Diabetes mellitus and depressive disorder, an undesirable association | Endocrinología y Nutrición (English Edition)

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This represents approximately 8.3% of the worldwide population.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> It is also estimated that 23 million quality-adjusted life years are lost every year because of diabetes complications.<a class="elsevierStyleCrossRef" href="#bib0015">3</a>On the contrary, approximately 340 million people have DD worldwide. In Europe, specifically, DD prevalence is estimated at 7% of the population.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> This is a highly relevant fact because DD is responsible for the majority of adverse non-fatal consequences related to health and accounts for 12% of total years lived with disability. DD is also associated with work absenteeism and decreased productivity, and also to a significant increase in healthcare resource utilization.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> In fact, DD is the second and tenth leading cause of disability-adjusted life years lost in females and males, respectively.<a class="elsevierStyleCrossRef" href="#bib0030">6</a>Relationship between diabetes and depressive disorderMore than 300 years ago, the British physician Thomas Willis suggested a probable relationship between T2DM and DD by stating that DM was the consequence of a “period of sadness”.<a class="elsevierStyleCrossRef" href="#bib0035">7</a>Since then, many studies have agreed that an association exists between T2DM and DD.<a class="elsevierStyleCrossRefs" href="#bib0040">8–24</a> In line with this, an Anderson et al. meta-analysis estimated an 11% prevalence of DD, diagnosed using a structured interview, in T2DM patients. This prevalence increased to 31% if subjects with clinically relevant depressive symptoms were included, even if they did not meet DD diagnostic criteria.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> DD prevalence may of course vary depending on the socioeconomic level of the country, the ethnic subgroup, diagnostic criteria, and the clinical characteristics of the diabetic population.<a class="elsevierStyleCrossRefs" href="#bib0045">9,14,17,19–24</a> On the contrary, most of these studies had a cross-sectional design that did not allow any temporal or causal relationship to be established. However, various prospective studies suggest an increased risk of DD in patients with T2DM, and of T2DM in depressed patients.<a class="elsevierStyleCrossRefs" href="#bib0050">10,13,16,17</a> Some meta-analyses have also detected a two-directional relationship between these conditions.<a class="elsevierStyleCrossRefs" href="#bib0045">9,11,12</a> In a systematic review, Renn et al.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> recently reported a relative risk (RR) of T2DM in patients with DD of 1.60 (95% confidence interval [CI] 1.37–1.88). A similar but lower increase in RR of DD was found in diabetic patients (1.15 [95% CI 1.02–1.30]). <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the different studies on DD prevalence in diabetes.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Depressive disorder as a consequence of diarrheaOne possible reason for the increased risk of DD in diabetic patients is the psychosocial impact involved in being diagnosed with a chronic disease.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> The need for self-care to maintain good metabolic control, the fear of experiencing chronic complications in the mid or short term, etc., may lead to an anxious-depressive state, especially in people with little social support and a low cultural level.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> However, the observation of a greater prevalence of depressive symptoms compared to the general population, even in undiagnosed diabetic patients, makes the psychosocial theory insufficient to explain per se the increased risk of DD in T2DM.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> On the contrary, various biochemical changes secondary to T2DM form the basis of a biological hypothesis that could explain the higher risk of DD among the diabetic population.<a class="elsevierStyleCrossRefs" href="#bib0040">8,11</a> According to this hypothesis, increased levels of circulating proinflammatory molecules, hyperglycemia, and probably hyperinsulinism contribute to a low-grade chronic inflammation state. The passage of these proinflammatory cytokines to the central nervous system through the blood–brain barrier would facilitate the development of DD by activating different pathways, such as cytokine synthesis by microglial cells, the activation of macrophage-like cells in periventricular areas, changes in neurotransmitter levels, decreased neuroplasticity, and adrenal axis hyperactivation.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> Indeed, a decreased volume of the brain areas implicated in the etiopathogenesis of DD, such as hippocampus and amygdala, has been shown in patients with T2DM.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> Finally, it is currently unknown whether the relationship between T2DM and DD could be explained through a genetic mechanism. DD is known to have a polygenic inheritance, with up to 40–50% heritability based on twin studies. Multiple genetic abnormalities have been suggested, including polymorphisms in the serotonin transporter promoter region, genes related to neurotrophic processes, polymorphisms in the brain-derived neurotrophic factor gene, etc., none of which have been confirmed or related to genetic defects of T2DM.<a class="elsevierStyleCrossRef" href="#bib0130">26</a>Depressive disorder as a predisposing factor for type 2 diabetes mellitusIt has been suggested that the increased risk of developing T2DM in subjects with DD may be attributed to the lifestyles adopted by most of them. DD is significantly associated with a higher body mass index, poorer dietary habits and a more sedentary lifestyle.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> Golden et al. examined the potential relation between DD and a higher incidence of T2DM, as well as its influence on lifestyle. De novo T2DM rates were significantly higher in the group with DD. However, these differences disappeared after adjustment for lifestyles (smoking, alcohol consumption, mean daily calorie consumption, and physical activity).<a class="elsevierStyleCrossRef" href="#bib0135">27</a> It is also known that drug treatment for DD may have harmful effects on blood glucose control, although this in itself does not fully explain the increased risk of T2DM, as this risk is also greater in individuals with undiagnosed or untreated DD.<a class="elsevierStyleCrossRefs" href="#bib0040">8,28</a> On the contrary, the biological hypothesis also attempts to explain the increased incidence of T2DM in subjects with DD. According to this theory, the increased synthesis of proinflammatory cytokines (interleukin-1β, tumor necrosis factor-α, interleukin-6) in the central nervous system results in systemic inflammation due to the passage of these substances through the blood-brain barrier. This leads to insulin resistance and β cell dysfunction and, finally, T2DM.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> In addition, hyperactivation of the corticotroph axis in DD induces a proinflammatory state by depressing the immune system, as well as insulin resistance due to the counterregulatory effect of cortisol.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> This would appear to suggest that diabetic patients with concomitant DD have higher levels of proinflammatory cytokines than those with no DD, and therefore have an increased risk of chronic complications. However, this hypothesis is yet to be proven.<a class="elsevierStyleCrossRef" href="#bib0135">27</a>Impact of depressive disorder on metabolic controlIn a four-year prospective study, Richardson et al. noted that glycosylated hemoglobin (HbA1c) levels were persistently higher in patients with T2DM who also had DD compared to that in those with no concomitant DD.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> Sufficient evidence is now available to show that DD impairs the care needed to maintain adequate control and drug treatment adherence and that it is associated with less healthy life habits (sedentary lifestyle and diets with high calorie contents).