FEATURES OF THERAPY OF PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE, INSULIN RESISTANCE AND INCREASED LEPTIN LEVELS
DOI:
https://doi.org/10.11603/1811-2471.2023.v.i3.14003Keywords:
non-alcoholic fatty liver disease, resistance insulin steatosis, leptin, metforminAbstract
SUMMARY. Non-alcoholic fatty liver disease is one of the most common liver diseases of non-alcoholic origin. The etiological factors responsible for the development and progression of this disease are numerous and not yet fully understood. One of these factors is the elevated level of leptin. This article presents the primary results of treating patients with non-alcoholic fatty liver disease and elevated leptin levels using metformin.
The aim – to investigate the effect of metformin on the severity of steatosis in patients with non-alcoholic fatty liver disease, insulin resistance and elevated leptin levels.
Material and Methods. The reseach included 25 patients (13 females and 12 males) aged between 35 and 60 years, who were divided into two treatment groups. All patients had signs of steatosis in non-alcoholic fatty liver disease, insulin resistance and elevated leptin levels. The inclusion criteria were clinical, instrumental, and laboratory manifestations of steatosis and non-alcoholic fatty liver disease (including the results of validated tests for detecting fibrosis in non-alcoholic fatty liver disease – Fib-4, NAFLD Fibrometer), insulin resistance (anthropometric data, НOMA index, glucose level ) and elevated leptin levels in the blood, the absence of alcohol or diabetes history. The calculation was performed three months after the start of therapy to monitor changes.
Results. The analysis of subjective complaints, laboratory, and instrumental findings showed that the treatment in both groups had a positive trend. It is worth noting that the indicators in group 2, which received metformin, showed a rapid tendency to improve. This is particularly true for glucose levels and leptin levels in the blood. Significant correlation changes were also observed in the patients' self-feeling, complaints, and ultrasound and elastography control checks, namely, a decrease in liver size and echogenicity. It is worth noting the complaints about thirst, which showed opposite results after treatment – this complaint was more often reduced in patients who did not receive metformin. This can be explained by the pharmacokinetics and the action of the drug during the first months of treatment.
Conclusions. The results of the study suggest a correlation between metformin, leptin, and NAFLD, as we observe a positive trend in indicators after a month of metformin use, even compared to the group where metformin was not included in the treatment. These data make it possible to assert that the treatment is effective and observation and control should continue at 6 months, and 1 year from the beginning of treatment.
References
Ioannou, G.N. (2021). Epidemiology and risk-stratification of NAFLD-associated HCC. Journal of Hepatology. DOI: 10.1016/j.jhep.2021.08.012 (date of access: 10.08.2023). DOI: https://doi.org/10.1016/j.jhep.2021.08.012
Rak, S.O. (2019). Neinfektsiyna epidemiya tsukrovoho diabetu [Non-infectious epidemic of diabetes]. Medsestrynstvo – Nursing, 3, 42-44. DOI: 11603/2411-1597.2019.3.10682 (access date: 10.08.2023) [in Ukrainian]. DOI: https://doi.org/10.11603/2411-1597.2019.3.10682
Radu, F., & Potcovaru, C.-G. The Link between NAFLD and Metabolic Syndrome. PubMed. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/36832102/ (date of access: 10.08.2023).
Sanyal, Arun J. (2021). Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease [Electronic resource]. New England Journal of Medicine, 385(17), 1559-1569. DOI: 10.1056/nejmoa2029349 (date of access: 10.08.2023). DOI: https://doi.org/10.1056/NEJMoa2029349
Seth, M. (2020). Leptin and obesity [Electronic resource]. Physiology International. DOI: 10.1556/2060.2020. 00038 (date of access: 10.08.2023).
