1 - 14: Conceptual Perspectives on the Co-Occurrence of Mental and Physical Disease: Diabetes and Depression as a Model

Amidst growing evidence of the bidirectional relationship between diabetes and depression at the pathophysiological, clinical, behavioral, and social levels [e.g. [1]], their co-occurrence also provides a window on a broader range of comorbidities among mental health, psychological distress, and diverse chronic diseases and health conditions. Diabetes itself is an excellent model of chronic disease in general, and depression, with its broad range of influences, severity and intervention strategies provides an excellent model for understanding psychological distress and mental health problems as they interact with other aspects of health and well-being.

How social and psychological factors ‘get under the skin' to influence biological processes is central to understanding the complexity of relationships between mental health and chronic disease [e.g. [2]]. Figure 1 provides a useful model in diabetes and depression that recognizes how depression and stressful life events can lead to the activation of the hypothalamic-pituitary-adrenal axis and complex hormonal interactions in the pathogenesis of metabolic disorders. These complex hormonal interactions can give rise to a wide range of metabolic and cardiovascular abnormalities which characterize diabetes and are increasingly observed in people with depression, thus threatening an increasing cycle of psychological and physical ill health [3].

Starting with epigenetic effects of early maternal care, a variety of social, psychological and biological influences may interact in the etiology and course of both depression and diabetes, and accelerate the psychological and metabolic abnormalities of each [1]. As symptoms and complications of diabetes increase, associated psychosocial stress and reduced coping ability may contribute to depression. Additionally, the psychological burdens of diabetes treatments, such as insulin injection or blood glucose self-monitoring, can increase negative emotions and maladaptive behaviors and lead to a loss of interest, low energy, abnormal eating patterns, sleep disturbance, poor treatment compliance and poor concentration. As diabetes may exacerbate depression, likewise evidence indicates deleterious effects of coexisting depression on clinical status, subsequent complications, mortality and increased healthcare expenditures [4].

Following the model in figure 1, broad social and economic contexts of family and social relationships as well as organizational, economic and cultural factors influence depression, diabetes and other mental and physical disorders. Examples of these are detailed in a report available at http://sph.unc.edu/profiles/edwin-b-fisher-phd/.

Illustrating the broad range of potential influences on mental and physical disorders, the next paragraphs provide examples of how neighborhood and architectural design may influence social relationships and health status.

One study on housing involving older adults showed that architectural features such as porches and stoops encouraged greater person-to-person contact and were positively associated with perceived social support. These in turn were associated with less self-reported depression and anxiety [5]. Other architectural features, such as windows, allowed for broader observation of the surrounding area, but removed individuals from close person-to-person contact and were associated with lower levels of perceived social support and greater psychological distress [5].

Research has also documented associations between neighborhood characteristics and diabetes prevalence and management. In a natural experiment in the mid-1990s, the Department of Housing and Urban Development randomly assigned approximately 4,500 women with children living in public housing in high-poverty urban areas to one of three conditions: housing vouchers to move to low-poverty areas and receive counseling, unrestricted vouchers and no counseling, and control - no vouchers. In follow-up data (2008-2010), those who had been offered vouchers for low-poverty neighborhoods were less likely than controls to have BMI ≥35 or ≥40, and less likely to have a glycated hemoglobin ≥6.5% (48 mmol/mol). Those receiving the unrestricted vouchers did not differ from controls [6].

A study in Quebec, Canada sheds light on specific neighborhood features that may be especially important. Individuals who reported their neighborhoods as having worse physical and social order (i.e. deteriorated buildings, graffiti, noise, trash, crime and vandalism), less social cohesion, and less access to services and resources had greater diabetes distress including emotional burden, dissatisfaction with medical care, difficulty with treatment regimen, interpersonal impacts and support for diabetes management. Even after controlling for confounders, such as income, education and race, these relationships remained significant [7].

The complex interweaving of multiple levels of influence results in sharp social and economic stratification of both diabetes and depression. Failure to recognize the influence of contextual factors may have at least three deleterious consequences. First, interventions may be less powerful than they might be. Second, benefits of medical or psychological interventions delivered to individuals may be underestimated if important contextual moderators of their effects are not accounted for in analyses. Third, individuals may be viewed as responsible for problems in a manner that constitutes a kind of ‘victim blaming'.

