Abstrakt
Insulinooporność jest zaburzeniem metabolicznym i kluczowym elementem patogenezy chorób, takich jak cukrzyca typu 2, stłuszczeniowa choroba wątroby związana z zaburzeniami metabolicznymi (MASLD), czy miażdżyca. Czynnikami ryzyka rozwoju obniżonej wrażliwości tkanek obwodowych na insulinę są czynniki genetyczne i środowiskowe, np. nadwaga/otyłość, niewielka aktywność fizyczna, ale także przyjmowanie niektórych leków, takich jak glikokortykosteroidy, czy leki przeciwpsychotyczne.
Leki przeciwpsychotyczne (neuroleptyki) są szeroko stosowane w leczeniu różnych zaburzeń psychicznych, przede wszystkim schizofrenii i zazwyczaj taka terapia trwa całe życie. Ze względu na mechanizm działania poprzez hamowanie receptorów, m.in. serotoninowych, muskarynowych, czy histaminowych, leki przeciwpsychotyczne atypowe (drugiej generacji) powodują zaburzenia metaboliczne o różnym stopniu nasilenia, z klozapiną i olanzapiną wykazującymi najgorsze profile metaboliczne i arypiprazolem i lurazydonem o najłagodniejszych profilach. Niezależnie od potencjału rozwoju powikłań metabolicznych po zastosowaniu konkretnego leku przeciwpsychotycznego, poszukuje się u pacjentów wyjściowych predyktorów podatności na ich występowanie. Do tej pory w badaniach opisane zostały takie czynniki ryzyka jak wyższa masa ciała, płeć męska i rasa inna niż biała. Ponadto, pacjenci chorujący na schizofrenię są bardziej narażeni na rozwój insulinooporności, na co wskazują badania w populacjach z pierwszym epizodem psychozy, co wspiera hipotezę, że schizofrenia i cukrzyca mogą mieć wspólną patogenezę. Pomimo ewidentnych dowodów na zwiększone ryzyko rozwoju insulinooporności, a w konsekwencji zespołu metabolicznego i wysokiego ryzyka sercowo-naczyniowego, niewiele uwagi przywiązuje się do wczesnego rozpoznawania, profilaktyki i leczenia zaburzeń gospodarki węglowodanowej i lipidowej u pacjentów stosujących neuroleptyki. Poprawa postępowania w tym zakresie może wpływać nie tylko na ich zdrowie fizyczne, ale także przestrzeganie zaleceń lekarskich i efekty leczenia zaburzeń psychicznych.
Bibliografia
1. Gałecki P, Szulc A. Psychiatria. Wyd. 1 Edra Urban & Partner. Wrocław 2018.
2. Wichniak A, Dudek D, Heitzman J, i wsp. Redukcja ryzyka metabolicznego u chorych na schizofrenię przyjmujących leki przeciwpsychotyczne – zalecenia Polskiego Towarzystwa Psychiatrycznego. Psychiatr Pol 2019;53(6):1191-1218. doi:10.12740/PP/113222.
3. Dayabandara M., Hanwella R., Ratnatunga, S. et al. Antipsychotic-associated weight gain: management strategies and impact on treatment adherence. Neuropsychiatr Dis Treat 2017;13:2231-2241 doi.org/10.2147/NDT.S113099.
4. Pillinger T, McCutcheon RA, Vano L, et al. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. Lancet Psychiatry 2020;7(1):64-77. doi:10.1016/S2215-0366(19)30416-X.
5. Kosmalski M, Różycka-Kosmalska M, Basiak M, i wsp. Diagnosis and management of hyperglycaemia in patients treated with antipsychotic drugs. Endokrynol Pol 2022;73(5):872-884. doi:10.5603/EP.a2022.0071.
6. Pillinger T, Beck K, Gobjila C, et al. Impaired glucose homeostasis in first-episode schizophrenia: a systematic review and meta-analysis. JAMA Psychiatry 2017;74(3):261-269. doi:10.1001/jamapsychiatry.2016.3803.
7. Vargas E, Joy NV, Carrillo Sepulveda MA. Biochemistry, Insulin Metabolic Effects. StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK525983/.
