Diabetes and depression: a review



Download 85.2 Kb.
Sana20.01.2017
Hajmi85.2 Kb.
Diabetes mellitus and depression

Website - Homepage

DIABETES AND DEPRESSION: A REVIEW


Diabetes and depression are both common conditions particularly in the western world and are frequently co-morbidities. For this reason we chose to conduct our research and produce a website highlighting these facts.

The aim of the study was to create a website targeted at primary care teams in order to highlight the link between diabetes mellitus and depression.  In order to do this we researched these subjects in detail whilst conducting small reviews on each paper to determine its weight. From this research this website was created including our conclusions on the topic.

Our review is split in the top menu as follows:


  • Introduction

  • Epidemiology and Prevalence

  • Impact

    • Distribution of Mortality

    • Mechanism of Disease Synergy

  • Treatment

    • Pharmacotherapy

    • Pharmacotherapy – Implications for Diabetes Development

    • Psychotherapy

  • Conclusion

 

  • This site was made by a group of University of Edinburgh medical students who studied this subject over 10 weeks as part of SSC2a.

  • This website has not been peer reviewed.

  • We certify that this website is our own work and that we have authorisation to use all the content (e.g. figures / images) used in this website

  • We would like to thank Dr. Werner Pretorius for his tutorship and guidance during the project

  • Word Count: [insert here]

Introduction

Diabetes mellitus (DM) is one of the most commonly diagnosed chronic conditions, particularly in the western world, and thus is an area for extended study.

The characteristic symptom of DM is chronic hyperglycaemia, defined as a random plasma glucose of higher than 11 mmol/L (1) or fasting glucose of 6.1-6.9 mmol/L. Around 3-4% of the general population are diagnosed with DM due to this elevated level of glucose being present (2). The treatment for hyperglycaemia is insulin injections, most commonly carried out by the patient at regular intervals. It is therefore very important to educate the patient on how to accurately measure doses of insulin, how to adjust these doses dependant on blood glucose, and also how to inject the insulin. (1) Patients with DM have an increased risk of strokes, myocardial infarction and vascular diseases. (3) Because of this it is important to retain glycaemic control so as to prevent these occurring.

Along with the physical health complications that DM brings, there are commonly mental health problems that can impact on the quality of life of the patient. (2) One of the most common psychiatric condition that is present in patients with DM is depression. Depression can decrease patients’ quality of life, and often requires long term treatment with a combination of medication and therapy. This long term treatment for depression alone is projected to cost the National Health Service (4)(NHS) 2.96 billion pounds by 2026 despite the cost in 2007 being 1.68 billion (an increase of 56.8%) (5). The diagnosis of depression is classified by Alder et al as a person having a collection of symptoms including insomnia, unplanned weight loss and reduced ability to concentrate over a period of two weeks. These symptoms are only included if they are not due to the effects of drugs or explained by recent bereavement.

Not only are there effects causing those with DM to develop depression, but it has also been proven that the use of antidepressants can induce the onset of DM by affecting weight and glycaemic control. As depression is becoming much more prevalent worldwide, this is an important factor to take into consideration when prescribing appropriate treatments (6). We have also looked into the preferred treatment for people who develop depressive symptoms having already been diagnosed with DM, and which treatments would have the least negative effects on weight fluctuations and glycaemic control (7).

It is crucial to look into the effects that co-morbid depression and DM have on the body, as having both these conditions leads to a markedly higher mortality, as explained later in this analysis (8).

Due to these co-morbidities and the cost of treatment of both, it is postulated that by providing psychological care regarding depression at the first point someone is diagnosed with DM, morbidity and mortality of these conditions may be reduced. This would alleviate the financial strain that these comorbidities place on the NHS by reducing the number of hospital visits these patients may have.

Epidemiology and Prevalence

Over recent years our understanding of mental health disorders has increased, allowing those individuals suffering from such conditions to seek more effective treatment and feel able to talk freely about their condition, with less of the social stigma traditionally associated with mental health disorders (although it is important to note that some stigma still remains). Depression is the most common of all mental illnesses, affecting approximately 350 million people worldwide (9). Most of those diagnosed are living in western cultures where there is also a wide prevalence of DM. It is therefore important to recognise any association between these two commonly occurring diseases to ensure effective treatment and control, enabling patients to live the best quality of life.

Studies have been conducted to determine an association or cause between DM and depression. The WHO (World Health Organisation) conducted a World Health Survey focusing on Asian, African, South American and European low- and middle- income countries (10). Their analysis identified an increased prevalence of depression amongst those with DM in all continents (except Africa). Despite a drastic increase in prevalence of DM in the populations of Asia, South America and Africa over recent years, the associated secondary morbidity of depression is not as prevalent as it is in western populations. This may be because the stigma associated with mental illness in countries such as Africa acts as a barrier to treatment-seeking, resulting in under-diagnosis.

Prevalence of depression as a co-morbidity of DM tends to be greater in women compared to men (11). This is particularly apparent in type 2 DM; potentially related to the impacts of other co-morbidities of type 2 DM, such as obesity. As women are more likely to approach their doctor for treatment of depression, this gender gap may realistically be much smaller than reported.

The link between DM and depression is only partially understood, and the correlation between them has been shown to be bi-directional (12). Depression has been demonstrated to be associated with a 60% raised risk of developing type 2 DM; the relationship between depression and type 1 DM, however, is still unclear.

Depression can affect an individual’s health in numerous ways, many of which are significant risk factors in the development of type 2 DM. Depression has been proven to be a clinical risk factor in the development of adolescent obesity (13) and a cause of poor glycaemic control (14). Poor health behaviours, such as physical inactivity and smoking, manifest in depression and all increase risk of developing type 2 DM. This finding is supported by further studies that demonstrate how depression is a vital predictor in poor adherence to medical self-care: Gonzalez (2007) highlights how this is particularly noticeable in a depressed individual’s adherence to diet, exercise programmes and medication control (in this case glycaemic control)(15); all of which are significant risk factors in developing DM in the future.