In order to develop comprehensive approaches to the effective prevention and/or management of diabetes and depression, it is necessary to clarify just how the problems and their interrelationships are to be approached. The term ‘comorbidity' connotes two well-defined and distinct clinical entities, occurring simultaneously and each tending to occur more frequently in the presence of the other, as simply illustrated in figure 2. However, the interrelationships between diabetes and depression may be viewed in other ways as well.

Both depression and diabetes are commonly defined categorically with specific criteria used to classify individuals as having either depression or diabetes. However, an alternative to this categorical definition of depression has been a dimensional characterization of mood or dysphoria, often using standardized instruments such as the popular Beck Depression Inventory which was originally developed and validated as a measure of depressed mood, not of categorical depression. As an example of the dimensional perspective in diabetes, the success of preventing incident diabetes in high-risk subjects has led to the identification of a dimension of dysglycemia including varying degrees of insulin resistance and deficiency that underlie manifest abnormalities in glucose metabolism. Supporting the dimensional perspective, ‘graded relationships' between depression and both myocardial infarction and all-cause mortality suggest that depression ‘is best viewed as a continuous variable that represents a chronic psychological characteristic rather than a discrete and episodic psychiatric condition' [8].

With both depression and diabetes, categorical definitions may be superimposed on the dimensional by defining the diagnostic category according to a convention of some criterion score as in common - and changing [9] - definitions of hypertension. Additionally, the International Classification of Diseases distinguishes three categories - mild, moderate and severe depression - that also reflect the practical usefulness of the dimensional approach.

In addition to the difference between viewing problems as distinct categories or as dimensions, diabetes and depression may each be categorized as part of a broader class of problems: cardiometabolic abnormalities for diabetes and negative emotions for depression. For example, studies of depression in various groups indicate high co-occurrence of depression, anxiety and other varieties of psychological distress [10]. Similarly, studies in cardiovascular risk indicate the utility of grouping together a set of negative emotions that includes depression, anxiety, hostility and stress, and their complex interactions in pathways related to cardiovascular pathogenesis [11]. Recent work in diabetes has also indicated that general measures of diabetes distress may be more closely related to poor metabolic control than measures of depressed mood alone [12]. Parallel to the overlap among measures of psychological disorder and distress, hyperlipidemia, central adiposity and hypertension often co-occur with ‘prediabetes' or diabetes, leading some to refer to the group as comprising a ‘metabolic syndrome' [13].

Whether depression and diabetes are best viewed as distinct or as members of broader categories is controversial. For example, some argue that, however much they may co-occur, one needs to treat the individual cardiovascular and metabolic problems encompassed by the term ‘metabolic syndrome' with appropriate medications for diabetes, hypertension and hyperlipidemia [14]. Similarly, one may argue that beyond the co-occurrence with anxiety, hostility and stress, depressed mood alone has a specific and distinctive role with both diabetes and cardiovascular disease, requiring specific treatment rather than a more generalized approach.

Whether diabetes or depression are best viewed as distinct entities or as parts of broader syndromes may depend on the purpose of the viewing. For example, Valderas et al. [15] noted that the value of different models of comorbidity would vary according to the perspective taken by specialist, primary care, public health or health services. From the perspective of clinical care of individuals, differentiating among specific problems - depression, anxiety and hostility on the one hand and diabetes, hypertension and hyperlipidemia on the other - makes great sense. Whether with psychotherapy or psychopharmacology, management of depressed mood differs from treatment of hostility or anxiety, just as medication for diabetes differs from that for hypertension or hypercholesterolemia. At the population level, however, co-prevalent problems may share common treatment and prevention targets, such as healthy diet, physical activity, weight management and communities that encourage them [e.g. [6]] for diabetes and cardiovascular disease, or, for negative emotions, socioeconomic well-being and communities and families that encourage cooperation and satisfying relationships among neighbors [5]. Thus, the broader categories of cardiometabolic abnormalities and negative emotions may help guide population-wide prevention and treatment campaigns. At the same time, their individual components are duly the focus of clinical intervention.

Viewing diabetes and depression as part of broader groupings or syndromes may also make sense across the categories of mental health and medical illness. Research such as from the Diabetes Prevention Program [16] raises the possibility that depression is an early sign or precursor of diabetes. Thus, as we think of the comorbidity of diabetes and depression, we might consider whether they are best viewed as distinct clinical entities that occasionally exist together, or as components of a broader syndrome encompassing both psychological and physical problems. The consideration of depression as part of such a broader syndrome would not necessarily include depressive disorders with specific symptoms, courses and outcomes such as severe depressive disorders with psychotic features (DSM 296.24) or depression in typical bipolar disorders. More generally, the term ‘depression' needs to be understood as referring to mood changes that may be combined with a large - probably larger than currently recognized - number of problems and syndromes, rather than as a single entity.