8. Lee SH, Park SY, Choi CS. Insulin resistance: from mechanisms to therapeutic strategies. Diabetes Metab J 2022;46(1):15-37. doi:10.4093/dmj.2021.0280.
9. Rahman MS, Hossain KS, Das S, et al. Role of insulin in health and disease: an update. Int J Mol Sci 2021;22(12):6403. doi:10.3390/ijms22126403.
10. Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev 2018;98(4):2133-2223. doi:10.1152/physrev.00063.2017.
11. White MF, Kahn CR. Insulin action at a molecular level - 100 years of progress. Mol Metab 2021;52:101304. doi:10.1016/j.molmet.2021.101304.
12. Dobrowolski P, Prejbisz A, Kuryłowicz A, i wsp. Zespół metaboliczny – nowa definicja i postępowanie w praktyce. Stanowisko PTNT, PTLO, PTL, PTH, PTMR,PTMSŻ, Sekcji Prewencji i Epidemiologii PTK, „Klubu 30” PTK oraz Sekcji Chirurgii Metabolicznej i Bariatrycznej TChP. Nadciśnienie Tętnicze Prakt 2022;8(2):47-72.
13. Li M, Chi X, Wang Y, et al. Trends in insulin resistance: insights into mechanisms and therapeutic strategy. Signal Transduct Target Ther 2022;7:216. doi:10.1038/s41392-022-01073-0.
14. Freeman AM, Acevedo LA, Pennings N. Insulin Resistance. StatPearls Publishing 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507839/.
15. van Winkel R, De Hert M, Wampers M, et al. Major changes in glucose metabolism, including new-onset diabetes, within 3 months after initiation of or switch to atypical antipsychotic medication in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 2008;69(3):472-479. doi:10.4088/jcp.v69n0320.
16. Ballon JS, Pajvani UB, Mayer LE, et al. Pathophysiology of drug induced weight and metabolic effects: findings from an RCT in healthy volunteers treated with olanzapine, iloperidone, or placebo. J Psychopharmacol 2018;32(5):533-540. doi:10.1177/0269881118754708.
17. Hahn MK, Wolever TM, Arenovich T, et al. Acute effects of single-dose olanzapine on metabolic, endocrine, and inflammatory markers in healthy controls. J Clin Psychopharmacol 2013;33(6):740-746. doi:10.1097/JCP.0b013e31829e8333.
18. Teff, K. L., Rickels, M. R., Grudziak, J., et al. Antipsychotic-induced insulin resistance and postprandial hormonal dysregulation independent of weight gain or psychiatric disease. Diabetes 2013; 62(9), 3232–3240. doi:10.2337/db13 0430
19. Boucher J, Kleinridders A, Kahn CR. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb Perspect Biol 2014;6(1):a009191. doi:10.1101/cshperspect.a009191.
20. Chen J, Huang XF, Shao R, et al. Molecular mechanisms of antipsychotic drug-induced diabetes. Front Neurosci 2017;11:643. doi:10.3389/fnins.2017.00643.
21. Engl J, Laimer M, Niederwanger A, et al. Olanzapine impairs glycogen synthesis and insulin signaling in L6 skeletal muscle cells. Mol Psychiatry 2005;10(12):1089-1096. doi:10.1038/sj.mp.4001729.
22. Panariello F, Perruolo G, Cassese A, et al. Clozapine impairs insulin action by up-regulating Akt phosphorylation and Ped/Pea-15 protein abundance. J Cell Physiol
2012;227(4):1485-1492. doi:10.1002/jcp.22864.
23. Bushe CJ, Slooff CJ, Haddad PM, et al. Weight change from 3-year observational data: findings from the worldwide schizophrenia outpatient health outcomes database.
J Clin Psychiatry 2012;73(6):e749. doi:10.4088/JCP.11m07246.
24. Sudar FP Zekerallah SS, Paulzen M, et al. Unraveling antipsychotic induced weight gain in schizophrenia – A proof-of-concept study exploring the impact of the cumulative historical occupancy of different receptors by antipsychotics. Psychiatry Res 2025, 348, 116452. doi.org/10.1016/j.psychres.2025.116452.