Various hypotheses have been formulated to try and explain the physiology behind the increased rate of DM in depressed patients: most notably the increased activity of the hypothalamic-pituitary-adrenal axis which can result in insulin resistance (16). More specifically, the HPA releases more glucocorticoids (cortisol) around the body. Raised cortisol levels damage the function of glucose transporter type 4 proteins (GLUT4), altering the homeostatic control of glucose in the blood and resulting clinically in hyperglycaemia. Hyperglycaemia can lead to glucotoxicity and ultimately insulin resistance. Another possible pathophysiological link involves inflammatory processes in the body. The ‘cytokine-hypothesis’ of depression associated with co-morbidities such as DM has come about due to the increase in cytokine levels as a result of inflammatory responses which are more pronounced in depressed patients. An increase of cytokines with pro-inflammatory actions, such as interleukin-1 (IL-1), IL-6 and TNF-α have been associated with mood changes in patients who have never experienced any mental illness in the past (17). This may be because serotonin - the mood improving neurotransmitter - is broken down by cytokines. Therefore as DM (particularly type 1) has been associated with an increased inflammatory response, this would increase cytokine levels, resulting in greater breakdown in serotonin and thus lower mood. This would increase the risk of depression, especially if other risk factors are also present (17).

Studies have approximated that depression is present in 5%-10% of primary care patients and as many as 10%-14% of all medical inpatients (18). The increased prevalence of type 2 DM in depressed patients relative to the increased risk of other chronic diseases is still unclear but it is important to note both the widespread prevalence of depression throughout primary care and specifically the relationship between depression and the raised risk of developing DM.



source: t. gadalla. 2008. association of comorbid mood disorders and chronic illness with disability and quality of life in ontario, canada, chronic diseases in canada 28 (4): 148-154

Created using data from: T. Gadalla. 2008. Association of Comorbid Mood Disorders and Chronic Illness with Disability and Quality of Life in Ontario, Canada, Chronic Diseases in Canada 28 (4): 148-154  (Click to enlarge)



Distribution of Mortality

There are a number of studies which look into the relationship between DM and depression and the effect of this co-morbidity on mortality in a population. A study by Ismail et al, entitled “A Cohort Study of People with Diabetes and Their First Foot Ulcer” found that not only did having the co-morbidity have a strong link with developing foot ulcers, but having depression which was clinically significant tripled the mortality risk. (19) Another such study conducted found a strong worsening effect on mortality risk, measured in days until death. It concluded that there was a 49% greater mortality risk in patients with both depression and DM than in patients with DM alone. The evidence was particularly strong for the elderly, with the mortality risk being 78% greater in elderly patients with both conditions compared to younger patients with just DM. This highlights the need for depression screening especially amongst elderly diabetic patients, compared with younger diabetics (8).

Another study entitled “Diabetes, Depression, and Death” investigated the difference in mortality risk between patients with the co-morbidity and those with DM alone. It concluded that over a 5-year interval, patients who were treated for both DM and depression were less likely to die than patients who had both conditions, but were being treated only for DM. It too found a strong link for this especially in the elderly. However the study did acknowledge that the results may have been slightly flawed as all the results were obtained from greater metropolitan areas, not taking into account data from other areas in the U.S. As well as this, the self-reported nature of the questionnaires in the study may have also skewed results. There were a number of reasons given for the high mortality rates in diabetic depressed patients. The study suggested that a combination of increased inflammation due to DM and poor adherence to treatment may be responsible (20).

mortality graph

Figure 1 – Created using data from: Black S, Markides K, Ray L. Depression Predicts Increased Incidence of Adverse Health Outcomes in Older Mexican Americans With Type 2 Diabetes. Diabetes Care. 2003;26(10):2822-2828. (Click to Enlarge)



There is significant evidence to suggest that DM combined with depression increases all-cause mortality. In particular, looking at suicide alone as a cause of death showed interesting results. A cross-sectional study by Radobuljac et al investigated the link between suicidal and self-injurious behaviour and DM in Slovenian adolescents. The study was conducted by means of a self-reported questionnaire, originally designed by Kienhorst et al, and compared adolescents with Type 1 DM to those without it. The questionnaire was quite thorough, taking 45 minutes to complete and covering a range of topics such as demographic and family characteristics, possible future suicide, and self-injurious behaviour. When dividing the patients into subgroups by gender and performing further statistical analysis, the results proved highly interesting. Type 1 DM was found to protect against suicide in adolescent males; contradicting other studies that the burden of having a chronic illness such as DM would increase rates of depression, which goes hand in hand with suicide and self-destructive behaviour. The reason given for this finding is that the structure implemented on the patient’s life in managing DM in terms of diet, exercise and frequent medical contact may impact positively on their mental health, making them less prone to developing depression or resorting to self-destructive behaviour, as well staying away from “risky” behaviours such as smoking or drinking alcohol (21).

