胰腺脂肪沉积的危险因素及相关疾病的研究进展
收稿日期: 2024-08-16
录用日期: 2024-12-08
网络出版日期: 2025-02-25
基金资助
温州市科技局基础性科研项目(Y20220321)
Advances in research on risk factors and associated diseases of intrapancreatic fat deposition
Received date: 2024-08-16
Accepted date: 2024-12-08
Online published: 2025-02-25
胰腺脂肪沉积（intrapancreatic fat deposition，IPFD）被定义为胰腺中脂肪的弥漫性存在，伴随术语是脂肪胰（fatty pancreas，FP），是指高于正常上限的IPFD（脂肪含量≥9.5%）。胰腺的脂肪变化也已被证明至少影响了全球16%的人口。IPFD的常见危险因素包括人群特点（年龄、性别、种族）、饮食、肥胖与代谢综合征、非酒精性脂肪性肝病、代谢功能障碍相关脂肪性肝病、代谢功能障碍相关脂肪变性肝病、铁超载、遗传疾病、胰管堵塞和其他可能相关的因素（如细菌病毒感染、多囊卵巢综合征、甲状腺疾病等）。现有研究已明确，IPFD是胰腺炎、胰腺癌及糖尿病发生、发展的关键危险因素；此外，新近证据表明其可能参与了胰瘘、移植后排斥反应和动脉粥样硬化等病理过程。诊断IPFD目前主要依靠影像学检查，而随着人工智能（artificial intelligence， AI）技术的进步，未来AI-影像学技术可能为IPFD诊断提供更加完备的依据。针对IPFD的常用干预措施包括生活方式的改变（如减肥、健康饮食、定期锻炼等）、药物治疗和减肥手术。目前，对于IPFD的认知仍不够明确。本文对IPFD的高危因素、诊断、危害和干预措施等相关文献进行综述，有助于提高临床医师对IPFD的认知。
雷朝闻尉 , 饶佳玲 , 周梦雪 , 杨虹 . 胰腺脂肪沉积的危险因素及相关疾病的研究进展[J]. 诊断学理论与实践, 2025 , 24(01) : 72 -79 . DOI: 10.16150/j.1671-2870.2025.01.011
Intrapancreatic fat deposition (IPFD) is defined as the diffuse accumulation of fat within the pancreas. A related term, fatty pancreas (FP), refers to an IPFD fat content of ≥9.5%, which exceeds the normal upper limit. Changes in pancreatic fat content have been shown to affect at least 16% of the global population. Known risk factors for IPFD include demographic characteristics (age, sex, ethnicity), dietary patterns, obesity and metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated fatty liver disease (MAFLD), iron overload, genetic disorders, pancreatic duct obstruction, and other potentially related conditions such as bacterial/viral infections, polycystic ovary syndrome, thyroid disorders. Accumulating evidence has established IPFD as a critical risk factor for the pathogenesis and progression of pancreatitis, pancreatic cancer, and diabetes mellitus; additionally, emerging evidence suggests its potential involvement in pancreatic fistula, post-transplant rejection, and atherosclerosis. Currently, the diagnosis of IPFD primarily relies on imaging techniques. With the rapid development of artificial intelligence (AI), AI-assisted imaging is expected to provide more accurate and comprehensive diagnostic tools for IPFD in the near future. Common intervention strategies for IPFD include lifestyle modifications (such as weight loss, dietary optimization, and regular physical activity), pharmacological treatments, and bariatric surgery. Currently, the understanding of IPFD is still unclear, so a review of the risk factors, diagnosis, harms, and intervention measures for IPFD would help improve clinical awareness of IPFD.