<a class="elsevierStyleCrossRefs" href="#bib0155">31–33</a> This is partly attributable to the fact that a positive attitude of patients with T2DM is crucial for disease management, and that DD is associated with a negative perception of the capacity for self-management.<a class="elsevierStyleCrossRef" href="#bib0170">34</a>Effect of depressive disorder on chronic complications of diabetesAs DD has been shown to impair metabolic control, it is only natural to think that diabetic patients with concomitant DD will experience more chronic complications. De Groot et al. published a meta-analysis of 27 studies conducted in T1DM and T2DM patients. There were more chronic complications among diabetic patients diagnosed with DD, including diabetic retinopathy, diabetic nephropathy, diabetic polyneuropathy, and erectile dysfunction.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> As regards macrovascular complications, an increased prevalence of cardiovascular disease has been noted in diabetic postmenopausal women with concomitant DD.<a class="elsevierStyleCrossRef" href="#bib0180">36</a>As regards the question of whether mortality is higher in patients with both T2DM and DD, epidemiological studies reported to date agree that such subjects have a more than 50% greater risk of all-cause death compared to healthy individuals and to patients with only one of the diseases.<a class="elsevierStyleCrossRef" href="#bib0185">37</a> Egede et al., in a cohort of 10,025 subjects from the National Health and Nutrition Examination Survey I followed up for eight years, showed an RR of all-cause death of 2.50 (95% CI 2.04–3.08).<a class="elsevierStyleCrossRef" href="#bib0190">38</a> The risk of all-cause death and cardiovascular death was also significantly increased in 78,282 women from the cohort of the Nurses Health Study (2.07 [CI 1.79–2.40] and 2.72 [CI 2.09–3.54] respectively).<a class="elsevierStyleCrossRef" href="#bib0195">39</a>Effect of depressive disorder on quality of life and work environmentT2DM and DD are two chronic diseases associated with a loss of functional capacity. In fact, the odds ratio for functional disability is up to seven times higher among subjects with T2DM and depression compared to that in those with none of these conditions, and it is also higher, although not significantly, compared to that in subjects with only one of the diseases.<a class="elsevierStyleCrossRef" href="#bib0200">40</a> This has an impact on work, and more than seven workdays per year may be lost on average.<a class="elsevierStyleCrossRef" href="#bib0205">41</a> This functional loss also has a negative impact on quality of life.<a class="elsevierStyleCrossRef" href="#bib0210">42</a> All of the foregoing shows that the coexistence of T2DM and DD in a same individual has a negative synergistic effect on functional capacity and quality of life.Health care resource consumptionA greater frequency of outpatient visits to primary and specialized care has been shown for patients with both T2DM and DD.<a class="elsevierStyleCrossRef" href="#bib0215">43</a> On the contrary, if a coexistent DD causes an increase in chronic complications in diabetic patients, health care expenses in these subjects may also be expected to be influenced by DD diagnosis and treatment. However, no cost studies supporting such assumption are yet available.Impact of treatmentThere is no doubt that DD has both metabolic and psychologically harmful effects on patients with T2DM, and treatment is directed at improving both areas. There are three types of interventions for ameliorating depressive symptoms: psychosocial, pharmacological, and mixed.<a class="elsevierStyleCrossRef" href="#bib0220">44</a>The psychosocial intervention most commonly used in patients with T2DM is cognitive-behavioral therapy (CBT). Studies reported to date show that CBT is effective for treating depressive symptoms in diabetic patients. However, there are conflicting results as to whether this type of intervention contributes to improvements in self-care and blood glucose control.<a class="elsevierStyleCrossRefs" href="#bib0220">44,45</a> Moreover, it is difficult to draw conclusions because of sample heterogeneity, different definitions of DD, the lack of subject stratification based on metabolic control, etc. In this regard, the only randomized study reported to date, conducted by Lustman et al., found that at six months of treatment, and despite the fact that no differences were seen immediately after the intervention, patients with T2DM randomized to CBT had lower HbA1c levels than patients who had only received diabetes education (9.5% vs 10.9% (p=0.03). Interestingly, patients with T2DM on CBT had a lower self-testing frequency.<a class="elsevierStyleCrossRef" href="#bib0230">46</a>As regards drug treatment, selective serotonin reuptake inhibitors are the class of antidepressants most commonly used because of their efficacy and safety profile. They have also been shown to be able to decrease glucose levels and promote weight loss, and are therefore the drugs of choice for the treatment of DD in the population with T2DM. By contrast, the use of tricyclic antidepressants and monoamine oxidase inhibitors in diabetic subjects is less popular. The reason for this is that their use has been associated with hyperglycemia and weight increase respectively.<a class="elsevierStyleCrossRef" href="#bib0225">45</a> Other antidepressants, such as bupropion, have shown significant reductions in both depressive symptoms and body mass index and HbA1c. However, this improvement in HbA1c values was only maintained if adequate control of the depression was maintained.<a class="elsevierStyleCrossRef" href="#bib0235">47</a> In most studies reported to date, DD improvement and/or remission was evident in patients with T2DM on drug treatment, but this appeared to be ineffective for optimizing metabolic control. Our group similarly noted that treatment with citalopram (a selective serotonin reuptake inhibitor) for six months in a sample of patients with T2DM with DD criteria improved quality of life and depressive symptoms, but not metabolic control.<a class="elsevierStyleCrossRef" href="#bib0240">48</a>Similar results are found when CBT and drug therapy to treat DD are combined. That is to say, the depressive symptoms are controlled, but no positive results are seen in blood glucose levels.<a class="elsevierStyleCrossRefs" href="#bib0220">44,45</a>It should be noted that the studies reported to date have all had significant limitations, such as small sample size and short duration (which may make it difficult to show metabolic improvement) and between- and within-study heterogeneity of the samples with regard to the type of diabetes and the antidepressive treatment being assessed. On the contrary, changes in depressive symptoms have usually been assessed based on statistical significance, rather than actual clinical impact. In other words, since improvements are assessed based on depression test scores, the degree of personal impact and its potential positive influence on lifestyle habits, T2DM management, or even a change in clinical severity of DD is unknown.With regard to whether or not improved metabolic control reduces depressive symptoms, this is a question that has not been elucidated yet. Nor do we know if different effects may be exerted on depressive symptoms depending on the hypoglycemic drug used to improve metabolic control. In this regard, it should be kept in mind that, unlike other hypoglycemic agents, some of the new glucagon-like peptide 1 receptor agonists cross the blood-brain barrier and affect cerebral physiology.<a class="elsevierStyleCrossRef" href="#bib0245">49</a>Future linesThe various societies of specialists in diabetes are becoming aware of the clinical association of T2DM and DD. In fact, their recommendations for the management of diabetes include an initial evaluation of the patient's mood, the stress caused by diabetes, and the social environment of the patient, and state that DD should be ruled out if any impairment in blood glucose control occurs which is otherwise difficult to explain.<a class="elsevierStyleCrossRef" href="#bib0250">50</a> Despite this, the understanding by professionals of the diagnosis and treatment of DD in diabetes is still suboptimal. Because of this, treatment is most often inadequate or, in the worst of cases, nonexistent. Thus, in a series of patients with T2DM, we found that a significant proportion were undiagnosed and, even more significantly, a high proportion of patients, even when diagnosed, received inadequate treatment.