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Diabetes and Mental Health

      Key Messages
      • The experience of living with diabetes is often associated with concerns specific to the illness and can cause conditions, such as diabetes distress, psychological insulin resistance and the persistent fear of hypoglycemic episodes.
      • A wide range of psychiatric disorders, including major depressive disorder, bipolar and related disorders, schizophrenia spectrum and other psychotic disorders, anxiety disorders, sleep disorders, eating disorders and stress-related disorders are more prevalent in people with diabetes compared to the general population.
      • People living with diabetes and depressive disorders are at increased risk for earlier all-cause mortality compared to people living with diabetes without a history of depression.
      • All individuals with diabetes should be regularly screened for the presence of diabetes distress, as well as symptoms of common psychiatric disorders.
      • Compared to those with diabetes only, individuals with diabetes and mental health concerns have decreased participation in diabetes self-care, a decreased quality of life, increased functional impairment, increased risk of complications associated with diabetes, and increased health-care costs.
      • Cognitive behaviour therapy, patient-centred approaches (e.g. motivational interviewing), stress management, coping skills training, family therapy and collaborative case management should be incorporated into primary care. Self-management skills, educational interventions that facilitate adaptation to diabetes, addressing co-occurring mental health issues, reducing diabetes-related distress, fear of hypoglycemia, and psychological insulin resistance are all helpful.
      • Individuals taking psychiatric medications, particularly (but not limited to) atypical antipsychotics, benefit from regular screening of metabolic parameters to identify glucose dysregulation, dyslipidemia and weight gain throughout the course of the illness so that appropriate interventions can be instituted.
      Key Messages for People with Diabetes
      • Living with diabetes can be burdensome and anxiety provoking, with the constant demands taking a psychological toll. As a result, many people experience distress, decreased mood and disabling levels of anxiety. Diabetes is often associated with a significant emotional burden, distress over the self-care regimen and stress in relationships (with family and friends, as well as health-care providers).
      • It is important to recognize your emotions and talk to your friends, family and members of your diabetes health-care team about how you are feeling. Your team can help you to learn effective coping skills and direct you to support services that can make a difference for you.
      • Mood and anxiety disorders are particularly common in people with diabetes. Eating, sleeping and stress-related disorders are also common. Speak to your health-care providers about any concerns you have if you think you may be developing any of these problems.
      • Mental health disorders can affect your ability to cope with and care for your diabetes. In view of this, it is just as important to look after your mental health as it is your physical health.
      • People diagnosed with serious mental illnesses, such as major depressive disorder, bipolar disorder and schizophrenia, have a higher risk of developing diabetes than the general population.

      Introduction

      Research has shown an increasingly clear relationship between diabetes and a variety of mental health issues. These include diagnosable psychiatric disorders, and other problems that are specific to the experience of living with diabetes. “Diabetes distress” refers to the negative emotions and burden of self-management related to living with diabetes. This term is used to describe the despondency and emotional turmoil specifically related to living with diabetes, in particular the need for continual monitoring and treatment, persistent concerns about complications, and the potential erosion of personal and professional relationships (
      • Hagger V.
      • Hendrieckx C.
      • Sturt J.
      • et al.
      Diabetes distress among adolescents with type 1 diabetes: A systematic review.
      ,
      • Polonsky W.H.
      • Fisher L.
      • Earles J.
      • et al.
      Assessing psychosocial distress in diabetes: Development of the diabetes distress scale.
      ). “Psychological insulin resistance” is the reluctance or refusal to initiate insulin therapy, which may delay the start of a necessary treatment for a period of time (
      • Polonsky W.H.
      • Hajos T.R.
      • Dain M.P.
      • et al.
      Are patients with type 2 diabetes reluctant to start insulin therapy? An examination of the scope and underpinnings of psychological insulin resistance in a large, international population.
      ). Fear of hypoglycemia is another common diabetes-specific concern. The presence of psychiatric and diabetes-specific psychosocial issues is associated with reduced participation in self-management activities and can lead to a decrease in quality of life. Psychiatric disorders among individuals with diabetes increases the risk of diabetes complications and early mortality (
      • Egede L.E.
      • Nietert P.J.
      • Zheng D.
      Depression and all-cause and coronary heart disease mortality among adults with and without diabetes.
      ).

      Psychological Effects of Diabetes in Adults

      Diabetes is a demanding chronic disease for both individuals and their families (
      • Snoek F.J.
      • Kersch N.Y.
      • Eldrup E.
      • et al.
      Monitoring of Individual Needs in Diabetes (MIND): Baseline data from the Cross-National Diabetes Attitudes, Wishes, and Needs (DAWN) MIND study.
      ). It is associated with a number of challenges, including adjusting to a new diagnosis, diabetes distress impairing self-management, psychological insulin resistance, and fear of hypoglycemia. In addition, a range of psychiatric disorders can arise that contributes to greater complexity in both assessment and treatment. For instance, distinguishing between diabetes distress, major depressive disorder (MDD) and the presence of depressive symptoms is important. Although these constructs have some shared symptomatology, diabetes distress has been most shown to have the strongest effect in causing adverse diabetes outcomes (
      • Fisher L.
      • Skaff M.M.
      • Mullan J.T.
      • et al.
      Clinical depression versus distress among patients with type 2 diabetes: Not just a question of semantics.
      ,
      • Gonzalez J.S.
      • Fisher L.
      • Polonsky W.H.
      Depression in diabetes: Have we been missing something important?.
      ,
      • Fisher L.
      • Glasgow R.E.
      • Strycker L.A.
      The relationship between diabetes distress and clinical depression with glycemic control among patients with type 2 diabetes.
      ,
      • Fisher L.
      • Mullan J.T.
      • Arean P.
      • et al.
      Diabetes distress but not clinical depression or depressive symptoms is associated with glycemic control in both cross-sectional and longitudinal analyses.
      ) (Table 1).
      Table 1Comparison of main features and assessment methods: diabetes distress vs. major depressive disorder
      Diabetes DistressMajor Depressive Disorder
      Assessment InstrumentDiabetes Distress Scale (17 items)
      • Polonsky W.H.
      • Fisher L.
      • Earles J.
      • et al.
      Assessing psychosocial distress in diabetes: Development of the diabetes distress scale.
      Patient Health Questionnaire for Depression: PHQ-9 (9 items) ,
      • van Steenbergen-Weijenburg K.M.
      • de Vroege L.
      • Ploeger R.R.
      • et al.
      Validation of the PHQ-9 as a screening instrument for depression in diabetes patients in specialized outpatient clinics.
      FormatSelf-report using ratings from 1 to 6 based on feelings and experiences over the past weekSelf-report using ratings from 0 to 3 based on feelings and experiences over the past 2 weeks
      FeaturesEmotional Burden Subscale (5 items)

      Physician-Related Distress Subscale (4 items)



      Regimen-Related Distress Subscale (5 items)

      Diabetes-Related Interpersonal Distress Subscale (3 items)
      Vegetative symptoms, such as sleep, appetite and energy level changes

      Emotional symptoms, such as low mood and reduced enjoyment of usual activities

      Behavioural symptoms, such as agitation or slowing of movements

      Cognitive symptoms, such as poor memory or reduced concentration or feelings of guilt; thoughts of self-harm
      CBT, cognitive behavioural therapy.
      Diabetes distress is comprised of 4 interconnected domains, which include: 1) the emotional burden of living with diabetes; 2) the distress associated with the diabetes self-management regimen; 3) the stress associated with social relationships; and 4) the stress associated with the patient-provider relationship. Diabetes distress is associated with elevated glycated hemoglobin (A1C levels), higher diastolic blood pressure (BP) and increased low-density lipoprotein cholesterol (LDL-C) levels (
      • Winchester R.J.
      • Williams J.S.
      • Wolfman T.E.
      • et al.
      Depressive symptoms, serious psychological distress, diabetes distress and cardiovascular risk factor control in patients with type 2 diabetes.
      ,
      • Strandberg R.B.
      • Graue M.
      • Wentzel-Larsen T.
      • et al.
      Relationships of diabetes-specific emotional distress, depression, anxiety, and overall well-being with HbA1c in adult persons with type 1 diabetes.
      ,
      • Strandberg R.B.
      • Graue M.
      • Wentzel-Larsen T.
      • et al.
      Longitudinal relationship between diabetes-specific emotional distress and follow-up HbA1c in adults with type 1 diabetes mellitus.
      ). Furthermore, individuals with higher levels of diabetes distress were found to have a 1.8-fold higher mortality rate, a 1.7-fold increased risk of cardiovascular (CV) disease (
      • Dalsgaard E.M.
      • Vestergaard M.
      • Skriver M.V.
      • et al.
      Psychological distress, cardiovascular complications and mortality among people with screen-detected type 2 diabetes: Follow-up of the ADDITION-Denmark trial.
      ), and have lower quality of life (
      • Carper M.M.
      • Traeger L.
      • Gonzalez J.S.
      • et al.
      The differential associations of depression and diabetes distress with quality of life domains in type 2 diabetes.
      ). Risk factors for developing diabetes distress include being younger, being female, having lower education, living alone, having a higher body mass index (BMI), lower perceived self-efficacy, lower perceived provider support, poorer quality diet, greater perceived impact of glycemic excursions and greater number of diabetes complications (
      • Pintaudi B.
      • Lucisano G.
      • Gentile S.
      • et al.
      Correlates of diabetes-related distress in type 2 diabetes: Findings from the benchmarking network for clinical and humanistic outcomes in diabetes (BENCH-D) study.
      ,
      • Wardian J.
      • Sun F.
      Factors associated with diabetes-related distress: Implications for diabetes self-management.
      ).
      Psychological insulin resistance refers to a strong negative response to the recommendation from health-care providers that a person may benefit from adding insulin to his or her diabetes regimen. This can be a common reaction, particularly for individuals with type 2 diabetes who may have previously been successfully managed with noninsulin antihyperglycemic agents. Individuals may hold maladaptive beliefs that requiring insulin is a sign of personal failure in their self-management, or that their illness has become much more serious. Further, many people report fear and anxiety about having to self-administer injections, or have a low level of confidence in their ability to manage their blood glucose with insulin (
      • Bahrmann A.
      • Abel A.
      • Zeyfang A.
      • et al.
      Psychological insulin resistance in geriatric patients with diabetes mellitus.
      ,
      • Holmes-Truscott E.
      • Skinner T.C.
      • Pouwer F.
      • et al.
      Explaining psychological insulin resistance in adults with non-insulin-treated type 2 diabetes: The roles of diabetes distress and current medication concerns. Results from Diabetes MILES-Australia.
      ).
      Fear of hypoglycemia is a common occurrence. Hypoglycemic experiences, especially serious or nocturnal episodes, can be traumatic for both individuals and their family members. A common strategy to minimize fears of hypoglycemia is compensatory hyperglycemia, where individuals either preventatively maintain a higher blood glucose (BG) level, or treat hypoglycemia in response to perceived somatic symptoms without objective confirmation by capillary blood glucose concentrations (
      • Hendrieckx C.
      • Halliday J.A.
      • Bowden J.P.
      • et al.
      Severe hypoglycaemia and its association with psychological well-being in Australian adults with type 1 diabetes attending specialist tertiary clinics.
      ,
      • Nefs G.
      • Bevelander S.
      • Hendrieckx C.
      • et al.
      Fear of hypoglycaemia in adults with Type 1 diabetes: Results from Diabetes MILES—The Netherlands.
      ,
      • Polonsky W.H.
      • Fisher L.
      • Hessler D.
      • et al.
      Identifying the worries and concerns about hypoglycemia in adults with type 2 diabetes.
      ,
      • Vallis M.
      • Jones A.
      • Pouwer F.
      Managing hypoglycemia in diabetes may be more fear management than glucose management: A practical guide for diabetes care providers.
      ). Over time, this maladaptive process, if left unmanaged, can negatively impact diabetes control, increase the risk of CV complications, and reduce quality of life.
      Challenges accompanying the diagnosis of diabetes include adjustment to the illness, participation in the treatment regimen and psychosocial difficulties at both a personal and an interpersonal level (
      • Peyrot M.
      • Rubin R.R.
      • Lauritzen T.
      • et al.
      Psychosocial problems and barriers to improved diabetes management: Results of the Cross-National Diabetes Attitudes, Wishes and Needs (DAWN) study.
      ,
      • Goebel-Fabbri A.E.
      • Fikkan J.
      • Franko D.L.
      • et al.
      Insulin restriction and associated morbidity and mortality in women with type 1 diabetes.
      ). Stress, deficient social supports and negative attitudes toward diabetes can impact on self-care and glycemic control (
      • Fisher L.
      • Glasgow R.E.
      A call for more effectively integrating behavioral and social science principles into comprehensive diabetes care.
      ,
      • Malik J.A.
      • Koot H.M.
      Explaining the adjustment of adolescents with type 1 diabetes: Role of diabetes-specific and psychosocial factors.
      ,
      • Zhang C.X.
      • Tse L.A.
      • Ye X.Q.
      • et al.
      Moderating effects of coping styles on anxiety and depressive symptoms caused by psychological stress in Chinese patients with type 2 diabetes.
      ,
      • Hampson S.E.
      • Tildesley E.
      • Andrews J.A.
      • et al.
      The relation of change in hostility and sociability during childhood to substance use in mid adolescence.
      ,
      • Luyckx K.
      • Seiffge-Krenke I.
      • Hampson S.E.
      Glycemic control, coping, and internalizing and externalizing symptoms in adolescents with type 1 diabetes: A cross-lagged longitudinal approach.
      ). Diabetes management strategies ideally incorporate a means of addressing the psychosocial factors that impact on individuals and their families. Both symptom measures (e.g. self-report measures of various symptoms) and methods to arrive at psychiatric diagnoses (e.g. structured interviews leading to Diagnostic and Statistical Manual of Mental Disorders Fifth Edition [DSM-5 diagnoses] (
      • American Psychiatric Association
      Diagnostic and statistical manual of mental disorders.
      ) have been assessed. Given that the person with diabetes is directly responsible for 95% of diabetes management (
      • Anderson R.M.
      Is the problem of noncompliance all in our heads?.
      ), identifying significant psychological reactions in diabetes is important since depressive symptoms are a risk factor for poor diabetes self-management (
      • Gonzalez J.S.
      • Peyrot M.
      • McCarl L.A.
      • et al.
      Depression and diabetes treatment nonadherence: A meta-analysis.
      ,
      • Gonzalez J.S.
      • Safren S.A.
      • Delahanty L.M.
      • et al.
      Symptoms of depression prospectively predict poorer self-care in patients with Type 2 diabetes.
      ,
      • Egede L.E.
      • Grubaugh A.L.
      • Ellis C.
      The effect of major depression on preventive care and quality of life among adults with diabetes.
      ) and outcomes, including early mortality (
      • Richardson L.K.
      • Egede L.E.
      • Mueller M.
      Effect of race/ethnicity and persistent recognition of depression on mortality in elderly men with type 2 diabetes and depression.
      ,
      • Hutter N.
      • Schnurr A.
      • Baumeister H.
      Healthcare costs in patients with diabetes mellitus and comorbid mental disorders–a systematic review.
      ).

