胰腺脂肪沉积与动脉粥样硬化的关联研究进展

doi:10.16138/j.1673-6087.2024.04.12

摘要/Abstract

摘要：

胰腺脂肪沉积（intrapancreatic fat deposition，IPFD）是我国最常见的胰腺疾病。近年来越来越多的证据表明IPFD与动脉粥样硬化密切相关，也有部分研究不支持两者的相关性，这可能受到研究人群、动脉粥样硬化检测方法和IPFD诊断标准不同的影响。因此，亟需大样本前瞻性研究进一步明确两者之间的联系。两者相关性涉及的机制可能与炎症、氧化应激、低脂联素血症以及糖代谢等有关。目前IPFD无特异性治疗方法，减肥已被证明可显著减少胰腺沉积的脂肪含量。临床上除关注IPFD本身的治疗外，还应重视对IPFD患者心血管疾病发病风险的评估，以便早干预、早诊治。

关键词: 胰腺脂肪沉积, 动脉粥样硬化, 心血管疾病, 机制, 治疗方法, 流行病学

Abstract:

Intra-pancreatic fat deposition (IPFD) is the most common disease of pancreas in our country. In recent years, there has been increasing evidence that IPFD is closely related to atherosclerosis. However, some studies do not support the correlation between them, which may be affected by differences in study population, atherosclerosis detection methods, and IPFD diagnostic criteria. Therefore, large-sample prospective studies are urgently needed to further clarify the correlation between IPFD and atherosclerosis. The mechanisms involved in correlation between them may be related to inflammation, oxidative stress, hypoadiponectinemia and glucose metabolism. There is currently no specific treatment for IPFD, while weight loss has been shown to significantly reduce the amount of fat deposited in the pancreas. In addition to the treatment of IPFD itself, clinicians should also pay attention to the assessment of the risk of cardiovascular disease in IPFD patients to facilitate early diagnosis and early intervention.

Key words: Intrapancreatic fat deposition, Atherosclerosis, Cardiovascular disease, Mechanism, Treatment, Epidemiology

中图分类号:

R576

李晨曦, 胡蕴, 吴文君. 胰腺脂肪沉积与动脉粥样硬化的关联研究进展[J]. 内科理论与实践, 2024, 19(04): 278-282.

LI Chenxi, HU Yun, WU Wenjun. Research progress of the association between intra-pancreatic fat deposition and atherosclerosis[J]. Journal of Internal Medicine Concepts & Practice, 2024, 19(04): 278-282.

