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Diabetes mellitus and severe mental illness: mechanisms and clinical implications

Key Points

  • Diabetes mellitus affects 12% of patients with severe mental illness (SMI)

  • In people with SMI, diabetes mellitus is associated with higher rates of microvascular and macrovascular complications, acute metabolic dysregulation and deaths related to diabetes mellitus than in people without SMI

  • The mechanisms underlying the association between diabetes mellitus and SMI are multifactorial and include genetic and environmental factors as well as effects of the illness and its treatment

  • Screening for diabetes mellitus in individuals with SMI is needed to identify the high proportion of people with undiagnosed diabetes mellitus

  • Tailored lifestyle interventions can decrease body weight in people with SMI and could potentially reduce the incidence of diabetes mellitus

  • Effective management of diabetes mellitus, incorporating primary care, diabetes mellitus services and mental health teams, is essential to reduce the poor health outcomes and current inequity experienced by people with SMI and diabetes mellitus

Abstract

The prevalence of diabetes mellitus is twofold to threefold higher in people with severe mental illness (SMI) than in the general population, with diabetes mellitus affecting 12% of people receiving antipsychotics. The consequences of diabetes mellitus are more severe and frequent in people with SMI than in those without these conditions, with increased rates of microvascular and macrovascular complications, acute metabolic dysregulation and deaths related to diabetes mellitus. Multiple complex mechanisms underlie the association between diabetes mellitus and SMI; these mechanisms include genetic, environmental and disease-specific factors, and treatment-specific factors. Although antipsychotics are the mainstay of treatment in SMI, a causative link, albeit of uncertain magnitude, seems to exist between antipsychotics and diabetes mellitus. The principles of managing diabetes mellitus in people with SMI are similar to those for the general population and should follow currently established treatment algorithms. Lifestyle interventions are needed to reduce incident diabetes mellitus. In addition, improved uptake of opportunities to screen for this disease will reduce the high prevalence of undiagnosed diabetes mellitus. Currently, people with SMI receive poorer treatment for diabetes mellitus than the general population. Thus, health-care professionals in primary care, diabetes mellitus services and mental health teams have a responsibility to ensure that patients with SMI are not disadvantaged.

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Figure 1: The mechanisms that explain the association between severe mental illness and type 2 diabetes mellitus.

References

  1. Brown, S., Kim, M., Mitchell, C. & Inskip, H. Twenty-five year mortality of a community cohort with schizophrenia. Br. J. Psychiatry 196, 116–121 (2010).

    PubMed  PubMed Central  Google Scholar 

  2. McGrath, J., Saha, S., Chant, D. & Welham, J. Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol. Rev. 30, 67–76 (2008).

    PubMed  Google Scholar 

  3. Saha, S., Chant, D. & McGrath, J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch. Gen. Psychiatry 64, 1123–1131 (2007).

    PubMed  Google Scholar 

  4. Vancampfort, D. et al. A meta-analysis of cardio-metabolic abnormalities in drug naive, first-episode and multi-episode patients with schizophrenia versus general population controls. World Psychiatry 12, 240–250 (2013).

    PubMed  PubMed Central  Google Scholar 

  5. Mitchell, A. J., Vancampfort, D., De Herdt, A., Yu, W. & De Hert, M. Is the prevalence of metabolic syndrome and metabolic abnormalities increased in early schizophrenia? A comparative meta-analysis of first episode, untreated and treated patients. Schizophr. Bull. 39, 295–305 (2013).

    PubMed  Google Scholar 

  6. De Hert, M., Detraux, J., van Winkel, R., Yu, W. & Correll, C. U. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat. Rev. Endocrinol. 8, 114–126 (2012).

    CAS  Google Scholar 

  7. Allison, D. B. et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am. J. Psychiatry 156, 1686–1696 (1999).

    CAS  PubMed  Google Scholar 

  8. American Diabetes Association, American Psychiatric Association; American Association of Clinical Endocrinologists and North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 27, 596–601 (2004).

  9. Holt, R. I. & Peveler, R. C. Antipsychotic drugs and diabetes—an application of the Austin Bradford Hill criteria. Diabetologia 49, 1467–1476 (2006).

    CAS  PubMed  Google Scholar 

  10. Holt, R. I. & Peveler, R. C. Association between antipsychotic drugs and diabetes. Diabetes Obes. Metab. 8, 125–135 (2006).