Table 1 depicts options to view diabetes and depression as: (1) distinct but comorbid conditions, (2) closely related conditions with appropriately coordinated care and (3) clinical problems that normally and commonly co-occur, requiring integrated care. In an integrated approach, the treatment of depression becomes a routine part of diabetes care, just as foot care and yearly retinal checks. So, too, the psychological or medical treatment of depression may be expanded to address its routine metabolic and cardiovascular dimensions. Consider, for example, physical activity, which is often included in diabetes self-management and increasingly recognized as helpful in reducing depression. When promoting physical activity in diabetes self-management, one should routinely consider reticence to engage in exercise as potentially linked to mood problems. Additionally, one should structure goal setting and monitoring to maximize the possible benefits not only of physical activity itself, but also of the mood-elevating effects of achieving a personal goal [17]. At the same time, promoting physical activity as part of depression treatment may draw added emphasis from the recognition of its value not only in increasing mood, but also in reducing cardiovascular risks to which those with depression are prone.

Bringing together a number of the points illustrated so far in this chapter, figure 3 outlines a biosocial complex of determinants of chronic disease ranging from genetic and epigenetic effects (including those of maternal nurturance during early childhood) to community design. Given sufficient deficiencies in this complex, some kind of chronic disease (diabetes, asthma, etc.) is very likely as is some variety of appreciable psychological distress or psychopathology. The particular expression of this biosocial complex in one or another chronic disease and one or another type of psychological problem may be hard to predict, but the likelihood of at least one of each - chronic disease and psychological distress - is highly likely. In a casual survey of practicing primary care clinicians, the common response is ‘That's half of my waiting room.'

Figure 3 raises an important point, ‘What is fundamental that requires attention?' In the simpler terms of figure 2, that fundamental may be, for example, diagnosed diabetes and diagnosed depression co-occurring in a particular individual. In the more developmental, genetic terms of figure 3, what is fundamental is the biosocial complex of events that make expression in diabetes and depression or some other varieties of medical and psychological morbidity highly likely. The particular choice of expressions may be almost accidental or perhaps guided by some specific factors, but the likelihood of such expressions is almost assured.

A range of pharmacologic and psychological [18] interventions have been found to be useful for comorbid diabetes and depression. Here we highlight those that reflect the integrative, social and community perspectives suggested in the preceding pages.

Recent reports [19,20] have documented improved clinical outcomes in diabetes through integrative care that includes team care, evidence-based guidelines, procedures for coordinating care, and registry-based monitoring and prioritization of cases and strategies. Self-management interventions are key components of integrative approaches to clinical care. They teach and promote skills for doing the things in day-to-day life that are necessary to enhance clinical status and well-being [21]. Diabetes self-management interventions have been well documented as effective in improving metabolic control [22]. Notable within the context of the present review, reports of diabetes self-management and education programs have included benefits in quality of life [23].

Integrative models have also emerged in mental health. Assertive community treatment focuses on treating individuals with severe mental illness (schizophrenia, depression, bipolar disorder) within the community through a team of professionals from psychiatry, nursing and social work. Rather than providing support within hospital or clinical settings, community care is provided 24 h a day, 7 days a week. Research has documented the effectiveness of assertive community treatment in reducing hospitalization days, inpatient psychiatric services and emergency room visits, especially among high utilizers of healthcare services [24]. Especially pertinent to the present volume, integrated assertive community treatment models have also been used to provide care for co-occurring physical and mental health problems [25].

Integrating such approaches to both mental and physical disorders, Katon and colleagues [26] developed ‘collaborative care' models that combined pharmacotherapy, psychotherapy, general counseling, problem solving and support provided by a depression care manager. They included those with depression as well as either diabetes and/or elevated cardiovascular risk, and found that collaborative care improved treatment (as indicated by medication adjustments), clinical risk measures (glycemic control, lipids, blood pressure), quality of life and social role disability [26]. A 2012 meta-analysis of 69 studies of collaborative care [27] documented substantial improvements on a variety of indicators, including adherence to depression treatment (OR = 2.22) and recovery from symptoms (OR = 1.75). Such findings have also been replicated with low-income ethnic minority patients in the USA [28].