      Psychiatric Conditions in Adults

      Individuals with serious mental illnesses, particularly those with depressive symptoms or syndromes, and people with diabetes share reciprocal susceptibility and a high degree of comorbidity (Figure 1). The mechanisms behind these relationships are multifactorial, complicated and presently only partially understood. Some evidence shows that treatment for mental health disorders may actually increase the risk of diabetes, particularly when second- and third-generation (atypical) antipsychotic agents are prescribed (
      • Lieberman J.A.
      • Stroup T.S.
      • McEvoy J.P.
      • et al.
      Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.
      ). Biochemical changes due to psychiatric disorders themselves also may play a role (
      • Brown E.S.
      • Varghese F.P.
      • McEwen B.S.
      Association of depression with medical illness: Does cortisol play a role?.
      ). Symptoms of mental health disorders and their impact on lifestyle are also likely to be contributing factors (
      • McCreadie R.G.
      Diet, smoking and cardiovascular risk in people with schizophrenia: Descriptive study.
      ).
      Figure 1
      Figure 1The interplay between diabetes, major depressive disorder and other psychiatric conditions.

      Major Depressive Disorder

      The prevalence of clinically relevant depressive symptoms among people with diabetes is approximately 30% (
      • Anderson R.J.
      • Freedland K.E.
      • Clouse R.E.
      • et al.
      The prevalence of comorbid depression in adults with diabetes: A meta-analysis.
      ,
      • Ali S.
      • Stone M.A.
      • Peters J.L.
      • et al.
      The prevalence of co-morbid depression in adults with type 2 diabetes: A systematic review and meta-analysis.
      ,
      • Barnard K.D.
      • Skinner T.C.
      • Peveler R.
      The prevalence of co-morbid depression in adults with type 1 diabetes: Systematic literature review.
      ). The prevalence of MDD is approximately 10% (
      • Egede L.E.
      Diabetes, major depression, and functional disability among U.S. adults.
      ,
      • Moussavi S.
      • Chatterji S.
      • Verdes E.
      • et al.
      Depression, chronic diseases, and decrements in health: Results from the World Health Surveys.
      ), which is double the overall prevalence in people without a chronic medical illness. The risk of developing MDD increases the longer a person has diabetes (
      • Almeida O.P.
      • McCaul K.
      • Hankey G.J.
      • et al.
      Duration of diabetes and its association with depression in later life: The Health In Men Study (HIMS).
      ). Clinically identified diabetes was associated with a doubling of the prescriptions for antidepressants, but undiagnosed diabetes was not, consistent with the hypothesis that the relationship between diabetes and depression may be attributable to factors related to diabetes management (
      • Mezuk B.
      • Johnson-Lawrence V.
      • Lee H.
      • et al.
      Is ignorance bliss? Depression, antidepressants, and the diagnosis of prediabetes and type 2 diabetes.
      ). Individuals with depression have an approximately 40% to 60% increased risk of developing type 2 diabetes (
      • Mezuk B.
      • Johnson-Lawrence V.
      • Lee H.
      • et al.
      Is ignorance bliss? Depression, antidepressants, and the diagnosis of prediabetes and type 2 diabetes.
      ,
      • Rotella F.
      • Mannucci E.
      Depression as a risk factor for diabetes: A meta-analysis of longitudinal studies.
      ,
      • Yu M.
      • Zhang X.
      • Lu F.
      • et al.
      Depression and risk for diabetes: A meta-analysis.
      ). The prognosis for comorbid depression and diabetes is worse than when each illness occurs separately (
      • Polonsky W.H.
      • Hajos T.R.
      • Dain M.P.
      • et al.
      Are patients with type 2 diabetes reluctant to start insulin therapy? An examination of the scope and underpinnings of psychological insulin resistance in a large, international population.
      ). Depression in people with diabetes amplifies symptom burden by a factor of about 4 (
      • Ludman E.J.
      • Katon W.
      • Russo J.
      • et al.
      Depression and diabetes symptom burden.
      ). Episodes of depression in individuals with diabetes are likely to last longer and have a higher chance of recurrence compared to those without diabetes (
      • Peyrot M.
      • Rubin R.R.
      Persistence of depressive symptoms in diabetic adults.
      ). Episodes of severe hypoglycemia have been correlated with the severity of depressive symptoms (
      • Kikuchi Y.
      • Iwase M.
      • Fujii H.
      • et al.
      Association of severe hypoglycemia with depressive symptoms in patients with type 2 diabetes: The Fukuoka Diabetes Registry.
      ,
      • Werremeyer A.
      • Maack B.
      • Strand M.A.
      • et al.
      Disease control among patients with diabetes and severe depressive symptoms.
      ). Major depressive disorder has been found to be underdiagnosed in people with diabetes (
      • Engum A.
      • Mykletun A.
      • Midthjell K.
      • et al.
      Depression and diabetes: A large population-based study of sociodemographic, lifestyle, and clinical factors associated with depression in type 1 and type 2 diabetes.
      ).
      Studies examining differential rates for the prevalence of depression in type 1 vs. type 2 diabetes have yielded inconsistent results (
      • Anderson R.J.
      • Freedland K.E.
      • Clouse R.E.
      • et al.
      The prevalence of comorbid depression in adults with diabetes: A meta-analysis.
      ,
      • Li C.
      • Ford E.S.
      • Zhao G.
      • et al.
      Prevalence and correlates of undiagnosed depression among U.S. adults with diabetes: The Behavioral Risk Factor Surveillance System, 2006.
      ). One study found that the requirement for insulin was the factor associated with the highest rate of depression, regardless of the type of diabetes involved (
      • Katon W.J.
      • Simon G.
      • Russo J.
      • et al.
      Quality of depression care in a population-based sample of patients with diabetes and major depression.
      ). Treatment with metformin may enhance recovery from MDD (
      • Guo M.
      • Mi J.
      • Jiang Q.M.
      • et al.
      Metformin may produce antidepressant effects through improvement of cognitive function among depressed patients with diabetes mellitus.
      ).
      Risk factors for developing depression in individuals with diabetes are as follows (
      • Eaton W.W.
      • Shao H.
      • Nestadt G.
      • et al.
      Population-based study of first onset and chronicity in major depressive disorder.
      ,
      • Kendler K.S.
      • Karkowski L.M.
      • Prescott C.A.
      Causal relationship between stressful life events and the onset of major depression.
      ,
      • Carvalhais S.M.
      • Lima-Costa M.F.
      • Peixoto S.V.
      • et al.
      The influence of socio-economic conditions on the prevalence of depressive symptoms and its covariates in an elderly population with slight income differences: The Bambui Health and Aging Study (BHAS).
      ,
      • Katon W.
      • Russo J.
      • Lin E.H.
      • et al.
      Depression and diabetes: Factors associated with major depression at five-year follow-up.
      ,
      • Bruce D.G.
      • Davis W.A.
      • Davis T.M.
      Longitudinal predictors of reduced mobility and physical disability in patients with type 2 diabetes: The Fremantle Diabetes Study.
      ):
      • Female sex
      • Adolescents/young adults and older adults
      • Poverty
      • Few social supports
      • Stressful life events
      • Poor glycemic control, particularly recurrent hypoglycemia
      • Higher illness burden
      • Longer duration of diabetes
      • Presence of long-term complications.
      Intensive lifestyle intervention for people with type 2 diabetes with overweight or obesity reduced the risk of depressive symptoms by 15% (
      • Rubin R.R.
      • Wadden T.A.
      • Bahnson J.L.
      • et al.
      Impact of intensive lifestyle intervention on depression and health-related quality of life in type 2 diabetes: The Look AHEAD Trial.
      ).
      Risk factors (with possible mechanisms) for developing diabetes in people with depression are as follows:
      • Physical inactivity (
        • Nyboe L.
        • Lund H.
        Low levels of physical activity in patients with severe mental illness.
        ) and overweight/obesity, which leads to insulin resistance
      • Psychological stress leading to chronic hypothalamic-pituitary-adrenal dysregulation and hyperactivity stimulating cortisol release, also leading to insulin resistance (
        • Lawlor D.A.
        • Smith G.D.
        • Ebrahim S.
        Association of insulin resistance with depression: Cross sectional findings from the British Women's Heart and Health Study.
        ,
        • Timonen M.
        • Salmenkaita I.
        • Jokelainen J.
        • et al.
        Insulin resistance and depressive symptoms in young adult males: Findings from Finnish military conscripts.
        ,
        • Okamura F.
        • Tashiro A.
        • Utumi A.
        • et al.
        Insulin resistance in patients with depression and its changes during the clinical course of depression: Minimal model analysis.
        ,
        • Anagnostis P.
        • Athyros V.G.
        • Tziomalos K.
        • et al.
        Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: A hypothesis.
        ,
        • Pariante C.M.
        • Miller A.H.
        Glucocorticoid receptors in major depression: Relevance to pathophysiology and treatment.
        ,
        • Belmaker R.H.
        • Agam G.
        Major depressive disorder.
        )
      • Hippocampal atrophy and decreased neurogenesis (
        • Semenkovich K.
        • Brown M.E.
        • Svrakic D.M.
        • et al.
        Depression in type 2 diabetes mellitus: Prevalence, impact, and treatment.
        ).
      Some of the mechanisms underlying this association have been found to be: autonomic and neurohormonal dysregulation, hippocampal structural changes, inflammatory processes and oxidative stress (
      • Semenkovich K.
      • Brown M.E.
      • Svrakic D.M.
      • et al.
      Depression in type 2 diabetes mellitus: Prevalence, impact, and treatment.
      ).
      Comorbid depression worsens clinical outcomes in diabetes, possibly because the accompanying lethargy lowers motivation for self-care, resulting in lowered physical and psychological fitness, higher use of health-care services and reduced participation in medication regimens (
      • Ciechanowski P.S.
      • Katon W.J.
      • Russo J.E.
      Depression and diabetes: Impact of depressive symptoms on adherence, function, and costs.
      ,
      • Lin E.H.
      • Katon W.
      • Von Korff M.
      • et al.
      Relationship of depression and diabetes self-care, medication adherence, and preventive care.
      ). Depression also appears to worsen CV mortality (
      • Katon W.J.
      • Rutter C.
      • Simon G.
      • et al.
      The association of comorbid depression with mortality in patients with type 2 diabetes.
      ,
      • Zhang X.
      • Norris S.L.
      • Gregg E.W.
      • et al.
      Depressive symptoms and mortality among persons with and without diabetes.
      ,
      • Vancampfort D.
      • Correll C.U.
      • Wampers M.
      • et al.
      Metabolic syndrome and metabolic abnormalities in patients with major depressive disorder: A meta-analysis of prevalences and moderating variables.
      ). Treating depressive symptoms more reliably improves mood than it does glycemic control (
      • Lustman P.J.
      • Freedland K.E.
      • Griffith L.S.
      • et al.
      Fluoxetine for depression in diabetes: A randomized double-blind placebo-controlled trial.
      ,
      • Lustman P.J.
      • Clouse R.E.
      • Nix B.D.
      • et al.
      Sertraline for prevention of depression recurrence in diabetes mellitus: A randomized, double-blind, placebo-controlled trial.
      ,
      • Lustman P.J.
      • Griffith L.S.
      • Clouse R.E.
      • et al.
      Effects of nortriptyline on depression and glycemic control in diabetes: Results of a double-blind, placebo-controlled trial.
      ,
      • Lustman P.J.
      • Griffith L.S.
      • Freedland K.E.
      • et al.
      Cognitive behavior therapy for depression in type 2 diabetes mellitus. A randomized, controlled trial.
      ).