25. Na J., Park B. S., Jang D., et al. Distinct Firing Activities of the Hypothalamic Arcuate Nucleus Neurons to Appetite Hormones. Int J Mol Sci 2022, 23(5), 2609. doi.org/10.3390/ijms23052609.
26. Mukherjee S, Skrede S, Milbank E, et al. Understanding the Effects of Antipsychotics on Appetite Control. Front Nutr 2022;8:815456. doi:10.3389/fnut.2021.815456.
27. Carnovale C, Lucenteforte E, Battini V, et al. Association between the glyco-metabolic adverse effects of antipsychotic drugs and their chemical and pharmacological profile: a network meta-analysis and regression. Psychol Med 2022;52(10):3768-3780. doi:10.1017/S0033291721000180.
28. Gautam D, Gavrilova O, Jeon J et al. Beneficial metabolic effects of M3 muscarinic acetylcholine receptor deficiency. Cell Metab 2006 Nov;4(5):363-75. doi: 10.1016/j.cmet.2006.09.008..
29. Wallace TJ, Zai CC, Brandl EJ, Müller DJ. Role of 5-HT(2C) receptor gene variants in antipsychotic-induced weight gain. Pharmgenomics Pers Med. 2011;4:83-93. doi:
10.2147/PGPM.S11866.
30. Müller DJ, Zai CC, Sicard M, Remington E, et al. Systematic analysis of dopamine receptor genes (DRD1-DRD5) in antipsychotic-induced weight gain. Pharmacogenomics J. 2012 Apr;12(2):156-64. doi: 10.1038/tpj.2010.65.
31. Galic, S., Oakhill, J. S., Steinberg, G. R. et al. Adipose tissue as an endocrine organ. Mol. Cell. Endocrinol 2010, 316(2), 129–139. doi:10.1016/j.mce.2009.08.018.
32. Fryk E, Olausson J, Mossberg K, et al. Hyperinsulinemia and insulin resistance in the obese may develop as part of a homeostatic response to elevated free fatty acids: a mechanistic case-control and a population-based cohort study. EBioMedicine 2021;65:103264. doi:10.1016/j.ebiom.2021.103264.
33. Verma S, Hussain ME. Obesity and diabetes: an update. Diabetes Metab Syndr 2017;11(Suppl 1):73-79. doi:10.1016/j.dsx.2016.06.017.
34. Davey K, Cotter P, O’Sullivan O, et al. Antipsychotics and the gut microbiome: olanzapine induced metabolic dysfunction is attenuated by antibiotic administration in the rat. Transl Psychiatry 2013;3:e309. doi:10.1038/tp.2013.83.
35. Maier L, Pruteanu M, Kuhn M, et al. Extensive impact of non-antibiotic drugs on
human gut bacteria. Nature 2018, 555:623–8. doi: 10.1038/nature25979.
36. Weston-Green K, Huang XF, Deng C. Second generation antipsychotic-induced type 2 diabetes: a role for the muscarinic M3 receptor. CNS Drugs 2013;27(12):1069-1080. doi:10.1007/s40263-013-0115-5.
37. Ozasa R, Okada T, Nadanaka S, et al. The antipsychotic olanzapine induces apoptosis in insulin-secreting pancreatic β cells by blocking PERK-mediated translational attenuation. Cell Struct Funct 2013;38(2):183-195. doi:10.1247/csf.13012.
38. Perry BI, McIntosh G, Weich S, et al. The association between first-episode psychosis and abnormal glycaemic control: systematic review and meta-analysis. Lancet Psychiatry 2016;3(11):1049-1058. doi:10.1016/S2215-0366(16)30262 0.
39. Yang W, Zheng L, Zheng B, et al. A meta-analysis of abnormal glucose metabolism in first-episode drug-naive schizophrenia. Psychiatr Danub 2020;32(1):46-54. doi:10.24869/psyd.2020.46.
40. Petrikis P, Tigas S, Tzallas AT, et al. Parameters of glucose and lipid metabolism at the fasted state in drug-naïve first-episode patients with psychosis: evidence for insulin resistance. Psychiatry Res 2015;229(3):901-904. doi:10.1016/j.psychres.2015.07.041.