参考文献 51

[1]	Cao MJ, Wu WJ, Chen JW, et al. Quantification of ectopic fat storage in the liver and pancreas using six-point Dixon MRI and its association with insulin sensitivity and β-cell function in patients with central obesity[J]. Eur Radiol, 2023, 33(12):9213-9222.
[2]	Filippatos TD, Alexakis K, Mavrikaki V, et al. Nonalcoholic fatty pancreas disease: role in metabolic syndrome, “prediabetes,” diabetes and atherosclerosis[J]. Dig Dis Sci, 2022, 67(1):26-41.
[3]	Petrov MS, Taylor R. Intra-pancreatic fat deposition: bringing hidden fat to the fore[J]. Nat Rev Gastroenterol Hepatol, 2022, 19(3):153-168.
[4]	Schaefer JH. The normal weight of the pancreas in the adult human being: a biometric study[J]. Anat Rec, 1926, 32(2):119-132.
[5]	Ogilvie RF. The islands of langerhans in 19 cases of obesity[J]. J Pathol Bacteriol, 1933, 37(3):473-481.
[6]	Stamm BH. Incidence and diagnostic significance of minor pathologic changes in the adult pancreas at autopsy: a systematic study of 112 autopsies in patients without known pancreatic disease[J]. Hum Pathol, 1984, 15(7):677-683. doi: 10.1016/s0046-8177(84)80294-4 pmid: 6745910
[7]	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[J]. Am J Gastroenterol, 2014, 109(4):589-597. doi: 10.1038/ajg.2014.1 pmid: 24492753
[8]	Sotoudehmanesh R, Tahmasbi A, Sadeghi A, et al. The prevalence of nonalcoholic fatty pancreas by endoscopic ultrasonography[J]. Pancreas, 2019, 48(9):1220-1224.
[9]	Lesmana CR, Pakasi LS, Inggriani S, et al. 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[J]. BMC Gastroenterol, 2015,15:174.
[10]	Hakim O, Bonadonna RC, Mohandas C, et al. Associations between pancreatic lipids and β-cell function in black african and white european men with type 2 diabetes[J]. J Clin Endocrinol Metab, 2019, 104(4):1201-1210. doi: 10.1210/jc.2018-01809 pmid: 30407535
[11]	Singh RG, Yoon HD, Wu LM, et al. Ectopic fat accumulation in the pancreas and its clinical relevance: a systematic review, meta-analysis, and meta-regression[J]. Metabolism, 2017,69:1-13.
[12]	Li Z, Yue Q, Chen Y, et al. Quantitative assessment of pancreatic fat by quantitative CT in type 2 diabetes mellitus[J]. Int J Gen Med, 2022,15:7977-7984.
[13]	Koç U, Taydaş O. Evaluation of pancreatic steatosis prevalence and anthropometric measurements using non-contrast computed tomography[J]. Turk J Gastroenterol, 2020, 31(9):640-648. doi: 10.5152/tjg.2020.19434 pmid: 33090101
[14]	Kameda F, Tanabe M, Onoda H, et al. Quantification of pancreas fat on dual-energy computed tomography: comparison with six-point Dixon magnetic resonance imaging[J]. Abdom Radiol (NY), 2020, 45(9):2779-2785. doi: 10.1007/s00261-020-02583-7 pmid: 32430511
[15]	Chen Y, Long L, Jiang Z, et al. Quantification of pancreatic proton density fat fraction in diabetic pigs using MR imaging and IDEAL-IQ sequence[J]. BMC Med Imaging, 2019, 19(1):38. doi: 10.1186/s12880-019-0336-2 pmid: 31088378
[16]	Bawden SJ, Hoad C, Kaye P, et al. Comparing magnetic resonance liver fat fraction measurements with histology in fibrosis: the difference between proton density fat fraction and tissue mass fat fraction[J]. MAGMA, 2023, 36(4):553-563.
[17]	Yi J, Xu F, Li T, et al. Quantitative study of 3T MRI qDixon-WIP applied in pancreatic fat infiltration in patients with type 2 diabetes mellitus[J]. Front Endocrinol (Lausanne), 2023,14:1140111.
[18]	Kim MK, Chun HJ, Park JH, et al. The association between ectopic fat in the pancreas and subclinical atherosclerosis in type 2 diabetes[J]. Diabetes Res Clin Pract, 2014, 106(3):590-596.
[19]	Kim HL, Kim SH. Pulse wave velocity in atherosclerosis[J]. Front Cardiovasc Med, 2019, 6:41.
[20]	Sánchez Bacaicoa C, Rico-Martín S, Morales E, et al. Brachial-ankle pulse wave velocity with a custom device[J]. Rev Clin Esp (Barc), 2021, 221(3):145-150.
[21]	Milan A, Zocaro G, Leone D, et al. Current assessment of pulse wave velocity: comprehensive review of validation studies[J]. J Hypertens, 2019, 37(8):1547-1557. doi: 10.1097/HJH.0000000000002081 pmid: 30882597
[22]	Böcskei RM, Benczúr B, Müller V, et al. Oscillometrically measured aortic pulse wave velocity reveals asymptomatic carotid atherosclerosis in a middle-aged, apparently healthy population[J]. Biomed Res Int, 2020,2020:8571062.
[23]	Sun P, Fan C, Wang R, et al. Computed tomography-estimated pancreatic steatosis is associated with carotid plaque in type 2 diabetes mellitus patients: a cross-sectional study from China[J]. Diabetes Metab Syndr Obes, 2021,14:1329-1337.
[24]	Koo BK, Denenberg JO, Wright CM, et al. The association between pancreatic fat and systemic calcified atherosclerosis[J]. Pancreas, 2020, 49(1):e16-e18.
[25]	Ozturk K, Dogan T, Celikkanat S, et al. The association of fatty pancreas with subclinical atherosclerosis in nonalcoholic fatty liver disease[J]. Eur J Gastroenterol Hepatol, 2018, 30(4):411-417.
[26]	Sahin S, Karadeniz A. Pancretic fat accummulation is associated with subclinical atherosclerosis[J]. Angiology, 2022, 73(6):508-513.