      Bipolar Disorder

      One study demonstrated that over half of people with bipolar disorder were found to have impaired glucose metabolism, which was found to worsen key aspects of the course of the mood disorder (
      • Mansur R.B.
      • Rizzo L.B.
      • Santos C.M.
      • et al.
      Impaired glucose metabolism moderates the course of illness in bipolar disorder.
      ). In this same study, impaired glucose tolerance (IGT) was deemed to be an etiologic factor in the development of bipolar disorder (
      • Mansur R.B.
      • Rizzo L.B.
      • Santos C.M.
      • et al.
      Impaired glucose metabolism moderates the course of illness in bipolar disorder.
      ). People with bipolar disorder have been found to have prevalence rates estimated to be double that of the general population for metabolic syndrome and triple for diabetes (
      • Fagiolini A.
      • Frank E.
      • Scott J.A.
      • et al.
      Metabolic syndrome in bipolar disorder: Findings from the Bipolar Disorder Center for Pennsylvanians.
      ,
      • Taylor V.
      • MacQueen G.
      Associations between bipolar disorder and metabolic syndrome: A review.
      ,
      • van Winkel R.
      • De Hert M.
      • Van Eyck D.
      • et al.
      Prevalence of diabetes and the metabolic syndrome in a sample of patients with bipolar disorder.
      ,
      • Vancampfort D.
      • Mitchell A.J.
      • De Hert M.
      • et al.
      Prevalence and predictors of type 2 diabetes mellitus in people with bipolar disorder.
      ). Insulin resistance is associated with a less favourable course of bipolar illness, more cycling between mood states, and a poorer response to lithium (
      • Calkin C.V.
      • Ruzickova M.
      • Uher R.
      • et al.
      Insulin resistance and outcome in bipolar disorder.
      ).

      Schizophrenia Spectrum Disorders

      Schizophrenia and other psychotic disorders may contribute an independent risk factor for diabetes. People diagnosed with psychotic disorders were reported to have had insulin resistance/glucose intolerance prior to the advent of antipsychotic medication, although this matter is still open to debate (
      • Haupt D.W.
      • Newcomer J.W.
      Hyperglycemia and antipsychotic medications.
      ,
      • Saddichha S.
      • Manjunatha N.
      • Ameen S.
      • et al.
      Diabetes and schizophrenia—effect of disease or drug? Results from a randomized, double-blind, controlled prospective study in first-episode schizophrenia.
      ,
      • Fleischhacker W.W.
      • Siu C.O.
      • Boden R.
      • et al.
      Metabolic risk factors in first-episode schizophrenia: Baseline prevalence and course analysed from the European First-Episode Schizophrenia Trial.
      ). The Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) study found that of the individuals with schizophrenia who participated in the study, 11% had diabetes at baseline (type 1 and 2 combined) (
      • Lieberman J.A.
      • Stroup T.S.
      • McEvoy J.P.
      • et al.
      Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.
      ). The prevalence of metabolic syndrome was approximately twice that of the general population (
      • McEvoy J.P.
      • Meyer J.M.
      • Goff D.C.
      • et al.
      Prevalence of the metabolic syndrome in patients with schizophrenia: Baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III.
      ). Diabetes and schizophrenia together lead to more CV complications and all-cause mortality compared to people with diabetes alone (
      • Wu C.S.
      • Lai M.S.
      • Gau S.S.
      Complications and mortality in patients with schizophrenia and diabetes: Population-based cohort study.
      ). Whether the increased prevalence of diabetes is due to the effect of the illness (such as advanced glycation end products), antipsychotic medications or other factors, individuals with psychotic disorders represent a particularly vulnerable population (
      • Kouidrat Y.
      • Amad A.
      • Arai M.
      • et al.
      Advanced glycation end products and schizophrenia: A systematic review.
      ).

      Personality Traits/Disorders

      Personality traits or disorders that put people in constant conflict with others or engender hostility have been found to increase the risk of developing type 2 diabetes (
      • Hackett R.A.
      • Lazzarino A.I.
      • Carvalho L.A.
      • et al.
      Hostility and physiological responses to acute stress in people with type 2 diabetes.
      ). People with chronic, significantly negative mood states and social inhibition were less likely to follow a healthy diet or to consult health-care professionals in case problems developed with their diabetes management. They report more barriers surrounding medication use, diabetes-specific social anxiety, loneliness and symptoms of depression and anxiety (
      • Nefs G.
      • Speight J.
      • Pouwer F.
      • et al.
      Type D personality, suboptimal health behaviors and emotional distress in adults with diabetes: Results from Diabetes MILES-The Netherlands.
      ).

      Stress, Trauma, Abuse and Neglect

      A history of significant adversity/trauma, particularly early in life, increases the risk of obesity, diabetes and CV disease (
      • Kelly S.J.
      • Ismail M.
      Stress and type 2 diabetes: A review of how stress contributes to the development of type 2 diabetes.
      ). Higher BMI, leptin, BP, fibrinogen and decreased insulin sensitivity have been found (
      • Farr O.M.
      • Ko B.J.
      • Joung K.E.
      • et al.
      Posttraumatic stress disorder, alone or additively with early life adversity, is associated with obesity and cardiometabolic risk.
      ). Post-traumatic stress disorder (PTSD) was found to cause a 40% increased risk of developing type 2 diabetes; those with sub-syndromal traumatic stress symptoms had a 20% increased risk (
      • Vaccarino V.
      • Goldberg J.
      • Magruder K.M.
      • et al.
      Posttraumatic stress disorder and incidence of type-2 diabetes: A prospective twin study.
      ).

      Anxiety

      Anxiety is commonly comorbid with depressive symptoms (
      • Katon W.
      • Lin E.H.
      • Kroenke K.
      The association of depression and anxiety with medical symptom burden in patients with chronic medical illness.
      ). One study estimated that 14% of individuals with diabetes suffered from generalized anxiety disorder, with double this figure experiencing a subclinical anxiety disorder and triple this figure having at least some anxiety symptoms (
      • Grigsby A.B.
      • Anderson R.J.
      • Freedland K.E.
      • et al.
      Prevalence of anxiety in adults with diabetes: A systematic review.
      ). Anxiety disorders were found in one-third of people with serious mental illnesses and type 2 diabetes, and were associated with increased depressive symptoms and decreased level of function (
      • Bajor L.A.
      • Gunzler D.
      • Einstadter D.
      • et al.
      Associations between comorbid anxiety, diabetes control, and overall medical burden in patients with serious mental illness and diabetes.
      ). Long-term anxiety has been associated with an increased risk of developing type 2 diabetes (
      • Hasan S.S.
      • Clavarino A.M.
      • Mamun A.A.
      • et al.
      Anxiety symptoms and the risk of diabetes mellitus in Australian women: Evidence from 21-year follow-up.
      ).

      Feeding and Eating Disorders

      Anorexia nervosa, bulimia nervosa and binge-eating disorder have been found to be more common in individuals with diabetes (both type 1 and type 2) than in the general population (
      • Crow S.
      • Kendall D.
      • Praus B.
      • et al.
      Binge eating and other psychopathology in patients with type II diabetes mellitus.
      ). Eating disorders are common and persistent, particularly in females with type 1 diabetes (
      • Colton P.A.
      • Olmsted M.P.
      • Daneman D.
      • et al.
      Eating disorders in girls and women with type 1 diabetes: A longitudinal study of prevalence, onset, remission, and recurrence.
      ,
      • Jones J.M.
      • Lawson M.L.
      • Daneman D.
      • et al.
      Eating disorders in adolescent females with and without type 1 diabetes: Cross sectional study.
      ). Elevated BMI is a risk factor for developing type 2 diabetes and MDD (
      • Asamsama O.H.
      • Lee J.W.
      • Morton K.R.
      • et al.
      Bidirectional longitudinal study of type 2 diabetes and depression symptoms in black and white church going adults.
      ). Depressive symptoms are highly comorbid with eating disorders, affecting up to 50% of individuals (
      • McCarthy M.
      The thin ideal, depression and eating disorders in women.
      ). Night eating syndrome is characterized by the consumption of >25% of daily caloric intake after the evening meal and waking at night to eat, on average, at least 3 times per week. Night eating syndrome has been noted to occur in individuals with type 2 diabetes and depressive symptoms. Night eating syndrome can result in weight gain, poor glycemic control and an increased number of diabetes complications (
      • Morse S.A.
      • Ciechanowski P.S.
      • Katon W.J.
      • et al.
      Isn't this just bedtime snacking? The potential adverse effects of night-eating symptoms on treatment adherence and outcomes in patients with diabetes.
      ).

      Sleep-Wake Disorders

      People with sleep apnea develop diabetes at higher rates than those without the condition (
      • Ramos A.R.
      • Wallace D.M.
      • Pandi-Perumal S.R.
      • et al.
      Associations between sleep disturbances and diabetes mellitus among blacks with metabolic syndrome: Results from the Metabolic Syndrome Outcome study (MetSO).
      ).

      Substance Use Disorders

      The exact prevalence of substance use disorders among individuals with diabetes is not well established, and the presence of substance use disorders may contribute to unique challenges in this population. Recreational substance abuse was associated with increased rates of hospitalization and readmissions for DKA (
      • Isidro M.L.
      • Jorge S.
      Recreational drug abuse in patients hospitalized for diabetic ketosis or diabetic ketoacidosis.
      ). Furthermore, substance abuse and psychosis among individuals with type 1 and type 2 diabetes increases the risk of all-cause mortality (
      • Lynch C.P.
      • Gebregziabher M.
      • Zhao Y.
      • et al.
      Impact of medical and psychiatric multi-morbidity on mortality in diabetes: Emerging evidence.
      ).

      Children and Adolescents with Diabetes

      For children, and particularly adolescents, there is a need to identify mental health disorders associated with diabetes and to intervene early to minimize the impact over the course of development. Children and adolescents with type 1 diabetes have significant risks for mental health problems, including depression, anxiety, eating disorders and disruptive behaviour disorders (
      • Fogel N.R.
      • Weissberg-Benchell J.
      Preventing poor psychological and health outcomes in pediatric type 1 diabetes.
      ,
      • Lawrence J.M.
      • Standiford D.A.
      • Loots B.
      • et al.
      Prevalence and correlates of depressed mood among youth with diabetes: The SEARCH for Diabetes in Youth study.
      ,
      • Hood K.K.
      • Huestis S.
      • Maher A.
      • et al.
      Depressive symptoms in children and adolescents with type 1 diabetes: Association with diabetes-specific characteristics.
      ). The risks increase significantly during adolescence (
      • Northam E.A.
      • Matthews L.K.
      • Anderson P.J.
      • et al.
      Psychiatric morbidity and health outcome in type 1 diabetes–perspectives from a prospective longitudinal study.
      ,
      • Kakleas K.
      • Kandyla B.
      • Karayianni C.
      • et al.
      Psychosocial problems in adolescents with type 1 diabetes mellitus.
      ). Studies have shown that mental health disorders predict poor diabetes management and control (
      • McDonnell C.M.
      • Northam E.A.
      • Donath S.M.
      • et al.
      Hyperglycemia and externalizing behavior in children with type 1 diabetes.
      ,
      • Korbel C.D.
      • Wiebe D.J.
      • Berg C.A.
      • et al.
      Gender differences in adherence to Type 1 diabetes management across adolescence: The mediating role of depression.
      ,
      • Bryden K.S.
      • Neil A.
      • Mayou R.A.
      • et al.
      Eating habits, body weight, and insulin misuse. A longitudinal study of teenagers and young adults with type 1 diabetes.
      ,
      • Herzer M.
      • Hood K.K.
      Anxiety symptoms in adolescents with type 1 diabetes: Association with blood glucose monitoring and glycemic control.
      ) and worsen medical outcomes (
      • Gonzalez J.S.
      • Peyrot M.
      • McCarl L.A.
      • et al.
      Depression and diabetes treatment nonadherence: A meta-analysis.
      ,
      • Chida Y.
      • Hamer M.
      An association of adverse psychosocial factors with diabetes mellitus: A meta-analytic review of longitudinal cohort studies.
      ,
      • Stewart S.M.
      • Rao U.
      • Emslie G.J.
      • et al.
      Depressive symptoms predict hospitalization for adolescents with type 1 diabetes mellitus.
      ,
      • Garrison M.M.
      • Katon W.J.
      • Richardson L.P.
      The Impact of psychiatric comorbidities on readmissions for diabetes in youth.
      ). Conversely, as glycemic control worsens, the probability of mental health problems increases (
      • Hassan K.
      • Loar R.
      • Anderson B.J.
      • et al.
      The role of socioeconomic status, depression, quality of life, and glycemic control in type 1 diabetes mellitus.
      ). Adolescents with type 1 diabetes have been shown to have generally comparable rates for diabetes distress compared to adults with type 1 diabetes (
      • Hagger V.
      • Hendrieckx C.
      • Sturt J.
      • et al.
      Diabetes distress among adolescents with type 1 diabetes: A systematic review.
      ).
      The presence of psychological symptoms and diabetes problems in children and adolescents with type 1 diabetes are often strongly affected by caregiver/family distress. It has been demonstrated that while parental psychological issues are often related to poor psychological adjustment and diabetes control (
      • Cunningham N.R.
      • Vesco A.T.
      • Dolan L.M.
      • et al.
      From caregiver psychological distress to adolescent glycemic control: The mediating role of perceived burden around diabetes management.
      ,
      • Butler J.M.
      • Skinner M.
      • Gelfand D.
      • et al.
      Maternal parenting style and adjustment in adolescents with type I diabetes.
      ,
      • Jaser S.S.
      • Whittemore R.
      • Ambrosino J.M.
      • et al.
      Mediators of depressive symptoms in children with type 1 diabetes and their mothers.
      ,
      • Eckshtain D.
      • Ellis D.A.
      • Kolmodin K.
      • et al.
      The effects of parental depression and parenting practices on depressive symptoms and metabolic control in urban youth with insulin dependent diabetes.
      ), they also distort perceptions of the child's diabetes control (
      • Hood K.K.
      The influence of caregiver depressive symptoms on proxy report of youth depressive symptoms: A test of the depression-distortion hypothesis in pediatric type 1 diabetes.
      ). Maternal anxiety and depression are associated with poor diabetes control in younger adolescents with type 1 diabetes and with reduced positive effects and motivation in older teens (
      • Cameron L.D.
      • Young M.J.
      • Wiebe D.J.
      Maternal trait anxiety and diabetes control in adolescents with type 1 diabetes.
      ).