Peer supporters, also known as ‘community health workers', ‘lay health advisors', ‘promotores' and a number of other terms, can assist individuals in self-management of diabetes and prevention and management of other diseases [e.g. [29]]. They may also provide emotional support and encourage problem solving to address depression and other emotional distress. Both the social isolation or lack of a confidant that often accompany psychopathology and distress [29] and the importance of simple social contact and emotional support suggest that simple, frequent, affirming and pleasant contact from a supporter may be especially helpful to those with emotional distress.

In a striking cluster randomized evaluation in Pakistan, ‘Lady Health Workers' implemented a cognitive-behavioral, problem-solving intervention for women who met criteria for major depression during the third trimester of their pregnancies. Relative to controls, the intervention substantially reduced depression 12 months postpartum (OR = 0.23, p < 0.0001) [30]. In India, peer support for depression, anxiety and other mental health problems included education about psychological problems and ways of coping with them (e.g. deep breathing for anxiety symptoms) as well as interpersonal therapy, and was delivered by lay health counselors with back-up by primary care and monthly consultations from psychiatrists. Results included a 30% decrease in the prevalence of depression and other common mental disorders among those with these problems at baseline, 36% reduction in suicide attempts or plans, and an average of 4.43 fewer days with no or reduced work in the previous 30 days [31], resulting in the intervention being both cost saving as well as cost-effective [32].

A population-based study in the USA evaluated Medicaid enrollees who had made a claim for both community mental health and peer support services. A comparison group who had made only claims for community mental health services was matched by gender, race, age, urban/rural residence and principle diagnosis. Those who had received peer support were less likely to be hospitalized (OR = 0.766) and more likely to achieve crisis stabilization (OR = 1.345) [33].

An important impact of psychological distress in chronic disease is its role in complicating efforts to reach and engage patients in recommended care. Peer support may be an especially effective strategy for reaching the ‘hardly reached' [34]. Asthma coaches pursuing a nondirective, flexible, stage-based approach were able to engage 89.7% of mothers of Medicaid-covered children hospitalized for asthma. The coaches sustained that engagement, averaging 21.1 contacts per parent over a 2-year intervention. Of those randomized to an asthma coach, 36.5% were rehospitalized over the 2 years compared to 59.1% receiving usual care (p < 0.01) [35].

In a successful peer support intervention for diabetes management among patients of safety net clinics in San Francisco, participants were categorized as low, medium or high medication adherence at baseline. The peer support led to greater reductions in glycated hemoglobin than in controls across all groups, but the differential impact of peer support was greatest among those initially in the low adherence group [36]. In a dyadic support intervention among veterans with diabetes, improvements in blood glucose measures were substantially more pronounced among those with low initial levels of diabetes support (p for interaction <0.001) and those with low health literacy (p for interaction <0.05) [37].

Community-wide health promotion programs focus on populations affected or at risk. The major community programs aiming to prevent cardiovascular disease [38] and encourage nonsmoking [39] may provide lessons for comprehensive approaches to management of physical and mental disorders. The North Karelia project in Finland addressed heightened cardiovascular disease through a broad range of interventions. In comparison to other parts of the country, North Karelia showed impressive reductions in cardiovascular risk factors and mortality, as well as reductions of cancer risk factors [38].

Several characteristics appear important in the North Karelia program. Its wide range of initiatives included development of new treatment guidelines for hypertension and care following myocardial infarction and other clinical preventive approaches, community-based health education and social marketing of preventive practices, and diverse engagement of community organizations, mass media and key businesses such as dairies, sausage factories, and food merchandising groups and grocery stores to improve the availability of healthy foods [40]. Across all interventions, great attention was given to collaborative planning and implementation with local organizations.

Similar lessons may be drawn from successful campaigns to encourage prevention and cessation of smoking in the USA [41]. Most notably, declines in per capita cigarette consumption and closely associated declines in cardiovascular mortality in California were attributable to a statewide campaign supported by taxes on cigarettes that included prevention programs for youth, cessation programs for adults, aggressive counteradvertising campaigns, and community-based program coordination and planning [42].