<a class="elsevierStyleCrossRef" href="#bib0255">51</a> This area of knowledge should therefore be reinforced in training programs on diabetes, and adequate patient management should be promoted. It should not be forgotten that, although the treatment of depression has not been shown to improve metabolic control, it does achieve significant improvements in both mood and quality of life scales.As regards research, further studies are needed to identify DD mediators in diabetes and vice versa, particularly modifiable or treatable mediators. Toward this end, the conduct of longitudinal and generalizable studies using homogeneous diagnostic criteria should be promoted. Thus, few data are available regarding the reliability and validity of different tools to diagnose depression in T2DM. Little information is also available about the applicability of these instruments in different sociocultural situations.<a class="elsevierStyleCrossRef" href="#bib0260">52</a> On the contrary, it is very important to identify, define, and homogenize the diagnosis of comorbid conditions and any associated sociodemographic factors that may influence the results.<a class="elsevierStyleCrossRef" href="#bib0265">53</a> Both approaches will allow us to better identify the different risk groups and will contribute to the design of better therapeutic strategies. As regards the latter, it should be noted that the use of different antidepressants, prevents us from making a comparison of their results. Larger and longer studies are needed to quantify the impact of the different antidepressant treatments not only on depression scales, but also on personal life, quality of life, and the management of diabetes. Special mention should be made of the few data available on health economics. It should finally be emphasized that the impact of improved metabolic control and the different hypoglycemic agents on DD remains unknown.In conclusion, it may be stated that T2DM and DD are two closely related conditions. They very often coexist, and DD is not uncommonly underdiagnosed and undertreated in diabetic patients. In addition, the coexistence of both diseases is associated with poorer metabolic control and more difficult management. It also involves an increased risk of chronic complications and a substantial increase in morbidity and mortality. It may therefore be stated that both further research into this undesirable combination and improvements in clinical practice will be well worth the effort. As regards research, the need for prospective studies using homogeneous criteria that make it possible to advance in different therapeutic strategies should be emphasized. As regards clinical practice, it is essential to promote training and increase awareness in the different health care professionals involved.Conflicts of interestThe authors state that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:2 [ "identificador" => "xres311188" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec294341" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres311189" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec294342" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Introduction" "secciones" => array:9 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Relationship between diabetes and depressive disorder" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Depressive disorder as a consequence of diarrhea" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Depressive disorder as a predisposing factor for type 2 diabetes mellitus" ] 3 => array:2 [ "identificador" => "sec0025" "titulo" => "Impact of depressive disorder on metabolic control" ] 4 => array:2 [ "identificador" => "sec0030" "titulo" => "Effect of depressive disorder on chronic complications of diabetes" ] 5 => array:2 [ "identificador" => "sec0035" "titulo" => "Effect of depressive disorder on quality of life and work environment" ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Health care resource consumption" ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Impact of treatment" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Future lines" ] ] ] 5 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflicts of interest" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-11-07" "fechaAceptado" => "2013-01-14" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec294341" "palabras" => array:3 [ 0 => "Type 2 diabetes mellitus" 1 => "Depressive disorder" 2 => "Quality of lifer" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec294342" "palabras" => array:3 [ 0 => "Diabetes mellitus tipo 2" 1 => "Trastorno depresivo" 2 => "Calidad de vida" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Type 2 diabetes and depressive disorder are 2 chronic diseases highly prevalent in developed countries and with a negative impact on quality of life and life expectancy. In recent years, both conditions have been shown to be strongly associated. Thus, diabetics have an increased risk of suffering depressive disorder, as well as impaired glucose homeostasis, if they experience depression. In diabetic patients, concurrent depression is associated to greater difficulties in disease management and metabolic control, increased risk of developing chronic complications, decreased quality of life, and higher healthcare expenses. As a result, the interest of diabetic scientific societies in this association has increased, and they recommend regular mood assessment in diabetic patients. However, the limited clinical experience available and the conflicting results reported to date make it difficult to draw conclusions." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La diabetes tipo 2 y el trastorno depresivo son 2 enfermedades crónicas con una alta prevalencia en los países desarrollados, y con un impacto negativo sobre la calidad y la esperanza de vida. En los últimos años se ha demostrado que ambas entidades se hallan fuertemente asociadas, existiendo un mayor riesgo de desarrollar un trastorno depresivo entre la población diabética, así como de presentar alteraciones en la homeostasis de la glucosa si existe un síndrome depresivo. La coexistencia de una depresión en los pacientes diabéticos condiciona una mayor dificultad en el manejo de la enfermedad y en el control metabólico, un riesgo incrementado de desarrollar complicaciones crónicas, una disminución de la calidad de vida y un aumento del gasto sanitario. Ello ha suscitado el interés de las sociedades científicas, que ya aconsejan evaluar periódicamente el estado de ánimo. Sin embargo, la escasa experiencia a nivel clínico y los resultados contradictorios a nivel científico hacen que la elaboración de conclusiones resulte prematura." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Nicolau J, Masmiquel L. Diabetes mellitus y trastorno depresivo, un mal binomio. Endocrinol Nutr. 2013;60:583–589." ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "DM, diabetes mellitus; CI, confidence interval; OR, odds ratio; DD, depressive disorder." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Author (year) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Type of study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Sample \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Screening method for depressive disorder \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Prevalence of depressive disorder in diabetes mellitus \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gavard et al.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> (1993) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Systematic review \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 studies (type 1 and 2 DM) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Self-administered questionnaires and/or structured interview \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DD prevalence in DM patients, 8.5–27.3% (mean 14%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anderson et al.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> (2001) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Meta-analysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42 studies (type 1 and 2 DM) No.=21,351 adults \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Self-administered questionnaires and/or structured interview \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11% prevalence, increasing to 31% if patients with relevant clinical symptoms but not meeting DD diagnostic criteria are included \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ali et al.