Boutari, C., & Mantzoros, Christos, S. (2020). Adiponectin and leptin in the diagnosis and therapy of NAFLD [Electronic resource]. Metabolism. DOI: 10.1016/j.metabol.2019.154028 (date of access: 10.08.2023). DOI: https://doi.org/10.1016/j.metabol.2019.154028
Herman, Rok (2022). Metformin and Insulin Resistance: A Review of the Underlying Mechanisms behind Changes in GLUT4-Mediated Glucose Transport [Electronic resource]. International Journal of Molecular Sciences, 23(3). DOI: 10.3390/ijms23031264 (date of access: 10.08.2023). DOI: https://doi.org/10.3390/ijms23031264
Zhao, Han (2021). Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: a network meta-analysis [Electronic resource]. Reproductive Health, 18(1). DOI: 10.1186/s12978-021-01207-7 (date of access: 10.08.2023). DOI: https://doi.org/10.1186/s12978-021-01207-7
Lee, Jenny (2020). Prognostic accuracy of FIB-4, NAFLD fibrosis score, and APRI for NAFLD-related events: a systematic review [Electronic resource]. Liver International. DOI: 10.1111/liv.14669 (date of access: 10.08.2023). DOI: https://doi.org/10.1111/liv.14669
Anania, Caterina (2018). Mediterranean diet and nonalcoholic fatty liver disease [Electronic resource]. World Journal of Gastroenterology, 24(19). DOI: 10.3748/wjg.v24.i19.2083 (date of access: 10.08.2023). DOI: https://doi.org/10.3748/wjg.v24.i19.2083
Holmer, Magnus (2021). Treatment of NAFLD with intermittent calorie restriction or low-carb high-fat diet – a randomised controlled trial [Electronic resource]. JHEP Reports, 3(3). DOI: 10.1016/j.jhepr.2021.100256 (date of access: 10.08.2023). DOI: https://doi.org/10.1016/j.jhepr.2021.100256
Nagashimada, M. & Ota, Tsuguhito (2018). Role of vitamin E in nonalcoholic fatty liver disease [Electronic resource]. IUBMB Life, 71(4), 516-522. DOI: 10.1002/iub.1991 (date of access: 10.08.2023). DOI: https://doi.org/10.1002/iub.1991
Perumpail, Brandon (2018). The Role of Vitamin E in the Treatment of NAFLD [Electronic resource]. Diseases, 6(4), 86. DOI: 10.3390/diseases6040086 (date of access: 10.08.2023). DOI: https://doi.org/10.3390/diseases6040086
Siddiqui, Mohammad S. (2019). Vibration-Controlled Transient Elastography to Assess Fibrosis and Steatosis in Patients With Nonalcoholic Fatty Liver Disease [Electronic resource]. Clinical Gastroenterology and Hepatology, 17(1), 156-163.e2. DOI: 10.1016/j.cgh.2018.04.043 (date of access: 10.08.2023). DOI: https://doi.org/10.1016/j.cgh.2018.04.043
Destrempes, François (2022). Quantitative ultrasound, elastography, and machine learning for assessment of steatosis, inflammation, and fibrosis in chronic liver disease [Electronic resource]. PLOS ONE, 17(1). DOI: 10.1371/journal.pone.0262291 (date of access: 10.08.2023). DOI: https://doi.org/10.1371/journal.pone.0262291
Kong, Wen (2015). Impact of Treatment with Metformin on Adipocytokines in Patients with Polycystic Ovary Syndrome: A Meta-Analysis [Electronic resource]. PLOS ONE, 10(10). DOI: 10.1371/journal.pone.0140565 (date of access: 10.08.2023). DOI: https://doi.org/10.1371/journal.pone.0140565
Pouwels, Sjaak (2022). Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss [Electronic resource]. BMC Endocrine Disorders. 22(1). DOI: 10.1186/s12902-022-00980-1 (date of access: 10.08.2023). DOI: https://doi.org/10.1186/s12902-022-00980-1
Baeza-Flores, Guadalupe Del Carmen (2020). Metformin: A Prospective Alternative for the Treatment of Chronic Pain [Electronic resource]. Frontiers in Pharmacology, 11. DOI: 10.3389/fphar.2020.558474 (date of access: 10.08.2023). DOI: https://doi.org/10.3389/fphar.2020.558474
Hvid, Henning (2018). Activation of insulin receptors and IGF-1 receptors in COLO-205 colon cancer xenografts by insulin and insulin analogue X10 does not enhance growth under normo- or hypoglycaemic conditions [Electronic resource]. Diabetologia. 61(11), 2447-2457. DOI: 10. 1007/s00125-018-4684-1 (date of access: 10.08.2023). DOI: https://doi.org/10.1007/s00125-018-4684-1
Zhuravlyova, L., Zhuravlyova, A., & Ognieva. O. (2018). Osnovy diahnostyky, likuvannya ta profilaktyky nealkoholnoyi zhyrovoyi khvoroby pechinky : navchalnyy posibnyk dlya likariv-interniv terapevtiv ta likariv zahalnoyi praktyky [Basics of diagnosis, treatment and prevention of non-alcoholic fatty liver disease: a study guide for interns of therapists and general practitioners]. Kharkiv: Medknyga [in Ukrainian].
Alvim de Lima, Luis Mauro (2009). Short-term treatment with metformin improves the cardiovascular risk profile in first-degree relatives of subjects with type 2 diabetes mellitus who have a metabolic syndrome and normal glucose tolerance without changes in C-reactive protein or fibrinogen [Electronic resource]. Clinics, 64(5). DOI: 10.1590/s1807-59322009000500008 (date of access: 10.08.2023). DOI: https://doi.org/10.1590/S1807-59322009000500008
Sokolova, L.K., Pushkarev, V. M., & Kovzun, O. I. (2020). Mekhanizmy diyi metforminu za diabetu ta povyazanykh iz diabetom patolohiy [Elektronnyy resurs] [Mechanisms of action of metformin in diabetes and diabetes-related pathologies [Electronic resource]]. Endokrynologia, 25(2), 143-157. DOI: 10.31793/1680-1466.2020.25-2.143 (access date: 10.08.2023) [in Ukrainian]. DOI: https://doi.org/10.31793/1680-1466.2020.25-2.143
Lalrawngbawli, Annie (2020). Effect of metformin on testicular expression and localization of leptin receptor and levels of leptin in the diabetic mice [Electronic resource]. Molecular Reproduction and Development, 87(5), 620-629. DOI: 10.1002/mrd.23342 (date of access: 10.08.2023). DOI: https://doi.org/10.1002/mrd.23342