Vol. 15 No. 2 (2023): Arch Pub Health
Clinical Science

Insulin resistance and metabolic syndrome in hepatitis C virus seronegative heroin dependents

Zanina Pereska
University Clinic for Toxicology; Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
Danijela Janicevic-Ivanovska
University Clinic for Clinical Biochemistry Skopje; Goce Delchev University-Shtip, Republic of North Macedonia
Natasa Simonovska
University Clinic for Toxicology; Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
Aleksandra Babulovska
University Clinic for Toxicology; Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
Aneta Trajanovska-Spasovska
Psychiatric Hospital Skopje; Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
Kiril Naumoski
University Clinic for Toxicology; Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
Kristin Kostadinoski
University Clinic for Toxicology; Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia

Published 2023-12-25


  • heroin dependents,
  • metabolic syndrome,
  • insulin resistance,
  • HOMA-IR,
  • HOMA-%B

How to Cite

Pereska Z, Janicevic-Ivanovska D, Simonovska N, Babulovska A, Trajanovska-Spasovska A, Naumoski K, Kostadinoski K. Insulin resistance and metabolic syndrome in hepatitis C virus seronegative heroin dependents. Arch Pub Health [Internet]. 2023 Dec. 25 [cited 2024 Mar. 2];15(2). Available from: https://id-press.eu/aph/article/view/6110


Initial studies on impaired glucose-insulin homeostasis in heroin dependents have not defined the impact of concomitant hepatitis C infection (HCV), which has been  strongly associated with the development of insulin resistanceand metabolic syndrome (MS). The aim of our study was to evaluate the association of heroin dependence with glucose-insulin homeostasis and MS in heroin dependents with HCV seronegativity. Materials and methods: The study was prospective and cross-sectional, including 160 heroin dependents compared to a control group of 60 participants.MS was diagnosed using International Diabetes Federation criteria. The homeostatic model assessment for insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-%B) were used for assessing insulin resistance and β-cell function of pancreas. Results: MS was detected in 9.32% of heroin addicts. Heroin dependents with MS compared to dependents without MS were older, had higher BMI, waist circumference and significantly higher systolic and diastolic blood pressure, increased triglycerides (F=8.233, df=2, p<0.001), apoB (F=8.154, df=2, p=0.001), and reduced HDL-C (F=25.926, df=2, p<0.001) and apoA-I (F=16.406, df=2, p<0.001), significantly increased inuslinemia (F=4.928, df=2, p<0.05), insulin resistance-HOMA-IR (F=4,928, df=2, p<0,05) and insignificantly increased pancreatic β-cell function (194.66 ±224.05) (F=2.461, df=2, p>0.05). Conclusions: Insulin resistance and МS, independent of HCV, was also registered in heroin dependence. Timely recognition will enable more successful treatment of comorbidities and illicit drug dependence.


