Background: Diabetes and depression are highly prevalent chronic conditions that have significant impact on health outcomes. This study tested and examined the effects and the connection between diabetes and enhancing the risk of depression, undoubtedly the relation is there, several studies suggest that diabetes doubles the risk of depression. Additionally, the emergence of diabetes-related health problems increases depression risk furthermore, and the reason behind this correlation is still unknown. Correspondingly, diabetes' metabolic effects on brain function in addition to the toll day-to-day management can take are suggested by some researchers to be the cause. In a context of the potential epidemic nature of both diabetes mellitus and depression, and the negative effects reported in cases of comorbidity, this review suggests that the association of the two conditions is multifaceted.
Community studies reported increased risks of prevalent depression and incident depression among diabetic patients. In fact, the finding that supports psychosomatic hypotheses regarding the increased risk of diabetes among depressed patients is more consistent. A recent pertinent finding is the increased risk of diabetes presented in depression that is generally found in the community, namely non-severe, persistent, untreated depression. Above all, the proposal that all clinically relevant cases of depression found in the community should be treated sounds logical due to the negative implications of the comorbidity of diabetes and depression. Anyways, the documentation of the efficacy of treatment of depression and the safety of antidepressant use in cases of comorbidity through new studies seems to be obligatory.
By chance alone, diabetes and depression occur together approximately twice as frequently as would be predicted. Co-morbid diabetes and depression are a major clinical challenge as the outcomes of both conditions are worsened by the other. Although, the psychological burden of diabetes may contribute to depression. Both conditions may be driven by shared underlying biological and behavioral mechanisms, such as hypothalamic-pituitary-adrenal axis activation, inflammation, sleep disturbance, inactive lifestyle, poor dietary habits, and environmental and cultural risk factors. Depression is often missed in diabetic patients despite effective screening tools being readily available. Psychological interventions and anti- depressants are effective in treating depressive symptoms in diabetics however alter the glycemic control. Palliative care is provided by a team of specialists in order to achieve both optimal medical and psychiatric outcomes for people with co-morbid diabetes and depression. To review the support for two hypotheses concerning the interrelationship between depression and diabetes and to identify areas in which more research is needed, reports from the International Diabetes Federation (IDF) indicate that the prevalence of diabetes mellitus has reached epidemic levels globally. Estimates for 2010 indicate that 285 million adults have diabetes in the seven regions of the IDF.
The first man who observed the relationship between them was Dr. Thomas Willis; a British physician made the observation that there was a relationship between diabetes and depression when he suggested that diabetes was the result of ‘‘sadness or long sorrow’’, more than 300 years ago,for the time being,Anderson et al. conducted a meta-analysis of 42 published studies that included 21,351 adults and found that the prevalence of major depression in people with diabetes was 11% and the prevalence of clinically relevant depression was 31%.
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(Fig. 1: Anderson et al study)
However, estimations worldwide of depression prevalence among diabetics appear to vary by diabetes type and the(Fig. 1: Anderson et al study) types of developed/developing nations. For example, in the U.S., Li et al. examined data from the 2006 Behavioral Risk Factor Surveillance System (BRFSS), a standardized telephone survey of U.S. adults aged 18 and older and found that the age adjusted rate of depression was 8.3% (95% CI 7.3-9.3), ranging from a low of 2.0% to a high of 28.8% among the 50 states. They also noted a 25-fold difference in the rates among racial/ ethnic subgroups (lowest, 1.1% among Asians; highest, 27.8% among American Indians/Alaska Natives).
The estimate of depression prevalence must be provided with greater accuracy in order to correctly measure the potential impact of depression management in diabetes, or vice versa.
Systematic studies were performed; studies that examined the association between diabetes and depression were reviewed. Instead, a qualitative aggregation of studies was performed. Reports from the International Diabetes Federation, we used broad search terms to include the widest literature possible in our mapping, and search strategy was deliberately inclusive, in order to map the available evidence as widely as possible.
On the other hand, data from population-based studies are important for the study of comorbidity. Cross-sectional research shows a consistent positive association of diabetes and depression. Prospective population-based studies are reviewed, showing that the temporal order may be from diabetes to depression, or from depression to diabetes, depending to some extent on the type of diabetes. The size of the effects is fairly consistent among the small number of studies and not trivial. Possibilities for future epidemiologic research on comorbidity are discussed.