| [1] | PETROV M S. Fatty change of the pancreas: the Pandora's box of pancreatology[J]. Lancet Gastroenterol Hepatol, 2023, 8(7):671-682. |
| [2] | JANSSENS L P, WESTON A D, SINGH D,et al. Determi-ning age and sex-specific distribution of pancreatic whole-gland CT attenuation using artificial intelligence aided image segmentation: Associations with body composition and pancreatic cancer risk[J]. Pancreatology, 2021, 21(8):1524-1530. |
| [3] | JANSSENS L P, TAKAHASHI H, NAGAYAMA H,et al. Artificial intelligence assisted whole organ pancreatic fat estimation on magnetic resonance imaging and correlation with pancreas attenuation on computed tomography[J]. Pancreatology, 2023, 23(5):556-562. |
| [4] | YANG W, XIE Y, SONG B,et al. Effects of aging and menopause on pancreatic fat fraction in healthy women population: A strobe-compliant article[J]. Medicine (Baltimore), 2019, 98(7):e14451. |
| [5] | LI J, XIE Y, YUAN F,et al. Noninvasive quantification of pancreatic fat in healthy male population using chemical shift magnetic resonance imaging: effect of aging on pancreatic fat content[J]. Pancreas, 2011, 40(2):295-299. |
| [6] | XIAO Y, WANG H, HAN L,et al. Predictive value of anthropometric and biochemical indices in non-alcoholic fatty pancreas disease: a cross-sectional study[J]. BMJ Open, 2024, 14(4):e081131. |
| [7] | SZCZEPANIAK L S, VICTOR R G, MATHUR R,et al. Pancreatic steatosis and its relationship to β-cell dysfunction in humans: racial and ethnic variations[J]. Diabetes Care, 2012, 35(11):2377-2383. |
| [8] | Lê K A, VENTURA E E, FISHER J Q,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. |
| [9] | CERVANTES A, WAYMOUTH E K, PETROV M S. African-Americans and indigenous peoples have increased burden of diseases of the exocrine pancreas: A systematic review and meta-analysis[J]. Dig Dis Sci, 2019, 64(1):249-261. |
| [10] | LEIU K H, POPPITT S D, MILES-CHAN J L,et al. Fatty pancreas and cardiometabolic risk: response of ectopic fat to lifestyle and surgical interventions[J]. Nutrients, 2022, 14(22):4873. |
| [11] | ICKIN GULEN M, GUVEN BAGLA A, YAVUZ O,et al. Histopathological changes in rat pancreas and skeletal muscle associated with high fat diet induced insulin resistance[J]. Biotech Histochem, 2015, 90(7):495-505. |
| [12] | RAVAUT G, LéGIOT A, BERGERON K F,et al. Monounsaturated fatty acids in obesity-related inflammation[J]. Int J Mol Sci, 2020, 22(1):330. |
| [13] | LONGO M, ZATTERALE F, NADERI J,et al. Adipose tissue dysfunction as determinant of obesity-associated metabolic complications[J]. Int J Mol Sci, 2019, 20(9):2358. |
| [14] | OOKURA R, USUKI N, MIKI Y. Correlation between pancreatic fat deposition and metabolic syndrome: Relationships with location in the pancreas and sex[J]. Intern Med, 2024, 63(15):2113-2123. |
| [15] | OKADA K, WATAHIKI T, HORIE K,et al. The prevalence and clinical implications of pancreatic fat accumulation identified during a medical check-up[J]. Medicine (Baltimore), 2021, 100(41):e27487. |
| [16] | WONGTRAKUL W, UNTAAVEESUP S, PAUSAWADI N,et al. Bidirectional association between non-alcoholic fatty liver disease and fatty pancreas: a systematic review and meta-analysis[J]. Eur J Gastroenterol Hepatol, 2023, 35(10):1107-1116. |
| [17] | RUGIVARODOM M, GEERATRAGOOL T, PAUSAWASDI N,et al. Fatty Pancreas: Linking Pancreas Pathophysiology to Nonalcoholic Fatty Liver Disease[J]. J Clin Transl Hepatol, 2022, 10(6):1229-1239. |
| [18] | IDILMAN I S, TUZUN A, SAVAS B,et al. Quantification of liver, pancreas, kidney, and vertebral body MRI-PDFF in non-alcoholic fatty liver disease[J]. Abdom Imaging, 2015, 40(6):1512-1519. |