41. Drexhage RC, Knijff EM, Padmos RC, et al. The mononuclear phagocyte system and its cytokine inflammatory networks in schizophrenia and bipolar disorder. Expert Rev Neurother 2010; 10: 59–76. doi: 10.1586/ern.09.144.
42. Marcinowicz P, Więdłocha M, Zborowska N, i wsp. A meta-analysis of the influence of antipsychotics on cytokines levels in first episode psychosis. J Clin Med 2021;10(11):2488. doi:10.3390/jcm10112488.
43. Ouabbou S, He Y, Butler K, et al. Inflammation in mental disorders: is the microbiota the missing link? Neurosci Bull 2020;36(9):1071-1084. doi:10.1007/s12264-020-00535-1.
44. Schwarz E, Steiner J, Guest PC, et al. Investigation of molecular serum profiles associated with predisposition to antipsychotic-induced weight gain. World J Biol Psychiatry 2015;16(1):22-30. doi:10.3109/15622975.2014.911298.
45. Kosmas CE, Sourlas A, Oikonomakis K, et al. Biomarkers of insulin sensitivity/resistance. J Int Med Res 2024;52(10):1285550. doi:10.1177/03000605241285550.
46. Steiner J, Berger M, Guest PC, et al. Assessment of insulin resistance among drug-naive patients with first-episode schizophrenia in the context of hormonal stress axis activation. JAMA Psychiatry 2017;74(9):968. doi:10.1001/jamapsychiatry.2017.1983.
47. Lin C, Chen K, Zhang R, et al. The prevalence, risk factors, and clinical characteristics of insulin resistance in Chinese patients with schizophrenia. Compr Psychiatry 2020;96:152145. doi:10.1016/j.comppsych.2019.152145.
48. Guina J, Roy S, Gupta A, et al. Oral glucose tolerance test performance in olanzapine-treated schizophrenia-spectrum patients is predicted by BMI and triglycerides but not olanzapine dose or duration. Hum Psychopharmacol 2017 Jul;32(4). doi: 10.1002/hup.2604. Epub 2017 Jun 1. PMID: 28573760.
49. Yang Y, Ning X, Wang X, et al. Triglyceride/glucose index is a reliable predictor of insulin resistance in schizophrenia. Schizophr Res 2020;223:366-367. doi:10.1016/j.schres.2020.07.005.
50. Chen VC, Chen CH, Chiu YH, et al. Leptin/adiponectin ratio as a potential biomarker for metabolic syndrome in patients with schizophrenia. Psychoneuroendocrinology 2018;92:34-40. doi:10.1016/j.psyneuen.2018.03.021.
51. Yuan X, Yang Q, Yao Y, et al. Role of HOMA-IR and IL-6 as screening markers for the metabolic syndrome in patients with chronic schizophrenia: a psychiatric hospital-based cross-sectional study. Eur Arch Psychiatry Clin Neurosci 2024;274(5):1063-1070. doi:10.1007/s00406-023-01618-6.
52. Fond G, Lançon C, Auquier P, et al. C-reactive protein as a peripheral biomarker in schizophrenia. An updated systematic review. Front Psychiatry 2018;9:392. doi:10.3389/fpsyt.2018.00392.
53. Mangurian C, Schillinger D, Newcomer JW, et al. Diabetes screening among antipsychotic-treated adults with severe mental illness in an integrated delivery system: a retrospective cohort study. J Gen Intern Med 2018;33(1):79-86. doi:10.1007/s11606-017-4205-9.
54. Cederholm J, Zethelius B. SPISE and other fasting indexes of insulin resistance: risks of coronary heart disease or type 2 diabetes. Comparative cross-sectional andlongitudinal aspects. Ups J Med Sci 2019;124(4):265-272. doi:10.1080/03009734.2019.1680583.
55. Sasaki, N., Ueno, Y. & Higashi, Y. Indicators of insulin resistance in clinical practice. Hypertens Res 47, 978–980 (2024). https://doi.org/10.1038/s41440-023-01566-7
56. Zhuo C, Zhang Q, Wang L, et al. Insulin resistance/diabetes and schizophrenia: potential shared genetic factors and implications for better management of patients with schizophrenia. CNS Drugs 2024;38(1):33-44. doi:10.1007/s40263-023-01057-w.
