İnsülin Direnci ve Ektopik Yağ Birikiminin HOMA İndeksleri ile İlişkisi: Tek Merkezli Bir Gözlem Çalışması

Yıl 2024, Cilt: 8 Sayı: 2, 97 - 106, 30.08.2024

Sevde Nur Emir , Servet Emir

https://doi.org/10.25048/tudod.1461623

Öz

Amaç: Bu çalışmanın amacı, diyabet mellitus tanısı olmayan obez hastalarda, rutin muayeneler sırasında yaygın bir non-invaziv tanı aracı olan ultrason (US) kullanılarak, non alkolik yağlı karaciğer hastalığı (NAFLD), non alkolik yağlı pankreas (veya pankreatik) hastalığı (NAFPD) ve HOMA indeksleri arasındaki ilişkiyi araştırmaktır.
Yöntemler: Bu tek merkezli, retrospektif çalışmada, 2023 yılında obezite polikliniğine başvuran hastaların kayıtları gözden geçirilmiştir. Dijital kayıtlar taranmış ve yaş, cinsiyet, vücut kitle indeksi (VKİ), açlık plazma glikozu, açlık plazma glikozu, C-peptid seviyesi ve pankreatik ve hepatik steatoz derecesini belirten abdominal ultrason raporlarına sahip hastalar çalışmaya dahil edilmiştir. Bilinen kronik hastalığı veya diyabet mellitusu olan ve belirli ilaçları kullanan hastalar çalışma dışı bırakılmıştır. Homa indeksleri, açlık plazma glikozu ve C-peptid seviyeleri kullanılarak hesaplanmıştır.
Sonuçlar: Toplam 62 hasta dahil edilmiştir. Ortalama vücut kitle indeksi 39.1, %91’inde NAFLD ve %82’sinde NAFPD bulunmuştur. VKİ ile NAFLD ve NAFPD arasında anlamlı pozitif bir korelasyon saptanmıştır. HOMA skorları, NAFLD'nin insülin direnci (HOMA-IR) ve insülin hassasiyeti (HOMA-S) üzerinde istatistiksel olarak anlamlı bir etkisi olduğunu, ancak beta-hücre fonksiyonu (HOMA-B) üzerinde anlamlı bir etkisinin olmadığını ortaya koymuştur. NAFPD'nin HOMA skorları üzerinde anlamlı bir etkisi gözlenmemiştir.
Sonuç: Bulgular, NAFLD ile insülin direnci arasındaki ilişkiyi vurgulamakta ve obez hastalarda ektopik yağ birikiminin metabolik yükünü ön plana çıkarmaktadır. Buna karşın, NAFPD ile insülin direnci veya beta-hücre fonksiyonu arasında anlamlı bir korelasyon bulunmamıştır, bu da pankreatik steatozun metabolik etkisinin farklı olabileceğini öne sürmektedir. Bu bulgular, obezitede metabolik bozuklukların tespiti ve tedavisi için klinik stratejileri yönlendirmede yardımcı olabilir.

Anahtar Kelimeler

İnsülin Direnci, Obezite, HOMA İndeksi, Ultrason Görüntüleme, Non alkolik Yağlı Pankreas Hastalığı, Non alkolik Yağlı Karaciğer Hastalığı

Association of Insulin Resistance and Ectopic Fat Accumulation with HOMA Indices: A Single-Centre Observational Study

Öz

Purpose: The aim of this study was to investigate the relationship between non-alcoholic fatty liver disease (NAFLD), non-alcoholic fatty pancreas (or pancreatic) disease (NAFPD) and HOMA indices in obese patients without a diagnosis of diabetes mellitus, using ultrasound (US) as a common non-invasive diagnostic tool during routine examinations.
Methods: In this single-centre, retrospective study, the records of patients who applied to the obesity outpatient clinic in 2023 were reviewed. Digital records were scanned and patients with abdominal ultrasound reports indicating age, gender, body mass index(BMI), fasting plasma glucose, fasting plasma glucose, C-peptide level and degree of pancreatic and hepatic steatosis were included in the study. Patients with known chronic disease or diabetes mellitus and patients with specific drug use were excluded from the study. Homa indices were calculated using fasting plasma glucose and C-peptide levels.
Results: A total of 62 patients were included. Body mass index was 39.1, 91% had NAFLD and 82% had NAFPD. There was a significant positive correlation between BMI and NAFLD and NAFPD. HOMA scores revealed a statistically significant impact of NAFLD on insulin resistance (HOMA-IR) and insulin sensitivity (HOMA-S) but not on beta-cell function (HOMA-B). No significant effect of NAFPD on HOMA scores was observed.
Conclusion: The findings underline the association between NAFLD and insulin resistance and highlight the metabolic burden of ectopic fat deposition in obese patients. In contrast, there was no significant correlation between NAFPD and either insulin resistance or beta-cell function, suggesting that the metabolic impact of pancreatic steatosis may be different. These findings may help to guide clinical strategies for detecting and treating metabolic disorders in obesity.

