). An increased risk of diabetes mellitus was also associated with characteristics such as non-severe and untreated depression.15 The relationship between diabetes and depression appears to be bidirectional. Diabetes and its complications lead to increased prevalence of depressive symptoms and depression leads to an increased risk of diabetes (Figure 1).


Diabetes and depression: the consequences

Depression has a negative impact on a person’s ability to take responsibility for their own self-care. This in turn may lead to poor glycaemic control and an increased risk of diabetes complications with reduced function and increased mortality.16

Figure 1 - Bidirectional relationship between diabetes and depression

Reduced function

The risk of dementia increases significantly in older people with comorbid depression and diabetes (HR 2.02) compared to those with diabetes but not depression.17 Physical function is also compromised. A prospective Canadian study of 1,064 older people with diabetes, mean (SD) age 59.2 (10.5) years, showed that for participants with four sub-threshold depressive episodes the risk of poor function and reduced quality of life was approximately three times higher compared to those with no or minimal depression when followed up at five years.18 Depression appears to interact with function in a reciprocal way; depression predicts poor function as well as poor function predicting depression.19


Increased mortality

Patients with comorbid diabetes and depression have a higher risk of mortality. Both cardiovascular and all cause mortality risks are 1.4 and 1.5 times higher respectively than in those people with diabetes alone.19 In the Nurses Health Study of 7,000 women (age range 54–79), the relative risk for all cause and cardiovascular mortality was 1.76 and 1.81 respectively for patients with depression alone, 1.71 and 2.67 respectively for those with diabetes alone and 3.11 and 5.38 respectively for comorbid diabetes and depression.20 The effect of depression on mortality is most significant for older people with diabetes. In a survival analysis the mortality risk in people of 65 years or more with depression was 78% greater than in those without depression. In contrast, for those under 65 years of age, the effect of depression on mortality was smaller and not statistically significant.21


Diabetes and depression: practical management

Managing depression in older people with diabetes should be directed towards improving psychological and physical health. Improvement in psychological wellbeing can lead to remission of depressive symptoms, which may help to improve physical functioning. Older people with diabetes should be monitored yearly for symptoms/signs of depression or more often if self-neglect is observed (Box 1). Depression is best treated within a collaborative care setting with a combination of lifestyle modifications, pharmacotherapy and psychotherapy. (Box 2)


Screening for depression should be part of the annual review and earlier if patients develop one of the following:
  • Non-compliance with medications
  • Diminished skills for performing insulin injections
  • Difficulties in checking own blood glucose
  • Patient is reluctant to make decisions regarding adjusting insulin doses
  • Eating pattern becomes erratic with over or under-eating
  • Significant weight gain or weight loss
  • Frequent or unexplained hypoglycaemia
  • Struggling with general self-care
  • Non-compliance with dietary requirements
  • Social isolation and reluctance to seek medical care
  • Lack of energy and fatigue
  • Self reporting symptoms of depression eg. depressed mood, insomnia or guilt
  • Short screening tools can be used for rapid assessment of depression followed by a detailed test for those who score positively
Patient Health Questionnaire (PHQ-2)30
  • Whether patient has little interest in doing things?
  • Whether patient is feeling down, depressed or hopeless?

  • Weight loss in over-weight patients
  • Exercise programmes
  • Tai chi mind and body exercise
  • SSRI are first choice
  • Citalopram, sertraline and escitalopram are well tolerated
  • Treatment for at least six months or longer.
  • Long term treatment in patients with recurrence
  • Tricyclic antidepressants are associated with unfavourable side effects
  • Electroconvulsive therapy can be used in severe depression.
  • Cognitive behavioural therapy eg. education and reducing negative attitudes
  • Interpersonal psychotherapy eg. improving interpersonal relationships.
Collaborative care
  • Combined depression and diabetes treatment through structured integrated care
  • Continuous education, support and acknowledgement of depression as an integral part of diabetes care.



Exercise can positively contribute to the effective treatment of diabetes and depression. In the AHEAD (Action for Health in Diabetes) study of 5,145 participants with type 2 diabetes, mean (SD) age 58.7 (6.8) years, participants were randomly allocated to intensive lifestyle intervention (ILI) or to continue usual care. Those patients that received the intensive lifestyle intervention were found to have a significantly reduced incidence of depressive symptoms (HR 0.85, 95% CI 0.75 to 0.97, P=0.02) and preserved better function (P <0.01).22 Tai chi is emerging as a form of mind and body exercise that can be integrated into the prevention and rehabilitation of a number of medical conditions, including diabetes and depression. Tai chi involves a number of slowly performed flowing postures, which require mental concentration, physical balance, muscle engagement and relaxed breathing techniques; all of which may have beneficial effects in improving general health and wellbeing as well as reducing depressive symptoms.23



