Skip to content
2000
image of Impaired Glucose Metabolism in Young Patients with First-episode Schizophrenia Aged from 16 to 35 Years

Abstract

Background

Previous studies in drug-naïve, first-episode patients with schizophrenia (FES) suggest glucose metabolism differences in the early stage of psychosis. However, we have limited knowledge of abnormalities in glucose metabolism in young and drug-naïve FES patients.

Methods

A total of 162 drug-naïve patients with schizophrenia (aged from 18 to 35 years) and 110 age-, sex-matched healthy control subjects were enrolled. Fasting glucose, fasting insulin, glycated hemoglobin (HbA1c), and insulin resistance (HOMA-IR) index were measured in patients and control subjects.

Results

We found that young drug-naïve FES patients exhibited abnormal glucose metabolism compared with control subjects. Fasting insulin, fasting glucose, and HOMA-IR were higher in patients than in controls (all 0.05). In addition, female patients had significantly higher fasting insulin levels and HOMA-IR than male patients (both 0.05), as well as in the healthy controls. Binary logistic regression analysis further identified that smoking status, HOMA-IR, and HbA1c were the contributing factors to schizophrenia, after controlling for age and sex.

Conclusion

This study suggests abnormal glucose metabolism in young drug-naïve FES patients, highlighting that these glucose metabolic issues are present at the very early stage of the disease. The identification of abnormal glucose metabolism at the early stages of schizophrenia provides insights into the biological underpinnings of schizophrenia and may lead to more targeted interventions for patients in the early stages of the disease.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cn/10.2174/011570159X358856250220114527
2025-10-22
2025-10-29