57. Carolan A, Hynes-Ryan C, Agarwal SM, et al. Metformin for the prevention of antipsychotic-induced weight gain: guideline development and consensus validation. Schizophr Bull 2024:sbae205. doi:10.1093/schbul/sbae205.
58. Agarwal SM, Panda R, Costa-Dookhan KA, et al. Metformin for early comorbid glucose dysregulation and schizophrenia spectrum disorders: a pilot double-blind randomized clinical trial. Transl Psychiatry 2021;11(1):219. doi:10.1038/s41398-021-01338-2.
59. Wang LJ, Ree SC, Huang YS, et al. Adjunctive effects of aripiprazole on metabolic profiles: comparison of patients treated with olanzapine to patients treated with other atypical antipsychotic drugs. Prog Neuropsychopharmacol Biol Psychiatry 2013;40:260-266. doi:10.1016/j.pnpbp.2012.10.010.
60. Gupta B, Chee KS, Neo LQ, et al. Effect of aripiprazole as an adjunct to atypical antipsychotics on weight and metabolic profile: a 12-week open-label trial. Ther Adv Psychopharmacol 2021;11:20451253211046765. doi:10.1177/20451253211046765.
2. Wichniak A, Dudek D, Heitzman J, i wsp. Redukcja ryzyka metabolicznego u chorych na schizofrenię przyjmujących leki przeciwpsychotyczne – zalecenia Polskiego Towarzystwa Psychiatrycznego. Psychiatr Pol 2019;53(6):1191-1218. doi:10.12740/PP/113222.
3. Dayabandara M., Hanwella R., Ratnatunga, S. et al. Antipsychotic-associated weight gain: management strategies and impact on treatment adherence. Neuropsychiatr Dis Treat 2017;13:2231-2241 doi.org/10.2147/NDT.S113099.
4. Pillinger T, McCutcheon RA, Vano L, et al. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. Lancet Psychiatry 2020;7(1):64-77. doi:10.1016/S2215-0366(19)30416-X.
5. Kosmalski M, Różycka-Kosmalska M, Basiak M, i wsp. Diagnosis and management of hyperglycaemia in patients treated with antipsychotic drugs. Endokrynol Pol 2022;73(5):872-884. doi:10.5603/EP.a2022.0071.
6. Pillinger T, Beck K, Gobjila C, et al. Impaired glucose homeostasis in first-episode schizophrenia: a systematic review and meta-analysis. JAMA Psychiatry 2017;74(3):261-269. doi:10.1001/jamapsychiatry.2016.3803.
7. Vargas E, Joy NV, Carrillo Sepulveda MA. Biochemistry, Insulin Metabolic Effects. StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK525983/.
8. Lee SH, Park SY, Choi CS. Insulin resistance: from mechanisms to therapeutic strategies. Diabetes Metab J 2022;46(1):15-37. doi:10.4093/dmj.2021.0280.
9. Rahman MS, Hossain KS, Das S, et al. Role of insulin in health and disease: an update. Int J Mol Sci 2021;22(12):6403. doi:10.3390/ijms22126403.
10. Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev 2018;98(4):2133-2223. doi:10.1152/physrev.00063.2017.
11. White MF, Kahn CR. Insulin action at a molecular level - 100 years of progress. Mol Metab 2021;52:101304. doi:10.1016/j.molmet.2021.101304.
12. Dobrowolski P, Prejbisz A, Kuryłowicz A, i wsp. Zespół metaboliczny – nowa definicja i postępowanie w praktyce. Stanowisko PTNT, PTLO, PTL, PTH, PTMR,PTMSŻ, Sekcji Prewencji i Epidemiologii PTK, „Klubu 30” PTK oraz Sekcji Chirurgii Metabolicznej i Bariatrycznej TChP. Nadciśnienie Tętnicze Prakt 2022;8(2):47-72.
13. Li M, Chi X, Wang Y, et al. Trends in insulin resistance: insights into mechanisms and therapeutic strategy. Signal Transduct Target Ther 2022;7:216. doi:10.1038/s41392-022-01073-0.