      Feeding and Eating Disorders in Pediatric Diabetes

      Ten per cent of adolescent females with type 1 diabetes met the Diagnostic and Statistical Manual of Mental Disorders (5th Edition) criteria for eating disorders (
      • American Psychiatric Association
      Diagnostic and statistical manual of mental disorders.
      ), compared to 4% of their age-matched peers without diabetes (
      • Cameron L.D.
      • Young M.J.
      • Wiebe D.J.
      Maternal trait anxiety and diabetes control in adolescents with type 1 diabetes.
      ). Eating disorders are also associated with poorer metabolic control, earlier onset and more rapid progression of microvascular complications (
      • Jones J.M.
      • Lawson M.L.
      • Daneman D.
      • et al.
      Eating disorders in adolescent females with and without type 1 diabetes: Cross sectional study.
      ). In adolescent and young adult females with type 1 diabetes who are unable to achieve and maintain glycemic targets, particularly if insulin omission is suspected, an eating disorder may be a potential cause. Individuals with eating disorders may require different management strategies to optimize glycemic control and prevent microvascular complications (
      • Rydall A.C.
      • Rodin G.M.
      • Olmsted M.P.
      • et al.
      Disordered eating behavior and microvascular complications in young women with insulin-dependent diabetes mellitus.
      ). Type 1 diabetes in young adolescent women appears to be a risk factor for development of an eating disorder, both in terms of an increased prevalence of established eating disorder features as well as through deliberate insulin omission or underdosing (called diabulimia) (
      • Young-Hyman D.L.
      • Davis C.L.
      Disordered eating behavior in individuals with diabetes: Importance of context, evaluation, and classification.
      ,
      • Bachle C.
      • Lange K.
      • Stahl-Pehe A.
      • et al.
      Symptoms of eating disorders and depression in emerging adults with early-onset, long-duration type 1 diabetes and their association with metabolic control.
      ).

      Other Considerations in Children and Adolescents

      The prevalence of anxiety disorders in children and adolescents with type 1 diabetes in 1 study was found to be 15.5%, and mood disorders was 3.5%, with one-third having a lifetime prevalence of at least one psychiatric condition (
      • Butwicka A.
      • Fendler W.
      • Zalepa A.
      • et al.
      Psychiatric disorders and health-related quality of life in children with type 1 diabetes mellitus.
      ). The presence of psychiatric disorders was related to elevated A1C levels and a lowered health-related quality of life score in the general pediatric quality of life inventory. In the diabetes mellitus-specific pediatric quality of life inventory, children with psychiatric disorders revealed more symptoms of diabetes, treatment barriers and lower adherence than children without psychiatric disorders (
      • Butwicka A.
      • Fendler W.
      • Zalepa A.
      • et al.
      Psychiatric disorders and health-related quality of life in children with type 1 diabetes mellitus.
      ). Adolescents with type 1 diabetes ranked school as their number 1 stressor, their social lives as number 2 and having diabetes as number 3 (
      • Chao A.M.
      • Minges K.E.
      • Park C.
      • et al.
      General life and diabetes-related stressors in early adolescents with type 1 diabetes.
      ).

      Prevention and Intervention

      Children and adolescents with diabetes, along with their families, should be screened throughout their development for mental health disorders (
      • Schwartz D.D.
      • Cline V.D.
      • Hansen J.A.
      • et al.
      Early risk factors for nonadherence in pediatric type 1 diabetes: A review of the recent literature.
      ). Given the prevalence of mental health issues, screening in this area is just as important as screening for microvascular complications in children and adolescents with diabetes (
      • Cameron F.J.
      • Northam E.A.
      • Ambler G.R.
      • et al.
      Routine psychological screening in youth with type 1 diabetes and their parents: A notion whose time has come?.
      ).
      Psychological interventions with children and adolescents, as well as families, have been shown to improve mental health (
      • Harkness E.
      • Macdonald W.
      • Valderas J.
      • et al.
      Identifying psychosocial interventions that improve both physical and mental health in patients with diabetes: A systematic review and meta-analysis.
      ), including overall well-being and perceived quality of life (
      • de Wit M.
      • Delemarre-van de Waal H.A.
      • Bokma J.A.
      • et al.
      Monitoring and discussing health-related quality of life in adolescents with type 1 diabetes improve psychosocial well-being: A randomized controlled trial.
      ), along with reducing depressive symptoms (
      • van der Feltz-Cornelis C.M.
      • Nuyen J.
      • Stoop C.
      • et al.
      Effect of interventions for major depressive disorder and significant depressive symptoms in patients with diabetes mellitus: A systematic review and meta-analysis.
      ). In addition, there is evidence to show that psychosocial interventions can positively affect glycemic control (
      • Winkley K.
      • Ismail K.
      • Landau S.
      • et al.
      Psychological interventions to improve glycaemic control in patients with type 1 diabetes: Systematic review and meta-analysis of randomised controlled trials.
      ,
      • Alam R.
      • Sturt J.
      • Lall R.
      • et al.
      An updated meta-analysis to assess the effectiveness of psychological interventions delivered by psychological specialists and generalist clinicians on glycaemic control and on psychological status.
      ). Most importantly, some studies have demonstrated that psychological interventions can increase both diabetes treatment adherence and glycemic control, as well as psychosocial functioning (
      • Delamater A.M.
      • Jacobson A.M.
      • Anderson B.
      • et al.
      Psychosocial therapies in diabetes: Report of the Psychosocial Therapies Working Group.
      ,
      • Méndez F.J.
      • Beléndez M.
      Effects of a behavioral intervention on treatment adherence and stress management in adolescents with IDDM.
      ).

      Type 2 Diabetes in Children and Adolescents

      Atypical antipsychotic medications are associated with significant weight gain, insulin resistance, IFG and type 2 diabetes in children (
      • Panagiotopoulos C.
      • Ronsley R.
      • Davidson J.
      Increased prevalence of obesity and glucose intolerance in youth treated with second—generation antipsychotic medications.
      ). Psychiatric disorders and the use of psychiatric medications are more common in children with obesity at diagnosis of type 2 diabetes compared to the general pediatric population (
      • Levitt Katz L.E.
      • Swami S.
      • Abraham M.
      • et al.
      Neuropsychiatric disorders at the presentation of type 2 diabetes mellitus in children.
      ). Children and adolescents prescribed an atypical antipsychotic have double the risk of developing diabetes (
      • Sohn M.
      • Talbert J.
      • Blumenschein K.
      • et al.
      Atypical antipsychotic initiation and the risk of type II diabetes in children and adolescents.
      ). The risk of developing diabetes may be higher in adolescents taking concomitant antipsychotic and antidepressant medications (
      • Rubin D.M.
      • Kreider A.R.
      • Matone M.
      • et al.
      Risk for incident diabetes mellitus following initiation of second-generation antipsychotics among Medicaid-enrolled youths.
      ).

      Considerations in Pregnancy

      One study found that gestational diabetes was strongly associated with increased risk for postpartum depression (PPD), regardless of prior depression history, whereas pregestational diabetes increased risk only for those with a prior history of depression. It was also found that for those with a history of depression, diabetes adds a 1.5-fold increased risk for PPD (
      • Silverman M.E.
      • Reichenberg A.
      • Savitz D.A.
      • et al.
      The risk factors for postpartum depression: A population-based study.
      ). Optimized glycemic control in pregnancy has been shown to have numerous benefits for pregnancy outcomes and may also be protective against PPD (
      • Crowther C.A.
      • Hiller J.E.
      • Moss J.R.
      • et al.
      Effect of treatment of gestational diabetes mellitus on pregnancy outcomes.
      ,
      • Langer N.
      • Langer O.
      Comparison of pregnancy mood profiles in gestational diabetes and preexisting diabetes.
      ). In another study, the presence of depressive symptoms in early pregnancy was associated with preterm delivery in women with pregestational diabetes (
      • Callesen N.F.
      • Secher A.L.
      • Cramon P.
      • et al.
      Mental health in early pregnancy is associated with pregnancy outcome in women with pregestational diabetes.
      ). Thus, there may be a role for improved screening and treatment of depression in optimizing pregnancy outcomes in women with diabetes (
      • Hinkle S.N.
      • Buck Louis G.M.
      • Rawal S.
      • et al.
      A longitudinal study of depression and gestational diabetes in pregnancy and the postpartum period.
      ).

      Considerations for Older People with Diabetes

      Type 2 diabetes does not appear to be more common in geriatric psychiatric patients than similarly aged controls. MDD and the use of antidepressants, cholinesterase inhibitors and valproate may increase fasting glucose levels (
      • Abitbol R.
      • Rej S.
      • Segal M.
      • et al.
      Diabetes mellitus onset in geriatric patients: Does long-term atypical antipsychotic exposure increase risk?.
      ). The risk of developing a dementing illness in people is increased with those who have MDD (hazard ratio [HR 1.83], type 2 diabetes [HR 1.20] or both [HR 2.17]) (
      • Katon W.
      • Pedersen H.S.
      • Ribe A.R.
      • et al.
      Effect of depression and diabetes mellitus on the risk for dementia: A national population-based cohort study.
      ). The presence of depressive symptoms in elderly people with type 2 diabetes is associated with increased mortality risk (
      • Limongi F.
      • Noale M.
      • Crepaldi G.
      • et al.
      Prevalence of diabetes and depressive symptomatology and their effect on mortality risk in elderly Italians: The Italian Longitudinal Study on Aging.
      ).

      Suicide

      A review article found that people with both type 1 and type 2 diabetes had increased rates of suicidal ideation, suicide attempts and completed suicide compared to the general population (
      • Sarkar S.
      • Balhara Y.P.S.
      Diabetes mellitus and suicide.
      ). Another study found that people with newly diagnosed type 2 diabetes had a rate of past suicide attempts of almost 10%, which is twice the rate estimated in the general population. The rate of past suicide attempts in currently depressed patients with diabetes was reported at over 20% (
      • Myers A.K.
      • Grannemann B.D.
      • Lingvay I.
      • et al.
      Brief report: Depression and history of suicide attempts in adults with new-onset type 2 diabetes.
      ).

      Psychiatric Disorders and Adverse Outcomes

      Two independent systematic reviews with meta-analyses showed that MDD significantly increases the risk of all-cause mortality among individuals with diabetes compared to those with diabetes without it (
      • Hoffmann M.
      • Kohler B.
      • Leichsenring F.
      • et al.
      Depression as a risk factor for mortality in individuals with diabetes: A meta-analysis of prospective studies.
      ,
      • Park M.
      • Katon W.J.
      • Wolf F.M.
      Depression and risk of mortality in individuals with diabetes: A meta-analysis and systematic review.
      ). Older adults with diabetes and depression may be at particular risk (
      • Lynch C.P.
      • Gebregziabher M.
      • Zhao Y.
      • et al.
      Impact of medical and psychiatric multi-morbidity on mortality in diabetes: Emerging evidence.
      ). Individuals with bipolar disorder, schizophrenia or other psychotic disorders, and who have comorbid diabetes, are at increased risk of rehospitalization following medical-surgical admissions (
      • Chwastiak L.A.
      • Davydow D.S.
      • McKibbin C.L.
      • et al.
      The effect of serious mental illness on the risk of rehospitalization among patients with diabetes.
      ).