Selective serotonin re-uptake inhibitors (SSRIs) are the preferred antidepressants for older people with depression and diabetes due to their efficacy in treating depression and their lesser effect on blood glucose levels.24 Treatment should be continued for at least six months or until complete remission of depression, and then stopped gradually. Long-term treatment is recommended in patients with recurrent depression. No single SSRI antidepressant has been found to be more effective than another and selection should be based on patient tolerability.25 Those that have been found to be particularly well tolerated in older patients due to their lesser side effect profile are: citalopram, sertraline and escitalopram.26 Tricyclic antidepressants are a less appropriate choice for older patients due to their anti-cholinergic side-effects—confusion, hyperglycaemia, orthostatic hypotension and cardiac arrhythmias.26 In severe cases of depression, electroconvulsive therapy is another safe treatment option, even in frail older patients.26



In older people with comorbid diabetes and depression there are two main forms of psychotherapy that have found to be effective in reducing depressive symptoms—cognitive behavioural therapy (CBT) and interpersonal psychotherapy (IPT). CBT can be delivered individually by a trained medical professional and it aims to promote self-care and medication adherence through the reduction of the patient’s own negative attitudes towards their health. IPT, on the other hand, focuses on helping patients to improve their interpersonal relationships; using this to help them overcome and deal with their depressive symptoms. A combination of pharmacological and psychological therapies is likely to be the most effective way of maintaining remission and/or reducing the number of relapses compared to either approach alone.27


Collaborative care

Collaborative care, which involves psychotherapy in conjunction with medical care can reduce depression and improve the management of self-care in patients with diabetes. In a cluster-randomised controlled trial of 387 patients with a record of diabetes associated with depressive symptoms, mean depressive scores were 0.23 points lower on the checklist-13 depression scale (95% CI -0.41 to -0.05) for patients on the collaborative care plan approach compared to conventional care after four months of follow-up. Patients receiving the collaborative care intervention also reported being able to manage their own health more effectively, rated their care as more patient-centred and were more satisfied overall.28 Another study in Canada showed that collaborative care resulted in greater 12-month improvements in the patient health questionnaire (PHQ) score {7.3 (SD 5.6)} when compared with control subjects [5.2 (SD 5.7), P=0.015]. Recovery of depressive symptoms (PHQ reduced by 50%) was greater among intervention patients (61% versus 44%, P=0.03).29,30



Depression tends to co-exist with diabetes in older people and appears to have a bi-directional relationship, acting as a risk factor and as a consequence of diabetes.

Early diagnosis and treatment of depression is vital in order to break this vicious cycle.

Healthcare professionals involved in the care of older people with diabetes need to be aware of this relationship and of the benefits that a collaborative care approach can bring to that patient’s physical and mental health.


Helen K Scarf, Department of Elderly Medicine, Rotherham General Hospital, Moorgate Road, Rotherham

Ahmed H Abdelhafiz, Department of Elderly Medicine, Rotherham General Hospital, Moorgate Road, Rotherham

Conflict of interest: none declared



1. Abi KC, Roussel R, Mohammedi K, et al. Cause specific mortality in diabetes: recent changes in trend mortality. Eur J Prev Cardiol. 2012, 19: 374–81

2. Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes in Older Adults. Diabetes Care 2012; 35: 2650–64

3. Da Silva MA, Singh-Manoux A, Brunner EJ, et al. Bidirectional association between physical activity and symptoms of anxiety and depression: The Whitehall II study. Eur J Epidemiol 2012; 27: 537-46

4. Simon GE, Katon WJ, Lin EH, et al. Diabetes complications and depression as predictors of health service costs. Gen Hosp Psychiatry 2005; 27: 344–51

5. Silva N, Atlantis E, Ismail, K. A review of the association between depression and insulin resistance: Pitfalls of secondary analyses or a promising new approach to prevention of type 2 diabetes? Current Psychiatry Reports 2012; 14: 8–14

6. Lyoo IK, Yoon S, Jacobson AM, et al. Prefrontal cortical deficits in type 1 diabetes mellitus: brain correlates of comorbid depression. Arch Gen Psychiatry 2012; 69: 1267–76

7. Ho N, Sommers MS, Lucki I. Effects of diabetes on hippocampal neurogenesis: links to cognition and depression. Neurosci Biobehav Rev 2013; 37: 1346–62

8. Kan C, Silva N, Golden SH, et al. A systematic review and meta-analysis of the association between depression and insulin resistance. Diabetes Care 2013; 36: 480–9

9. Courtet P, Olie E. Circadian dimension and severity of depression. Eur Neuropsychopharmacol 2012; 22(Suppl. 3): S476–81

10. Gangwisch JE. Epidemiological evidence for the links between sleep, circadian rhythms and metabolism. Obes Rev 2009; 10(Suppl 2): 37–45.