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  1. Reed JL, Ghodse AH. Oral glucose tolerance and hormonal response in heroin-dependent males. Br Med J. 1973;2(5866):2(5866):582-5. doi: 10.1136/bmj.2.5866.582.
  2. Maccari S, Bassi C, Zanoni P, Plancher AC. Plasma cholesterol and triglycerides in heroin addicts. Drug Alcohol Depend. 1991;29(2):183-7. doi: 10.1016/0376-8716(91)90047-3.
  3. Wilczek H, Češka R, Zlatohlávek L. Sérové lipidy u drogově závislých osob. Vnitr Lek. 2004;50(8):584-6.PMID: 15521200
  4. Mattoo SK, Chakraborty K, Basu D, Ghosh A, Vijaya Kumar KG, Kulhara P. Prevalence & correlates of metabolic syndrome in alcohol & opioid dependent inpatients. Indian Journal of Medical Research. 2011;134(9):341-8. PMID: 21985817.
  5. Frishman WH, Del Vecchio A, Sanal S, Ismail A. Cardiovascular manifestations of substance abuse: Part 2: Alcohol, amphetamines, heroin, cannabis, and caffeine. Heart Disease. 2003; 5(4):253-71. doi: 10.1097/01.hdx.0000080713.09303.a6.
  6. Galante A, Deluca A, Pietroiusti A, Tiratterra F, Benincasa E, Domenici B, et al. Effects of opiates on blood rheology. Clin Toxicol. 1994;32(4):411-17.doi: 10.3109/15563659409011042
  7. ReeceAS, Hulse GK. Opiate dependence as an independent and interactive risk factor for arterial stiffness and cardiovascular ageing - A longitudinal study in females. J Clin Med Res. 2013;5(5):356-67. doi: 10.4021/jocmr1496w.
  8. Woyesa S, Robinson A. Hepatitis C virus infection, genotypes and mechanism of insulin resistance. Journal of Molecular Pathophysiology. 2019;8(1):1-13.doi:10.5455/jmp.20190703070703.
  9. Nolan CJ, Prentki M. Insulin resistance and insulin hypersecretion in the metabolic syndrome and type 2 diabetes: Time for a conceptual framework shift. Diabetes and Vascular Disease Research. 2019;16(2):118-127.doi.org/10.1177/1479164119827.
  10. Cui Y, Tang TY, Lu CQ, Ju S. Insulin resistance and cognitive impairment: evidence from neuroimaging. J Magn Reson Imaging. 2022;56(6):1621-1649. doi: 10.1002/jmri.28358
  11. Zhang M, Chen J, Yin Z, Wang L, Peng L. The association between depression and metabolic syndrome and its components: a bidirectional two-sample Mendelian randomization study. Translational psychiatry. 2021;11(1):633. doi.org/10.1038/s41398-021-01759-z
  12. Brinkman Gl, Coates EO. The effect of bronchitis, smoking, and occupation on ventilation. Am Rev Respir Dis. 1963;87: 87-93. doi: 10.1164/arrd.1963.87.5.684.
  13. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7): 412-9. doi: 10.1007/BF00280883.
  14. Alberti K, Zimmet P, Shaw J. IDF Epidemiology Task Force Consensus Group. The metabolic syndrome: a new worldwide definition. Lancet. 2005;366(9491):1059-62. doi: 10.1016/S0140-6736(05)67402-8.
  15. Vallecillo G, Robles MJ, Torrens M, Samos P, Roquer A, Martires PK, et al. Metabolic syndrome among individuals with heroin use disorders on methadone therapy: prevalence, characteristics, and related factors. Subst Abus. 2018;39(1):46–51. doi: 10.1080/08897077.2017.1363122
  16. Nebhinani N, Gupta S, Mattoo SK, Basu D. Prevalence of the metabolic syndrome in substance-dependent men. German Journal of Psychiatry. 2013;16(2):61-7.
  17. Balhara YPS, Jain R, Kuppili PP, Shukla A, Chawla N, Gupta R. Which criteria to use to identify metabolic syndrome among patients with addictive disorders?: Observations among patients with alcohol and opioid dependence syndrome. Indian J Endocrinol Metab. 2018;22(4):565-8.doi: 10.4103/ijem.IJEM_617_17