Anahtar Kelimeler

Non-Alcoholic Fatty Liver Disease, Non-Alcoholic Fatty Pancreas Disease, Insulin Resistance, Obesity, HOMA Index, Ultrasound Imaging

Etik Beyan

Ethics committee approval was obtained from University of Health Sciences, Umraniye Training and Research Hospital Clinical Research Ethics Committee on 01/04/2024.

Destekleyen Kurum

University of Health Sciences, Umraniye Training and Research Hospital Clinical Research Ethics Committee on 01/04/2024.

Kaynakça

• 1. Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of Obesity Among Adults and Youth: United States, 2011-2014. NCHS Data Brief. 2015; (219):1-8.
• 2. Katsiki N, Athyros VG, Mikhailidis DP. Abnormal Peri-Organ or Intra-organ Fat (APIFat) Deposition: An Underestimated Predictor of Vascular Risk?. Curr Vasc Pharmacol. 2016;14 (5):432-441. doi:10.2174/1570161114666160722112738
• 3. Britton KA, Fox CS. Ectopic fat depots and cardiovascular disease. Circulation. 2011;124 (24):e837-e841. doi:10.1161/CIRCULATIONAHA. 111.077602
• 4. Smits MM, van Geenen EJ. The clinical significance of pancreatic steatosis. Nat Rev Gastroenterol Hepatol. 2011;8 (3):169- 177. doi:10.1038/nrgastro.2011.4
• 5. Majumder S, Philip NA, Takahashi N, Levy MJ, Singh VP, Chari ST. Fatty Pancreas: Should We Be Concerned?. Pancreas. 2017;46 (10):1251-1258. doi:10.1097/MPA.0000000000000941
• 6. Heni M, Machann J, Staiger H, et al. Pancreatic fat is negatively associated with insulin secretion in individuals with impaired fasting glucose and/or impaired glucose tolerance: a nuclear magnetic resonance study. Diabetes Metab Res Rev. 2010;26 (3):200-205. doi:10.1002/dmrr.1073
• 7. Mathur A, Marine M, Lu D, et al. Nonalcoholic fatty pancreas disease. HPB (Oxford). 2007;9 (4):312-318. doi:10.1080/13651820701504157
• 8. Lingvay I, Esser V, Legendre JL, et al. Noninvasive quantification of pancreatic fat in humans. J Clin Endocrinol Metab. 2009;94 (10):4070-4076. doi:10.1210/jc.2009-0584
• 9. Tariq H, Nayudu S, Akella S, Glandt M, Chilimuri S. Non-Alcoholic Fatty Pancreatic Disease: A Review of Literature. Gastroenterology Res. 2016;9 (6):87-91. doi:10.14740/gr731w
• 10. Dasarathy S, Dasarathy J, Khiyami A, Joseph R, Lopez R, Mc- Cullough AJ. Validity of real time ultrasound in the diagnosis of hepatic steatosis: a prospective study. J Hepatol. 2009;51 (6):1061-1067. doi:10.1016/j.jhep.2009.09.001
• 11. Lee JS, Kim SH, Jun DW, et al. Clinical implications of fatty pancreas: correlations between fatty pancreas and metabolic syndrome. World J Gastroenterol. 2009;15 (15):1869-1875. doi:10.3748/wjg.15.1869
• 12. Ou HY, Wang CY, Yang YC, Chen MF, Chang CJ. The association between nonalcoholic fatty pancreas disease and diabetes. PLoS One. 2013;8 (5):e62561. Published 2013 May 3. doi:10.1371/journal.pone.0062561
• 13. Lesmana CR, Pakasi LS, Inggriani S, Aidawati ML, Lesmana LA. Prevalence of Non-Alcoholic Fatty Pancreas Disease (NAFPD) and its risk factors among adult medical check-up patients in a private hospital: a large cross sectional study. BMC Gastroenterol. 2015;15:174. Published 2015 Dec 12. doi:10.1186/s12876-015-0404-1
• 14. Wang CY, Ou HY, Chen MF, Chang TC, Chang CJ. Enigmatic ectopic fat: prevalence of nonalcoholic fatty pancreas disease and its associated factors in a Chinese population. J Am Heart Assoc. 2014;3 (1):e000297. Published 2014 Feb 26. doi:10.1161/ JAHA.113.000297
• 15. den Biggelaar LJ, Sep SJ, Eussen SJ, et al. Discriminatory ability of simple OGTT-based beta cell function indices for prediction of prediabetes and type 2 diabetes: the CODAM study. Diabetologia. 2017;60 (3):432-441. doi:10.1007/s00125-016- 4165-3