Mechanism of Disease Synergy

Previous chapters in this review have looked at the epidemiology of DM and depression comorbidity and its effect on mortality. This section aims to review possible reconciliatory models which may explain the (so far poorly understood) synergistic detrimental effect of DM and depression on patient outcome.
Biochemical:
Both depression and DM display serological profiles of chronic inflammatory disease. Cytokines such as IL-1, IL-6, IL-8 and TNF –α, and activation and production of various acute phase proteins such as activated CRP, amyloid A, and α1-acid glycoprotein have been shown to be elevated in both conditions individually, and excessively elevated in those suffering from the comorbidity (22-26). The literature base for this assertion is robust; most significant in establishing the hypothesis was perhaps Pickup et al’s study into association of non-insulin dependent DM/Metabolic syndrome X with inflammatory markers in 1997. Although the study used a small case population (n=19) the authors were able to show a significant relationship by: using well validated and extensively described assay techniques; validated diagnoses of DM/metabolic syndrome; control subjects and only accepting associations with p<0.01 or 0.001. The vascular implications of a sustained systemic inflammatory response are, in general terms, ones of adhesion, immune recruitment, and atherogenesis (27-30). How the inflammatory milieu arises in both conditions is relatively unknown, although evidence suggests that elevated serum cytokines and acute phase proteins both predict and are caused by diabetic and depressed states (31-34), indicating a bidirectional and reciprocal relationship. An interesting therapeutic feature of TNF-α serum levels has been exhibited in one study, in which successful antidepressant treatment led to reduction of both TNF-α serum levels and depressive symptoms. This strengthens the evidence for either a causative or resultant link between the cytokine and depression (35). As an end-note on cytokine involvement, the role of obesity as a primary disease course which may encourage the development of low-level chronic inflammation should not be overlooked. Studies have shown constitutive adipocyte production of TNF-α (36) and subsequent dose-related and reversible insulin resistance development; interesting considering the rate of coincidence of obesity with type 2 DM in particular (37, 38).
Stimulation of the HPA axis and cortisol release, with resulting increased sympathetic tone and catecholamine production, has also been noted in both diseases (22). Mechanisms of activation are unclear, but studies have shown a dose related activation of the HPA axis by inflammatory markers, some of which are present in diabetic and depressed individuals. This indicates another facet to the self-perpetuating cycle that a chronic inflammatory disease seems to present (39). It has also been shown that in depressed patients the normal inhibitory effects of cortisol in the HPA axis negative feedback loop are suppressed, leaving unfettered expression and activation (40).
A low level chronic increase of allostatic load, as presented by the above mechanisms, has various implications for vascular health. Biochemically at least it appears that an accentuated cytokine mediated inflammatory response, coupled with HPA axis hyperactivity and cortisol negative feedback attenuation, is the primary catalyst of the micro/macro vascular damage. This ultimately leads to the cardiovascular and cerebrovascular events that lead to adverse outcomes in depressed diabetic populations (41, 42).
Behavioural
Routes by which the depression-DM comorbidity impacts patient mortality appear to be focused on the negative impacts of the depressive state on diabetic self-care behaviour, the result being decreased glycaemic control and increased incidence of DM-related morbidities.
Among the most common behavioural factors induced or at least promoted by depression are a sedentary lifestyle, lack of medication/diet adherence, inconsistent glucose monitoring and smoking (43, 44). All the above factors are also commonly associated with a myriad of other determinants such as socioeconomic standing, distress caused by having DM itself, personal relationships and other lifestyle factors that often also show association with DM and depression individually (45, 46). As such it is difficult to tease apart a definitive and causative pathway by which behavioural changes and tendencies may result in increased mortality, but what evidence does show is a significant negative modification of diabetic control behaviour strongly associated with major depression.

Various behavioural and psychosocial factors are included in the below schematic in order to try and convey some level of the complexities of the DM and depression comorbidity.

schematic representation of the above text produced by oliver shipston-sharman (click to enlarge)

Schematic Representation of the above text produced by Oliver Shipston-Sharman (Click to Enlarge)
Although research into the synergistic mechanism by which depression and DM causes increased mortality is ongoing, large scale controlled studies have already conclusively proven a common mechanism. Prolonged low level inflammation influenced by HPA axis activation, increased sympathetic tone, obesity, and damaging behavioural patterns all result in a chronic affront to the vascular systems of diabetic depressed individuals. The body of evidence that this leads to the greatly increased mortality and morbidities in such populations is significant.

Pharmacotherapy

Antidepressant therapy in patients with DM who suffer from depression is an effective way of reducing depressive symptoms. This has been proven for SSRIs such as fluoxetine and citalopram (47), sertraline (48) and paroxetine (49); and tricyclic antidepressants such as nortriptyline (7). However, the evidence as to whether antidepressant therapy is useful in improving glycaemic control is fairly inconclusive. Certainly, remission of depression is beneficial for glycaemic control, as the presence of psychiatric illness in diabetic patients is associated with poorer glucose homeostasis, health behaviours and adherence to medication (50). However, it is important that the potential benefits of treating depression for metabolic control are not cancelled out by adverse effects of antidepressant drugs.

Some drug classes, such as tricyclic antidepressants (TCAs), have been shown to have deteriorative effects on glycaemic control – this was the case with nortriptyline, which was found to cause hyperglycaemia. This hyperglycaemia was not attributable to weight gain; however, weight gain is a well-documented side effect of tricyclic antidepressants (7), and as a result they should be avoided in diabetic patients. Another tricyclic antidepressant, imipramine, may also have a negative impact on glycaemic control by increasing fasting blood glucose levels (51). Although no longer widely prescribed due to its adverse effects and the development of newer and safer drugs, it is especially important that MAOIs are not prescribed for depression in diabetic patients, as they increase sensitivity to insulin and can directly induce hypoglycaemia (52).

SSRIs may be a preferable option for the treatment of depression in diabetic patients, as evidence suggests that drugs such as citalopram and fluoxetine may improve parameters such as fasting blood glucose and HbA1c (47). Fluoxetine in particular was found to have a favourable impact on glycaemic control (53, 54), as was sertraline (55). However, the evidence on this is still somewhat lacking, as several studies found that there was no significant change in glucose control when patients were prescribed SSRIs. This has been found with sertraline (56) and citalopram (57). Despite the conflicting information, it is likely that SSRIs are a better choice for depression in diabetic patients than drugs such as TCAs and MAOIs, given the evidence available to date.