    CAS  PubMed  Google Scholar 

  11. Holt, R. I., Bushe, C. & Citrome, L. Diabetes and schizophrenia 2005: are we any closer to understanding the link? J. Psychopharmacol. 19 (Suppl. 6), 56–65 (2005).

    PubMed  Google Scholar 

  12. Holt, R. I. & Peveler, R. C. Obesity, serious mental illness and antipsychotic drugs. Diabetes Obes. Metab. 11, 665–679 (2009).

    PubMed  Google Scholar 

  13. Holt, R. I. Undoing Descartes: integrating diabetes care for those with mental illness. Pract. Diabet. Int. 28, 270–275 (2011).

    Google Scholar 

  14. Subramaniam, M., Chong, S. A. & Pek, E. Diabetes mellitus and impaired glucose tolerance in patients with schizophrenia. Can. J. Psychiatry 48, 345–347 (2003).

    PubMed  Google Scholar 

  15. Taylor, D., Young, C., Mohamed, R., Paton, C. & Walwyn, R. Undiagnosed impaired fasting glucose and diabetes mellitus amongst inpatients receiving antipsychotic drugs. J. Psychopharmacol. 19, 182–186 (2005).

    CAS  PubMed  Google Scholar 

  16. Voruganti, L. P. et al. Dysglycemia in a community sample of people treated for schizophrenia: the Diabetes in Schizophrenia in Central-South Ontario (DiSCO) study. Schizophr. Res. 96, 215–222 (2007).

    CAS  PubMed  Google Scholar 

  17. Sernyak, M. J., Leslie, D. L., Alarcon, R. D., Losonczy, M. F. & Rosenheck, R. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am. J. Psychiatry 159, 561–566 (2002).

    PubMed  Google Scholar 

  18. McEvoy, J. P. 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. 80, 19–32 (2005).

    PubMed  Google Scholar 

  19. Cohen, D., Batstra, M. R. & Gispen-de Wied, C. C. Immunological characteristics of diabetes in schizophrenia. Diabetologia 48, 1941–1942 (2005).

    PubMed  Google Scholar 

  20. Spelman, L. M., Walsh, P. I., Sharifi, N., Collins, P. & Thakore, J. H. Impaired glucose tolerance in first-episode drug-naive patients with schizophrenia. Diabet. Med. 24, 481–485 (2007).

    CAS  PubMed  Google Scholar 

  21. Hammerman, A. et al. Antipsychotics and diabetes: an age-related association. Ann. Pharmacother. 42, 1316–1322 (2008).

    PubMed  Google Scholar 

  22. Becker, T. & Hux, J. Risk of acute complications of diabetes among people with schizophrenia in Ontario, Canada. Diabetes Care 34, 398–402 (2011).

    PubMed  PubMed Central  Google Scholar 

  23. Jones, L. E., Clarke, W. & Carney, C. P. Receipt of diabetes services by insured adults with and without claims for mental disorders. Med. Care 42, 1167–1175 (2004).

    PubMed  Google Scholar 

  24. Ribe, A. R. et al. Long-term mortality of persons with severe mental illness and diabetes: a population-based cohort study in Denmark. Psychol. Med. 44, 3097–3107 (2014).

    CAS  PubMed  Google Scholar 

  25. Fernandez-Egea, E., Miller, B., Bernardo, M., Donner, T. & Kirkpatrick, B. Parental history of type 2 diabetes in patients with nonaffective psychosis. Schizophr. Res. 98, 302–306 (2008).

    PubMed  Google Scholar 

  26. Gough, S. C. & O'Donovan, M. C. Clustering of metabolic comorbidity in schizophrenia: a genetic contribution? J. Psychopharmacol. 19 (Suppl. 6), 47–55 (2005).

    PubMed  Google Scholar 

  27. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421–427 (2014).

  28. Brunetti, A., Chiefari, E. & Foti, D. Recent advances in the molecular genetics of type 2 diabetes mellitus. World J. Diabetes 5, 128–140 (2014).

    PubMed  PubMed Central  Google Scholar 

  29. Lin, P. I. & Shuldiner, A. R. Rethinking the genetic basis for comorbidity of schizophrenia and type 2 diabetes. Schizophr. Res. 123, 234–243 (2010).

    CAS  PubMed  Google Scholar 

  30. Lovestone, S., Killick, R., Di Forti, M. & Murray, R. Schizophrenia as a GSK-3 dysregulation disorder. Trends Neurosci. 30, 142–149 (2007).