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> (2006) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Systematic review \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 randomized studies (type 1 and 2 DM) No.=51,331 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Self-administered questionnaires and/or structured interview \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DD prevalence in DM patients of 17.6% (OR 1.6; 95% CI 1.2–2) vs 9.8% in the general population. Greater prevalence in women with DM (23.8% vs 12.8%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">De Jonge et al.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> (2006) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Epidemiological study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4803 subjects older than 55 years, 597 with DM (12.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Self-administered questionnaires and/or structured interview \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DD prevalence in DM patients of 15.4% (after adjusting for confounding factors) (OR 1.41; 95% CI 1.08–1.83) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Knol et al.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> (2006) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cross-sectional study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4747 subjects older than 18 years with or without DM (type 1 or 2) diagnosis, prediabetes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Self-administered questionnaire and/or being on antidepressant treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DD prevalence in subjects diagnosed with DM of 29.7% (vs 20% in undiagnosed DM and 17.5% in prediabetes) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Li et al.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> (2008) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Epidemiological study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18,814 subjects older than 18 years (type 1 and 2 DM) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Self-administered questionnaire \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean age-adjusted DD prevalence rate: 8.3% (ranging from 2% to 28.8% in the different American states) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Koopmans et al.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> (2009) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cross-sectional study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1269 patients with T2DM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Self-administered questionnaire \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DD prevalence of 11% in DM patients \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Shehatah et al.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> (2010) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cross-sectional study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">458 patients with T2DM vs 546 subjects with no DM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Self-administered questionnaire and/or being on antidepressant treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DD prevalence of 32.1% in patients with T2DM vs 16% in subjects with no DM (p<0.0001) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ali et al.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> (2010) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Systematic review \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 studies conducted in adults with DM (type 1 and 2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Self-administered questionnaires and/or structured interview \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DD prevalence of 17.6% in DM patients vs 9.8% in subjects with no DM \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nicolau et al.<a class="elsevierStyleCrossRef" href="#bib0240">48</a> (2012) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cross-sectional study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">213 patients with T2DM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Self-administered questionnaire and structured interview or being on antidepressant treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DD prevalence of 54.9% in patients with T2DM \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab457219.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Prevalence of depressive disorder in the diabetic population in different studies conducted." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:53 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Does diabetes double the risk of depression?" 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Diabetes mellitus and depressive disorder, an undesirable association

Diabetes mellitus y trastorno depresivo, un mal binomio

Joana Nicolau

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jnicolauramis@gmail.com

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, Lluís Masmiquel

Servicio de Endocrinología y Nutrición, Hospital Son Llàtzer, Palma de Mallorca, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Type 2 diabetes mellitus &#40;T2DM&#41; and depressive disorder &#40;DD&#41; are two chronic diseases that have a negative impact on both quality of life and life expectancy&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Data from the International Diabetes Federation suggest that some 366 million adult individuals currently have T2DM&#46; This represents approximately 8&#46;3&#37; of the worldwide population&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It is also estimated that 23 million quality-adjusted life years are lost every year because of diabetes complications&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">On the contrary&#44; approximately 340 million people have DD worldwide&#46; In Europe&#44; specifically&#44; DD prevalence is estimated at 7&#37; of the population&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> This is a highly relevant fact because DD is responsible for the majority of adverse non-fatal consequences related to health and accounts for 12&#37; of total years lived with disability&#46; DD is also associated with work absenteeism and decreased productivity&#44; and also to a significant increase in healthcare resource utilization&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> In fact&#44; DD is the second and tenth leading cause of disability-adjusted life years lost in females and males&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Relationship between diabetes and depressive disorder</span><p id="par0020" class="elsevierStylePara elsevierViewall">More than 300 years ago&#44; the British physician Thomas Willis suggested a probable relationship between T2DM and DD by stating that DM was the consequence of a &#8220;period of sadness&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Since then&#44; many studies have agreed that an association exists between T2DM and DD&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;24</span></a> In line with this&#44; an Anderson et al&#46; meta-analysis estimated an 11&#37; prevalence of DD&#44; diagnosed using a structured interview&#44; in T2DM patients&#46; This prevalence increased to 31&#37; if subjects with clinically relevant depressive symptoms were included&#44; even if they did not meet DD diagnostic criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> DD prevalence may of course vary depending on the socioeconomic level of the country&#44; the ethnic subgroup&#44; diagnostic criteria&#44; and the clinical characteristics of the diabetic population&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;14&#44;17&#44;19&#8211;24</span></a> On the contrary&#44; most of these studies had a cross-sectional design that did not allow any temporal or causal relationship to be established&#46; However&#44; various prospective studies suggest an increased risk of DD in patients with T2DM&#44; and of T2DM in depressed patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;13&#44;16&#44;17</span></a> Some meta-analyses have also detected a two-directional relationship between these conditions&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;11&#44;12</span></a> In a systematic review&#44; Renn et al&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> recently reported a relative risk &#40;RR&#41; of T2DM in patients with DD of 1&#46;60 &#40;95&#37; confidence interval &#91;CI&#93; 1&#46;37&#8211;1&#46;88&#41;&#46; A