      Screening and Assessment of Mental Health Symptoms

      Because of the prevalence of diabetes distress and psychiatric comorbidity and the negative impact that these factors have on glycemic control, early morbidity and quality of life, it is recommended that individuals with diabetes should be regularly screened with validated questionnaires or clinical interviews. The available data does not currently support the superiority of any particular depression screening tool (
      • Pignone M.P.
      • Gaynes B.N.
      • Rushton J.L.
      • et al.
      Screening for depression in adults: A summary of the evidence for the U.S. Preventive Services Task Force.
      ). Currently available screening instruments have a sensitivity of between 80% and 90% and a specificity of 70% to 85% (
      • Pignone M.P.
      • Gaynes B.N.
      • Rushton J.L.
      • et al.
      Screening for depression in adults: A summary of the evidence for the U.S. Preventive Services Task Force.
      ). Scales that are in the public domain are available at www.outcometracker.org/scales_library.php. Patient Health Questionnaire (PHQ) Screeners are available at www.phqscreeners.com. PHQ-9 (for MDD) scores of ≥10 and Generalized Anxiety Disorders (GAD)-7 scores ≥10 have been associated with increased diabetes complications (
      • Ishizawa K.
      • Babazono T.
      • Horiba Y.
      • et al.
      The relationship between depressive symptoms and diabetic complications in elderly patients with diabetes: Analysis using the diabetes study from the Center of Tokyo Women's Medical University (DIACET).
      ,
      • van Dooren F.E.
      • Denollet J.
      • Verhey F.R.
      • et al.
      Psychological and personality factors in type 2 diabetes mellitus, presenting the rationale and exploratory results from The Maastricht Study, a population-based cohort study.
      ).
      Screening instruments fall into 3 categories:
      • Diabetes-specific measures, such as the Problem Areas in Diabetes (PAID) Scale or the Diabetes Distress Scale (DDS) (
        • Polonsky W.H.
        • Anderson B.J.
        • Lohrer P.A.
        • et al.
        Assessment of diabetes-related distress.
        ,
        • van Bastelaar K.M.
        • Pouwer F.
        • Geelhoed-Duijvestijn P.H.
        • et al.
        Diabetes-specific emotional distress mediates the association between depressive symptoms and glycaemic control in type 1 and type 2 diabetes.
        )
      • Quality of life measures, such as the WHO-5 screening instrument (
        • Furuya M.
        • Hayashino Y.
        • Tsujii S.
        • et al.
        Comparative validity of the WHO-5 Well-Being Index and two-question instrument for screening depressive symptoms in patients with type 2 diabetes.
        )
      • Depressive/anxiety symptoms, such as the Hospital Anxiety and Depression Scale (HADS) (
        • Collins M.M.
        • Corcoran P.
        • Perry I.J.
        Anxiety and depression symptoms in patients with diabetes.
        ), the Patient Health Questionnaire (PHQ-9) (,
        • van Steenbergen-Weijenburg K.M.
        • de Vroege L.
        • Ploeger R.R.
        • et al.
        Validation of the PHQ-9 as a screening instrument for depression in diabetes patients in specialized outpatient clinics.
        ), the Centre for Epidemiological Studies-Depression Scale (CES-D) (
        • Fisher L.
        • Skaff M.M.
        • Mullan J.T.
        • et al.
        A longitudinal study of affective and anxiety disorders, depressive affect and diabetes distress in adults with Type 2 diabetes.
        ) or the Beck Depression Inventory (BDI) (
        • Mantyselka P.
        • Korniloff K.
        • Saaristo T.
        • et al.
        Association of depressive symptoms with impaired glucose regulation, screen-detected, and previously known type 2 diabetes: Findings from the Finnish D2D survey.
        ).
      Table 1 outlines the principal features and assessment methods to differentiate diabetes distress from MDD.

      Psychosocial (Non-Pharmacological) Treatments

      Efforts to promote well-being to mitigate distress should be incorporated into diabetes management for all individuals (
      • Piatt G.A.
      • Anderson R.M.
      • Brooks M.M.
      • et al.
      3-year follow-up of clinical and behavioral improvements following a multifaceted diabetes care intervention: Results of a randomized controlled trial.
      ). Motivational interventions (
      • Osborn C.Y.
      • Egede L.E.
      Validation of an Information-Motivation-Behavioral skills model of Diabetes Self-Care (IMB-DSC).
      ,
      • Maindal H.T.
      • Sandbaek A.
      • Kirkevold M.
      • et al.
      Effect on motivation, perceived competence, and activation after participation in the “‘Ready to Act’” programme for people with screen-detected dysglycaemia: A 1-year randomised controlled trial, Addition-DK.
      ), coping skills, self-efficacy enhancement, stress management (
      • Attari A.
      • Sartippour M.
      • Amini M.
      • et al.
      Effect of stress management training on glycemic control in patients with type 1 diabetes.
      ,
      • Soo H.
      • Lam S.
      Stress management training in diabetes mellitus.
      ) and family interventions (
      • Keogh K.M.
      • Smith S.M.
      • White P.
      • et al.
      Psychological family intervention for poorly controlled type 2 diabetes.
      ,
      • Wysocki T.
      • Harris M.A.
      • Buckloh L.M.
      • et al.
      Randomized trial of behavioral family systems therapy for diabetes: Maintenance of effects on diabetes outcomes in adolescents.
      ,
      • Wysocki T.
      • Harris M.A.
      • Buckloh L.M.
      • et al.
      Randomized, controlled trial of Behavioral Family Systems Therapy for Diabetes: Maintenance and generalization of effects on parent-adolescent communication.
      ,
      • Armour T.A.
      • Norris S.L.
      • Jack Jr, L.
      • et al.
      The effectiveness of family interventions in people with diabetes mellitus: A systematic review.
      ) all have been shown to be helpful. Case management by a nurse working with the patient's primary care provider and providing guideline-based, patient-centred care resulted in improved A1C, lipid levels, BP and depression scores (
      • Osborn C.Y.
      • Egede L.E.
      Validation of an Information-Motivation-Behavioral skills model of Diabetes Self-Care (IMB-DSC).
      ,
      • Chen S.M.
      • Creedy D.
      • Lin H.S.
      • et al.
      Effects of motivational interviewing intervention on self-management, psychological and glycemic outcomes in type 2 diabetes: A randomized controlled trial.
      ,
      • Huang Y.
      • Wei X.
      • Wu T.
      • et al.
      Collaborative care for patients with depression and diabetes mellitus: A systematic review and meta-analysis.
      ,
      • Atlantis E.
      • Fahey P.
      • Foster J.
      Collaborative care for comorbid depression and diabetes: A systematic review and meta-analysis.
      ). Individuals with diabetes distress and/or psychiatric disorders benefit from professional interventions, either some form of psychotherapy or prescription medication. Evidence from systematic reviews of randomized controlled trials supports cognitive behaviour therapies (CBT) and antidepressant medication, both solely or in combination (
      • van der Feltz-Cornelis C.M.
      • Nuyen J.
      • Stoop C.
      • et al.
      Effect of interventions for major depressive disorder and significant depressive symptoms in patients with diabetes mellitus: A systematic review and meta-analysis.
      ,
      • Petrak F.
      • Herpertz S.
      Treatment of depression in diabetes: An update.
      ,
      • Baumeister H.
      • Hutter N.
      • Bengel J.
      Psychological and pharmacological interventions for depression in patients with diabetes mellitus: An abridged Cochrane review.
      ). No evidence presently shows that the combination of CBT and medication is superior to these treatments given individually. A pilot study of 50 people with type 2 diabetes who initially had a moderate level of depression at baseline showed an improvement in the severity of their depression (moving to the mild range) with a 12-week intervention of 10 CBT sessions combined with exercise in the form of 150 minutes of aerobic activity weekly. This effect was sustained at 3 months (
      • van der Feltz-Cornelis C.M.
      • Nuyen J.
      • Stoop C.
      • et al.
      Effect of interventions for major depressive disorder and significant depressive symptoms in patients with diabetes mellitus: A systematic review and meta-analysis.
      ).
      Table 2 illustrates some of the major features of CBT as applied to diabetes care. Gains from treatment with psychotherapy are more likely to benefit psychological symptoms and glycemic control in adults than will psychiatric medications (which usually reduce psychological symptoms only) (
      • de Groot M.
      • Doyle T.
      • Kushnick M.
      • et al.
      Can lifestyle interventions do more than reduce diabetes risk? Treating depression in adults with type 2 diabetes with exercise and cognitive behavioral therapy.
      ). Meta-analyses of psychological interventions found that they improved glycemic control (A1C) in children and adolescents with type 1 diabetes (
      • Wang M.Y.
      • Tsai P.S.
      • Chou K.R.
      • et al.
      A systematic review of the efficacy of non-pharmacological treatments for depression on glycaemic control in type 2 diabetics.
      ), and adults with type 2 diabetes (
      • Chapman A.
      • Liu S.
      • Merkouris S.
      • et al.
      Psychological interventions for the management of glycemic and psychological outcomes of type 2 diabetes mellitus in china: A systematic review and meta-analyses of randomized controlled trials.
      ). Furthermore, evidence suggests interventions are best implemented in a collaborative fashion and when combined with self-management interventions (
      • de Groot M.
      • Doyle T.
      • Kushnick M.
      • et al.
      Can lifestyle interventions do more than reduce diabetes risk? Treating depression in adults with type 2 diabetes with exercise and cognitive behavioral therapy.
      ). Recent evidence also supports the effectiveness of mindfulness-based CBT (
      • van Son J.
      • Nyklicek I.
      • Nefs G.
      • et al.
      The association between mindfulness and emotional distress in adults with diabetes: Could mindfulness serve as a buffer? Results from Diabetes MILES: The Netherlands.
      ,
      • Tovote K.A.
      • Fleer J.
      • Snippe E.
      • et al.
      Individual mindfulness-based cognitive therapy and cognitive behavior therapy for treating depressive symptoms in patients with diabetes: Results of a randomized controlled trial.
      ).
      Table 2Features of CBT that can be applied to diabetes treatment
      Cognitive ComponentBehavioural Component
      Record keeping to identify distressing automatic thoughts

      Understanding the link between thoughts and feelings







      Learning the common “thinking errors” that mediate distress (e.g. all-or-nothing thinking, personalization, magnification, minimization, etc.)

      Analyzing negative thoughts and promoting more functional ones

      Identifying basic assumptions about oneself (e.g. “unless I am very successful, my life is not worth living) and being encouraged to adopt healthier ones (e.g. “when I am doing my best, I should be proud of myself”)
      Strategies to help get the person moving (behavioural activation)

      Scheduling pleasant and meaningful events

      Learning assertive and effective communication skills

      Focusing on feelings of mastery and accomplishment





      Learning problem-solving strategies

      Exposure to new experiences

      Shaping behaviours by breaking them down into smaller steps to develop skills
      CBT, cognitive behavioural therapy.
      Among adults with type 2 diabetes and subclinical depression, CBT resulted in reductions in diabetes distress and depressive symptoms compared to controls (
      • Hermanns N.
      • Schmitt A.
      • Gahr A.
      • et al.
      The effect of a Diabetes-Specific Cognitive Behavioral Treatment Program (DIAMOS) for patients with diabetes and subclinical depression: Results of a randomized controlled trial.
      ). Lower diabetes regimen distress (produced by an intervention combining education, problem solving and support for accountability) led to improvements in medication adherence, physical activity and decreased A1C over 1 year (
      • Hessler D.
      • Fisher L.
      • Glasgow R.E.
      • et al.
      Reductions in regimen distress are associated with improved management and glycemic control over time.
      ,
      • Katon W.J.
      • Lin E.H.B.
      • Von Korff M.
      • et al.
      Collaborative care for patients with depression and chronic illnesses.
      ).
      Recent research suggests that CBT can be used to address psychological insulin resistance by specifically addressing the beliefs that underlie it (
      • Polonsky W.H.
      • Hajos T.R.
      • Dain M.P.
      • et al.
      Are patients with type 2 diabetes reluctant to start insulin therapy? An examination of the scope and underpinnings of psychological insulin resistance in a large, international population.
      ,
      • Polonsky W.H.
      • Jackson R.A.
      What's so tough about taking insulin? Addressing the problem of psychological insulin resistance in type 2 diabetes.
      ,
      • Polonsky W.H.
      • Fisher L.
      • Guzman S.
      • et al.
      Psychological insulin resistance in patients with type 2 diabetes.
      ,
      • Barnard K.
      • Thomas S.
      • Royle P.
      • et al.
      Fear of hypoglycaemia in parents of young children with type 1 diabetes: A systematic review.
      ) (Figure 2). Fear of hypoglycemia is amenable to treatment, such as with the behavioural desensitization process illustrated in Figure 3 (
      • Polonsky W.H.
      • Fisher L.
      • Hessler D.
      • et al.
      Identifying the worries and concerns about hypoglycemia in adults with type 2 diabetes.
      ,
      • Vallis M.
      • Jones A.
      • Pouwer F.
      Managing hypoglycemia in diabetes may be more fear management than glucose management: A practical guide for diabetes care providers.
      ,
      • Barnard K.
      • Thomas S.
      • Royle P.
      • et al.
      Fear of hypoglycaemia in parents of young children with type 1 diabetes: A systematic review.
      ,
      • Wild D.
      • von Maltzahn R.
      • Brohan E.
      • et al.
      A critical review of the literature on fear of hypoglycemia in diabetes: Implications for diabetes management and patient education.
      ).
      Figure 2
      Figure 2Features of psychological insulin resistance.
      Figure 3
      Figure 3Suggested cognitive behaviour therapy for fear of hypoglycemia.
      Since diabetes outcomes are heavily dependent on the sustained participation of the individual with the illness, motivational and behavioural change strategies can be effective. Diabetes care providers can enhance successful behaviour changes through motivational strategies, such as having individuals weigh the advantages and disadvantages of change, as well as encouraging their sense of self-efficacy (
      • Ekong G.
      • Kavookjian J.
      Motivational interviewing and outcomes in adults with type 2 diabetes: A systematic review.
      ,
      • Abidi S.
      • Vallis M.
      • Raza Abidi S.S.
      • et al.
      D-WISE: Diabetes Web-Centric Information and Support Environment: Conceptual specification and proposed evaluation.
      ,
      • Graves H.
      • Garrett C.
      • Amiel S.A.
      • et al.
      Psychological skills training to support diabetes self-management: Qualitative assessment of nurses' experiences.
      ). Optimism and compassion have been shown to be helpful (
      • Fournier M.
      • De Ridder D.
      • Bensing J.
      Optimism and adaptation to chronic disease: The role of optimism in relation to self-care options of type 1 diabetes mellitus, rheumatoid arthritis and multiple sclerosis.
      ,
      • Seligman M.E.
      • Csikszentmihalyi M.
      Positive psychology. an introduction.
      ).