Illustrating community approaches to mental health, the German city of Nuremberg implemented a multilevel 2-year community intervention to treat depression and suicide [43]. Using community facilitators, the program intervened with three sectors of society: primary care physicians to provide training and awareness about depression, the general public to raise awareness and knowledge of services, and depressed patients to provide support. After 2 years, the program found significant reductions in suicide acts and depressive symptoms, and the program was expanded to other regions of Europe under the name ‘The European Alliance against Depression' [43].

How such community approaches might be extended to multimorbidity of physical and mental disorders is unclear. One might begin with behaviors that community health promotion programs have been able to improve and that are also pertinent to diabetes and depression, such as healthy diet, regular physical activity, medication adherence, and regular clinical care, and in successful approaches to hypertension, such as strategically directed screening. In addition to broad involvement of community organizations, business and local government, intervention strategies might include:

(1) Attention to the built environment and design of neighborhoods and housing to promote physical activity as well as enhance psychological adjustment and well-being

(2) Engaging worksites to recognize two roles they may play: useful and socially influential sites for implementation of programs, and identifying ways in which personnel policies and procedures might be improved to facilitate daily management of diabetes (e.g. blood glucose monitoring, healthy diet) and to reduce stress and enhance emotional as well as physical health

(3) Community organization and social marketing to build social capital and promote the kinds of community values, social interactions and approaches to conflict resolution that may also enhance emotional and physical health

(4) Recruiting members of key audiences as peer supporters to build links between programs and those audiences as well as providing emotional and tangible support to those most in need

Promising results from Web-based and telehealth interventions have spurred interest in new modalities for intervening with people experiencing depression and diabetes [44]. A recent systematic review of Internet support groups for individuals with depressive symptoms provides evidence for the role of e-health in managing depression [45]. Of the 16 studies reviewed, a majority (62.5%) reported a positive effect of Internet support on depressive symptoms. Although only 20% of the studies used a control group, other randomized control trials of Internet interventions have demonstrated statistically significant reductions in depression compared to control groups [46]. Telephone-delivered cognitive-behavioral programs have also been successfully used with Veterans Administration patients in the USA to reduce depressive symptoms and improve quality of life and functioning [17]. For patients who have been ‘hardly reached' by the traditional medical care system, these new modalities offer a model for enhanced patient outreach and care.

Articulation of the roles of social and economic factors is sometimes perceived as being in opposition to the articulation of individual-level factors or clinical treatment. The intent of the broad ecological perspective taken here is an integration rather than opposition of multiple levels of explanation. Recognition of the range of influences on mental health and chronic disease will best illuminate the relationships between them. Understanding the utilities of different perspectives on those relationships will best guide selection of perspectives that serve specific purposes. Furthermore, integrating clinical, social and community approaches to prevention and management will best meet the global burden of multimorbidities.

There is often a tendency to see the world of clinical care as separate and distinct from that of prevention and population health; however, these are overlapping. Healthy communities may enable patient adherence to diabetes management and treatment of depression. At the same time, the availability of quality clinical care may provide both a channel for reaching populations as well as a resource for promoting healthy lifestyles [47].

As discussed above, peer support may be an especially promising strategy for integrating clinical and preventive as well as individual and population approaches. Peer supporters can help sustain the behaviors that comprise diabetes and depression management [29] and provide emotional support and encourage problem solving to address depression and other emotional distress [30] while engaging those who otherwise fail to receive appropriate care [35,48]. All of these can assist in identifying and recruiting into treatment those with mental and physical disorders and in helping them take full advantage of the available resources.

A simple consideration that is too often unrecognized cuts across all the approaches to intervention outlined here. The emotional aspect is an important part of chronic disease care. Attention to depression, emotional well-being and healthy relationships is not a secondary consideration in chronic disease care, but - based on the evidence [e.g. [1]] - of central importance. In diabetes and cardiovascular disease, for example, the recognition and treatment of depression may be as important as biological treatment targets. Further, knowledge gained by a comprehensive approach to diabetes and depression may be highly relevant to the care of other chronic diseases. Attention to depression, anxiety and stress disorders is likely to have impacts on health and healthcare costs far greater than currently appreciated.

Self-management programs in chronic disease may provide important models for approaches to mental health problems in general as well as those which co-occur with physical disorders. Surely the core elements of chronic disease self-management - healthy diet, physical activity, adherence to medication regimens, stress management, problem solving, and cultivating family and friend support - would all seem equally pertinent to the management of depression. It should also be noted that meta-analysis of interventions for depression and diabetes has implicated diabetes self-management education in the metabolic benefits associated with cognitive behavioral interventions [18].