| [19] | GOFTON C, UPENDRAN Y, ZHENG M H,et al. MAFLD: How is it different from NAFLD?[J]. Clin Mol Hepatol, 2023, 29(Suppl):S17-S31. |
| [20] | DE A, BHAGAT N, MEHTA M,et al. Metabolic dysfunction-associated steatotic liver disease (MASLD) definition is better than MAFLD criteria for lean patients with NAFLD[J]. J Hepatol, 2024, 80(2):e61-e62. |
| [21] | MAK A L, WASSENAAR N, VAN DIJK A M,et al. Intrapancreatic fat deposition is unrelated to liver steatosis in metabolic dysfunction-associated steatotic liver disease[J]. JHEP Rep, 2024, 6(3):100998. |
| [22] | ENGJOM T, KAVALIAUSKIENE G, TJORA E,et al. Sonographic pancreas echogenicity in cystic fibrosis compared to exocrine pancreatic function and pancreas fat content at Dixon-MRI[J]. PLoS One, 2018, 13(7):e0201019. |
| [23] | GODOY-MATOS A F, VALERIO C M, MOREIRA R O,et al. Pancreatic fat deposition is increased and related to beta-cell function in women with familial partial lipodystrophy[J]. Diabetol Metab Syndr, 2018, 10:71. |
| [24] | MELONI A, NOBILE M, KEILBERG P,et al. Pancreatic fatty replacement as risk marker for altered glucose metabolism and cardiac iron and complications in thalassemia major[J]. Eur Radiol, 2023, 33(10):7215-7225. |
| [25] | KATZ D S, HINES J, MATH K R,et al. Using CT to reveal fat-containing abnormalities of the pancreas[J]. Am J Roentgenol, 1999, 172(2):393-396. |
| [26] | MAHYOUB M A, ELHOUMED M, MAQUL A H,et al. Fatty infiltration of the pancreas: a systematic concept analysis[J]. Front Med (Lausanne), 2023, 10:1227188. |
| [27] | SANTOS M L C, DE BRITO B B, SILVA F A F DA,et al. Helicobacter pylori infection: Beyond gastric manifestations[J]. World J Gastroenterol, 2020, 26(28):4076-4093. |
| [28] | RABELO-GON?ALVES E M, ROESLER B M, ZEITUNE J M. Extragastric manifestations of Helicobacter pylori infection: Possible role of bacterium in liver and pancreas diseases[J]. World J Hepatol, 2015, 7(30):2968-2979. |
| [29] | OSMAN M A A, ALKHOULY M, ELMOHASEB G F,et al. Relation between non-alcoholic fatty pancreas and clinical and biochemical parameters in women with polycystic ovary syndrome: A multi-centric study[J]. Int J Gen Med, 2022, 15:8225-8233. |
| [30] | WARE M A, KAAR J L, DINIZ BEHN C,et al. Pancreatic fat relates to fasting insulin and postprandial lipids but not polycystic ovary syndrome in adolescents with obesity[J]. Obesity (Silver Spring), 2022, 30(1):191-200. |
| [31] | BAYYIGIT A, GOKDEN Y, ONOL S,et al. Hypothyroi-dism and subclinical hypothyroidism are associated with fatty pancreas (Non-alcoholic fatty pancreas disease)[J]. Diabetes Metab Res Rev, 2024, 40(2):e3720. |
| [32] | PAUL J, SHIHAZ A V H. Pancreatic steatosis: A new diagnosis and therapeutic challenge in gastroenterology[J]. Arq Gastroenterol, 2020, 57(2):216-220. |
| [33] | NORONHA M, SALGADINHO A, FERREIRA DE ALMEIDA M J,et al. Alcohol and the pancreas. I. Clinical associations and histopathology of minimal pancreatic inflammation[J]. Am J Gastroenterol, 1981, 76(2):114-119. |
| [34] | MEZA V, ARNOLD J, DíAZ L A,et al. Alcohol Consumption: Medical Implications, the Liver and Beyond[J]. Alcohol Alcohol, 2022, 57(3):283-291. |
| [35] | STUART C E, KO J, MODESTO A E,et al. Implications of tobacco smoking and alcohol consumption on ectopic fat deposition in individuals after pancreatitis[J]. Pancreas, 2020, 49(7):924-934. |
| [36] | SBEIT W, ELHEJA F ABU, MSHEIIL B,et al. Fatty pancreas was associated with a higher acute pancreatitis Systemic Inflammatory Response Syndrome score at hospital admission[J]. Eur J Gastroenterol Hepatol, 2023, 35(9):980-984. |