    CAS  PubMed  Google Scholar 

  31. Kvajo, M. et al. A mutation in mouse Disc1 that models a schizophrenia risk allele leads to specific alterations in neuronal architecture and cognition. Proc. Natl Acad. Sci. USA 105, 7076–7081 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Liu, Y. et al. Exploring the pathogenetic association between schizophrenia and type 2 diabetes mellitus diseases based on pathway analysis. BMC Med. Genomics 6 (Suppl. 1), S17 (2013).

    PubMed  PubMed Central  Google Scholar 

  33. Jenkinson, C. P. et al. Association of dopamine D2 receptor polymorphisms Ser311Cys and TaqIA with obesity or type 2 diabetes mellitus in Pima Indians. Int. J. Obes. Relat. Metab. Disord. 24, 1233–1238 (2000).

    CAS  PubMed  Google Scholar 

  34. Chiba, M. et al. Tyrosine hydroxylase gene microsatellite polymorphism associated with insulin resistance in depressive disorder. Metabolism 49, 1145–1149 (2000).

    CAS  PubMed  Google Scholar 

  35. Kao, A. C. & Muller, D. J. Genetics of antipsychotic-induced weight gain: update and current perspectives. Pharmacogenomics 14, 2067–2083 (2013).

    CAS  PubMed  Google Scholar 

  36. Newsome, C. A. et al. Is birth weight related to later glucose and insulin metabolism?—A systematic review. Diabet. Med. 20, 339–348 (2003).

    CAS  PubMed  Google Scholar 

  37. Thompson, C., Syddall, H., Rodin, I., Osmond, C. & Barker, D. J. Birth weight and the risk of depressive disorder in late life. Br. J. Psychiatry 179, 450–455 (2001).

    CAS  PubMed  Google Scholar 

  38. Kajantie, E. & Raikkonen, K. Early life predictors of the physiological stress response later in life. Neurosci. Biobehav. Rev. 35, 23–32 (2010).

    PubMed  Google Scholar 

  39. Colman, I., Ataullahjan, A., Naicker, K. & Van Lieshout, R. J. Birth weight, stress, and symptoms of depression in adolescence: evidence of fetal programming in a national Canadian cohort. Can. J. Psychiatry 57, 422–428 (2012).

    PubMed  Google Scholar 

  40. Vasiliadis, H. M., Gilman, S. E. & Buka, S. L. Fetal growth restriction and the development of major depression. Acta Psychiatr. Scand. 117, 306–312 (2008).

    PubMed  Google Scholar 

  41. Susser, E. et al. Schizophrenia after prenatal famine. Further evidence. Arch. Gen. Psychiatry 53, 25–31 (1996).

    CAS  PubMed  Google Scholar 

  42. St Clair, D. et al. Rates of adult schizophrenia following prenatal exposure to the Chinese famine of 1959–1961. JAMA 294, 557–562 (2005).

    CAS  PubMed  Google Scholar 

  43. McCreadie, R. G. Diet, smoking and cardiovascular risk in people with schizophrenia: descriptive study. Br. J. Psychiatry 183, 534–539 (2003).

    CAS  PubMed  Google Scholar 

  44. Brown, S., Birtwistle, J., Roe, L. & Thompson, C. The unhealthy lifestyle of people with schizophrenia. Psychol. Med. 29, 697–701 (1999).

    CAS  PubMed  Google Scholar 

  45. Chwastiak, L. A., Rosenheck, R. A. & Kazis, L. E. Association of psychiatric illness and obesity, physical inactivity, and smoking among a national sample of veterans. Psychosomatics 52, 230–236 (2011).

    PubMed  PubMed Central  Google Scholar 

  46. Peet, M. Diet, diabetes and schizophrenia: review and hypothesis. Br. J. Psychiatry Suppl. 47, S102–S105 (2004).

    PubMed  Google Scholar 

  47. Mitri, J., Muraru, M. D. & Pittas, A. G. Vitamin D and type 2 diabetes: a systematic review. Eur. J. Clin. Nutr. 65, 1005–1015 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Valipour, G., Saneei, P. & Esmaillzadeh, A. Serum vitamin D levels in relation to schizophrenia: a systematic review and meta-analysis of observational studies. J. Clin. Endocrinol. Metab. 99, 3863–3872 (2014).