      Pharmacological Treatments

      Psychiatric medications have the capacity to affect metabolic parameters and cause changes in weight, glycemic control, lipid profile and can have immunomodulating effects (
      • Xia Z.
      • DePierre J.W.
      • Nassberger L.
      Tricyclic antidepressants inhibit IL-6, IL-1 beta and TNF-alpha release in human blood monocytes and IL-2 and interferon-gamma in T cells.
      ,
      • Maes M.
      • Song C.
      • Lin A.H.
      • et al.
      Negative immunoregulatory effects of antidepressants: Inhibition of interferon-gamma and stimulation of interleukin-10 secretion.
      ,
      • Kauffman R.P.
      • Castracane V.D.
      • White D.L.
      • et al.
      Impact of the selective serotonin reuptake inhibitor citalopram on insulin sensitivity, leptin and basal cortisol secretion in depressed and non-depressed euglycemic women of reproductive age.
      ,
      • Weber-Hamann B.
      • Gilles M.
      • Lederbogen F.
      • et al.
      Improved insulin sensitivity in 80 nondiabetic patients with MDD after clinical remission in a double-blind, randomized trial of amitriptyline and paroxetine.
      ). A systematic review estimated and compared the effects of antipsychotics, both novel and conventional, and noted variable effects on weight gain (
      • Allison D.B.
      • Mentore J.L.
      • Heo M.
      • et al.
      Antipsychotic-induced weight gain: A comprehensive research synthesis.
      ). The weight gain potential of clozapine and olanzapine has been established (
      • American Diabetes Association
      • American Psychiatric Association
      • American Association of Clinical Endocrinologists
      • North American Association for the Study of Obesity
      Consensus development conference on antipsychotic drugs and obesity and diabetes.
      ,
      • Woo V.
      • Harris S.B.
      • Houlden R.L.
      Canadian Diabetes Association position paper: Antipsychotic medications and associated risks of weight gain and diabetes.
      ). Children and adolescents using antipsychotics had a 2- to 3-fold increased risk of type 2 diabetes (
      • Bobo W.V.
      • Cooper W.O.
      • Stein C.M.
      • et al.
      Antipsychotics and the risk of type 2 diabetes mellitus in children and youth.
      ,
      • Nielsen R.E.
      • Laursen M.F.
      • Lammers Vernal D.
      • et al.
      Risk of diabetes in children and adolescents exposed to antipsychotics: A nationwide 12-year case-control study.
      ), which was apparent within the first year of follow up. Metformin has been shown to have a modest ability to reduce weight gain due to antipsychotic medication (
      • Jarskog L.F.
      • Hamer R.M.
      • Catellier D.J.
      • et al.
      Metformin for weight loss and metabolic control in overweight outpatients with schizophrenia and schizoaffective disorder.
      ).
      A comprehensive review and meta-analysis looked at the effect of antidepressants on body weight (
      • Serretti A.
      • Mandelli L.
      Antidepressants and body weight: A comprehensive review and meta-analysis.
      ). Serotonin-norepinephrine reuptake inhibitors (SNRIs) are generally more active on the serotonergic component, with levomilnacipran having the strongest preference among the group for blocking norepinephrine reuptake. Desipramine is the tricyclic antidepressant (TCA) with the strongest action in blocking norepinephrine reuptake (
      • Auclair A.L.
      • Martel J.C.
      • Assié M.B.
      • et al.
      Levomilnacipran (F2695), a norepinephrine-preferring SNRI: Profile in vitro and in models of depression and anxiety.
      ), and has the potential to affect glucose homeostasis.
      The CATIE study investigated 4 aspects of the effectiveness of antipsychotic medications: efficacy, tolerability, emergence of medical problems and patient choice (
      • Anagnostis P.
      • Athyros V.G.
      • Tziomalos K.
      • et al.
      Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: A hypothesis.
      ). The results did indicate that some antipsychotic medications were more likely to cause weight gain, worsen glycemic control and induce unfavourable changes in lipid profile. However, when these effects were considered in the context of efficacy, tolerability and patient choice, no conclusive statements could be made about which medications to clearly use or avoid. Consequently, all 4 aspects are important and reinforce the need for regular and comprehensive metabolic monitoring. Non-pharmacological interventions can be effective in reducing antipsychotic-associated weight gain and glucose changes (
      • Caemmerer J.
      • Correll C.U.
      • Maayan L.
      Acute and maintenance effects of non-pharmacologic interventions for antipsychotic associated weight gain and metabolic abnormalities: A meta-analytic comparison of randomized controlled trials.
      ).
      Should medical problems arise while a person is taking psychiatric medications, clinical judgement will dictate on a case-by-case basis whether healthy behaviour interventions, such as diet or exercise, adding a medication to address the emergent issue (e.g. side effect or medical complication) or changing the psychiatric prescription is the most reasonable step (
      • Stroup T.S.
      • Lieberman J.A.
      • McEvoy J.P.
      • et al.
      Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic.
      ,
      • Stroup T.S.
      • McEvoy J.P.
      • Ring K.D.
      • et al.
      A randomized trial examining the effectiveness of switching from olanzapine, quetiapine, or risperidone to aripiprazole to reduce metabolic risk: Comparison of Antipsychotics for Metabolic Problems (CAMP).
      ). Resources are available to help clinicians quickly review the major side effect profiles of psychiatric medications (
      • Stahl S.
      The prescriber's guide.
      ,
      • Procyshyn R.M.
      Clinical handbook of psychotropic drugs.
      ).

      Monitoring Metabolic Risks

      Metabolic syndrome is found at higher rates in individuals with psychiatric illnesses than in the general population (
      • Vancampfort D.
      • Mitchell A.J.
      • De Hert M.
      • et al.
      Prevalence and predictors of type 2 diabetes mellitus in people with bipolar disorder.
      ,
      • Gardner-Sood P.
      • Lally J.
      • Smith S.
      • et al.
      Cardiovascular risk factors and metabolic syndrome in people with established psychotic illnesses: Baseline data from the IMPaCT randomized controlled trial.
      ). Patients with diabetes and comorbid psychiatric illnesses are at an elevated risk for developing metabolic syndrome, possibly due to a combination of the following factors (
      • Meyer J.
      Medical illness and schizophrenia.
      ):
      • Patient factors (e.g. health behaviour choices, diet, tobacco consumption, substance use, exercise, obesity, low degree of implementation of education programs)
      • Illness factors (e.g. pro-inflammatory states from MDD or depressive symptoms, possible disease-related risks for developing diabetes) (
        • Smith R.S.
        The macrophage theory of depression.
        ,
        • Fernandez-Real J.M.
        • Pickup J.C.
        Innate immunity, insulin resistance and type 2 diabetes.
        )
      • Medication factors (e.g. psychiatric medications have variable effects on glycemic control, weight and lipids)
      • Environmental factors (e.g. access to health care, availability of screening and monitoring programs, social supports, education programs).
      Many psychiatric medications (primarily second- and third-generation or atypical antipsychotics), have the potential to affect weight, lipids and glycemic control even in patients without diabetes (
      • Lieberman J.A.
      • Stroup T.S.
      • McEvoy J.P.
      • et al.
      Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.
      ,
      • Spoelstra J.A.
      • Stolk R.P.
      • Cohen D.
      • et al.
      Antipsychotic drugs may worsen metabolic control in type 2 diabetes mellitus.
      ). A weight gain of between 2 to 3 kg was found within a 1-year time frame with the antidepressants amitriptyline, mirtazapine and paroxetine (
      • Serretti A.
      • Mandelli L.
      Antidepressants and body weight: A comprehensive review and meta-analysis.
      ). A study of people with type 2 diabetes and schizophrenia who were treated with antipsychotic medications also showed worsening glycemic control, requiring the addition of insulin therapy over a 2-year period with a HR of 2.0 (
      • Newcomer J.W.
      • Haupt D.W.
      The metabolic effects of antipsychotic medications.
      ). The reported weight gain over a 1-year period ranges from <1 kg to >4 kg for various antipsychotic medications. The main impact on lipid profile is an increase in triglyceride and total cholesterol levels, especially with clozapine, olanzapine and quetiapine (
      • Lieberman J.A.
      • Stroup T.S.
      • McEvoy J.P.
      • et al.
      Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.
      ,
      • Lambert T.J.
      • Chapman L.H.
      Consensus Working Group
      Diabetes, psychotic disorders and antipsychotic therapy: A consensus statement.
      ). Table 3 lists the likelihood for weight gain with use of psychiatric medications.
      Table 3Psychiatric medications and risk of weight gain
      UnlikelyLikelyVery LikelyHighly Likely
      AnticholinergicsBenztropineTrihexyphenidylProcyclidineDiphenhydramine
      AntidepressantsBupropion

      Citalopram

      Desvenlafaxine

      Duloxetine

      Escitalopram

      Fluoxetine
      Levomilnacipran

      Moclobemide

      Sertraline

      Trazodone

      Venlafaxine

      Vortioxetine
      Paroxetine

      Tranylcypromine
      Amitriptyline

      Clomipramine

      Desipramine

      Doxepin

      Fluvoxamine

      Imipramine
      Maprotiline

      Mirtazapine

      Nortriptyline

      Phenelzine

      Trimipramine
      AntipsychoticsAripiprazole

      Brexpiprazole

      Loxapine
      Thiothixene

      Trifluoperazine

      Ziprasidone
      Asenapine

      Fluphenazine

      Haloperidol

      Methotrimeprazine

      Pericyazine

      Perphenazine

      Pimozide
      Amoxapine

      Chlorpromazine

      Flupenthixol

      Lurasidone

      Paliperidone
      Pipotiazine

      Quetiapine

      Risperidone

      Thioridazine

      Zuclopenthixol
      Clozapine

      Olanzapine
      AnxiolyticsClonazepam

      Clorazepate

      Diazepam

      Flurazepam

      Lorazepam
      Nitrazepam

      Oxazepam

      Temazepam

      Triazolam
      Cholinesterase inhibitorsDonepezil

      Galantamine
      Rivastigmine
      Mood stabilizersLamotrigineTopiramateCarbamazepine

      Gabapentin

      Oxcarbazepine
      LithiumValproate
      Sedatives / hypnoticsZolpidemZopiclone
      StimulantsAtomoxetine