Several studies have shown that an integrated approach to the care of patients with comorbid depression and DM could be very useful in improving clinical outcomes (58). Collaborative care is highly likely to improve recovery from depression as a direct outcome (59), thereby enabling diabetic patients to achieve better glycaemic control due to absence or lessened severity of psychiatric comorbidities (60). Patients who are given a personalised care plan, involving education about their comorbidity and the importance of managing depression in order to keep DM under control, may be more likely to achieve desired HbA1c levels, remission of depression, and satisfactory medication adherence (61).

Pharmacotherapy - Implications for Diabetes Development

It is important to consider how the treatment of mental illness may affect the risk of developing DM; particularly with respect to antidepressants and antipsychotics.

Being overweight or obese strongly influences the likelihood of developing DM. If none of the population had a BMI of over 25, then 64% of males and 74% of females could have been prevented from developing non-insulin dependent DM (62). A major concern for physicians now is the prescription of antidepressants and antipsychotics, as a variety of these are known to induce weight gain (6).

Antidepressants

Some antidepressants, particularly those used in persistent depression where other treatments have failed, are likely to cause considerable weight gain and thus predispose patients to DM. However, patients with the same depressive symptoms who were not treated with antidepressants had a lower prevalence of type 2 DM. This suggests that there is a stronger correlation between depression and DM when antidepressant therapy is given, compared to when it is not. This study involved a large cohort of 151,347 participants, which makes the results reliable by reducing the influence of chance (63). Antidepressants which are linked with weight gain include those with antihistamine mechanisms, tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs) (64). The antidepressant which has been proven to have the greatest effect on weight gain in Mirtazapine, which has interactions with specific serotonin receptors, as well as histaminergic receptors. The effects of these interactions include an increased appetite which causes the weight gain (65).



Antipsychotics

There are 2 strands of antipsychotic medications; First Generation Antipsychotics (FGAs), and Second Generation Antipsychotics (SGAs). FGAs are also known as typical antipsychotics, and SGAs as atypical antipsychotics. The difference with adverse effects appear to be that SGAs carry an increased risk of weight gain and Type II DM compared to FGAs (66). However, they have a lesser effect on the extrapyramidal system, and a more positive effect on depressive symptoms (compared to FGAs) and are therefore important in the treatment of some depressed patients (67). Olanzapine and Clozapine have been shown to cause patients to gain roughly 6kg in the first year of use. These drugs have also affect glucose regulation, which can induce the onset of DM. This is because dysregulation of glucose occurs as a result of insulin dysfunction, which can lead to hyperglycaemia - a sign of untreated DM (68).

One study has found that Clozapine in particular has a significant effect on the onset of DM in younger people (20-34 years old), with 5% of those taking Clozapine developing DM compared with only 2% of those using other antipsychotics. However, in other age groups there was no marked difference between using Clozapine versus any other antipsychotic (69).

It has been found that in patients taking atypical antipsychotics (SGAs) there is weight gain due to increased fat deposition in the body, leading to insulin resistance which causes DM (70). Another study found that Clozapine gives rise to a 7 fold greater chance of developing DM compared with conventional antipsychotics; Risperidone a 3.4 times greater risk; and Olanzapine a 3.2 times greater risk (71). Analysis of an UK General Practice Database, showed a six fold increase in the incidence of diabetes in those who had been prescribed Olanzapine at any point compared to controls not taking any antipsychotics and a fourfold increase compared to controls taking first generation antipsychotics (72, 73).

Data regarding the links between both antidepressants and antipsychotics with DM is somewhat limited to an extent. Trends suggest that they do induce the onset of DM, however evidence as to why this actually happens is inconclusive. Drugs must be further examined individually in order to understand the mechanisms by which they can encourage onset of DM.

Psychotherapy

For those in the diabetic and depressed population, the treatment options without pharmacological intervention usually lean towards the use of cognitive behavioural therapy (CBT) in an effort to decrease the depressive symptoms and improve glycaemic control. Many studies have been conducted in order to determine the effectiveness of CBT in the treatment of DM related depression, and to ascertain whether the solution is cost effective.

CBT is the name given to a series of discussions with a patient that explore the thoughts they are experiencing, with specific emphasis on the negative and positive thoughts they have regarding their condition (74). CBT does not, however, focus only on thoughts; it also explores the patient’s physical reactions to thoughts, and the environment that the patient is in. The idea of CBT is to manage the patient’s emotional response to their condition in order to reduce depressive symptoms (74).

Trials investigating the effects of CBT on glycaemic control and depressive symptoms in depressed diabetic patients have had fairly mixed results. An early prominent study by Lustman et al. was conducted in this area, and found that at follow-up 70% of depressed diabetic patients in the CBT group achieved remission compared to only 33.3% in the control (75). Glycaemic control was also better in the CBT group; glycated haemoglobin (GHb) levels decreased by 0.7% in the CBT group, whereas they increased by 0.9% in the control. A possible association was also found between depression and glycaemic control. The experiment was well-planned, with confounding factors accounted for, and only included patients who were diagnosed with depression. However, the sample size for the Lustman study was quite small (with 51 participants) and the follow-up period was only 6 months, raising the question of whether the positive results would have been sustained (especially as the percentage of patients with depression in remission decreased from post-treatment to follow-up).

The results from other studies have been varied. A randomized controlled trial by Penckofer et al. tested the efficacy of group CBT and found that within a group of 74 women, there was a lasting change in depression for the CBT group (76). Conversely, there was no indication that CBT was more effective in decreasing HbA1c over time than the control. On the other hand, a study by Snoek et al. (77) comparing CBT to blood glucose awareness training (BGAT) found a significant decrease in HbA1c in the CBT group, and a non-significant reduction of depression in both groups, raising the question of why glycaemic control was superior in the intervention group, despite no difference between the two in psychological outcome.