Within self-management, problem solving may have a special role in integration of care for depression and diabetes. Problem solving is central to almost all models of self-management in diabetes and chronic disease. At the same time, problem solving has emerged as a prominent approach to psychotherapy for depression and other problems [49]. Indeed, recent research indicates that the benefits of cognitive behavior therapy for depression rest largely on the more behavioral, skill-oriented components of problem solving and ‘behavioral activation' within cognitive behavior therapy [50]. Thus, problem solving can address the management of both mental and physical disorders. For example, helping individuals set objectives for increasing physical activity, take steps to accomplish those objectives, and reflect on the pleasure of reaching them may advance both diabetes self-management as well as self-management of depression.

In addition to its effectiveness in both domains, an emphasis on problem solving may also provide a useful framework for providing coherence to the individual's tasks in management of mental and physical disorders. Organizing overall care as problem solving or self-management to achieve a healthy diet, physical activity, adherence to medications, stress management, and maintenance of satisfying social and community engagements may provide patients a coherent framework for accommodating the changes that emerge inevitably in the natural history of chronic disease. It may also avoid concerns about stigma surrounding depression, other forms of emotional distress or chronic diseases in many cultures.

Self-management procedures emerged largely out of research on self-control and related processes in psychology, behavior therapy and health psychology. This might lead one to expect great attention to self-management approaches to depression and other mental health problems that psychology has traditionally addressed. Yet, while a search of PubMed (January 13, 2014) for papers with ‘self-management' and cognates of ‘diabetes' in their titles yielded 762, a parallel search for papers with ‘self-management' and cognates of ‘depression' in their titles yielded only 36. When expanded to include mention in abstracts, results were 2,390 for ‘self-management' with cognates of ‘diabetes' and 567 with cognates of ‘depression'. Further, many of those mentioning depression were focused on self-management of other diseases and simply included a measure of depression, not the focus of the self-management program. It should be noted that mental health researchers may use other terms like ‘psychotherapy', ‘supportive therapy', and ‘bibliotherapy' to refer to similar services as ‘self-management'. Nevertheless, it appears that the combination of proactive medical treatment and self-management which constitutes the state-of-the-art in diabetes has not been fully recognized in mental health.

Experience teaches that paradigm or conceptual shifts do not follow from rational argument as often as they emerge in response to events. The growing burden of diabetes, depression and other multimorbidities may compel medicine, public health and mental health to move forward with improved and comprehensive interventions. Closely related to this, the pressure of healthcare costs has led (e.g. US Affordable Care Act) to increased emphasis on primary care and integration of chronic disease management and behavioral health.

The perspectives here have substantial implications for training professionals. Beyond covering chronic diseases and the behavioral health issues that so often accompany them, training needs to inculcate an understanding of the integration of these, as they are experienced by patients and as they need to be treated by clinicians. Moving down the problem list from diabetes, to joint problem, down to depression is not an approach to organizing clinical care that reflects the ways in which these problems emerge and function. One might argue that such an approach is, indeed, bad medicine. Beyond the pitfalls of polypharmacy that it engenders, it fails to recognize the interconnected nature of behavioral health and biological problems and to bring to bear evidence-based models for addressing them.

Whether through mental health, primary care, specialty care or community-based programs, individuals should receive services that reflect the co-occurrence of diabetes and other chronic diseases with depression and other emotional distress and that provide integration and continuity of services for these. Integrating the clinical with social, organizational and community approaches as advocated here may offer a strong model not only for the global burdens of diabetes, depression and other mental and physical health problems, but also for more general prevention and healthcare in an era of aging populations, growing prevalence and burden of noncommunicable diseases, and normativemultimorbidity.

Dr. Fisher and Ms. Kowitt are supported by the American Academy of Family Physicians Foundation through its program, Peers for Progress, which is supported by the Eli Lilly and Company Foundation, the Bristol-Myers Squibb Foundation and Sanofi US.

The Association for the Improvement of Mental Health Programmes, directed by Dr. Sartorius, received a grant from Eli Lilly and Company to assist in the development of the Dialogue on Diabetes and Depression from deliberations of which the present manuscript developed. With the exception of support for travel to meetings provided through the Dialogue on Diabetes and Depression, and the support of Dr. Fisher and Ms. Kowitt by Peers for Progress of the American Academy of Family Physicians Foundation, the authors have collaborated in the development of this paper without any support for the work.