    CAS  PubMed  Google Scholar 

  49. Seida, J. C. et al. Effect of Vitamin D supplementation on improving glucose homeostasis and preventing diabetes: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 99, 3551–3560 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. de Vet, E., de Ridder, D. T. & de Wit, J. B. Environmental correlates of physical activity and dietary behaviours among young people: a systematic review of reviews. Obes. Rev. 12, e130–e142 (2011).

    CAS  PubMed  Google Scholar 

  51. Bhavsar, V., Boydell, J., Murray, R. & Power, P. Identifying aspects of neighbourhood deprivation associated with increased incidence of schizophrenia. Schizophr. Res. 156, 115–121 (2014).

    PubMed  Google Scholar 

  52. Mitchell, A. J. & Dinan, T. G. Schizophrenia: a multisystem disease? J. Psychopharmacol. 24 (Suppl. 4), 5–7 (2010).

    PubMed  PubMed Central  Google Scholar 

  53. Fineberg, A. M. & Ellman, L. M. Inflammatory cytokines and neurological and neurocognitive alterations in the course of schizophrenia. Biol. Psychiatry 73, 951–966 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Bradley, A. J. & Dinan, T. G. A systematic review of hypothalamic-pituitary-adrenal axis function in schizophrenia: implications for mortality. J. Psychopharmacol. 24 (Suppl. 4), 91–118 (2010).

    PubMed  PubMed Central  Google Scholar 

  55. Venkatasubramanian, G. et al. Insulin and insulin-like growth factor-1 abnormalities in antipsychotic-naive schizophrenia. Am. J. Psychiatry 164, 1557–1560 (2007).

    PubMed  Google Scholar 

  56. Huber, T. J., Tettenborn, C., Leifke, E. & Emrich, H. M. Sex hormones in psychotic men. Psychoneuroendocrinology 30, 111–114 (2005).

    CAS  PubMed  Google Scholar 

  57. Tiihonen, J. et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 374, 620–627 (2009).

    PubMed  Google Scholar 

  58. Haddad, P. M. & Dursun, S. M. Neurological complications of psychiatric drugs: clinical features and management. Hum. Psychopharmacol. 23 (Suppl. 1), 15–26 (2008).

    PubMed  Google Scholar 

  59. Haddad, P. M. & Sharma, S. G. Adverse effects of atypical antipsychotics: differential risk and clinical implications. CNS Drugs 21, 911–936 (2007).

    CAS  PubMed  Google Scholar 

  60. De Hert, M. et al. Typical and atypical antipsychotics differentially affect long-term incidence rates of the metabolic syndrome in first-episode patients with schizophrenia: a retrospective chart review. Schizophr. Res. 101, 295–303 (2008).

    PubMed  Google Scholar 

  61. Jin, H., Meyer, J. M. & Jeste, D. V. Phenomenology of and risk factors for new-onset diabetes mellitus and diabetic ketoacidosis associated with atypical antipsychotics: an analysis of 45 published cases. Ann. Clin. Psychiatry 14, 59–64 (2002).

    PubMed  Google Scholar 

  62. Citrome, L. L. The increase in risk of diabetes mellitus from exposure to second-generation antipsychotic agents. Drugs Today (Barc.) 40, 445–464 (2004).

    CAS  Google Scholar 

  63. Smith, M. et al. First- v. second-generation antipsychotics and risk for diabetes in schizophrenia: systematic review and meta-analysis. Br. J. Psychiatry 192, 406–411 (2008).

    CAS  PubMed  Google Scholar 

  64. Citrome, L. L. et al. Risk of treatment-emergent diabetes mellitus in patients receiving antipsychotics. Ann. Pharmacother. 41, 1593–1603 (2007).

    CAS  PubMed  Google Scholar 

  65. Vancampfort, D. et al. Metabolic syndrome and metabolic abnormalities in bipolar disorder: a meta-analysis of prevalence rates and moderators. Am. J. Psychiatry 170, 265–274 (2013).

    PubMed  Google Scholar 

  66. Vancampfort, D. et al. Metabolic syndrome and metabolic abnormalities in patients with major depressive disorder: a meta-analysis of prevalences and moderating variables. Psychol. Med. 44, 2017–2028 (2014).

    CAS  PubMed  Google Scholar 

  67. Bobo, W. V. et al. Antipsychotics and the risk of type 2 diabetes mellitus in children and youth. JAMA Psychiatry 70, 1067–1075 (2013).