similar but lower increase in RR of DD was found in diabetic patients &#40;1&#46;15 &#91;95&#37; CI 1&#46;02&#8211;1&#46;30&#93;&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the different studies on DD prevalence in diabetes&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Depressive disorder as a consequence of diarrhea</span><p id="par0030" class="elsevierStylePara elsevierViewall">One possible reason for the increased risk of DD in diabetic patients is the psychosocial impact involved in being diagnosed with a chronic disease&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The need for self-care to maintain good metabolic control&#44; the fear of experiencing chronic complications in the mid or short term&#44; etc&#46;&#44; may lead to an anxious-depressive state&#44; especially in people with little social support and a low cultural level&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> However&#44; the observation of a greater prevalence of depressive symptoms compared to the general population&#44; even in undiagnosed diabetic patients&#44; makes the psychosocial theory insufficient to explain per se the increased risk of DD in T2DM&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> On the contrary&#44; various biochemical changes secondary to T2DM form the basis of a biological hypothesis that could explain the higher risk of DD among the diabetic population&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;11</span></a> According to this hypothesis&#44; increased levels of circulating proinflammatory molecules&#44; hyperglycemia&#44; and probably hyperinsulinism contribute to a low-grade chronic inflammation state&#46; The passage of these proinflammatory cytokines to the central nervous system through the blood&#8211;brain barrier would facilitate the development of DD by activating different pathways&#44; such as cytokine synthesis by microglial cells&#44; the activation of macrophage-like cells in periventricular areas&#44; changes in neurotransmitter levels&#44; decreased neuroplasticity&#44; and adrenal axis hyperactivation&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Indeed&#44; a decreased volume of the brain areas implicated in the etiopathogenesis of DD&#44; such as hippocampus and amygdala&#44; has been shown in patients with T2DM&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Finally&#44; it is currently unknown whether the relationship between T2DM and DD could be explained through a genetic mechanism&#46; DD is known to have a polygenic inheritance&#44; with up to 40&#8211;50&#37; heritability based on twin studies&#46; Multiple genetic abnormalities have been suggested&#44; including polymorphisms in the serotonin transporter promoter region&#44; genes related to neurotrophic processes&#44; polymorphisms in the brain-derived neurotrophic factor gene&#44; etc&#46;&#44; none of which have been confirmed or related to genetic defects of T2DM&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Depressive disorder as a predisposing factor for type 2 diabetes mellitus</span><p id="par0035" class="elsevierStylePara elsevierViewall">It has been suggested that the increased risk of developing T2DM in subjects with DD may be attributed to the lifestyles adopted by most of them&#46; DD is significantly associated with a higher body mass index&#44; poorer dietary habits and a more sedentary lifestyle&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Golden et al&#46; examined the potential relation between DD and a higher incidence of T2DM&#44; as well as its influence on lifestyle&#46; De novo T2DM rates were significantly higher in the group with DD&#46; However&#44; these differences disappeared after adjustment for lifestyles &#40;smoking&#44; alcohol consumption&#44; mean daily calorie consumption&#44; and physical activity&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> It is also known that drug treatment for DD may have harmful effects on blood glucose control&#44; although this in itself does not fully explain the increased risk of T2DM&#44; as this risk is also greater in individuals with undiagnosed or untreated DD&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;28</span></a> On the contrary&#44; the biological hypothesis also attempts to explain the increased incidence of T2DM in subjects with DD&#46; According to this theory&#44; the increased synthesis of proinflammatory cytokines &#40;interleukin-1&#946;&#44; tumor necrosis factor-&#945;&#44; interleukin-6&#41; in the central nervous system results in systemic inflammation due to the passage of these substances through the blood-brain barrier&#46; This leads to insulin resistance and &#946; cell dysfunction and&#44; finally&#44; T2DM&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> In addition&#44; hyperactivation of the corticotroph axis in DD induces a proinflammatory state by depressing the immune system&#44; as well as insulin resistance due to the counterregulatory effect of cortisol&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> This would appear to suggest that diabetic patients with concomitant DD have higher levels of proinflammatory cytokines than those with no DD&#44; and therefore have an increased risk of chronic complications&#46; However&#44; this hypothesis is yet to be proven&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Impact of depressive disorder on metabolic control</span><p id="par0040" class="elsevierStylePara elsevierViewall">In a four-year prospective study&#44; Richardson et al&#46; noted that glycosylated hemoglobin &#40;HbA<span class="elsevierStyleInf">1c</span>&#41; levels were persistently higher in patients with T2DM who also had DD compared to that in those with no concomitant DD&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> Sufficient evidence is now available to show that DD impairs the care needed to maintain adequate control and drug treatment adherence and that it is associated with less healthy life habits &#40;sedentary lifestyle and diets with high calorie contents&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31&#8211;33</span></a> This is partly attributable to the fact that a positive attitude of patients with T2DM is crucial for disease management&#44; and that DD is associated with a negative perception of the capacity for self-management&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Effect of depressive disorder on chronic complications of diabetes</span><p id="par0045" class="elsevierStylePara elsevierViewall">As DD has been shown to impair metabolic control&#44; it is only natural to think that diabetic patients with concomitant DD will experience more chronic complications&#46; De Groot et al&#46; published a meta-analysis of 27 studies conducted in T1DM and T2DM patients&#46; There were more chronic complications among diabetic patients diagnosed with DD&#44; including diabetic retinopathy&#44; diabetic nephropathy&#44; diabetic polyneuropathy&#44; and erectile dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> As regards macrovascular complications&#44; an increased prevalence of cardiovascular disease has been noted in diabetic postmenopausal women with concomitant DD&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">As regards the question of whether mortality is higher in patients with both T2DM and DD&#44; epidemiological studies reported to date agree that such subjects have a more than 50&#37; greater risk of all-cause death compared to healthy individuals and to patients with only one of the diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> Egede et al&#46;&#44; in a cohort of 10&#44;025 subjects from the National Health and Nutrition Examination Survey I followed up for eight years&#44; showed an RR of all-cause death of 2&#46;50 &#40;95&#37; CI 2&#46;04&#8211;3&#46;08&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> The risk of all-cause death and cardiovascular death was also significantly increased in 78&#44;282 women from the cohort of the Nurses Health Study &#40;2&#46;07 &#91;CI 1&#46;79&#8211;2&#46;40&#93; and 2&#46;72 &#91;CI 2&#46;09&#8211;3&#46;54&#93; respectively&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Effect of depressive disorder on quality of life and work environment</span><p id="par0055" class="elsevierStylePara elsevierViewall">T2DM and DD are two chronic diseases associated with a loss of functional capacity&#46; In fact&#44; the odds ratio for functional disability is up to seven times higher among subjects with T2DM