  • From This Site

    /content/journals/cn/10.2174/011570159X358856250220114527
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Fleishhacker W.W. Cetkovich-Bakmas M. De Hert M. Hennekens C.H. Lambert M. Leucht S. Maj M. McIntyre R.S. Naber D. Newcomer J.W. Olfson M. Ösby U. Sartorius N. Lieberman J.A. Comorbid somatic illnesses in patients with severe mental disorders: Clinical, policy, and research challenges. J. Clin. Psychiatry 2008 69 4 514 519 10.4088/JCP.v69n0401 18370570
    [Google Scholar]
  2. Lawrence D.M. D’Arcy C. Holman J. Jablensky A.V. Hobbs M.S.T. Death rate from ischaemic heart disease in Western Australian psychiatric patients 1980–1998. Br. J. Psychiatry 2003 182 1 31 36 10.1192/bjp.182.1.31 12509315
    [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 2007 64 10 1123 1131 10.1001/archpsyc.64.10.1123 17909124
    [Google Scholar]
  4. De Hert M. Schreurs V. Vancampfort D. Van Winkel R. Metabolic syndrome in people with schizophrenia: A review. World Psychiatry 2009 8 1 15 22 10.1002/j.2051‑5545.2009.tb00199.x 19293950
    [Google Scholar]
  5. Ösby U. Correia N. Brandt L. Ekbom A. Sparén P. Mortality and causes of death in schizophrenia in Stockholm County, Sweden. Schizophr. Res. 2000 45 1-2 21 28 10.1016/S0920‑9964(99)00191‑7 10978869
    [Google Scholar]
  6. Crump C. Winkleby M.A. Sundquist K. Sundquist J. Comorbidities and mortality in persons with schizophrenia: A Swedish national cohort study. Am. J. Psychiatry 2013 170 3 324 333 10.1176/appi.ajp.2012.12050599 23318474
    [Google Scholar]
  7. Laursen T.M. Nordentoft M. Mortensen P.B. Excess early mortality in schizophrenia. Annu. Rev. Clin. Psychol. 2014 10 1 425 448 10.1146/annurev‑clinpsy‑032813‑153657 24313570
    [Google Scholar]
  8. Kohen D. Diabetes mellitus and schizophrenia: Historical perspective. Br. J. Psychiatry 2004 184 S47 s64 s66 10.1192/bjp.184.47.s64 15056595
    [Google Scholar]
  9. Greenhalgh A.M. Gonzalez-Blanco L. Garcia-Rizo C. Fernandez-Egea E. Miller B. Arroyo M.B. Kirkpatrick B. Meta-analysis of glucose tolerance, insulin, and insulin resistance in antipsychotic-naïve patients with nonaffective psychosis. Schizophr. Res. 2017 179 57 63 10.1016/j.schres.2016.09.026 27743650
    [Google Scholar]
  10. Perry B.I. McIntosh G. Weich S. Singh S. Rees K. The association between first-episode psychosis and abnormal glycaemic control: Systematic review and meta-analysis. Lancet Psychiatry 2016 3 11 1049 1058 10.1016/S2215‑0366(16)30262‑0 27720402
    [Google Scholar]
  11. Garcia-Rizo C. Kirkpatrick B. Fernandez-Egea E. Oliveira C. Meseguer A. Grande I. Undurraga J. Vieta E. Bernardo M. “Is bipolar disorder an endocrine condition?” Glucose abnormalities in bipolar disorder. Acta Psychiatr. Scand. 2014 129 1 73 74 10.1111/acps.12194 24024599
    [Google Scholar]
  12. Pillinger T. Beck K. Gobjila C. Donocik J.G. Jauhar S. Howes O.D. Impaired glucose homeostasis in first-episode schizophrenia: A systematic review and meta-analysis. JAMA Psychiatry 2017 74 3 261 269 10.1001/jamapsychiatry.2016.3803 28097367
    [Google Scholar]
  13. Garrido-Torres N. Rocha-Gonzalez I. Alameda L. Rodriguez-Gangoso A. Vilches A. Canal-Rivero M. Crespo-Facorro B. Ruiz-Veguilla M. Metabolic syndrome in antipsychotic-naïve patients with first-episode psychosis: A systematic review and meta-analysis. Psychol. Med. 2021 51 14 2307 2320 10.1017/S0033291721002853 34493353
    [Google Scholar]
  14. de Bartolomeis A. De Simone G. De Prisco M. Barone A. Napoli R. Beguinot F. Billeci M. Fornaro M. Insulin effects on core neurotransmitter pathways involved in schizophrenia neurobiology: A meta-analysis of preclinical studies. Implications for the treatment. Mol. Psychiatry 2023 28 7 2811 2825 10.1038/s41380‑023‑02065‑4 37085712
    [Google Scholar]
  15. Xiu M. Fan Y. Liu Q. Chen S. Wu F. Zhang X. Glucose metabolism, hippocampal subfields and cognition in first-episode and never-treated schizophrenia. Int. J. Clin. Health Psychol. 2023 23 4 100402 10.1016/j.ijchp.2023.100402 37663043
    [Google Scholar]
  16. Thakore J.H. Metabolic disturbance in first-episode schizophrenia. Br. J. Psychiatry 2004 184 S47 s76 s79 10.1192/bjp.184.47.s76 15056598
    [Google Scholar]
  17. 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. 2013 39 2 295 305 10.1093/schbul/sbs082 22927670