An interesting point made in Lustman et al’s study, however, was that adherence to self-monitoring of glucose actually declined in the CBT group (75). In response to the inconsistent findings of other trials in the improvement of glycaemic control, a study was conducted by Safren et al. (78) which tested an integrative treatment of CBT for adherence and depression (CBT-AD) in type 2 DM. Unsurprisingly, this proved much more successful in improving adherence to glucose monitoring, with the CBT-AD achieving 30.2% points higher than the control group, even though this declined to 16.9% points after a 4 month follow-up.

A randomised controlled trial by N C W Van der Ven et al (79) looked at adult type 1 DM patients with prolonged poor glycaemic control. They found results similar to Lustman et al, which showed that CBT was of some benefit when measuring glycaemic control using HbAC1 as an indicator (75). Additionally, it found that along with depressive symptoms being reduced in patients receiving CBT, there was an increase in DM management self-efficacy from 71.6 to 74.3 using the confidence in DM self-care scale.

Unlike the other studies, in which the education level of the intervention and control groups were relatively equal, a study by Bosma et al. (80) examined patients with either type 2 DM or COPD to see whether the benefits of self-management intervention (including CBT) would differ across education levels. Contrary to their hypothesis, it was found that the only group who showed a significant improvement (a 50% or greater reduction in depression compared to baseline) was the intervention group for those with the highest level of education. Despite having a mix of COPD and DM patients, stratification (dividing COPD and DM patients and choosing equal numbers of each strata at random) was utilised to ensure an equal spread of patients with both underlying diseases in all groups. Analysis showed that findings did not differ significantly by disease or severity of disease.

A study by Lamers et al (81) also found that those of a higher education level are more likely to benefit from CBT; over 9 months, only those of a high education level showed a statistically significant (P=0.03) reduction in both emotional distress and symptom distress. However, the study concluded that nurse administered CBT had limited effects on diabetic specific quality of life, despite the fact that it is potentially beneficial in glycaemic control.

From reviewing the literature on the subject there is little evidence to prove that CBT affects diabetic control in all patients with DM. However there is potential for CBT to be used as a first line prophylactic intervention by GPs or mental health professionals, in order to prevent deterioration in glycaemic control in diabetic patients with depression. The use of CBT to decrease depressive symptoms in diabetic patients and increase their quality of life is a topic that may require more research. Using CBT as a prophylactic measure in diabetic patients with depression may be appropriate and cost effective, as it could reduce admissions for depression and events from these co-morbidities.



Conclusion

The increase in obesity in the Western world has in turn led to a rise in DM. There is also a well-established link between DM and depression. This link is bi-directional, with the presence of one dramatically increasing the likelihood of developing the other. There are many possible explanations for the presence of depression increasing the risk of developing DM, though the most apparent seems to be the presence of worse health behaviours in the depressed, including smoking and lack of exercise. Poor adherence to medical self-care also contributes. Additionally, some classes of anti-depressants have been shown to lead to weight gain and therefore should be avoided in diabetics. This is primarily evident in people between the ages of 20 and 34, and careful consideration should be given to alternative treatments accordingly, for example CBT. Conversely, in diabetics, the burden of having to live with a chronic condition predisposes to depression. Furthermore, both DM and depression increase cortisol levels in the body, increasing inflammatory stress. Because of the overlapping pathogenic mechanisms, the combination of the two diseases increases the risk of death.


People living with the co-morbidity have a 40% greater risk of mortality than patients living with just one of the two. Particular attention should be paid to the elderly age bracket, and depression screening should be performed in this patient group in order to reduce mortality, as there is a 78% greater risk of death in elderly patients with the co-morbidity compared with patients without the co-morbidity. Although importance must be given to treating DM, as it is a persisting chronic illness, treating depression should not be neglected as patients being treated for both depression and DM are less likely to die. Interestingly, adolescent males with type 1 DM are shown to have better health behaviours in order to control their disease. This acts almost as a protective mechanism against depression as the positive attitude towards their health makes them less likely to get depressed.


Antidepressants have been shown to indirectly improve glycaemic control, by directly improving symptoms of depression. A reduction in depressive symptoms enhances patients’ control of their DM and manifests in individuals being more likely to self-manage their condition effectively. A strong correlation has been demonstrated between antidepressants and antipsychotics causing weight gain. These treatments should be carefully prescribed for depression because they are predisposing risk factors in the development of DM. Nortriptyline (TCA), for example, has been shown to directly induce hyperglycaemia. Clinicians should also be wary of prescribing MAOIs for depressed patients suffering from DM, as they increase sensitivity to insulin and have been shown to induce hypoglycaemia.
SSRIs are a better treatment choice for depressed diabetics than the previous mentioned classes of drugs. Primary care workers should also be aware of the increased risk of weight gain associated with 2nd generation anti-psychotics. In particular, commonly prescribed antipsychotics such as olanzapine and clozapine exhibit similar weight gain side effects as many antidepressants.
CBT is the gold standard psychotherapy for depression, with those undergoing CBT being twice as likely to achieve remission. GPs should note that CBT is not successful on all patients, however, and alternatives may be necessary. CBT may also be clinically relevant as preventive intervention, as a method of preventing the deterioration of glycaemic control.
Patients suffering comorbid depression and DM who are treated with a personalised and integrated approach to care exhibit improved clinical outcomes. A collaborative care approach increases remission from depression, and consequently patients achieve improved glycaemic control through better health behaviours.