and depression compared to that in those with none of these conditions&#44; and it is also higher&#44; although not significantly&#44; compared to that in subjects with only one of the diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> This has an impact on work&#44; and more than seven workdays per year may be lost on average&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> This functional loss also has a negative impact on quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> All of the foregoing shows that the coexistence of T2DM and DD in a same individual has a negative synergistic effect on functional capacity and quality of life&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Health care resource consumption</span><p id="par0060" class="elsevierStylePara elsevierViewall">A greater frequency of outpatient visits to primary and specialized care has been shown for patients with both T2DM and DD&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> On the contrary&#44; if a coexistent DD causes an increase in chronic complications in diabetic patients&#44; health care expenses in these subjects may also be expected to be influenced by DD diagnosis and treatment&#46; However&#44; no cost studies supporting such assumption are yet available&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Impact of treatment</span><p id="par0065" class="elsevierStylePara elsevierViewall">There is no doubt that DD has both metabolic and psychologically harmful effects on patients with T2DM&#44; and treatment is directed at improving both areas&#46; There are three types of interventions for ameliorating depressive symptoms&#58; psychosocial&#44; pharmacological&#44; and mixed&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The psychosocial intervention most commonly used in patients with T2DM is cognitive-behavioral therapy &#40;CBT&#41;&#46; Studies reported to date show that CBT is effective for treating depressive symptoms in diabetic patients&#46; However&#44; there are conflicting results as to whether this type of intervention contributes to improvements in self-care and blood glucose control&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">44&#44;45</span></a> Moreover&#44; it is difficult to draw conclusions because of sample heterogeneity&#44; different definitions of DD&#44; the lack of subject stratification based on metabolic control&#44; etc&#46; In this regard&#44; the only randomized study reported to date&#44; conducted by Lustman et al&#46;&#44; found that at six months of treatment&#44; and despite the fact that no differences were seen immediately after the intervention&#44; patients with T2DM randomized to CBT had lower HbA<span class="elsevierStyleInf">1c</span> levels than patients who had only received diabetes education &#40;9&#46;5&#37; vs 10&#46;9&#37; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&#46; Interestingly&#44; patients with T2DM on CBT had a lower self-testing frequency&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">As regards drug treatment&#44; selective serotonin reuptake inhibitors are the class of antidepressants most commonly used because of their efficacy and safety profile&#46; They have also been shown to be able to decrease glucose levels and promote weight loss&#44; and are therefore the drugs of choice for the treatment of DD in the population with T2DM&#46; By contrast&#44; the use of tricyclic antidepressants and monoamine oxidase inhibitors in diabetic subjects is less popular&#46; The reason for this is that their use has been associated with hyperglycemia and weight increase respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> Other antidepressants&#44; such as bupropion&#44; have shown significant reductions in both depressive symptoms and body mass index and HbA<span class="elsevierStyleInf">1c</span>&#46; However&#44; this improvement in HbA<span class="elsevierStyleInf">1c</span> values was only maintained if adequate control of the depression was maintained&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> In most studies reported to date&#44; DD improvement and&#47;or remission was evident in patients with T2DM on drug treatment&#44; but this appeared to be ineffective for optimizing metabolic control&#46; Our group similarly noted that treatment with citalopram &#40;a selective serotonin reuptake inhibitor&#41; for six months in a sample of patients with T2DM with DD criteria improved quality of life and depressive symptoms&#44; but not metabolic control&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Similar results are found when CBT and drug therapy to treat DD are combined&#46; That is to say&#44; the depressive symptoms are controlled&#44; but no positive results are seen in blood glucose levels&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">44&#44;45</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">It should be noted that the studies reported to date have all had significant limitations&#44; such as small sample size and short duration &#40;which may make it difficult to show metabolic improvement&#41; and between- and within-study heterogeneity of the samples with regard to the type of diabetes and the antidepressive treatment being assessed&#46; On the contrary&#44; changes in depressive symptoms have usually been assessed based on statistical significance&#44; rather than actual clinical impact&#46; In other words&#44; since improvements are assessed based on depression test scores&#44; the degree of personal impact and its potential positive influence on lifestyle habits&#44; T2DM management&#44; or even a change in clinical severity of DD is unknown&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">With regard to whether or not improved metabolic control reduces depressive symptoms&#44; this is a question that has not been elucidated yet&#46; Nor do we know if different effects may be exerted on depressive symptoms depending on the hypoglycemic drug used to improve metabolic control&#46; In this regard&#44; it should be kept in mind that&#44; unlike other hypoglycemic agents&#44; some of the new glucagon-like peptide 1 receptor agonists cross the blood-brain barrier and affect cerebral physiology&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Future lines</span><p id="par0095" class="elsevierStylePara elsevierViewall">The various societies of specialists in diabetes are becoming aware of the clinical association of T2DM and DD&#46; In fact&#44; their recommendations for the management of diabetes include an initial evaluation of the patient&#39;s mood&#44; the stress caused by diabetes&#44; and the social environment of the patient&#44; and state that DD should be ruled out if any impairment in blood glucose control occurs which is otherwise difficult to explain&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> Despite this&#44; the understanding by professionals of the diagnosis and treatment of DD in diabetes is still suboptimal&#46; Because of this&#44; treatment is most often inadequate or&#44; in the worst of cases&#44; nonexistent&#46; Thus&#44; in a series of patients with T2DM&#44; we found that a significant proportion were undiagnosed and&#44; even more significantly&#44; a high proportion of patients&#44; even when diagnosed&#44; received inadequate treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> This area of knowledge should therefore be reinforced in training programs on diabetes&#44; and adequate patient management should be promoted&#46; It should not be forgotten that&#44; although the treatment of depression has not been shown to improve metabolic control&#44; it does achieve significant improvements in both mood and quality of life scales&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">As regards research&#44; further studies are needed to identify DD mediators in diabetes and vice versa&#44; particularly modifiable or treatable mediators&#46; Toward this end&#44; the conduct of longitudinal and generalizable studies using homogeneous diagnostic criteria should be promoted&#46; Thus&#44; few data are available regarding the reliability and validity of different tools to diagnose depression in T2DM&#46; Little information is also available about the applicability of these instruments in different sociocultural situations&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a> On the contrary&#44; it is very important to identify&#44; define&#44; and homogenize the diagnosis of comorbid conditions and any associated sociodemographic factors