14. Freeman AM, Acevedo LA, Pennings N. Insulin Resistance. StatPearls Publishing 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507839/.
15. van Winkel R, De Hert M, Wampers M, et al. Major changes in glucose metabolism, including new-onset diabetes, within 3 months after initiation of or switch to atypical antipsychotic medication in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 2008;69(3):472-479. doi:10.4088/jcp.v69n0320.
16. Ballon JS, Pajvani UB, Mayer LE, et al. Pathophysiology of drug induced weight and metabolic effects: findings from an RCT in healthy volunteers treated with olanzapine, iloperidone, or placebo. J Psychopharmacol 2018;32(5):533-540. doi:10.1177/0269881118754708.
17. Hahn MK, Wolever TM, Arenovich T, et al. Acute effects of single-dose olanzapine on metabolic, endocrine, and inflammatory markers in healthy controls. J Clin Psychopharmacol 2013;33(6):740-746. doi:10.1097/JCP.0b013e31829e8333.
18. Teff, K. L., Rickels, M. R., Grudziak, J., et al. Antipsychotic-induced insulin resistance and postprandial hormonal dysregulation independent of weight gain or psychiatric disease. Diabetes 2013; 62(9), 3232–3240. doi:10.2337/db13 0430
19. Boucher J, Kleinridders A, Kahn CR. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb Perspect Biol 2014;6(1):a009191. doi:10.1101/cshperspect.a009191.
20. Chen J, Huang XF, Shao R, et al. Molecular mechanisms of antipsychotic drug-induced diabetes. Front Neurosci 2017;11:643. doi:10.3389/fnins.2017.00643.
21. Engl J, Laimer M, Niederwanger A, et al. Olanzapine impairs glycogen synthesis and insulin signaling in L6 skeletal muscle cells. Mol Psychiatry 2005;10(12):1089-1096. doi:10.1038/sj.mp.4001729.
22. Panariello F, Perruolo G, Cassese A, et al. Clozapine impairs insulin action by up-regulating Akt phosphorylation and Ped/Pea-15 protein abundance. J Cell Physiol
2012;227(4):1485-1492. doi:10.1002/jcp.22864.
23. Bushe CJ, Slooff CJ, Haddad PM, et al. Weight change from 3-year observational data: findings from the worldwide schizophrenia outpatient health outcomes database.
J Clin Psychiatry 2012;73(6):e749. doi:10.4088/JCP.11m07246.
24. Sudar FP Zekerallah SS, Paulzen M, et al. Unraveling antipsychotic induced weight gain in schizophrenia – A proof-of-concept study exploring the impact of the cumulative historical occupancy of different receptors by antipsychotics. Psychiatry Res 2025, 348, 116452. doi.org/10.1016/j.psychres.2025.116452.
25. Na J., Park B. S., Jang D., et al. Distinct Firing Activities of the Hypothalamic Arcuate Nucleus Neurons to Appetite Hormones. Int J Mol Sci 2022, 23(5), 2609. doi.org/10.3390/ijms23052609.
26. Mukherjee S, Skrede S, Milbank E, et al. Understanding the Effects of Antipsychotics on Appetite Control. Front Nutr 2022;8:815456. doi:10.3389/fnut.2021.815456.
27. Carnovale C, Lucenteforte E, Battini V, et al. Association between the glyco-metabolic adverse effects of antipsychotic drugs and their chemical and pharmacological profile: a network meta-analysis and regression. Psychol Med 2022;52(10):3768-3780. doi:10.1017/S0033291721000180.
28. Gautam D, Gavrilova O, Jeon J et al. Beneficial metabolic effects of M3 muscarinic acetylcholine receptor deficiency. Cell Metab 2006 Nov;4(5):363-75. doi: 10.1016/j.cmet.2006.09.008..
29. Wallace TJ, Zai CC, Brandl EJ, Müller DJ. Role of 5-HT(2C) receptor gene variants in antipsychotic-induced weight gain. Pharmgenomics Pers Med. 2011;4:83-93. doi:
10.2147/PGPM.S11866.
30. Müller DJ, Zai CC, Sicard M, Remington E, et al. Systematic analysis of dopamine receptor genes (DRD1-DRD5) in antipsychotic-induced weight gain. Pharmacogenomics J. 2012 Apr;12(2):156-64. doi: 10.1038/tpj.2010.65.