1. Pearson, McCrimmon. Davidson's Principles and Practice of Medicine. 22 ed. Walker B, Colledge N, Ralston S, Penman I, editors: Churchill Livingston; 2014.

2. Ismail K, Peveler R. Handbook of Liaison Psychiatry. Lloyd G, Guthrie E, editors: Cambridge University Press; 2007.

3. Naish J, Revest P, Syndercombe Court D. Medical Sciences: Sauders/Elsevier; 2009.

4. NHS. Clinical Depression NHS Online2013. Available from: http://www.nhs.uk/Conditions/Depression/Pages/Introduction.aspx.

5. McCrone P, Dhanasiri S, Patel A, Knapp M, Lawton-Smith S. Paying The Price: The cost of mental health care in England to 2026. British Library: King's Fund, 2008.

6. Andersohn F, Schade R, Suissa S, Garbe E. Long-term use of antidepressants for depressive disorders and the risk of diabetes mellitus. The American journal of psychiatry. 2009;166(5):591-8.

7. Lustman PJ, Griffith LS, Clouse RE, Freedland KE, Eisen SA, Rubin EH, et al. Effects of Nortriptyline on Depression and Glycemic Control in Diabetes: Results of a Double-blind, Placebo-controlled Trial. Psychosomatic Medicine. 1997;59(3):241-50.

8. Kimbro LB, Mangione CM, Steers WN, Duru OK, McEwen L, Karter A, 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. Journal of the American Geriatrics Society. 2014;62(6):1017-22.

9. WHO. Depression. World Health Organisation, 2012.

10. Mommersteeg PMC, Herr R, Pouwer F, Holt RIG, Loerbroks A. The association between diabetes and an episode of depressive symptoms in the 2002 World Health Survey: an analysis of 231 797 individuals from 47 countries. Diabetic Medicine. 2013;30(6):e208-e14.

11. Pouwer F, Geelhoed-Duijvestijn PHLM, Tack CJ, Bazelmans E, Beekman AJ, Heine RJ, et al. Prevalence of comorbid depression is high in out-patients with Type 1 or Type 2 diabetes mellitus. Results from three out-patient clinics in the Netherlands. Diabetic Medicine. 2010;27(2):217-24.

12. Golden SH, Lazo M, Carnethon M, Bertoni AG, Schreiner PJ, Roux AVD, et al. Examining a Bidirectional Association Between Depressive Symptoms and Diabetes. JAMA : the journal of the American Medical Association. 2008;299(23):2751-9.

13. Goodman E, Whitaker RC. A Prospective Study of the Role of Depression in the Development and Persistence of Adolescent Obesity. Pediatrics. 2002;110(3):497-504.

14. Lustman PJ, Clouse RE. Depression in diabetic patients: the relationship between mood and glycemic control. Journal of Diabetes and its Complications. 2005;19(2):113-22.

15. Gonzalez JS, Safren SA, Cagliero E, Wexler DJ, Delahanty L, Wittenberg E, et al. Depression, self-care, and medication adherence in type 2 diabetes: relationships across the full range of symptom severity. Diabetes care. 2007;30(9):2222-7.

16. Tsigos C, Chrousos GP. Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress. Journal of Psychosomatic Research. 2002;53(4):865-71.

17. Himmerich H, Fulda S, Linseisen J, Seiler H, Wolfram G, Himmerich S, et al. Depression, comorbidities and the TNF-α system. European Psychiatry. 2008;23(6):421-9.

18. Katon W, Schulberg H. Epidemiology of depression in primary care. General hospital psychiatry. 1992;14(4):237-47.

19. Ismail K, Winkley K, Stahl D, Chalder T, Edmonds M. A Cohort Study of People With Diabetes and Their First Foot Ulcer: The role of depression on mortality. Diabetes care. 2007;30(6):1473-9.

20. Bogner HR, Morales KH, Post EP, Bruce ML. DIABETES, DEPRESSION, AND DEATH: A RANDOMIZED CONTROLLED TRIAL OF A DEPRESSION TREATMENT PROGRAM FOR OLDER ADULTS BASED IN PRIMARY CARE (PROSPECT). Diabetes care. 2007;30(12):3005-10.

21. Radobuljac MD, Bratina NU, Battelino T, Tomori M. Lifetime prevalence of suicidal and self-injurious behaviors in a representative cohort of Slovenian adolescents with type 1 diabetes. Pediatric Diabetes. 2009;10(7):424-31.

22. Steptoe A, Hackett RA, Lazzarino AI, Bostock S, La Marca R, Carvalho LA, et al. Disruption of multisystem responses to stress in type 2 diabetes: Investigating the dynamics of allostatic load. Proceedings of the National Academy of Sciences. 2014;111(44):15693-8.

23. Pickup JC, Mattock MB, Chusney GD, Burt D. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia. 1997;40(11):1286-92.

24. Suarez EC, Krishnan RR, Lewis JG. The relation of severity of depressive symptoms to monocyte-associated proinflammatory cytokines and chemokines in apparently healthy men. Psychosom Med. 2003;65(3):362-8.

25. Miller AH, Maletic V, Raison CL. Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. Biological psychiatry. 2009;65(9):732-41.

26. Laake J-PS, Stahl D, Amiel SA, Petrak F, Sherwood RA, Pickup JC, et al. The Association Between Depressive Symptoms and Systemic Inflammation in People With Type 2 Diabetes: Findings From the South London Diabetes Study. Diabetes care. 2014;37(8):2186-92.

27. Stehouwer CD, Gall MA, Twisk JW, Knudsen E, Emeis JJ, Parving HH. Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death. Diabetes. 2002;51(4):1157-65.

28. Devaraj S, Xu DY, Jialal I. C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis. Circulation. 2003;107(3):398-404.