    PubMed  Google Scholar 

  68. Samaras, K., Correll, C. U., Mitchell, A. J. & De Hert, M. Diabetes risk potentially underestimated in youth and children receiving antipsychotics. JAMA Psychiatry 71, 209–210 (2014).

    PubMed  Google Scholar 

  69. Bushe, C. J. & Leonard, B. E. Blood glucose and schizophrenia: a systematic review of prospective randomized clinical trials. J. Clin. Psychiatry 68, 1682–1690 (2007).

    CAS  PubMed  Google Scholar 

  70. Rummel-Kluge, C. et al. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr. Res. 123, 225–233 (2010).

    PubMed  PubMed Central  Google Scholar 

  71. De Hert, M. et al. Body weight and metabolic adverse effects of asenapine, iloperidone, lurasidone and paliperidone in the treatment of schizophrenia and bipolar disorder: a systematic review and exploratory meta-analysis. CNS Drugs 26, 733–759 (2012).

    CAS  PubMed  Google Scholar 

  72. Kahn, R. S. et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 371, 1085–1097 (2008).

    CAS  PubMed  Google Scholar 

  73. Saddichha, S., Manjunatha, N., Ameen, S. & Akhtar, S. Diabetes and schizophrenia—effect of disease or drug? Results from a randomized, double-blind, controlled prospective study in first-episode schizophrenia. Acta Psychiatr. Scand. 117, 342–347 (2008).

    CAS  PubMed  Google Scholar 

  74. Graham, K. A., Cho, H., Brownley, K. A. & Harp, J. B. Early treatment-related changes in diabetes and cardiovascular disease risk markers in first episode psychosis subjects. Schizophr. Res. 101, 287–294 (2008).

    PubMed  PubMed Central  Google Scholar 

  75. Manu, P. et al. Insulin secretion in patients receiving clozapine, olanzapine, quetiapine and risperidone. Schizophr. Res. 143, 358–362 (2013).

    PubMed  Google Scholar 

  76. Ngai, Y. F. et al. Quetiapine treatment in youth is associated with decreased insulin secretion. J. Clin. Psychopharmacol. 34, 359–364 (2014).

    CAS  PubMed  Google Scholar 

  77. Ardizzone, T. D., Bradley, R. J., Freeman, A. M. III. & Dwyer, D. S. Inhibition of glucose transport in PC12 cells by the atypical antipsychotic drugs risperidone and clozapine, and structural analogs of clozapine. Brain Res. 923, 82–90 (2001).

    CAS  PubMed  Google Scholar 

  78. Engl, J. et al. Olanzapine impairs glycogen synthesis and insulin signaling in L6 skeletal muscle cells. Mol. Psychiatry 10, 1089–1096 (2005).

    CAS  PubMed  Google Scholar 

  79. Ballon, J. S., Pajvani, U., Freyberg, Z., Leibel, R. L. & Lieberman, J. A. Molecular pathophysiology of metabolic effects of antipsychotic medications. Trends Endocrinol. Metab. 25, 593–600 (2014).

    CAS  PubMed  Google Scholar 

  80. Bak, M., Fransen, A., Janssen, J., van Os, J. & Drukker, M. Almost all antipsychotics result in weight gain: a meta-analysis. PLoS ONE 9, e94112 (2014).

    PubMed  PubMed Central  Google Scholar 

  81. Alvarez-Jimenez, M. et al. Antipsychotic-induced weight gain in chronic and first-episode psychotic disorders: a systematic critical reappraisal. CNS Drugs 22, 547–562 (2008).

    CAS  PubMed  Google Scholar 

  82. Correll, C. U. et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA 302, 1765–1773 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Haro, J. M. & Salvador-Carulla, L. The SOHO (Schizophrenia Outpatient Health Outcome) study: implications for the treatment of schizophrenia. CNS Drugs 20, 293–301 (2006).

    CAS  PubMed  Google Scholar 

  84. Starrenburg, F. C. & Bogers, J. P. How can antipsychotics cause diabetes mellitus? Insights based on receptor-binding profiles, humoral factors and transporter proteins. Eur. Psychiatry 24, 164–170 (2009).

    CAS  PubMed  Google Scholar 

  85. Garcia-Tornadu, I. et al. Disruption of the dopamine d2 receptor impairs insulin secretion and causes glucose intolerance. Endocrinology 151, 1441–1450 (2010).