      Dextroamphetamine

      Lisdexamfetamine
      Methylphenidate

      Modafinil
      Substance use disorder treatmentsBuprenorphine

      Clonidine
      Naltrexone

      Varenicline
      Methadone
      Amalgamated from references
      • Stahl S.
      The prescriber's guide.
      ,
      • Procyshyn R.M.
      Clinical handbook of psychotropic drugs.
      .
      Regular, comprehensive monitoring of metabolic parameters is recommended for all persons who receive antipsychotic medications, whether or not they have diabetes. A1C was shown to be a more stable parameter in identifying psychiatric patients with diabetes (
      • Steylen P.M.
      • van der Heijden F.M.
      • Hoogendijk W.J.
      • et al.
      Glycosylated hemoglobin as a screening test for hyperglycemia in antipsychotic-treated patients: A follow-up study.
      ). Table 4 outlines a Psychiatric Medication Metabolic Monitoring Protocol.
      Recommendations
      • 1.
        Individuals with diabetes should be regularly screened for diabetes-related psychological distress (e.g. diabetes distress, psychological insulin resistance, fear of hypoglycemia) and psychiatric disorders (e.g. depression, anxiety disorders) by validated self-report questionnaire or clinical interview [Grade D, Consensus]. Plans for self harm should be asked about regularly as well [Grade C, Level 3 (
        • Sarkar S.
        • Balhara Y.P.S.
        Diabetes mellitus and suicide.
        )].
      • 2.
        The following groups of people with diabetes should be referred to specialized mental health-care professionals [Grade D, Consensus for all of the following]:
        • a.
          Significant distress related to diabetes management
        • b.
          Persistent fear of hypoglycemia
        • c.
          Psychological insulin resistance
        • d.
          Psychiatric disorders (i.e. depression, anxiety, eating disorders).
      • 3.
        Collaborative care by interprofessional teams should be provided for individuals with diabetes and depression to improve:
        • a.
          Depressive symptoms [Grade A, Level 1 (
          • Huang Y.
          • Wei X.
          • Wu T.
          • et al.
          Collaborative care for patients with depression and diabetes mellitus: A systematic review and meta-analysis.
          ,
          • Atlantis E.
          • Fahey P.
          • Foster J.
          Collaborative care for comorbid depression and diabetes: A systematic review and meta-analysis.
          )]
        • b.
          Adherence to antidepressant and noninsulin antihyperglycemic medications [Grade A, Level 1 (
          • Huang Y.
          • Wei X.
          • Wu T.
          • et al.
          Collaborative care for patients with depression and diabetes mellitus: A systematic review and meta-analysis.
          )]
        • c.
          Glycemic control [Grade A, Level 1 (
          • Atlantis E.
          • Fahey P.
          • Foster J.
          Collaborative care for comorbid depression and diabetes: A systematic review and meta-analysis.
          )].
      • 4.
        Psychosocial interventions should be integrated into diabetes care plans, including:
        • a.
          Motivational interventions [Grade D, Consensus]
        • b.
          Stress management strategies [Grade C, Level 3 (
          • Soo H.
          • Lam S.
          Stress management training in diabetes mellitus.
          )]
        • c.
          Coping skills training [Grade A, Level 1A (
          • Ismail K.
          • Winkley K.
          • Rabe-Hesketh S.
          Systematic review and meta-analysis of randomised controlled trials of psychological interventions to improve glycaemic control in patients with type 2 diabetes.
          ) for type 2 diabetes; Grade B, Level 2 (
          • Grey M.
          • Boland E.A.
          • Davidson M.
          • et al.
          Short-term effects of coping skills training as adjunct to intensive therapy in adolescents.
          ) for type 1 diabetes]
        • d.
          Family therapy [Grade A, Level 1B (
          • Keogh K.M.
          • Smith S.M.
          • White P.
          • et al.
          Psychological family intervention for poorly controlled type 2 diabetes.
          ,
          • Wysocki T.
          • Harris M.A.
          • Buckloh L.M.
          • et al.
          Randomized, controlled trial of Behavioral Family Systems Therapy for Diabetes: Maintenance and generalization of effects on parent-adolescent communication.
          ,
          • Ellis D.A.
          • Frey M.A.
          • Naar-King S.
          • et al.
          The effects of multisystemic therapy on diabetes stress among adolescents with chronically poorly controlled type 1 diabetes: Findings from a randomized, controlled trial.
          )]
        • e.
          Case management [Grade B, Level 2 (
          • Katon W.J.
          • Lin E.H.B.
          • Von Korff M.
          • et al.
          Collaborative care for patients with depression and chronic illnesses.
          )].
      • 5.
        Antidepressant medication should be used to treat acute depression in people with diabetes [Grade A, Level 1 (
        • Lustman P.J.
        • Griffith L.S.
        • Clouse R.E.
        • et al.
        Effects of nortriptyline on depression and glycemic control in diabetes: Results of a double-blind, placebo-controlled trial.
        )] and for maintenance treatment to prevent recurrence of depression [Grade A, Level 1A (
        • Lustman P.J.
        • Clouse R.E.
        • Nix B.D.
        • et al.
        Sertraline for prevention of depression recurrence in diabetes mellitus: A randomized, double-blind, placebo-controlled trial.
        )]. Cognitive behaviour therapy (CBT) can be used to treat depression in individuals with depression alone [Grade B, Level 2 (
        • Lustman P.J.
        • Griffith L.S.
        • Freedland K.E.
        • et al.
        Cognitive behavior therapy for depression in type 2 diabetes mellitus. A randomized, controlled trial.
        )] or in combination with antidepressant medication [Grade A, Level 1 (
        • van der Feltz-Cornelis C.M.
        • Nuyen J.
        • Stoop C.
        • et al.
        Effect of interventions for major depressive disorder and significant depressive symptoms in patients with diabetes mellitus: A systematic review and meta-analysis.
        ,
        • Baumeister H.
        • Hutter N.
        • Bengel J.
        Psychological and pharmacological interventions for depression in patients with diabetes mellitus: An abridged Cochrane review.
        )].
      • 6.
        Because of the risk of adverse metabolic effects of many antipsychotic medications (especially atypical/second and third generation) [Grade A, Level 1 (
        • Lieberman J.A.
        • Stroup T.S.
        • McEvoy J.P.
        • et al.
        Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.
        )], regular metabolic monitoring should be performed in people with and without diabetes who are treated with these medications [Grade D, Consensus].
      • 7.
        Children and adolescents with diabetes should be screened at diagnosis for major depressive disorder [Grade D, Consensus] and regularly for psychosocial difficulties, family distress or mental health disorders [Grade D, Consensus]. An expert in mental health and/or psychosocial issues should provide intervention when required; this individual may be part of the pediatric diabetes health-care team or enlisted by referral [Grade D, Consensus]. Individual and family educational interventions should be included to address stress or diabetes-related conflict when indicated [Grade D, Consensus].
      • 8.
        Adolescents with type 1 diabetes should be regularly screened using non-judgemental questions about weight and body image concerns, dieting, binge eating and insulin omission for weight loss [Grade D, Level 2 (
        • Bachle C.
        • Lange K.
        • Stahl-Pehe A.
        • et al.
        Symptoms of eating disorders and depression in emerging adults with early-onset, long-duration type 1 diabetes and their association with metabolic control.
        )].
      Abbreviations:
      A1C, glycated hemoglobin; BMI, body mass index; BP, blood pressure; CBT, cognitive behavior therapy; CV, cardiovascular; DKA, diabetic ketoacidosis; HR, hazard ratio; IFG, impaired fasting glucose; LDL-C, low density lipoprotein; MDD, major depressive disorder; PPD, postpartum depression; PTSD, post-traumatic stress disorder.
      Table 4Psychiatric medication metabolic monitoring protocol
      ParameterBaseline1 month2 months3 monthsEvery 3 to 6 monthsAnnually
      Weight (BMI)xxxxx
      Waist circumferencexxx
      Blood pressurexxx
      A1C preferred ± Fasting Plasma Glucosexxx
      Fasting lipid profilexxx
      Personal history, particularly alcohol, tobacco and recreational substance usexxx
      Family historyxx
      A1C, glycated hemoglobin; BMI, body mass index.

      Other Relevant Guidelines

      • Nutrition Therapy, p. S64
      • Glycemic Management in Adults With Type 1 Diabetes, p. S80
      • Pharmacologic Glycemic Management of Type 2 Diabetes in Adults, p. S88
      • Type 1 Diabetes in Children and Adolescents, p. S234
      • Type 2 Diabetes in Children and Adolescents, p. S247
      Unlabelled image
      *Excluded based on: population, intervention/exposure, comparator/control or study design.
      From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(6): e1000097. doi:10.1371/journal.pmed1000097 (
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • et al.
      Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement.
      ).
      For more information, visit www.prisma-statement.org.

      Author Disclosures

      Dr. Robinson reports personal fees from Janssen, Otsuka, Lundbeck, and Allergan, outside the submitted work. Dr. Coons has received honoraria from the Canadian Medical and Surgical Knowledge Translation Working Group. Dr. Vallis reports personal fees from Novo Nordisk, Valeant, Sanofi, Pfizer, CSL Behring, Merck, and Abbvie, outside the submitted work. Dr. Yale reports grants and personal fees from Eli Lilly Canada, Sanofi, Merck, AstraZeneca, Boehringer Ingelheim, Janssen, and Medtronic; personal fees from Novo Nordisk, Takeda, Abbott, and Bayer; and grants from Mylan. No other author has anything to disclose.