that may influence the results&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a> Both approaches will allow us to better identify the different risk groups and will contribute to the design of better therapeutic strategies&#46; As regards the latter&#44; it should be noted that the use of different antidepressants&#44; prevents us from making a comparison of their results&#46; Larger and longer studies are needed to quantify the impact of the different antidepressant treatments not only on depression scales&#44; but also on personal life&#44; quality of life&#44; and the management of diabetes&#46; Special mention should be made of the few data available on health economics&#46; It should finally be emphasized that the impact of improved metabolic control and the different hypoglycemic agents on DD remains unknown&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">In conclusion&#44; it may be stated that T2DM and DD are two closely related conditions&#46; They very often coexist&#44; and DD is not uncommonly underdiagnosed and undertreated in diabetic patients&#46; In addition&#44; the coexistence of both diseases is associated with poorer metabolic control and more difficult management&#46; It also involves an increased risk of chronic complications and a substantial increase in morbidity and mortality&#46; It may therefore be stated that both further research into this undesirable combination and improvements in clinical practice will be well worth the effort&#46; As regards research&#44; the need for prospective studies using homogeneous criteria that make it possible to advance in different therapeutic strategies should be emphasized&#46; As regards clinical practice&#44; it is essential to promote training and increase awareness in the different health care professionals involved&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflicts of interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors state that they have no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Introduction"
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            0 => array:2 [
              "identificador" => "sec0010"
              "titulo" => "Relationship between diabetes and depressive disorder"
            ]
            1 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Depressive disorder as a consequence of diarrhea"
            ]
            2 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Depressive disorder as a predisposing factor for type 2 diabetes mellitus"
            ]
            3 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Impact of depressive disorder on metabolic control"
            ]
            4 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Effect of depressive disorder on chronic complications of diabetes"
            ]
            5 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Effect of depressive disorder on quality of life and work environment"
            ]
            6 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Health care resource consumption"
            ]
            7 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Impact of treatment"
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              "identificador" => "sec0050"
              "titulo" => "Future lines"
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          ]
        ]
        5 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Conflicts of interest"
        ]
        6 => array:1 [
          "titulo" => "References"
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      ]
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    "fechaRecibido" => "2012-11-07"
    "fechaAceptado" => "2013-01-14"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec294341"
          "palabras" => array:3 [
            0 => "Type 2 diabetes mellitus"
            1 => "Depressive disorder"
            2 => "Quality of lifer"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec294342"
          "palabras" => array:3 [
            0 => "Diabetes mellitus tipo 2"
            1 => "Trastorno depresivo"
            2 => "Calidad de vida"
          ]
        ]
      ]
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      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Type 2 diabetes and depressive disorder are 2 chronic diseases highly prevalent in developed countries and with a negative impact on quality of life and life expectancy&#46; In recent years&#44; both conditions have been shown to be strongly associated&#46; Thus&#44; diabetics have an increased risk of suffering depressive disorder&#44; as well as impaired glucose homeostasis&#44; if they experience depression&#46; In diabetic patients&#44; concurrent depression is associated to greater difficulties in disease management and metabolic control&#44; increased risk of developing chronic complications&#44; decreased quality of life&#44; and higher healthcare expenses&#46; As a result&#44; the interest of diabetic scientific societies in this association has increased&#44; and they recommend regular mood assessment in diabetic patients&#46; However&#44; the limited clinical experience available and the conflicting results reported to date make it difficult to draw conclusions&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La diabetes tipo 2 y el trastorno depresivo son 2 enfermedades cr&#243;nicas con una alta prevalencia en los pa&#237;ses desarrollados&#44; y con un impacto negativo sobre la calidad y la esperanza de vida&#46; En los &#250;ltimos a&#241;os se ha demostrado que ambas entidades se hallan fuertemente asociadas&#44; existiendo un mayor riesgo de desarrollar un trastorno depresivo entre la poblaci&#243;n diab&#233;tica&#44; as&#237; como de presentar alteraciones en la homeostasis de la glucosa si existe un s&#237;ndrome depresivo&#46; La coexistencia de una depresi&#243;n en los pacientes diab&#233;ticos condiciona una mayor dificultad en el manejo de la enfermedad y en el control metab&#243;lico&#44; un riesgo incrementado de desarrollar complicaciones cr&#243;nicas&#44; una disminuci&#243;n de la calidad de vida y un aumento del gasto sanitario&#46; Ello ha suscitado el inter&#233;s de las sociedades cient&#237;ficas&#44; que ya aconsejan evaluar peri&#243;dicamente el estado de &#225;nimo&#46; Sin embargo&#44; la escasa experiencia a nivel cl&#237;nico y los resultados contradictorios a nivel cient&#237;fico hacen que la elaboraci&#243;n de conclusiones resulte prematura&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Nicolau J&#44; Masmiquel L&#46; Diabetes mellitus y trastorno depresivo&#44; un mal binomio&#46; Endocrinol Nutr&#46; 2013&#59;60&#58;583&#8211;589&#46;</p>"
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        "etiqueta" => "Table 1"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">DM&#44; diabetes mellitus&#59; CI&#44; confidence interval&#59; OR&#44; odds ratio&#59; DD&#44; depressive disorder&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Author &#40;year&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Type of study&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Sample&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Screening method for depressive disorder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Prevalence of depressive disorder in diabetes mellitus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Gavard et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> &#40;1993&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systematic review&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">20 studies &#40;type 1 and 2 DM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Self-administered questionnaires and&#47;or structured interview&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">DD prevalence in DM patients&#44; 8&#46;5&#8211;27&#46;3&#37; &#40;mean 14&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Anderson et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> &#40;2001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Meta-analysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">42 studies &#40;type 1 and 2 DM&#41; No&#46;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#44;351 adults&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Self-administered questionnaires and&#47;or structured interview&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#37; prevalence&#44; increasing to 31&#37; if patients with relevant clinical symptoms but not meeting DD diagnostic criteria are