    CAS  PubMed  Google Scholar 

  86. Alvarez-Jimenez, M. et al. Healthy Active Lives (HeAL). Keeping the body in mind in youth with psychosis. iphYs [online], (2014).

    Google Scholar 

  87. NICE. Preventing type 2 diabetes: risk identification and interventions for individuals at high risk [online], (2012).

  88. De Hert, M. et al. Cardiovascular disease and diabetes in people with severe mental illness position statement from the European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC). Eur. Psychiatry 24, 412–424 (2009).

    CAS  PubMed  Google Scholar 

  89. NICE. Psychosis and schizophrenia in adults: treatment and management [online], (2014).

  90. Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines Team for the Treatment of Schizophrenia and Related Disorders. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of schizophrenia and related disorders. Aust. N. Z. J. Psychiatry 39, 1–30 (2005).

  91. Poulin, M. J., Cortese, L., Williams, R., Wine, N. & McIntyre, R. S. Atypical antipsychotics in psychiatric practice: practical implications for clinical monitoring. Can. J. Psychiatry 50, 555–562 (2005).

    PubMed  Google Scholar 

  92. Curtis, J., Newall, H. D. & Samaras, K. The heart of the matter: cardiometabolic care in youth with psychosis. Early Interv. Psychiatry 6, 347–353 (2012).

    PubMed  Google Scholar 

  93. Pringsheim, T., Panagiotopoulos, C., Davidson, J. & Ho, J. Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth. Paediatr. Child. Health 16, 581–589 (2011).

    PubMed  PubMed Central  Google Scholar 

  94. Konz, H. W. et al. Screening for metabolic syndrome in older patients with severe mental illness. Am. J. Geriatr. Psychiatry 22, 1116–1120 (2014).

    PubMed  Google Scholar 

  95. van Winkel, R. et al. Screening for diabetes and other metabolic abnormalities in patients with schizophrenia and schizoaffective disorder: evaluation of incidence and screening methods. J. Clin. Psychiatry 67, 1493–1500 (2006).

    PubMed  Google Scholar 

  96. Mitchell, A. J., Delaffon, V., Vancampfort, D., Correll, C. U. & De Hert, M. Guideline concordant monitoring of metabolic risk in people treated with antipsychotic medication: systematic review and meta-analysis of screening practices. Psychol. Med. 42, 125–147 (2012).

    CAS  PubMed  Google Scholar 

  97. Morrato, E. H. et al. Metabolic screening after the American Diabetes Association's consensus statement on antipsychotic drugs and diabetes. Diabetes Care 32, 1037–1042 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Lord, O., Malone, D. & Mitchell, A. J. Receipt of preventive medical care and medical screening for patients with mental illness: a comparative analysis. Gen. Hosp. Psychiatry 32, 519–543 (2010).

    PubMed  Google Scholar 

  99. Druss, B. G., Rosenheck, R. A., Desai, M. M. & Perlin, J. B. Quality ofpreventive medical care for patients with mental disorders. Med. Care 40, 129–136 (2002).

    PubMed  Google Scholar 

  100. Hardy, S., Hinks, P. & Gray, R. Screening for cardiovascular risk in patients with severe mental illness in primary care: a comparison with patients with diabetes. J. Ment. Health 22, 42–50 (2013).

    PubMed  Google Scholar 

  101. Mitchell, A. J. & Hardy, S. A. Screening for metabolic risk among patients with severe mental illness and diabetes: a national comparison. Psychiatr. Serv. 64, 1060–1063 (2013).

    PubMed  Google Scholar 

  102. Barnes, T. R., Paton, C., Cavanagh, M. R., Hancock, E. & Taylor, D. M. A UK audit of screening for the metabolic side effects of antipsychotics in community patients. Schizophr. Bull. 33, 1397–1403 (2007).

    PubMed  PubMed Central  Google Scholar 

  103. Norris, S. L. et al. Screening adults for type 2 diabetes: a review of the evidence for the, U. S. Preventive Services Task Force. Ann. Intern. Med. 148, 855–868 (2008).

    PubMed  Google Scholar 

  104. 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. Schizophr. Res. 140, 159–168 (2012).

    PubMed  Google Scholar 

  105. McCreadie, R. G. et al. Dietary improvement in people with schizophrenia: randomised controlled trial. Br. J. Psychiatry 187, 346–351 (2005).