31. Galic, S., Oakhill, J. S., Steinberg, G. R. et al. Adipose tissue as an endocrine organ. Mol. Cell. Endocrinol 2010, 316(2), 129–139. doi:10.1016/j.mce.2009.08.018.
32. Fryk E, Olausson J, Mossberg K, et al. Hyperinsulinemia and insulin resistance in the obese may develop as part of a homeostatic response to elevated free fatty acids: a mechanistic case-control and a population-based cohort study. EBioMedicine 2021;65:103264. doi:10.1016/j.ebiom.2021.103264.
33. Verma S, Hussain ME. Obesity and diabetes: an update. Diabetes Metab Syndr 2017;11(Suppl 1):73-79. doi:10.1016/j.dsx.2016.06.017.
34. Davey K, Cotter P, O’Sullivan O, et al. Antipsychotics and the gut microbiome: olanzapine induced metabolic dysfunction is attenuated by antibiotic administration in the rat. Transl Psychiatry 2013;3:e309. doi:10.1038/tp.2013.83.
35. Maier L, Pruteanu M, Kuhn M, et al. Extensive impact of non-antibiotic drugs on
human gut bacteria. Nature 2018, 555:623–8. doi: 10.1038/nature25979.
36. Weston-Green K, Huang XF, Deng C. Second generation antipsychotic-induced type 2 diabetes: a role for the muscarinic M3 receptor. CNS Drugs 2013;27(12):1069-1080. doi:10.1007/s40263-013-0115-5.
37. Ozasa R, Okada T, Nadanaka S, et al. The antipsychotic olanzapine induces apoptosis in insulin-secreting pancreatic β cells by blocking PERK-mediated translational attenuation. Cell Struct Funct 2013;38(2):183-195. doi:10.1247/csf.13012.
38. Perry BI, McIntosh G, Weich S, et al. The association between first-episode psychosis and abnormal glycaemic control: systematic review and meta-analysis. Lancet Psychiatry 2016;3(11):1049-1058. doi:10.1016/S2215-0366(16)30262 0.
39. Yang W, Zheng L, Zheng B, et al. A meta-analysis of abnormal glucose metabolism in first-episode drug-naive schizophrenia. Psychiatr Danub 2020;32(1):46-54. doi:10.24869/psyd.2020.46.
40. Petrikis P, Tigas S, Tzallas AT, et al. Parameters of glucose and lipid metabolism at the fasted state in drug-naïve first-episode patients with psychosis: evidence for insulin resistance. Psychiatry Res 2015;229(3):901-904. doi:10.1016/j.psychres.2015.07.041.
41. Drexhage RC, Knijff EM, Padmos RC, et al. The mononuclear phagocyte system and its cytokine inflammatory networks in schizophrenia and bipolar disorder. Expert Rev Neurother 2010; 10: 59–76. doi: 10.1586/ern.09.144.
42. Marcinowicz P, Więdłocha M, Zborowska N, i wsp. A meta-analysis of the influence of antipsychotics on cytokines levels in first episode psychosis. J Clin Med 2021;10(11):2488. doi:10.3390/jcm10112488.
43. Ouabbou S, He Y, Butler K, et al. Inflammation in mental disorders: is the microbiota the missing link? Neurosci Bull 2020;36(9):1071-1084. doi:10.1007/s12264-020-00535-1.
44. Schwarz E, Steiner J, Guest PC, et al. Investigation of molecular serum profiles associated with predisposition to antipsychotic-induced weight gain. World J Biol Psychiatry 2015;16(1):22-30. doi:10.3109/15622975.2014.911298.
45. Kosmas CE, Sourlas A, Oikonomakis K, et al. Biomarkers of insulin sensitivity/resistance. J Int Med Res 2024;52(10):1285550. doi:10.1177/03000605241285550.
46. Steiner J, Berger M, Guest PC, et al. Assessment of insulin resistance among drug-naive patients with first-episode schizophrenia in the context of hormonal stress axis activation. JAMA Psychiatry 2017;74(9):968. doi:10.1001/jamapsychiatry.2017.1983.