Most studies show that the relation between diabetes and depression is a bidirectional relationship, so each condition increases the risk of having the other, and those studies either studied both arms of this relationship or one arm.
One of the most recent studies by Chen and his colleagues was published in 2013,the study objective was to address the strength of association of the bidirectional relationship between type 2 diabetes and depression.The study was conducted by Chen and his colleagues and published in 2013 and it was also in agreement with previous studies like that done by Mekuz and his colleagues published in 2008. They used two cohort studies with the same source of the database to determine the link between depression and type 2 diabetes. First cohort study followed diabetic patients and non-diabetic subjects (control group) predicting the depression onset, both groups consisted of the same number of people (16,957) with matching age and sex.
The second cohort study followed depressed patients and non-depressed subjects (control group) predicting the diabetes onset, both groups consisted of the same number of people (5,847) with matching age and sex. The follow-up period was between 2000 and 2013, and onset of end points was identified from ambulatory care claims. He calculated the hazard ratio i.e. the incidence of becoming depressed and diabetic and the ratio between the two. And the first cohort analysis noted an incidence density (ID) of 7.03 per 1,000 person years (PY) and 5.04 per 1,000 PY for depression in diabetic and non-diabetic subjects, respectively. Which means that diabetes increases the risk of depression more than non-diabetic subjects, and hazard ratio (HR) of 1.43 (95% CI 1.16- 1.77).The second cohort analysis noted an ID of 27.59 per 1,000 PY and 9.22 per 1,000 PY for diabetes in depressive and non-depressive subjects, respectively. This means that depressed patients are more likely to develop diabetes than non-depressed subjects, and HR of 2.02 (1.80-2.27).The two cohort studies provided evidence for the bidirectional relationship between diabetes and depression, with a stronger association noted for the depression predicting onset of diabetes since the HR was stronger (2.02) compared to that of diabetes predicting onset of depression (1.43).Thus, the risk of diabetes in depressed patients is more than the risk of depression in diabetic patients.
Evidence suggests a bi-directional relationship between depression and type 2 diabetes. For example, research by Knol et al. suggests that in addition to depression being a consequence of diabetes, depression may also be a risk factor for the onset of diabetes. Mezuk et al. completed a review of studies from 1950 to 2007 of diabetes and depression to examine the bi-directional relationship between diabetes and type 2 diabetes. The pooled relative risk of incident depression associated with baseline diabetes was 1.15 (95% CI 1.02-1.30) while the relative risk of incident diabetes associated with baseline depression was 1.60 (95% CI 1.37- 1.88). In summary, depression was associated with a 60% increase of type 2 diabetes while type 2 diabetes was only associated with a moderate (15%) risk of depression.
This bidirectional relationship was confirmed in a recent study by Golden et al. in which they found that among individuals without elevated depressive symptoms at baseline, patients treated for diabetes had higher odds of developing depressive symptoms during the follow-up period. In contrast, individuals with impaired fasting glucose and those with untreated diabetes had reduced risk of incident depressive symptoms. The authors found that these findings were comparable across racial/ethnic group, and this is the problem with his study.
For one arm studies, there are two subtypes, either studies show that diabetes increases the risk of depression or vice versa. So, for studies which show that depression plays a role in increasing the risk of diabetes, Eaton et al in 1996, Eaton’s objective was to determine whether depression is associated with an increased risk for onset of diabetes. He followed up with certain patients to determine who became depressed, diabetic, and non-diabetic. Through his logistic models, major depressive disorder, if not mild depression or other psychiatric disorders, predicted the onset of diabetes to have an odds ratio of 2.23.Another study by Kont et al calculated the pooled risk ratio (also known as meta-analysis) which he used to investigate the interaction of depression with diabetes where limitations arose from the difficulty in determining historical order with two chronic conditions, even when the historical order of measurement is clear. In conclusion, it is possible that the treatment for depression led to an earlier diagnosis of diabetes. So, he calculated the pooled relative risk this usually means it is a meta-analysis meaning he looked at the studies collected data and analyzed them again.