      References

        • Hagger V.
        • Hendrieckx C.
        • Sturt J.
        • et al.
        Diabetes distress among adolescents with type 1 diabetes: A systematic review.
        Curr Diab Rep. 2016; 16: 9
        • Polonsky W.H.
        • Fisher L.
        • Earles J.
        • et al.
        Assessing psychosocial distress in diabetes: Development of the diabetes distress scale.
        Diabetes Care. 2005; 28: 626-631
        • Polonsky W.H.
        • Hajos T.R.
        • Dain M.P.
        • et al.
        Are patients with type 2 diabetes reluctant to start insulin therapy? An examination of the scope and underpinnings of psychological insulin resistance in a large, international population.
        Curr Med Res Opin. 2011; 27: 1169-1174
        • Egede L.E.
        • Nietert P.J.
        • Zheng D.
        Depression and all-cause and coronary heart disease mortality among adults with and without diabetes.
        Diabetes Care. 2005; 28: 1339-1345
        • Snoek F.J.
        • Kersch N.Y.
        • Eldrup E.
        • et al.
        Monitoring of Individual Needs in Diabetes (MIND): Baseline data from the Cross-National Diabetes Attitudes, Wishes, and Needs (DAWN) MIND study.
        Diabetes Care. 2011; 34: 601-603
        • Fisher L.
        • Skaff M.M.
        • Mullan J.T.
        • et al.
        Clinical depression versus distress among patients with type 2 diabetes: Not just a question of semantics.
        Diabetes Care. 2007; 30: 542-548
        • Gonzalez J.S.
        • Fisher L.
        • Polonsky W.H.
        Depression in diabetes: Have we been missing something important?.
        Diabetes Care. 2011; 34: 236-239
        • Fisher L.
        • Glasgow R.E.
        • Strycker L.A.
        The relationship between diabetes distress and clinical depression with glycemic control among patients with type 2 diabetes.
        Diabetes Care. 2010; 33: 1034-1036
        • Fisher L.
        • Mullan J.T.
        • Arean P.
        • et al.
        Diabetes distress but not clinical depression or depressive symptoms is associated with glycemic control in both cross-sectional and longitudinal analyses.
        Diabetes Care. 2010; 33: 23-28
        • Winchester R.J.
        • Williams J.S.
        • Wolfman T.E.
        • et al.
        Depressive symptoms, serious psychological distress, diabetes distress and cardiovascular risk factor control in patients with type 2 diabetes.
        J Diabetes Complications. 2016; 30: 312-317
        • Strandberg R.B.
        • Graue M.
        • Wentzel-Larsen T.
        • et al.
        Relationships of diabetes-specific emotional distress, depression, anxiety, and overall well-being with HbA1c in adult persons with type 1 diabetes.
        J Psychosom Res. 2014; 77: 174-179
        • Strandberg R.B.
        • Graue M.
        • Wentzel-Larsen T.
        • et al.
        Longitudinal relationship between diabetes-specific emotional distress and follow-up HbA1c in adults with type 1 diabetes mellitus.
        Diabet Med. 2015; 32: 1304-1310
        • Dalsgaard E.M.
        • Vestergaard M.
        • Skriver M.V.
        • et al.
        Psychological distress, cardiovascular complications and mortality among people with screen-detected type 2 diabetes: Follow-up of the ADDITION-Denmark trial.
        Diabetologia. 2014; 57: 710-717
        • Carper M.M.
        • Traeger L.
        • Gonzalez J.S.
        • et al.
        The differential associations of depression and diabetes distress with quality of life domains in type 2 diabetes.
        J Behav Med. 2014; 37: 501-510
        • Pintaudi B.
        • Lucisano G.
        • Gentile S.
        • et al.
        Correlates of diabetes-related distress in type 2 diabetes: Findings from the benchmarking network for clinical and humanistic outcomes in diabetes (BENCH-D) study.
        J Psychosom Res. 2015; 79: 348-354
        • Wardian J.
        • Sun F.
        Factors associated with diabetes-related distress: Implications for diabetes self-management.
        Soc Work Health Care. 2014; 53: 364-381
        • Bahrmann A.
        • Abel A.
        • Zeyfang A.
        • et al.
        Psychological insulin resistance in geriatric patients with diabetes mellitus.
        Patient Educ Couns. 2014; 94: 417-422
        • Holmes-Truscott E.
        • Skinner T.C.
        • Pouwer F.
        • et al.
        Explaining psychological insulin resistance in adults with non-insulin-treated type 2 diabetes: The roles of diabetes distress and current medication concerns. Results from Diabetes MILES-Australia.
        Prim Care Diabetes. 2016; 10: 75-82
        • Hendrieckx C.
        • Halliday J.A.
        • Bowden J.P.
        • et al.
        Severe hypoglycaemia and its association with psychological well-being in Australian adults with type 1 diabetes attending specialist tertiary clinics.
        Diabetes Res Clin Pract. 2014; 103: 430-436
        • Nefs G.
        • Bevelander S.
        • Hendrieckx C.
        • et al.
        Fear of hypoglycaemia in adults with Type 1 diabetes: Results from Diabetes MILES—The Netherlands.
        Diabet Med. 2015; 32: 1289-1296
        • Polonsky W.H.
        • Fisher L.
        • Hessler D.
        • et al.
        Identifying the worries and concerns about hypoglycemia in adults with type 2 diabetes.
        J Diabetes Complications. 2015; 29: 1171-1176
        • Vallis M.
        • Jones A.
        • Pouwer F.
        Managing hypoglycemia in diabetes may be more fear management than glucose management: A practical guide for diabetes care providers.
        Curr Diabetes Rev. 2014; 10: 364-370
        • Peyrot M.
        • Rubin R.R.
        • Lauritzen T.
        • et al.
        Psychosocial problems and barriers to improved diabetes management: Results of the Cross-National Diabetes Attitudes, Wishes and Needs (DAWN) study.
        Diabet Med. 2005; 22: 1379-1385
        • Goebel-Fabbri A.E.
        • Fikkan J.
        • Franko D.L.
        • et al.
        Insulin restriction and associated morbidity and mortality in women with type 1 diabetes.
        Diabetes Care. 2008; 31: 415-419
        • Fisher L.
        • Glasgow R.E.
        A call for more effectively integrating behavioral and social science principles into comprehensive diabetes care.
        Diabetes Care. 2007; 30: 2746-2749
        • Malik J.A.
        • Koot H.M.
        Explaining the adjustment of adolescents with type 1 diabetes: Role of diabetes-specific and psychosocial factors.
        Diabetes Care. 2009; 32: 774-779
        • Zhang C.X.
        • Tse L.A.
        • Ye X.Q.
        • et al.
        Moderating effects of coping styles on anxiety and depressive symptoms caused by psychological stress in Chinese patients with type 2 diabetes.
        Diabet Med. 2009; 26: 1282-1288
        • Hampson S.E.
        • Tildesley E.
        • Andrews J.A.
        • et al.
        The relation of change in hostility and sociability during childhood to substance use in mid adolescence.
        J Res Pers. 2010; 44: 103-114
        • Luyckx K.
        • Seiffge-Krenke I.
        • Hampson S.E.
        Glycemic control, coping, and internalizing and externalizing symptoms in adolescents with type 1 diabetes: A cross-lagged longitudinal approach.
        Diabetes Care. 2010; 33: 1424-1429
        • American Psychiatric Association
        Diagnostic and statistical manual of mental disorders.
        5th edn. American Psychiatric Association, Arlington2013
        • Anderson R.M.
        Is the problem of noncompliance all in our heads?.
        Diabetes Educ. 1985; 11: 31-34
        • Gonzalez J.S.
        • Peyrot M.
        • McCarl L.A.
        • et al.
        Depression and diabetes treatment nonadherence: A meta-analysis.
        Diabetes Care. 2008; 31: 2398-2403
        • Gonzalez J.S.
        • Safren S.A.
        • Delahanty L.M.
        • et al.
        Symptoms of depression prospectively predict poorer self-care in patients with Type 2 diabetes.
        Diabet Med. 2008; 25: 1102-1107
        • Egede L.E.
        • Grubaugh A.L.
        • Ellis C.
        The effect of major depression on preventive care and quality of life among adults with diabetes.
        Gen Hosp Psychiatry. 2010; 32: 563-569
        • Richardson L.K.
        • Egede L.E.
        • Mueller M.
        Effect of race/ethnicity and persistent recognition of depression on mortality in elderly men with type 2 diabetes and depression.
        Diabetes Care. 2008; 31: 880-881
        • Hutter N.
        • Schnurr A.
        • Baumeister H.
        Healthcare costs in patients with diabetes mellitus and comorbid mental disorders–a systematic review.
        Diabetologia. 2010; 53: 2470-2479
        • Lieberman J.A.
        • Stroup T.S.
        • McEvoy J.P.
        • et al.
        Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.
        N Engl J Med. 2005; 353: 1209-1223
        • Brown E.S.
        • Varghese F.P.
        • McEwen B.S.
        Association of depression with medical illness: Does cortisol play a role?.
        Biol Psychiatry. 2004; 55: 1-9
        • McCreadie R.G.
        Diet, smoking and cardiovascular risk in people with schizophrenia: Descriptive study.
        Br J Psychiatry. 2003; 183: 534-539
        • Anderson R.J.
        • Freedland K.E.
        • Clouse R.E.
        • et al.
        The prevalence of comorbid depression in adults with diabetes: A meta-analysis.
        Diabetes Care. 2001; 24: 1069-1078
        • Ali S.
        • Stone M.A.
        • Peters J.L.
        • et al.
        The prevalence of co-morbid depression in adults with type 2 diabetes: A systematic review and meta-analysis.
        Diabet Med. 2006; 23: 1165-1173
        • Barnard K.D.
        • Skinner T.C.
        • Peveler R.
        The prevalence of co-morbid depression in adults with type 1 diabetes: Systematic literature review.
        Diabet Med. 2006; 23: 445-448
        • Egede L.E.
        Diabetes, major depression, and functional disability among U.S. adults.
        Diabetes Care. 2004; 27: 421-428
        • Moussavi S.
        • Chatterji S.
        • Verdes E.
        • et al.
        Depression, chronic diseases, and decrements in health: Results from the World Health Surveys.
        Lancet. 2007; 370: 851-858
        • Almeida O.P.
        • McCaul K.
        • Hankey G.J.
        • et al.
        Duration of diabetes and its association with depression in later life: The Health In Men Study (HIMS).
        Maturitas. 2016; 86: 3-9
        • Mezuk B.
        • Johnson-Lawrence V.
        • Lee H.
        • et al.
        Is ignorance bliss? Depression, antidepressants, and the diagnosis of prediabetes and type 2 diabetes.
        Health Psychol. 2013; 32: 254-263
        • Rotella F.
        • Mannucci E.
        Depression as a risk factor for diabetes: A meta-analysis of longitudinal studies.
        J Clin Psychiatry. 2013; 74: 31-37
        • Yu M.
        • Zhang X.
        • Lu F.
        • et al.
        Depression and risk for diabetes: A meta-analysis.
        Can J Diabetes. 2015; 39: 266-272
        • Ludman E.J.
        • Katon W.
        • Russo J.
        • et al.
        Depression and diabetes symptom burden.
        Gen Hosp Psychiatry. 2004; 26: 430-436
        • Peyrot M.
        • Rubin R.R.
        Persistence of depressive symptoms in diabetic adults.
        Diabetes Care. 1999; 22: 448-452
        • Kikuchi Y.
        • Iwase M.
        • Fujii H.
        • et al.
        Association of severe hypoglycemia with depressive symptoms in patients with type 2 diabetes: The Fukuoka Diabetes Registry.
        BMJ Open Diabetes Res Care. 2015; 3: e000063
        • Werremeyer A.
        • Maack B.
        • Strand M.A.
        • et al.
        Disease control among patients with diabetes and severe depressive symptoms.
        J Prim Care Community Health. 2016; 7: 130-134
        • Engum A.
        • Mykletun A.
        • Midthjell K.
        • et al.
        Depression and diabetes: A large population-based study of sociodemographic, lifestyle, and clinical factors associated with depression in type 1 and type 2 diabetes.
        Diabetes Care. 2005; 28: 1904-1909
        • Li C.
        • Ford E.S.
        • Zhao G.
        • et al.
        Prevalence and correlates of undiagnosed depression among U.S. adults with diabetes: The Behavioral Risk Factor Surveillance System, 2006.
        Diabetes Res Clin Pract. 2009; 83: 268-279
        • Katon W.J.
        • Simon G.
        • Russo J.
        • et al.
        Quality of depression care in a population-based sample of patients with diabetes and major depression.
        Med Care. 2004; 42: 1222-1229
        • Guo M.
        • Mi J.
        • Jiang Q.M.
        • et al.
        Metformin may produce antidepressant effects through improvement of cognitive function among depressed patients with diabetes mellitus.
        Clin Exp Pharmacol Physiol. 2014; 41: 650-656
        • Eaton W.W.
        • Shao H.
        • Nestadt G.
        • et al.
        Population-based study of first onset and chronicity in major depressive disorder.
        Arch Gen Psychiatry. 2008; 65: 513-520
        • Kendler K.S.
        • Karkowski L.M.
        • Prescott C.A.
        Causal relationship between stressful life events and the onset of major depression.
        Am J Psychiatry. 1999; 156: 837-841
        • Carvalhais S.M.
        • Lima-Costa M.F.
        • Peixoto S.V.
        • et al.
        The influence of socio-economic conditions on the prevalence of depressive symptoms and its covariates in an elderly population with slight income differences: The Bambui Health and Aging Study (BHAS).
        Int J Soc Psychiatry. 2008; 54: 447-456
        • Katon W.
        • Russo J.
        • Lin E.H.
        • et al.
        Depression and diabetes: Factors associated with major depression at five-year follow-up.
        Psychosomatics. 2009; 50: 570-579
        • Bruce D.G.
        • Davis W.A.
        • Davis T.M.
        Longitudinal predictors of reduced mobility and physical disability in patients with type 2 diabetes: The Fremantle Diabetes Study.
        Diabetes Care. 2005; 28: 2441-2447
        • Rubin R.R.
        • Wadden T.A.
        • Bahnson J.L.
        • et al.
        Impact of intensive lifestyle intervention on depression and health-related quality of life in type 2 diabetes: The Look AHEAD Trial.
        Diabetes Care. 2014; 37: 1544-1553
        • Nyboe L.
        • Lund H.
        Low levels of physical activity in patients with severe mental illness.
        Nord J Psychiatry. 2013; 67: 43-46
        • Lawlor D.A.
        • Smith G.D.
        • Ebrahim S.
        Association of insulin resistance with depression: Cross sectional findings from the British Women's Heart and Health Study.
        BMJ. 2003; 327: 1383-1384
        • Timonen M.
        • Salmenkaita I.
        • Jokelainen J.
        • et al.
        Insulin resistance and depressive symptoms in young adult males: Findings from Finnish military conscripts.
        Psychosom Med. 2007; 69: 723-728
        • Okamura F.
        • Tashiro A.
        • Utumi A.
        • et al.
        Insulin resistance in patients with depression and its changes during the clinical course of depression: Minimal model analysis.
        Metabolism. 2000; 49: 1255-1260
        • Anagnostis P.
        • Athyros V.G.
        • Tziomalos K.
        • et al.
        Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: A hypothesis.
        J Clin Endocrinol Metab. 2009; 94: 2692-2701
        • Pariante C.M.
        • Miller A.H.
        Glucocorticoid receptors in major depression: Relevance to pathophysiology and treatment.
        Biol Psychiatry. 2001; 49: 391-404
        • Belmaker R.H.
        • Agam G.
        Major depressive disorder.
        N Engl J Med. 2008; 358: 55-68
        • Semenkovich K.
        • Brown M.E.
        • Svrakic D.M.
        • et al.
        Depression in type 2 diabetes mellitus: Prevalence, impact, and treatment.
        Drugs. 2015; 75: 577-587
        • Ciechanowski P.S.
        • Katon W.J.
        • Russo J.E.
        Depression and diabetes: Impact of depressive symptoms on adherence, function, and costs.
        Arch Intern Med. 2000; 160: 3278-3285
        • Lin E.H.
        • Katon W.
        • Von Korff M.
        • et al.
        Relationship of depression and diabetes self-care, medication adherence, and preventive care.
        Diabetes Care. 2004; 27: 2154-2160
        • Katon W.J.
        • Rutter C.
        • Simon G.
        • et al.
        The association of comorbid depression with mortality in patients with type 2 diabetes.
        Diabetes Care. 2005; 28: 2668-2672
        • Zhang X.
        • Norris S.L.
        • Gregg E.W.
        • et al.
        Depressive symptoms and mortality among persons with and without diabetes.
        Am J Epidemiol. 2005; 161: 652-660
        • Vancampfort D.
        • Correll C.U.
        • Wampers M.
        • et al.
        Metabolic syndrome and metabolic abnormalities in patients with major depressive disorder: A meta-analysis of prevalences and moderating variables.
        Psychol Med. 2014; 44: 2017-2028
        • Lustman P.J.
        • Freedland K.E.
        • Griffith L.S.
        • et al.
        Fluoxetine for depression in diabetes: A randomized double-blind placebo-controlled trial.
        Diabetes Care. 2000; 23: 618-623
        • Lustman P.J.
        • Clouse R.E.
        • Nix B.D.
        • et al.
        Sertraline for prevention of depression recurrence in diabetes mellitus: A randomized, double-blind, placebo-controlled trial.
        Arch Gen Psychiatry. 2006; 63: 521-529
        • Lustman P.J.
        • Griffith L.S.
        • Clouse R.E.
        • et al.
        Effects of nortriptyline on depression and glycemic control in diabetes: Results of a double-blind, placebo-controlled trial.
        Psychosom Med. 1997; 59: 241-250
        • Lustman P.J.
        • Griffith L.S.
        • Freedland K.E.
        • et al.
        Cognitive behavior therapy for depression in type 2 diabetes mellitus. A randomized, controlled trial.
        Ann Intern Med. 1998; 129: 613-621
        • Mansur R.B.
        • Rizzo L.B.
        • Santos C.M.
        • et al.
        Impaired glucose metabolism moderates the course of illness in bipolar disorder.
        J Affect Disord. 2016; 195: 57-62
        • Fagiolini A.
        • Frank E.
        • Scott J.A.
        • et al.
        Metabolic syndrome in bipolar disorder: Findings from the Bipolar Disorder Center for Pennsylvanians.
        Bipolar Disord. 2005; 7: 424-430
        • Taylor V.
        • MacQueen G.
        Associations between bipolar disorder and metabolic syndrome: A review.
        J Clin Psychiatry. 2006; 67: 1034-1041
        • van Winkel R.
        • De Hert M.
        • Van Eyck D.
        • et al.
        Prevalence of diabetes and the metabolic syndrome in a sample of patients with bipolar disorder.
        Bipolar Disord. 2008; 10: 342-348
        • Vancampfort D.
        • Mitchell A.J.
        • De Hert M.
        • et al.
        Prevalence and predictors of type 2 diabetes mellitus in people with bipolar disorder.
        J Clin Psychiatry. 2015; 76: 1490-1499
        • Calkin C.V.
        • Ruzickova M.
        • Uher R.
        • et al.
        Insulin resistance and outcome in bipolar disorder.
        Br J Psychiatry. 2015; 206: 52-57
        • Haupt D.W.
        • Newcomer J.W.
        Hyperglycemia and antipsychotic medications.
        J Clin Psychiatry. 2001; 62 (discussion 40-1): 15-26
        • Saddichha S.
        • Manjunatha N.
        • Ameen S.
        • et al.
        Diabetes and schizophrenia—effect of disease or drug? Results from a randomized, double-blind, controlled prospective study in first-episode schizophrenia.
        Acta Psychiatr Scand. 2008; 117: 342-347
        • Fleischhacker W.W.
        • Siu C.O.
        • Boden R.
        • et al.
        Metabolic risk factors in first-episode schizophrenia: Baseline prevalence and course analysed from the European First-Episode Schizophrenia Trial.
        Int J Neuropsychopharmacol. 2013; 16: 987-995
        • McEvoy J.P.
        • Meyer J.M.
        • Goff D.C.
        • et al.
        Prevalence of the metabolic syndrome in patients with schizophrenia: Baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III.
        Schizophr Res. 2005; 80: 19-32