    [Google Scholar]
  18. Arranz B. Rosel P. Ramírez N. Dueñas R. Fernández P. Sanchez J.M. Navarro M.A. San L. Insulin resistance and increased leptin concentrations in noncompliant schizophrenia patients but not in antipsychotic-naive first-episode schizophrenia patients. J. Clin. Psychiatry 2004 65 10 1335 1342 10.4088/JCP.v65n1007 15491236
    [Google Scholar]
  19. Misiak B. Łaczmański Ł. Słoka N.K. Szmida E. Piotrowski P. Loska O. Ślęzak R. Kiejna A. Frydecka D. Metabolic dysregulation in first-episode schizophrenia patients with respect to genetic variation in one-carbon metabolism. Psychiatry Res. 2016 238 60 67 10.1016/j.psychres.2016.01.077 27086212
    [Google Scholar]
  20. Ryan M.C.M. Collins P. Thakore J.H. Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia. Am. J. Psychiatry 2003 160 2 284 289 10.1176/appi.ajp.160.2.284 12562574
    [Google Scholar]
  21. Spelman L.M. Walsh P.I. Sharifi N. Collins P. Thakore J.H. Impaired glucose tolerance in first‐episode drug‐naïve patients with schizophrenia. Diabet. Med. 2007 24 5 481 485 10.1111/j.1464‑5491.2007.02092.x 17381506
    [Google Scholar]
  22. Jensen K.G. Correll C.U. Rudå D. Klauber D.G. Stentebjerg-Olesen M. Fagerlund B. Jepsen J.R.M. Fink-Jensen A. Pagsberg A.K. Pretreatment cardiometabolic status in youth with early-onset psychosis. J. Clin. Psychiatry 2017 78 8 e1035 e1046 10.4088/JCP.15m10479 28102978
    [Google Scholar]
  23. Petruzzelli M.G. Margari M. Peschechera A. de Giambattista C. De Giacomo A. Matera E. Margari F. Hyperprolactinemia and insulin resistance in drug naive patients with early onset first episode psychosis. BMC Psychiatry 2018 18 1 246 10.1186/s12888‑018‑1827‑3 30068291
    [Google Scholar]
  24. Yang W. Zheng L. Zheng B. Zeng S. Li J. Liang B. Zhu J. Zhang M. A meta-analysis of abnormal glucose metabolism in first-episode drug-naive schizophrenia. Psychiatr. Danub. 2020 32 1 46 54 10.24869/psyd.2020.46 32303029
    [Google Scholar]
  25. Chouinard V.A. Henderson D.C. Dalla Man C. Valeri L. Gray B.E. Ryan K.P. Cypess A.M. Cobelli C. Cohen B.M. Öngür D. Impaired insulin signaling in unaffected siblings and patients with first-episode psychosis. Mol. Psychiatry 2019 24 10 1513 1522 10.1038/s41380‑018‑0045‑1 29523870
    [Google Scholar]
  26. Deng W. Aimone J.B. Gage F.H. New neurons and new memories: How does adult hippocampal neurogenesis affect learning and memory? Nat. Rev. Neurosci. 2010 11 5 339 350 10.1038/nrn2822 20354534
    [Google Scholar]
  27. Zhao W.Q. Alkon D.L. Role of insulin and insulin receptor in learning and memory. Mol. Cell. Endocrinol. 2001 177 1-2 125 134 10.1016/S0303‑7207(01)00455‑5 11377828
    [Google Scholar]
  28. Milstein J.L. Ferris H.A. The brain as an insulin-sensitive metabolic organ. Mol. Metab. 2021 52 101234 10.1016/j.molmet.2021.101234 33845179
    [Google Scholar]
  29. García-Cáceres C. Quarta C. Varela L. Gao Y. Gruber T. Legutko B. Jastroch M. Johansson P. Ninkovic J. Yi C.X. Le Thuc O. Szigeti-Buck K. Cai W. Meyer C.W. Pfluger P.T. Fernandez A.M. Luquet S. Woods S.C. Torres-Alemán I. Kahn C.R. Götz M. Horvath T.L. Tschöp M.H. Astrocytic insulin signaling couples brain glucose uptake with nutrient availability. Cell 2016 166 4 867 880 10.1016/j.cell.2016.07.028 27518562
    [Google Scholar]
  30. Shoelson S.E. Lee J. Goldfine A.B. Inflammation and insulin resistance. J. Clin. Invest. 2006 116 7 1793 1801 10.1172/JCI29069 16823477
    [Google Scholar]
  31. Wu H. Ballantyne C.M. Metabolic inflammation and insulin resistance in obesity. Circ. Res. 2020 126 11 1549 1564 10.1161/CIRCRESAHA.119.315896 32437299
    [Google Scholar]
  32. Zand H. Morshedzadeh N. Naghashian F. Signaling pathways linking inflammation to insulin resistance. Diabetes Metab. Syndr. 2017 11 Suppl. 1 S307 S309 10.1016/j.dsx.2017.03.006 28365222
    [Google Scholar]
  33. Day C.P. From fat to inflammation. Gastroenterology 2006 130 1 207 210 10.1053/j.gastro.2005.11.017 16401483
    [Google Scholar]
  34. Suryavanshi S.V. Kulkarni Y.A. NF-κβ: A potential target in the management of vascular complications of diabetes. Front. Pharmacol. 2017 8 798 10.3389/fphar.2017.00798 29163178
    [Google Scholar]