  18. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: Findings from the Third National Health and Nutrition Examination Survey. J Am Med Assoc. 2002;287(3): 356-9.doi: 10.1001/jama.287.3.356
  19. Al-Lawati JA, Mohammed AJ, Al-Hinai HQ, Jousilahti P. Prevalence of the metabolic syndrome among Omani adults. Diabetes Care. 2003;26(6):1781-5. doi: 10.2337/diacare.26.6.1781.
  20. Azizi F, Salehi P, Etemadi A, Zahedi-Asl S. Prevalence of metabolic syndrome in an urban population: Tehran Lipid and Glucose Study. Diabetes Res Clin Pract. 2003;61(1):29-37. doi: 10.1016/s0168-8227(03)00066-4.
  21. Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: Prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Intern Med. 2003;163(4):427-36. doi: 10.1001/archinte.163.4.427
  22. Hildrum B, Mykletun A, Hole T, Midthjell K, Dahl AA. Age-specific prevalence of the metabolic syndrome defined by the International Diabetes Federation and the National Cholesterol Education Program: The Norwegian HUNT 2 study. BMC Public Health. 2007;7:220. doi: 10.1186/1471-2458-7-220.
  23. Smyth B, Hoffman V, Fan J, Hser YI. Years of potential life lost among heroin addicts 33 years after treatment. Prev Med (Baltim). 2007;44(4):369-74.doi: 10.1016/j.ypmed.2006.10.003.
  24. Gluvic Z, Zaric B, Resanovic I, Obradovic M, Mitrovic A, Radak D, et al. Link between Metabolic Syndrome and Insulin Resistance. Curr Vasc Pharmacol. 2016;15(1):30–9. doi: 10.2174/1570161114666161007164510.
  25. Li Y, Eitan S, Wu J, Evans CJ, Kieffer B, Sun X, et al. Morphine induces desensitization of insulin receptor signaling. Mol Cell Biol. 2003;23(17):6255-66.doi: 10.1128/MCB.23.17.6255-6266.2003.
  26. Louis M, Punjabi NM. Effects of acute intermittent hypoxia on glucose metabolism in awake healthy volunteers. J Appl Physiol. 2009;106(5):1538-44.doi: 10.1152/japplphysiol.91523.2008.
  27. Stoermer R, Drewe J, Farland KMD Mac, Hock C, Mueller-Spahn F, Ladewig D, et al. Safety of injectable opioid maintenance treatment for heroin dependence. Biol Psychiatry. 2003;54(8): 854-61. doi: 10.1016/s0006-3223(03)00290-7.
  28. Rudich A, Tlrosh A, Potashnik R, Hemi R, Kanety H, Bashan N. Prolonged oxidative stress impairs insulin-induced GLUT4 translocation in 3T3-L1 adipocytes. Diabetes. 1998;47(10):1562-9.doi: 10.1016/s0006-3223(03)00290-7.
  29. Zhou JF, Yan XF, Ruan ZR, Peng FY, Gai D, Yuan H, et al. Heroin abuse and nitric oxide, oxidation, peroxidation, lipoperoxidation. Biomedical and Environmental Sciences. 2000;13(2):131-9.PMID: 11055015.
  30. Chen L, Cao ZL, Han F, Gao ZC, He QY. Chronic intermittent hypoxia from pedo-stage decreases glucose transporter 4 expression in adipose tissue and causes insulin resistance. Chin Med J (Engl). 2010;123(4):463-70.PMID: 20193488.
  31. Housová J, Wilczek H, Haluzík MM, Křemen J, Křížová J, Haluzík M. Adipocyte-derived hormones in heroin addicts: The influence of methadone maintenance treatment. Physiol Res. 2005;54(1). doi: 10.33549/physiolres.930568.
  32. Cnop M, Havel PJ, Utzschneider KM, Carr DB, Sinha MK, Boyko EJ, et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: Evidence for independent roles of age and sex. Diabetologia. 2003;46(4) :459-69. doi: 10.1007/s00125-003-1074-z.
  33. Elnimr T, Hashem A, Assar R. Heroin dependence effects on some major and trace elements. Biol Trace Elem Res. 1996;54(2). doi: 10.1007/s00125-003-1074-z.