[27]	Kul S, Karadeniz A, Dursun İ, et al. Non-alcoholic fatty pancreas disease is associated with increased epicardial adipose tissue and aortic intima-media thickness[J]. Acta Cardiol Sin, 2019, 35(2):118-125. doi: 10.6515/ACS.201903_35(2).20181009A pmid: 30930559
[28]	Li C, Chen X, Zhu X, et al. MRI-measured pancreatic fat correlates with increased arterial stiffness in patients who are overweight and obese[J]. Diabetes Metab Syndr Obes, 2024,17:2283-2291.
[29]	Lê KA, Ventura EE, Fisher JQ, et al. Ethnic differences in pancreatic fat accumulation and its relationship with other fat depots and inflammatory markers[J]. Diabetes Care, 2011, 34(2):485-490.
[30]	Mallick R, Duttaroy AK. Modulation of endothelium function by fatty acids[J]. Mol Cell Biochem, 2022, 477(1):15-38.
[31]	Makino N, Shirahata N, Honda T, et al. Pancreatic hyperechogenicity associated with hypoadiponectinemia and insulin resistance: a Japanese population study[J]. World J Hepatol, 2016, 8(33):1452-1458. pmid: 27957243
[32]	Choi HM, Doss HM, Kim KS. Multifaceted physiological roles of adiponectin in inflammation and diseases[J]. Int J Mol Sci, 2020, 21(4):1219.
[33]	Fatima J, Gupta N, Karoli R, et al. Association of sonographically assessed visceral and subcutaneous abdominal fat with insulin resistance in prediabetes[J]. J Assoc Physicians India, 2019, 67(4):68-70. pmid: 31299843
[34]	Li Y, Liu Y, Liu S, et al. Diabetic vascular diseases: molecular mechanisms and therapeutic strategies[J]. Signal Transduct Target Ther, 2023, 8(1):152.
[35]	Rosenblatt R, Mehta A, Snell D, et al. Ultrasonographic nonalcoholic fatty pancreas is associated with advanced fibrosis in NAFLD: a retrospective analysis[J]. Dig Dis Sci, 2019, 64(1):262-268.
[36]	Taharboucht S, Guermaz R, Brouri M, et al. Subclinical atherosclerosis and arterial stiffness in nonalcoholic fatty liver disease: a case-control study in Algerian population[J]. J Med Vasc, 2021, 46(3):129-138. doi: 10.1016/j.jdmv.2021.03.008 pmid: 33990287
[37]	Oni E, Budoff MJ, Zeb I, et al. Nonalcoholic fatty liver disease is associated with arterial distensibility and carotid intima-media thickness: (from the multi-ethnic study of atherosclerosis)[J]. Am J Cardiol, 2019, 124(4):534-538. doi: S0002-9149(19)30595-8 pmid: 31262497
[38]	Bi Y, Wang JL, Li ML, et al. The association between pancreas steatosis and metabolic syndrome: a systematic review and meta-analysis[J]. Diabetes Metab Res Rev, 2019, 35(5):e3142.
[39]	Shah N, Rocha JP, Bhutiani N, et al. Nonalcoholic fatty pancreas disease[J]. Nutr Clin Pract, 2019,34 Suppl 1:S49-S56.
[40]	Koyuncu Sokmen B, Sahin T, Oral A, et al. The comparison of pancreatic and hepatic steatosis in healthy liver donor candidates[J]. Sci Rep, 2021, 11(1):4507. doi: 10.1038/s41598-021-83871-0 pmid: 33627704
[41]	Kato S, Iwasaki A, Kurita Y, et al. Three-dimensional analysis of pancreatic fat by fat-water magnetic resonance imaging provides detailed characterization of pancreatic steatosis with improved reproducibility[J]. PLoS One, 2019, 14(12):e0224921.
[42]	Milovanovic T, Dragasevic S, Stojkovic Lalosevic M, et al. Ultrasonographic evaluation of fatty pancreas in serbian patients with non alcoholic fatty liver disease-a cross sectional study[J]. Medicina (Kaunas), 2019, 55(10):697.
[43]	Kawai T, Autieri MV, Scalia R. Adipose tissue inflammation and metabolic dysfunction in obesity[J]. Am J Physiol Cell Physiol, 2021, 320(3):C375-C391.
[44]	Neeland IJ, Ross R, Després JP, et al. Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement[J]. Lancet Diabetes Endocrinol, 2019, 7(9):715-725.
[45]	Della Pepa G, Salamone D, Testa R, et al. Intrapancreatic fat deposition and nutritional treatment: the role of various dietary approaches[J/OL]. Nutr Rev, 2023.https://academic.oup.com/nutritionreviews/advance-article-abstract/doi/10.1093/nutrit/nuad159/7503165?redirectedFrom=fulltext&login=false.
[46]	Wagner R, Eckstein SS, Yamazaki H, et al. Metabolic implications of pancreatic fat accumulation[J]. Nat Rev Endocrinol, 2022, 18(1):43-54.
[47]	Hui SCN, Wong SKH, Ai Q, et al. Observed changes in brown, white, hepatic and pancreatic fat after bariatric surgery: evaluation with MRI[J]. Eur Radiol, 2019, 29(2):849-856. doi: 10.1007/s00330-018-5611-z pmid: 30062524
[48]	Covarrubias Y, Fowler KJ, Mamidipalli A, et al. Pilot study on longitudinal change in pancreatic proton density fat fraction during a weight-loss surgery program in adults with obesity[J]. J Magn Reson Imaging, 2019, 50(4):1092-1102. doi: 10.1002/jmri.26671 pmid: 30701611
[49]	Zsóri G, Illés D, Ivány E, et al. In new-onset diabetes mellitus, metformin reduces fat accumulation in the liver, but not in the pancreas or pericardium[J]. Metab Syndr Relat Disord, 2019, 17(5):289-295. doi: 10.1089/met.2018.0086 pmid: 31013454
[50]	Kuriyama T, Ishibashi C, Kozawa J, et al. Effects of liraglutide on intrapancreatic fat deposition in patients with type 2 diabetes[J]. Clin Nutr ESPEN, 2024,59:208-213.
[51]	Kuchay MS, Krishan S, Mishra SK, et al. Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD[J]. Diabetologia, 2020, 63(11):2434-2445.