• 16. Stern SE, Williams K, Ferrannini E, DeFronzo RA, Bogardus C, Stern MP. Identification of individuals with insulin resistance using routine clinical measurements. Diabetes. 2005;54 (2):333-339. doi:10.2337/diabetes.54.2.333
• 17. Borai A, Livingstone C, Kaddam I, Ferns G. Selection of the appropriate method for the assessment of insulin resistance. BMC Med Res Methodol. 2011;11:158. Published 2011 Nov 23. doi:10.1186/1471-2288-11-158
• 18. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 2008;294 (1):E15-E26. doi:10.1152/ajpendo. 00645.2007
• 19. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004;27 (6):1487-1495. doi:10.2337/ diacare.27.6.1487
• 20. Ahuja V, Kadowaki T, Evans RW, et al. Comparison of HOMA- IR, HOMA-β% and disposition index between US white men and Japanese men in Japan: the ERA JUMP study. Diabetologia. 2015;58 (2):265-271. doi:10.1007/s00125-014-3414-6
• 21. European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL- EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64 (6):1388-1402. doi:10.1016/j.jhep.2015.11.004
• 22. Fan JG, Wei L, Zhuang H; National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association; Fatty Liver Disease Expert Committee, Chinese Medical Doctor Association. Guidelines of prevention and treatment of nonalcoholic fatty liver disease (2018, China). J Dig Dis. 2019;20 (4):163-173. doi:10.1111/1751-2980.12685
• 23. Hernaez R, Lazo M, Bonekamp S, et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology. 2011;54 (3):1082-1090. doi:10.1002/hep.24452
• 24. Oh H, Park HJ, Oh J, et al. Hyperechoic pancreas on ultrasonography: an analysis of its severity and clinical implications. Ultrasonography. 2022;41 (2):335-343. doi:10.14366/ usg.21099
• 25. Marks WM, Filly RA, Callen PW. Ultrasonic evaluation of normal pancreatic echogenicity and its relationship to fat deposition. Radiology. 1980;137 (2):475-479. doi:10.1148/radiology. 137.2.7433680
• 26. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28 (7):412- 419. doi:10.1007/BF00280883
• 27. Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 1998;21 (12):2191-2192. doi:10.2337/ diacare.21.12.2191
• 28. Mooy JM, Grootenhuis PA, de Vries H, Kostense PJ, Popp- Snijders C, Bouter LM, Heine RJ. Intra-individual variation of glucose, specific insulin and proinsulin concentrations measured by two oral glucose tolerance tests in a general Caucasian population: the Hoorn Study. Diabetologia. 1996;39 (3):298– 305. doi: 10.1007/BF00418345.
• 29. Oxford TUo. HOMA Calculator. 2018. https://www.dtu.ox.ac. uk/ homacalculator/download.php
• 30. Freeman AM, Acevedo LA, Pennings N. Insulin Resistance. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 17, 2023.
• 31. Park SE, Park CY, Sweeney G. Biomarkers of insulin sensitivity and insulin resistance: Past, present and future. Crit Rev Clin Lab Sci. 2015;52 (4):180-190. doi:10.3109/10408363.2015 .1023429
• 32. 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
• 33. Salgado AL, Carvalho Ld, Oliveira AC, Santos VN, Vieira JG, Parise ER. Insulin resistance index (HOMA-IR) in the differentiation of patients with non-alcoholic fatty liver disease and healthy individuals. Arq Gastroenterol. 2010;47 (2):165-169. doi:10.1590/s0004-28032010000200009
• 34. Villanueva-Ortega E, Garcés-Hernández MJ, Herrera-Rosas A, et al. Gender-specific differences in clinical and metabolic variables associated with NAFLD in a Mexican pediatric population. Ann Hepatol. 2019;18 (5):693-700. doi:10.1016/j. aohep.2019.04.012
• 35. Hossain IA, Rahman Shah MM, Rahman MK, Ali L. Gamma glutamyl transferase is an independent determinant for the association of insulin resistance with nonalcoholic fatty liver disease in Bangladeshi adults: Association of GGT and HOMA- IR with NAFLD. Diabetes Metab Syndr. 2016;10 (1 Suppl 1):S25-S29. doi:10.1016/j.dsx.2015.09.005