Currently, the most recent one was done by Shmitz and his colleagues in 2016. They used another factor to the study; which is “Metabolic dysregulation”, and divided the patients into 3 groups (Depressed, Having Metabolic dysregulation and both depressed and having metabolic dysregulation). Controls; were not depressed, have no metabolic dysregulation (free of both conditions). They Followed them up for several years, we would expect that the second and the third group are going to develop diabetes, and synergistic effect was found in the third group; having two risk factors actually adds a synergistic effect to become diabetic, then he calculated the odds ratio and a got 6.61 as a result which is the highest number we got so far. Now, having diabetes increases the risk of depression, in order to see this relationship; four things have to be taken into consideration, such as how it increases the number of cases of depression; which is the prevalence, and how this relationship will affect the glycemic control of diabetes, then how it's going to affect the complications and its effects on mortality.
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If we start with the prevalence we have many studies, and the strongest one is a study by Anderson et al in 2001, he found that diabetes doubles the odds of depression by 2.2. Then for the glycemic control, we have conflicting data over this relationship some studies suggest that it leads to worsened glycemic control and hyperglycemia while others did not support this relationship. The first one is a study by Lostman and his colleague in 2000 they said that depression will lead to hyperglycemia, and what they did is that, they took patients with depression from the baseline data and after several months, they saw that the patients who had diabetes and depression had worse glycemic control than those who had diabetes alone, and their conclusion was that depression increases the risk of hyperglycemia. (Fig. 2: Lostman et al study).
On the other hand, Aikon and his colleague in 2009 said that depressive symptoms don’t necessarily lead to worsened glycemic control, and what they did, they took two groups and saw them after months and they didn’t see any statistical difference in the values of HbA1c between the two groups. Actually, they thought that if we separated the patients based on the regimen that they are taken, maybe that will affect the depression and he found that patients in insulin have worse glycemic control than those in oral medication. In the same way, Fisher was in agreement with what Aikon said and there is a lack of association between hyperglycemia and depression.
All the studies agreed that diabetes or the depression increases the risk of both complications whether they were macrovascular or microvascular. The depressed patients will have a higher risk of microvascular complications by 36% and macrovascular complications by 25%. At the same time, different studies were done with the same conclusion that depression increases the risk of mortality in diabetic patients the first study calculated the hazard ratio and they found a difference between degrees of the depression if the patients have modest symptoms 63% and if the patient has severe depression 49%.
There are two major hypotheses that explain the causal relationship between diabetes and depression. One of them states that depression precedes type 2 diabetes. Unfortunately, the mechanisms that are underlying the association between diabetes and depression are not clearly understood. Theoretically, it is believed that the increased risk of type 2 diabetes in individuals with depression is due to increased counterregulatory hormone release and action, alterations in transport function of glucose, and increased immunoinflammatory activation. It is thought that these physiologic alterations contribute to insulin resistance and beta islet cell dysfunction, which eventually lead to the development of type 2 diabetes. The second hypothesis is that having a chronic medical condition such as diabetes; whether it was of type 1 or type 2 creates psychosocial stressors which contribute to developing depression.
This hypothesis is supported by at least two important studies. First, from the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Survey 8870 participants who were free of diabetes at the beginning were evaluated for depression and then followed for 9 years. Over the study period; participants who had moderate or high symptoms of depression did not have significantly higher incidence of diabetes compared with those who did not have symptoms of depression at the beginning. Second, 1586 older adults from the Rancho Bernardo study were chosen to take a 75-g oral glucose tolerance test which is used to screen for type 2 diabetes. They were also assessed for depression with a modified Beck’s Depression Inventory. No evidence was found that shows an association between depression and incident diabetes, instead, the study showed that participants with a prior diabetes diagnosis had a 3.7- fold increased odds of depression.
There is considerable evidence that comorbid depression among individuals with diabetes is associated with poor diabetes outcomes such as glycemic control. Lustman et al. completed a meta-analysis of 24 studies and found that depression was significantly associated with poor glycemic control in individuals with type 1 and type 2 diabetes. The standard effect size was 0.17 (small to moderate) and was consistent (95% CE 0.13-0.21). Similar effect sizes were noted for type 1 and type 2 diabetes, but they were larger when using standardized interviews and diagnostic criteria rather than using self-reported questionnaire. Richardson et al. assessed the longitudinal effects of depression on glycemic control. It was found that there was a significant longitudinal relationship between depression and glycemic control over 4 years of follow-up and that depression was associated with persistently higher HbA1c levels over the time period. Wagner et al. found that African Americans with higher depressive symptoms had more diabetes complications after controlling for confounders. Finally, Miranda et al. reported that variations in depressive mood below the level of clinical depression were associated with differences in glycemic control among patients with type1 diabetes.
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