  34. Steiner DF, Park SY, Støy J, Philipson LH, Bell GI. A brief perspective on insulin production. Diabetes Obes Metab. 2009;11(SUPPL. 4): 189-96. doi: 10.1111/j.1463-1326.2009.01106.x.
  35. Morcuende A, Navarrete F, Nieto E, Manzanares J, Femenía T. Inflammatory biomarkers in addictive disorders. Biomolecules. 2021;11(12):1824.doi: 10.3390/biom11121824
  36. Holáň V, Zajícová A, Krulová M, Blahoutová V, Wilczek H. Augmented production of proinflammatory cytokines and accelerated allotransplantation reactions in heroin-treated mice. Clin Exp Immunol. 2003;132(1) ):40-5. doi: 10.1046/j.1365-2249.2003.02103.x.
  37. Giugliano D, Quatraro A, Consoli G, Stante A, Simeone V, Ceriello A, et al. Sodium salicylate restores the impaired insulin response to glucose and improves glucose tolerance in heroin addicts. Acta Diabetol Lat. 1987;24(3): 205-12. doi: 10.1007/BF02732039.
  38. Verma M, Govil N, Chahal S, Sharma P, Kalra S. Determinants of metabolic syndrome among people with substance abuse. Prim Care Companion CNS Disord. 2022;24(4): 21m03172. doi: 10.4088/PCC.21m03172.
  39. Quesada O, Claggett B, Rodriguez F, Cai J, Moncrieft AE, Garcia K, et al. Associations of insulin resistance with systolic and diastolic blood pressure: a study from the HCHS/SOL. Hypertension. 2021 Sep 1;78(3):716–25.doi: 10.1161/HYPERTENSIONAHA.120.16905.
  40. Kim JA, Montagnani M, Kwang KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: Molecular and pathophysiological mechanisms. Circulation. 2006;113(15):1888-904. doi: 10.1161/CIRCULATIONAHA.105.563213.
  41. Zhao D, Grundy SM, Wang W, Liu J, Zeng Z, Wang W, et al. Ten-year cardiovascular disease risk of metabolic syndrome without central obesity in middle-aged chinese. American Journal of Cardiology. 2007;100(5) :835-9. doi: 10.1016/j.amjcard.2007.03.103.
  42. Pluta W, Dudzińska W, Lubkowska A. Metabolic obesity in people with normal body weight (monw)—review of diagnostic criteria. Int J Environ Res Public Health. 2022;19(2):624. doi: 10.3390/ijerph19020624.
  43. Elman I, Howard M, Borodovsky JT, Mysels D, Rott D, Borsook D, et al. Metabolic and addiction indices in patients on opioid agonist medication-assisted treatment: a comparison of buprenorphine and methadone. Sci Rep. 2020;10(1) :5617. doi: 10.1038/s41598-020-62556-0.
  44. Sablé-Amplis R, Agid R, Abadie D. Some effects of morphine on lipid metabolism in normal, tolerant and abstinent rats. Life Sci. 1975;16(9):1477-82. doi: 10.1016/0024-3205(75)90045-4.
  45. Jun JC, Shin MK, Yao Q, Bevans-Fonti S, Poole J, Drager LF, et al. Acute hypoxia induces hypertriglyceridemia by decreasing plasma triglyceride clearance in mice. Am J Physiol Endocrinol Metab. 2012;303(3) :E377-88. doi: 10.1152/ajpendo.00641.2011.
  46. Kazemi M, Bazyar M, Naghizadeh MM, Dehghan A, Rahimabadi MS, Chijan MR, et al. Lipid profile dysregulation in opium users based on Fasa PERSIAN cohort study results. Sci Rep 2021;11(1):12058. doi: 10.1038/s41598-021-91533-4
  47. Schneider JG, Von Eynatten M, Schiekofer S, Nawroth PP, Dugi KA. Low plasma adiponectin levels are associated with increased hepatic lipase activity in vivo. Diabetes Care. 2005;28(9):2181-6. doi: 10.2337/diacare.28.9.2181.
  48. Kauss AR, Antunes M, de La Bourdonnaye G, Pouly S, Hankins M, Heremans A, et al. Smoking and apolipoprotein levels: A meta-analysis of published data. Toxicol Rep. 2022;9:1150–71. doi: 10.1016/j.toxrep.2022.05.009.