29. Festa A, D’Agostino R, Howard G, Mykkänen L, Tracy RP, Haffner SM. Chronic Subclinical Inflammation as Part of the Insulin Resistance Syndrome: The Insulin Resistance Atherosclerosis Study (IRAS). Circulation. 2000;102(1):42-7.

30. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. Journal of Clinical Investigation. 2005;115(5):1111-9.

31. Duncan BB, Schmidt MI, Pankow JS, Ballantyne CM, Couper D, Vigo A, et al. Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes. 2003;52(7):1799-805.

32. Spranger J, Kroke A, Mohlig M, Hoffmann K, Bergmann MM, Ristow M, et al. Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes. 2003;52(3):812-7.

33. Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, et al. Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans: Role of Oxidative Stress. Circulation. 2002;106(16):2067-72.

34. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. Jama. 2001;286(3):327-34.

35. Tuglu C, Kara SH, Caliyurt O, Vardar E, Abay E. Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder. Psychopharmacology. 2003;170(4):429-33.

36. Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB. The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. The Journal of clinical investigation. 1995;95(5):2111-9.

37. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. Journal of Clinical Investigation. 1995;95(5):2409-15.

38. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science (New York, NY). 1993;259(5091):87-91.

39. Chrousos GP. The Hypothalamic–Pituitary–Adrenal Axis and Immune-Mediated Inflammation. New England Journal of Medicine. 1995;332(20):1351-63.

40. Pariante CM, Lightman SL. The HPA axis in major depression: classical theories and new developments. Trends in Neurosciences. 2008;31(9):464-8.

41. Bruce DG, Davis WA, Starkstein SE, Davis TME. A prospective study of depression and mortality in patients with type 2 diabetes: the Fremantle Diabetes Study. Diabetologia. 2005;48(12):2532-9.

42. Lin E, Heckbert S, Rutter C, Katon W, Ciechanowski P, Ludman E, et al. Depression and Increased Mortality in Diabetes: Unexpected Causes of Death. Annals of family medicine. 2009;7(5):414-21.

43. Ciechanowski PS, Katon WJ, Russo JE. Depression and diabetes: impact of depressive symptoms on adherence, function, and costs. Archives of internal medicine. 2000;160(21):3278-85.

44. Lin EH, Katon W, Von Korff M, Rutter C, Simon GE, Oliver M, et al. Relationship of depression and diabetes self-care, medication adherence, and preventive care. Diabetes care. 2004;27(9):2154-60.

45. Stringhini S, Dugravot A, Shipley M, Goldberg M, Zins M, Kivimaki M, et al. Health behaviours, socioeconomic status, and mortality: further analyses of the British Whitehall II and the French GAZEL prospective cohorts. PLoS medicine. 2011;8(2):e1000419.

46. Everson S, Maty S, Lynch J, Kaplan G. Epidemiologic Evidence for the Relation Between Socioeconomic Status and Depression, Obesity, and Diabetes. Journal of Psychosomatic Research. 2002;53(4):891-5.

47. Khazaie H, Rahimi M, Tatari F, Rezaei M, Najafi F, Tahmasian M. Treatment of depression in type 2 diabetes with Fluoxetine or Citalopram? Neurosciences (Riyadh, Saudi Arabia). 2011;16(1):42-5.

48. Lustman PJ, Clouse RE, Nix BD, Freedland KE, Rubin EH, McGill JB, et al. Sertraline for prevention of depression recurrence in diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2006;63(5):521-9.

49. Gulseren L, Gulseren S, Hekimsoy Z, Mete L. Comparison of fluoxetine and paroxetine in type II diabetes mellitus patients. Archives of medical research. 2005;36(2):159-65.

50. Dirmaier J, Watzke B, Koch U, Schulz H, Lehnert H, Pieper L, et al. Diabetes in primary care: prospective associations between depression, nonadherence and glycemic control. Psychotherapy and psychosomatics. 2010;79(3):172-8.

51. Ghaeli P, Shahsavand E, Mesbahi M, Kamkar M-Z, Sadeghi M, Dashti-Khavidaki S. Comparing the effects of 8-week treatment with fluoxetine and imipramine on fasting blood glucose of patients with major depressive disorder. Journal of clinical psychopharmacology. 2004;24(4):386-8.

52. Adnitt PI. Hypoglycemic Action of Monoamineoxidase Inhibitors (MAOI'S). Diabetes. 1968;17(10):628-33.

53. Breum L, Bjerre U, Bak JF, Jacobsen S, Astrup A. Long-term effects of fluoxetine on glycemic control in obese patients with non-insulin-dependent diabetes mellitus or glucose intolerance: influence on muscle glycogen synthase and insulin receptor kinase activity. Metabolism: clinical and experimental. 1995;44(12):1570-6.

54. O'Kane M, Wiles PG, Wales JK. Fluoxetine in the treatment of obese type 2 diabetic patients. Diabetic medicine : a journal of the British Diabetic Association. 1994;11(1):105-10.

55. Goodnick PJ, Kumar A, Henry JH, Buki VM, Goldberg RB. Sertraline in coexisting major depression and diabetes mellitus. Psychopharmacology bulletin. 1997;33(2):261-4.

56. Karaiskos D, Tzavellas E, Ilias I, Liappas I, Paparrigopoulos T. Agomelatine and sertraline for the treatment of depression in type 2 diabetes mellitus. International journal of clinical practice. 2013;67(3):257-60.

57. Nicolau J, Rivera R, Francés C, Chacártegui B, Masmiquel L. Treatment of depression in type 2 diabetic patients: Effects on depressive symptoms, quality of life and metabolic control. Diabetes Research and Clinical Practice. 2013;101(2):148-52.

58. McGregor M, Lin EH, Katon WJ. TEAMcare: an integrated multicondition collaborative care program for chronic illnesses and depression. The Journal of ambulatory care management. 2011;34(2):152-62.