47. Lin C, Chen K, Zhang R, et al. The prevalence, risk factors, and clinical characteristics of insulin resistance in Chinese patients with schizophrenia. Compr Psychiatry 2020;96:152145. doi:10.1016/j.comppsych.2019.152145.
48. Guina J, Roy S, Gupta A, et al. Oral glucose tolerance test performance in olanzapine-treated schizophrenia-spectrum patients is predicted by BMI and triglycerides but not olanzapine dose or duration. Hum Psychopharmacol 2017 Jul;32(4). doi: 10.1002/hup.2604. Epub 2017 Jun 1. PMID: 28573760.
49. Yang Y, Ning X, Wang X, et al. Triglyceride/glucose index is a reliable predictor of insulin resistance in schizophrenia. Schizophr Res 2020;223:366-367. doi:10.1016/j.schres.2020.07.005.
50. Chen VC, Chen CH, Chiu YH, et al. Leptin/adiponectin ratio as a potential biomarker for metabolic syndrome in patients with schizophrenia. Psychoneuroendocrinology 2018;92:34-40. doi:10.1016/j.psyneuen.2018.03.021.
51. Yuan X, Yang Q, Yao Y, et al. Role of HOMA-IR and IL-6 as screening markers for the metabolic syndrome in patients with chronic schizophrenia: a psychiatric hospital-based cross-sectional study. Eur Arch Psychiatry Clin Neurosci 2024;274(5):1063-1070. doi:10.1007/s00406-023-01618-6.
52. Fond G, Lançon C, Auquier P, et al. C-reactive protein as a peripheral biomarker in schizophrenia. An updated systematic review. Front Psychiatry 2018;9:392. doi:10.3389/fpsyt.2018.00392.
53. Mangurian C, Schillinger D, Newcomer JW, et al. Diabetes screening among antipsychotic-treated adults with severe mental illness in an integrated delivery system: a retrospective cohort study. J Gen Intern Med 2018;33(1):79-86. doi:10.1007/s11606-017-4205-9.
54. Cederholm J, Zethelius B. SPISE and other fasting indexes of insulin resistance: risks of coronary heart disease or type 2 diabetes. Comparative cross-sectional andlongitudinal aspects. Ups J Med Sci 2019;124(4):265-272. doi:10.1080/03009734.2019.1680583.
55. Sasaki, N., Ueno, Y. & Higashi, Y. Indicators of insulin resistance in clinical practice. Hypertens Res 47, 978–980 (2024). https://doi.org/10.1038/s41440-023-01566-7
56. Zhuo C, Zhang Q, Wang L, et al. Insulin resistance/diabetes and schizophrenia: potential shared genetic factors and implications for better management of patients with schizophrenia. CNS Drugs 2024;38(1):33-44. doi:10.1007/s40263-023-01057-w.
57. Carolan A, Hynes-Ryan C, Agarwal SM, et al. Metformin for the prevention of antipsychotic-induced weight gain: guideline development and consensus validation. Schizophr Bull 2024:sbae205. doi:10.1093/schbul/sbae205.
58. Agarwal SM, Panda R, Costa-Dookhan KA, et al. Metformin for early comorbid glucose dysregulation and schizophrenia spectrum disorders: a pilot double-blind randomized clinical trial. Transl Psychiatry 2021;11(1):219. doi:10.1038/s41398-021-01338-2.
59. Wang LJ, Ree SC, Huang YS, et al. Adjunctive effects of aripiprazole on metabolic profiles: comparison of patients treated with olanzapine to patients treated with other atypical antipsychotic drugs. Prog Neuropsychopharmacol Biol Psychiatry 2013;40:260-266. doi:10.1016/j.pnpbp.2012.10.010.
60. Gupta B, Chee KS, Neo LQ, et al. Effect of aripiprazole as an adjunct to atypical antipsychotics on weight and metabolic profile: a 12-week open-label trial. Ther Adv Psychopharmacol 2021;11:20451253211046765. doi:10.1177/20451253211046765.
Utwór dostępny jest na licencji Creative Commons Uznanie autorstwa 4.0 Międzynarodowe.
Metrics
Downloads
Download data is not yet available.