• 36. Gruben N, Shiri-Sverdlov R, Koonen DP, Hofker MH. Nonalcoholic fatty liver disease: A main driver of insulin resistance or a dangerous liaison?. Biochim Biophys Acta. 2014;1842 (11):2329-2343. doi:10.1016/j.bbadis.2014.08.004
• 37. Pirgon Ö, Bilgin H, Çekmez F, Kurku H, Dündar BN. Association between insulin resistance and oxidative stress parameters in obese adolescents with non-alcoholic fatty liver disease. J Clin Res Pediatr Endocrinol. 2013;5 (1):33-39. doi:10.4274/ Jcrpe.825
• 38. Motamed B, Kohansal Vajargah M, Kalantari S, Shafaghi A. HOMA-IR index in non-diabetic patient, a reliable method for early diagnosis of liver steatosis. Caspian J Intern Med. 2022;13 (3):519-526. doi:10.22088/cjim.13.3.519
• 39. Motamed N, Miresmail SJ, Rabiee B, et al. Optimal cutoff points for HOMA-IR and QUICKI in the diagnosis of metabolic syndrome and non-alcoholic fatty liver disease: A population based study. J Diabetes Complications. 2016;30 (2):269- 274. doi:10.1016/j.jdiacomp.2015.11.019
• 40. Gutierrez-Buey G, Núñez-Córdoba JM, Llavero-Valero M, Gargallo J, Salvador J, Escalada J. Is HOMA-IR a potential screening test for non-alcoholic fatty liver disease in adults with type 2 diabetes?. Eur J Intern Med. 2017;41:74-78. doi:10.1016/j.ejim.2017.03.006
• 41. Isokuortti E, Zhou Y, Peltonen M, et al. Use of HOMA-IR to diagnose non-alcoholic fatty liver disease: a population-based and inter-laboratory study. Diabetologia. 2017;60 (10):1873- 1882. doi:10.1007/s00125-017-4340-1
• 42. Lozano M, Navarro S, Pérez-Ayuso R, et al. Lipomatosis of the pancreas: an unusual cause of massive steatorrhea. Pancreas. 1988;3 (5):580-582. doi:10.1097/00006676-198810000-00012
• 43. Carter R, Mouralidarane A, Soeda J, et al. Non-alcoholic fatty pancreas disease pathogenesis: a role for developmental programming and altered circadian rhythms. PLoS One. 2014;9 (3):e89505. Published 2014 Mar 21. doi:10.1371/journal. pone.0089505
• 44. Catanzaro R, Cuffari B, Italia A, Marotta F. Exploring the metabolic syndrome: Nonalcoholic fatty pancreas disease. World J Gastroenterol. 2016;22 (34):7660-7675. doi:10.3748/wjg.v22. i34.7660
• 45. Wong VW, Wong GL, Yeung DK, et al. Fatty pancreas, insulin resistance, and β-cell function: a population study using fat-water magnetic resonance imaging. Am J Gastroenterol. 2014;109 (4):589-597. doi:10.1038/ajg.2014.1
• 46. Della Corte C, Mosca A, Majo F, et al. Nonalcoholic fatty pancreas disease and Nonalcoholic fatty liver disease: more than ectopic fat. Clin Endocrinol (Oxf). 2015;83 (5):656-662. doi:10.1111/cen.12862
• 47. Pezzilli R, Calculli L. Pancreatic steatosis: Is it related to either obesity or diabetes mellitus?. World J Diabetes. 2014;5 (4):415-419. doi:10.4239/wjd.v5.i4.415
• 48. Saisho Y, Butler AE, Meier JJ, et al. Pancreas volumes in humans from birth to age one hundred taking into account sex, obesity, and presence of type-2 diabetes. Clin Anat. 2007;20 (8):933-942. doi:10.1002/ca.20543
• 49. Kühn JP, Berthold F, Mayerle J, et al. Pancreatic Steatosis Demonstrated at MR Imaging in the General Population: Clinical Relevance. Radiology. 2015;276 (1):129-136. doi:10.1148/ radiol.15140446
• 50. van der Zijl NJ, Goossens GH, Moors CC, et al. Ectopic fat storage in the pancreas, liver, and abdominal fat depots: impact on β-cell function in individuals with impaired glucose metabolism. J Clin Endocrinol Metab. 2011;96 (2):459-467. doi:10.1210/jc.2010-1722
• 51. Ookura R, Usuki N. Visual assessment of pancreatic fat deposition: useful grading system and the relation to BMI and diabetes. Jpn J Radiol. 2023;41 (2):172-179. doi:10.1007/s11604- 022-01334-6