59. Williams JW, Jr., Katon W, Lin EH, Noel PH, Worchel J, Cornell J, et al. The effectiveness of depression care management on diabetes-related outcomes in older patients. Annals of internal medicine. 2004;140(12):1015-24.

60. Lustman PJ, Griffith LS, Clouse RE, Cryer PE. Psychiatric illness in diabetes mellitus. Relationship to symptoms and glucose control. The Journal of nervous and mental disease. 1986;174(12):736-42.

61. Bogner HR, Morales KH, de Vries HF, Cappola AR. Integrated management of type 2 diabetes mellitus and depression treatment to improve medication adherence: a randomized controlled trial. Annals of family medicine. 2012;10(1):15-22.

62. WHO. Obesity: preventing and managing the global epidemic. Technical Report Series. World Health Organisation, 2000.

63. Kivimaki M, Hamer M, Batty GD, Geddes JR, Tabak AG, Pentti J, et al. Antidepressant medication use, weight gain, and risk of type 2 diabetes: a population-based study. Diabetes care. 2010;33(12):2611-6.

64. Schultz E, Malone DA. A practical approach to prescribing antidepressants. Cleveland Clinic Journal of Medicine. 2013;80(10):625-31.

65. Chiu H, Li T. Rapid Weight Gain During Mirtazapine Treatment. The Journal of Neuropsychiatry and Clinical Neurosciences. 2011;23(1):E7-E.

66. Moore R, 2nd, DeJoseph D, Simmons BB. Managing patients on antipsychotics: your domain, too. The Journal Of Family Practice. 2014;63(3):142-9.

67. Farah A. Atypicality of atypical antipsychotics. Primary care companion to the Journal of clinical psychiatry. 2005;7(6):268-74.

68. Vieweg V, Hasnain N. Schizophrenia, Antipsychotic Drugs, and Drug Induced Weight Gain and Obesity. Healthy Body- Healthy Mind. 2012;26(1):19-22.

69. Lund BC, Perry PJ, Brooks JM, Arndt S. Clozapine use in patients with schizophrenia and the risk of diabetes, hyperlipidemia, and hypertension: a claims-based approach. Arch Gen Psychiatry. 2001;58:1172-6.

70. Bergman RN, Ader M. Atypical antipsychotics and glucose homeostasis. The Journal of clinical psychiatry. 2005;66(4):504-14.

71. Guo JJ, Keck PE, Jr., Corey-Lisle PK, Li H, Jiang D, Jang R, et al. Risk of diabetes mellitus associated with atypical antipsychotic use among patients with bipolar disorder: A retrospective, population-based, case-control study. The Journal of clinical psychiatry. 2006;67(7):1055-61.

72. Dixon L, Weiden P, Delahanty J, Goldberg R, Postrado L, Lucksted A, et al. Prevalence and correlates of diabetes in national schizophrenia samples. Schizophrenia bulletin. 2000;26(4):903-12.

73. Koro CE, Fedder DO, L'Italien GJ, Weiss SS, Magder LS, Kreyenbuhl J, et al. Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study. BMJ : British Medical Journal. 2002;325(7358):243-.

74. David L. 10-Minute CBT in Primary Care: a brief introduction.

75. Lustman PJ, Griffith LS, Freedland KE, Kissel SS, Clouse RE. Cognitive behavior therapy for depression in type 2 diabetes mellitus. A randomized, controlled trial. Annals of internal medicine. 1998;129(8):613-21.

76. Penckofer SM, Ferrans C, Mumby P, Byrn M, Emanuele MA, Harrison PR, et al. A psychoeducational intervention (SWEEP) for depressed women with diabetes. Annals of behavioral medicine : a publication of the Society of Behavioral Medicine. 2012;44(2):192-206.

77. Snoek FJ, van der Ven NC, Twisk JW, Hogenelst MH, Tromp-Wever AM, van der Ploeg HM, et al. Cognitive behavioural therapy (CBT) compared with blood glucose awareness training (BGAT) in poorly controlled Type 1 diabetic patients: long-term effects on HbA moderated by depression. A randomized controlled trial. Diabetic medicine : a journal of the British Diabetic Association. 2008;25(11):1337-42.

78. Safren SA, Gonzalez JS, Wexler DJ, Psaros C, Delahanty LM, Blashill AJ, et al. A Randomized Controlled Trial of Cognitive Behavioral Therapy for Adherence and Depression (CBT-AD) in Patients With Uncontrolled Type 2 Diabetes. Diabetes care. 2014;37(3):625-33.

79. van Der Ven NCW, Hogenelst MHE, Tromp-Wever AME, Twisk JWR, van Der Ploeg HM, Heine RJ, et al. Short-term effects of cognitive behavioural group training (CBGT) in adult Type 1 diabetes patients in prolonged poor glycaemic control. A randomized controlled trial. Diabetic Medicine. 2005;22(11):1619-23.



80. Bosma H, Lamers F, Jonkers C, van Eijk J. Disparities by Education Level in Outcomes of a Self-Management Intervention: The DELTA Trial in the Netherlands. Psychiatric Services. 2011;62(7):793-5.

81. Lamers F, Jonkers CCM, Bosma H, Knottnerus JA, van Eijk JTM. Treating depression in diabetes patients: does a nurse-administered minimal psychological intervention affect diabetes-specific quality of life and glycaemic control? A randomized controlled trial. Journal of Advanced Nursing. 2011;67(4):788-99.

Do'stlaringiz bilan baham:


Ma'lumotlar bazasi mualliflik huquqi bilan himoyalangan ©hozir.org 2017
ma'muriyatiga murojaat qiling

    Bosh sahifa