    PubMed  Google Scholar 

  106. Menza, M. et al. Managing atypical antipsychotic-associated weight gain: 12-month data on a multimodal weight control program. J. Clin. Psychiatry 65, 471–477 (2004).

    PubMed  Google Scholar 

  107. Chen, C. K., Chen, Y. C. & Huang, Y. S. Effects of a 10-week weight control program on obese patients with schizophrenia or schizoaffective disorder: a 12-month follow up. Psychiatry Clin. Neurosci. 63, 17–22 (2009).

    PubMed  Google Scholar 

  108. Holt, R. I., Pendlebury, J., Wildgust, H. J. & Bushe, C. J. Intentional weight loss in overweight and obese patients with severe mental illness: 8-year experience of a behavioral treatment program. J. Clin. Psychiatry 71, 800–805 (2010).

    PubMed  Google Scholar 

  109. Taylor, J. et al. Identifying risk and preventing progression to type 2 diabetes in vulnerable and disadvantaged adults: a pragmatic review. Diabet. Med. 30, 16–25 (2013).

    CAS  PubMed  Google Scholar 

  110. Knowler, W. C. et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 346, 393–403 (2002).

    CAS  PubMed  Google Scholar 

  111. Chiasson, J. L. et al. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 359, 2072–2077 (2002).

    CAS  PubMed  Google Scholar 

  112. Mizuno, Y. et al. Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis. Schizophr. Bull. 40, 1385–1403 (2014).

    PubMed  PubMed Central  Google Scholar 

  113. McIntyre, R. S. et al. The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid metabolic disorders. Ann. Clin. Psychiatry 24, 69–81 (2012).

    PubMed  Google Scholar 

  114. Joffe, G. et al. Orlistat in clozapine- or olanzapine-treated patients with overweight or obesity: a 16-week randomized, double-blind, placebo-controlled trial. J. Clin. Psychiatry 69, 706–711 (2008).

    CAS  PubMed  Google Scholar 

  115. Maayan, L., Vakhrusheva, J. & Correll, C. U. Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: a systematic review and meta-analysis. Neuropsychopharmacology 35, 1520–1530 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. NICE Type 2 diabetes: The management of type 2 diabetes [online], (2009).

  117. American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care 37 (Suppl. 1), S14–S80 (2014).

  118. Larsen, J. R. et al. Does a GLP-1 receptor agonist change glucose tolerance in patients treated with antipsychotic medications? Design of a randomised, double-blinded, placebo-controlled clinical trial. BMJ Open 4, e004227 (2014).

    PubMed  PubMed Central  Google Scholar 

  119. Ho, P. M. et al. Effect of medication nonadherence on hospitalization and mortality among patients with diabetes mellitus. Arch. Intern. Med. 166, 1836–1841 (2006).

    PubMed  Google Scholar 

  120. Gorczynski, P., Patel, H. & Ganguli, R. Adherence to diabetes medication in individuals with schizophrenia. Clin. Schizophr. Relat. Psychoses http://dx.doi.org/10.3371/CSRP.GOPA.013114.

  121. Mitchell, A. J., Malone, D. & Doebbeling, C. C. Quality of medical care for people with and without comorbid mental illness and substance misuse: systematic review of comparative studies. Br. J. Psychiatry 194, 491–499 (2009).

    PubMed  Google Scholar 

  122. Arnoldy, R., Curtis, J. & Samaras, K. The effects of antipsychotic switching on diabetes in chronic schizophrenia. Diabet. Med. 31, e16–e19 (2014).

    CAS  PubMed  Google Scholar 

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R.I.G.H. researched data for the article, contributed to discussion of the content and wrote the article. A.J.M. researched data for the article, contributed to discussion of the content and reviewed/edited the manuscript before submission.

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Correspondence to Richard I. G. Holt.

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R.I.G.H. has acted as an advisory board member and speaker for Novo Nordisk, and as a speaker for Boehringer Ingelheim, Bristol–Myers Squibb, Eli Lilly, Janssen, Lundbeck, Merck Sharpe and Dohme, Otsuka and Sanofi–Aventis. He has received grants in support of investigator trials from Novo Nordisk. A.J.M. declares no competing interests.

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Holt, R., Mitchell, A. Diabetes mellitus and severe mental illness: mechanisms and clinical implications. Nat Rev Endocrinol 11, 79–89 (2015). https://doi.org/10.1038/nrendo.2014.203

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