11. Mezuk B, Eaton WW, Albrecht S, et al. Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care. 2008; 31(12): 2383–90

12. Phillips DI. Programming of the stress response: a fundamental mechanism underlying the long-term effects of the fetal environment? J Intern Med 2007; 261: 453–60

13. Hasan SS, Mamun AA, Clavarino AM, et al. Incidence and Risk of Depression Associated with Diabetes in Adults: Evidence from Longitudinal Studies. Community Ment Health J 2015; 51: 204–10

14. Maraldi C, Volpato S, Penninx BW, et al. Diabetes mellitus, glycemic control, and incident depressive symptoms among 70- to 79-year-old persons: the Health, Aging, and Body Composition Study. Arch Intern Med 2007; 167: 1137–44

15. Campayo A, de Jonge P, Roy JF, et al. Depressive Disorder and Incident Diabetes Mellitus: The Effect of Characteristics of Depression. Am J Psychiatry 2010; 167: 580–88

16. Somerset SM, Graham L, Markwell K. Depression scores predict adherence in a dietary weight loss intervention trial. Clin Nutr 2011; 30: 593–98

17. Katon W, Lyles CR, Parker MM, et al. Association of depression with increased risk of dementia in patients with type 2 diabetes: the Diabetes and Aging Study. Arch. Gen. Psychiatry 2012; 69: 410–7.

18. Schmitz N, Gariepy G, Smith KJ, et al. Recurrent Subthreshold Depression in Type 2 Diabetes: An Important Risk Factor for Poor Health Outcomes. Diabetes Care 2014; 37: 970–8.

19. Schmitz N, Gariépy G, Smith KJ, et al. Longitudinal Relationships Between Depression and Functioning in People with Type 2 Diabetes. Ann Behav Med 2014; 47: 172–79

20. Pan A, Lucas M, Sun Q, et al. Increased mortality risk in women with depression and diabetes mellitus. Arch Gen Psychiatry 2011; 68: 42–50

21. Kimbro LB, Mangione CM, Steers WN, et al. Depression and All-Cause Mortality in Persons with Diabetes Mellitus: Are Older Adults at Higher Risk? Results from the Translating Research Into Action for Diabetes Study. J Am Geriatr Soc 2014; 62: 1017–22

22. The Look AHEAD Research Group. Impact of Intensive Lifestyle Intervention on Depression and Health-Related Quality of Life in Type 2Diabetes: The Look AHEAD Trial. Diabetes Care 2014; 37: 1544–53

23. Wang F, Lee EKO, Wu T, et al. The Effects of Tai Chi on Depression, Anxiety, and Psychological Well-Being: A Systematic Review and Meta-Analysis. Int J Behav Med 2014; 21: 605–17

24. Blazer DG. Depression in late life: review and commentary. Focus 2009; 7: 118–36

25. Mottram P, Wilson K, Stroble J. Antidepressants for depressed elderly. Cochrane Database Syst Rev 2006, Issue 1. Art. No.: CD003491. DOI: 10.1002/14651858.CD003491. pub2

26. Ciraulo DA, Evans JA, Qiu WQ, et al. Antidepressant treatment of geriatric depression. In: Ciraulo DA, Shader RI, eds. Pharmacotherapy of Depression. 2nd ed. New York, NY: Humana Press; 2011: 125–83

27. Stiefel F, Zdrojewski C, Bel Hadj F, et al. Effects of a multifaceted psychiatric intervention targeted for the complex medically ill: a randomized controlled trial. Psychother Psychosom 2008; 77: 247–56

28. Coventry P, Lovell K, Dickens C, et al. Integrated primary care for patients with mental and physical multimorbidity: cluster randomised controlled trial of collaborative care for patients with depression comorbid with diabetes or cardiovascular disease. BMJ 2015; 350:h638. doi: 10.1136/ bmj.h638

29. Johnson JA, Al Sayah F, Wozniak L, et al. Collaborative Care Versus Screening and Follow-up for Patients With Diabetes and Depressive Symptoms: Results of a Primary Care-Based Comparative Effectiveness Trial. Diabetes Care 2014; 37: 3220–26

30. Maurer DM. Screening for depression. Am Fam Physician 2012; 85: 139–44