  35. Spielman L.J. Klegeris A. The role of insulin and incretins in neuroinflammation and neurodegeneration. Immunoendocrinology (Houst.) 2014 1 1 10 14800
    [Google Scholar]
  36. Dandona P. Chaudhuri A. Ghanim H. Mohanty P. Insulin as an anti-inflammatory and antiatherogenic modulator. J. Am. Coll. Cardiol. 2009 53 5 Suppl. S14 S20 10.1016/j.jacc.2008.10.038 19179212
    [Google Scholar]
  37. Ferreira S.T. Clarke J.R. Bomfim T.R. De Felice F.G. Inflammation, defective insulin signaling, and neuronal dysfunction in Alzheimer’s disease. Alzheimers Dement. 2014 10 1S Suppl. S76 S83 10.1016/j.jalz.2013.12.010 24529528
    [Google Scholar]
  38. Garcia-Rizo C. Cabrera B. Bioque M. Mezquida G. Lobo A. Gonzalez-Pinto A. Diaz-Caneja C.M. Corripio I. Vieta E. Baeza I. Garcia-Portilla M.P. Gutierrez-Fraile M. Rodriguez-Jimenez R. Garriga M. Fernandez-Egea E. Bernardo M. The effect of early life events on glucose levels in first-episode psychosis. Front. Endocrinol. (Lausanne) 2022 13 983792 10.3389/fendo.2022.983792 36545332
    [Google Scholar]
  39. Garcia-Rizo C. Bitanihirwe B.K.Y. Implications of early life stress on fetal metabolic programming of schizophrenia: A focus on epiphenomena underlying morbidity and early mortality. Prog. Neuropsychopharmacol. Biol. Psychiatry 2020 101 109910 10.1016/j.pnpbp.2020.109910 32142745
    [Google Scholar]
  40. Pillinger T. McCutcheon R.A. Howes O.D. Variability of glucose, insulin, and lipid disturbances in first-episode psychosis: A meta-analysis. Psychol. Med. 2023 53 7 3150 3156 10.1017/S0033291721005213 37449481
    [Google Scholar]
  41. Friedrich N. Thuesen B. Jørgensen T. Juul A. Spielhagen C. Wallaschofksi H. Linneberg A. The association between IGF-I and insulin resistance: A general population study in Danish adults. Diabetes Care 2012 35 4 768 773 10.2337/dc11‑1833 22374641
    [Google Scholar]
  42. Abel K.M. Drake R. Goldstein J.M. Sex differences in schizophrenia. Int. Rev. Psychiatry 2010 22 5 417 428 10.3109/09540261.2010.515205 21047156
    [Google Scholar]
  43. da Silva T.L. Ravindran A.V. Contribution of sex hormones to gender differences in schizophrenia: A review. Asian J. Psychiatr. 2015 18 2 14 10.1016/j.ajp.2015.07.016 26321672
    [Google Scholar]
  44. Riecher-Rössler A. Häfner H. Gender aspects in schizophrenia: Bridging the border between social and biological psychiatry. Acta Psychiatr. Scand. 2000 102 s407 58 62 10.1034/j.1600‑0447.2000.00011.x 11261642
    [Google Scholar]
  45. Mauvais-Jarvis F. Clegg D.J. Hevener A.L. The role of estrogens in control of energy balance and glucose homeostasis. Endocr. Rev. 2013 34 3 309 338 10.1210/er.2012‑1055 23460719
    [Google Scholar]
  46. Kelly D.M. Jones T.H. Testosterone: A metabolic hormone in health and disease. J. Endocrinol. 2013 217 3 R25 R45 10.1530/JOE‑12‑0455 23378050
    [Google Scholar]
  47. Alemany M. Estrogens and the regulation of glucose metabolism. World J. Diabetes 2021 12 10 1622 1654 10.4239/wjd.v12.i10.1622 34754368
    [Google Scholar]
  48. Kautzky-Willer A. Leutner M. Harreiter J. Sex differences in type 2 diabetes. Diabetologia 2023 66 6 986 1002 10.1007/s00125‑023‑05891‑x 36897358
    [Google Scholar]
  49. Fernandez-Egea E. García-Rizo C. Miller B. Parellada E. Justicia A. Bernardo M. Kirkpatrick B. Testosterone in newly diagnosed, antipsychotic-naive men with nonaffective psychosis: A test of the accelerated aging hypothesis. Psychosom. Med. 2011 73 8 643 647 10.1097/PSY.0b013e318230343f 21949421
    [Google Scholar]
  50. Brand B.A. de Boer J.N. Sommer I.E.C. Estrogens in schizophrenia: Progress, current challenges and opportunities. Curr. Opin. Psychiatry 2021 34 3 228 237 10.1097/YCO.0000000000000699 33560022
    [Google Scholar]
/content/journals/cn/10.2174/011570159X358856250220114527
Loading
Impaired Glucose Metabolism in Young Patients with First-episode Schizophrenia Aged from 16 to 35 Years
Bentham Science Publishers ; https://doi.org/10.2174/011570159X358856250220114527
/content/journals/cn/10.2174/011570159X358856250220114527
/content/journals/cn/10.2174/011570159X358856250220114527
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: early stage of psychosis ; Schizophrenia ; glucose metabolism ; young patients ; sex difference ; insulin resistance

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test