included&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ali et al&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> &#40;2006&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systematic review&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 randomized studies &#40;type 1 and 2 DM&#41; No&#46;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>51&#44;331&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Self-administered questionnaires and&#47;or structured interview&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DD prevalence in DM patients of 17&#46;6&#37; &#40;OR 1&#46;6&#59; 95&#37; CI 1&#46;2&#8211;2&#41; vs 9&#46;8&#37; in the general population&#46; Greater prevalence in women with DM &#40;23&#46;8&#37; vs 12&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">De Jonge et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> &#40;2006&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Epidemiological study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4803 subjects older than 55 years&#44; 597 with DM &#40;12&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Self-administered questionnaires and&#47;or structured interview&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DD prevalence in DM patients of 15&#46;4&#37; &#40;after adjusting for confounding factors&#41; &#40;OR 1&#46;41&#59; 95&#37; CI 1&#46;08&#8211;1&#46;83&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Knol et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> &#40;2006&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4747 subjects older than 18 years with or without DM &#40;type 1 or 2&#41; diagnosis&#44; prediabetes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Self-administered questionnaire and&#47;or being on antidepressant treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DD prevalence in subjects diagnosed with DM of 29&#46;7&#37; &#40;vs 20&#37; in undiagnosed DM and 17&#46;5&#37; in prediabetes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Li et al&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> &#40;2008&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Epidemiological study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#44;814 subjects older than 18 years &#40;type 1 and 2 DM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Self-administered questionnaire&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mean age-adjusted DD prevalence rate&#58; 8&#46;3&#37; &#40;ranging from 2&#37; to 28&#46;8&#37; in the different American states&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Koopmans et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> &#40;2009&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1269 patients with T2DM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Self-administered questionnaire&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DD prevalence of 11&#37; in DM patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Shehatah et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> &#40;2010&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">458 patients with T2DM vs 546 subjects with no DM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Self-administered questionnaire and&#47;or being on antidepressant treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DD prevalence of 32&#46;1&#37; in patients with T2DM vs 16&#37; in subjects with no DM &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ali et al&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> &#40;2010&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systematic review&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 studies conducted in adults with DM &#40;type 1 and 2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Self-administered questionnaires and&#47;or structured interview&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DD prevalence of 17&#46;6&#37; in DM patients vs 9&#46;8&#37; in subjects with no DM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nicolau et al&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> &#40;2012&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">213 patients with T2DM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Self-administered questionnaire and structured interview or being on antidepressant treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DD prevalence of 54&#46;9&#37; in patients with T2DM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Prevalence of depressive disorder in the diabetic population in different studies conducted&#46;</p>"
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                    0 => array:2 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            1 => "A&#46; Crain"
                            2 => "W&#46;A&#46; Rush"
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                      "doi" => "10.1370/afm.964"
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                        "link" => array:1 [
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                    0 => array:1 [
                      "Libro" => array:4 [
                        "edicion" => "5th ed&#46;"
                        "fecha" => "2011"
                        "editorial" => "International Diabetes Federation"
                        "editorialLocalizacion" => "Brussels&#44; Belgium"
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                    ]
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            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The human&#44; social and economic impact of diabetes"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                0 => array:2 [
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                            0 => "T&#46; Willis"
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Article information

ISSN: 21735093
Original language: English

DOI:10.1016/j.endoen.2013.12.004

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	4	1	5
2024 October	21	4	25
2024 September	16	6	22
2024 August	12	2	14
2024 July	6	1	7
2024 June	20	5	25
2024 May	10	5	15
2024 April	16	4	20
2024 March	34	3	37
2024 February	21	7	28
2024 January	25	5	30
2023 December	23	6	29
2023 November	24	8	32
2023 October	26	6	32
2023 September	23	9	32
2023 August	23	4	27
2023 July	24	7	31
2023 June	18	3	21
2023 May	38	5	43
2023 April	29	5	34
2023 March	32	10	42
2023 February	23	26	49
2023 January	29	29	58
2022 December	28	14	42
2022 November	34	10	44
2022 October	27	11	38
2022 September	25	21	46
2022 August	13	18	31
2022 July	12	10	22
2022 June	11	5	16
2022 May	33	6	39
2022 April	34	14	48
2022 March	28	7	35
2022 February	36	10	46
2022 January	43	7	50
2021 December	36	9	45
2021 November	32	7	39
2021 October	104	9	113
2021 September	54	16	70
2021 August	63	14	77
2021 July	15	10	25
2021 June	22	9	31
2021 May	18	18	36
2021 April	25	10	35
2021 March	16	15	31
2021 February	18	10	28
2021 January	16	9	25
2020 December	23	10	33
2020 November	19	10	29
2020 October	13	10	23
2020 September	19	15	34
2020 August	24	5	29
2020 July	7	11	18
2020 June	15	9	24
2020 May	17	3	20
2020 April	8	9	17
2020 March	23	8	31
2020 February	25	6	31
2020 January	16	9	25
2019 December	24	9	33
2019 November	12	9	21
2019 October	11	4	15
2019 September	14	14	28
2019 August	13	7	20
2019 July	14	21	35
2019 June	33	9	42
2019 May	119	17	136
2019 April	31	19	50
2019 March	9	5	14
2019 February	17	9	26
2019 January	16	4	20
2018 December	9	9	18
2018 November	16	4	20
2018 October	14	3	17
2018 September	17	5	22
2018 August	6	10	16
2018 July	7	1	8
2018 June	4	5	9
2018 May	13	6	19
2018 April	13	2	15
2018 March	2	2	4
2018 February	5	4	9
2018 January	7	1	8
2017 December	7	1	8
2017 November	15	3	18
2017 October	15	3	18
2017 September	16	3	19
2017 August	25	6	31
2017 July	17	3	20
2017 June	16	2	18
2017 May	16	1	17
2017 April	19	6	25
2017 March	33	17	50
2017 February	53	6	59
2017 January	17	0	17
2016 December	12	2	14
2016 November	17	2	19
2016 October	24	3	27
2016 September	19	5	24
2016 August	13	3	16
2016 July	15	1	16
2016 June	23	0	23
2016 May	18	5	23
2016 April	12	6	18
2016 March	16	7	23
2016 February	19	6	25
2016 January	20	10	30
2015 December	16	8	24
2015 November	20	9	29
2014 November	1	0	1
2014 April	0	1	1

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Now is Endocrinología, Diabetes y Nutrición (English ed.). More information

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Now is Endocrinología, Diabetes y Nutrición (English ed.). More information

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