| [37] | KO J, AL-ANI Z, LONG K,et al. Intrapancreatic, liver, and skeletal muscle fat depositions in first attack of acute pancreatitis versus health[J]. Am J Gastroenterol, 2022, 117(10):1693-1701. |
| [38] | TIRKES T, YADAV D, CONWELL D L,et al. Quantitative MRI of chronic pancreatitis: results from a multi-institutional prospective study, magnetic resonance imaging as a non-invasive method for assessment of pancreatic fibrosis (MINIMAP)[J]. Abdom Radiol (NY), 2022, 47(11):3792-3805. |
| [39] | ACHARYA C, NAVINA S, SINGH V P. Role of panc-reatic fat in the outcomes of pancreatitis[J]. Pancreatology, 2014, 14(5):403-408. |
| [40] | SINGHI A D, PAI R K, KANT J A,et al. The histopatho-logy of PRSS1 hereditary pancreatitis[J]. Am J Surg Pathol, 2014, 38(3):346-353. |
| [41] | CHAN T T, TSE Y K, LUI R N,et al. Fatty pancreas is independently associated with subsequent diabetes mellitus development: A 10-year prospective cohort study[J]. Clin Gastroenterol Hepatol, 2022, 20(9):2014-2022, e4. |
| [42] | YAMAZAKI H, TSUBOYA T, KATANUMA A,et al. Lack of independent association between fatty pancreas and incidence of type 2 diabetes: 5-year japanese cohort study[J]. Diabetes Care, 2016, 39(10):1677-1683. |
| [43] | DONG X, ZHU Q, YUAN C,et al. Associations of intrapancreatic fat deposition with incident diseases of the exocrine and endocrine pancreas: A UK biobank prospective cohort study[J]. Am J Gastroenterol, 2024, 119(6):1158-1166. |
| [44] | KO J, SKUDDER-HILL L, CHO J, et al. Pancreatic enzymes and abdominal adipose tissue distribution in new-onset prediabetes/diabetes after acute pancreatitis[J]. World J Gastroenterol, 2021, 27(23):3357-3371. |
| [45] | TIRKES T, JEON C Y, LI L,et al. Association of pancrea-tic steatosis with chronic pancreatitis, obesity, and type 2 diabetes mellitus[J]. Pancreas, 2019, 48(3):420-426. |
| [46] | SREEDHAR U L, DESOUZA S V, PARK B,et al. A systematic review of intra-pancreatic fat deposition and pancreatic carcinogenesis[J]. J Gastrointest Surg, 2020, 24(11):2560-2569. |
| [47] | LIPP M, TARJáN D, LEE J,et al. Fatty pancreas is a risk factor for pancreatic cancer: A systematic review and meta-analysis of 2956 patients[J]. Cancers (Basel), 2023, 15(19):4876. |
| [48] | YYAMAZAKI H, STREICHER S A, WU L,et al. Evidence for a causal link between intra-pancreatic fat deposition and pancreatic cancer: A prospective cohort and Mendelian randomization study[J]. Cell Rep Med, 2024, 5(2):101391. |
| [49] | ZHOU L, XIAO W M, LI C P,et al. Impact of fatty pancreas on postoperative pancreatic fistulae: A meta-analysis[J]. Front Oncol, 2021, 11:622282. |
| [50] | KUL S, KARADENIZ A, DURSUN ?,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. |
| [51] | 孙朋涛, 都雪朝, 王若顿, 等. 胰腺脂肪浸润对2型糖尿病患者冠状动脉粥样硬化严重程度的预测价值[J]. 中国医学科学院学报, 2020, 42(2):172-177. |
| SUN P T, DU X C, WANG R D,et al. Predictive value of pancreatic steatosis for severity of coronary atherosclerosis in patients with type 2 diabetes mellitus[J]. Acta Acad Med Sinicae, 2020, 42(2)172–177. | |
| [52] | LIU Y, SHAMAITIJIANG X, SKUDDER-HILL L,et al. Relationship of high-density lipoprotein subfractions and apolipoprotein A-I with fat in the pancreas[J]. Diabetes Obes Metab, 2025, 27(1):123-133. |
| [53] | THOMSEN M N, SKYTTE M J, SAMKANI A,et al. Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: a randomised controlled trial[J]. Diabetologia, 2022, 65(3):506-517. |
| [54] | DELLA PEPA G, BRANCATO V, COSTABILE G,et al. An isoenergetic multifactorial diet reduces pancreatic fat and increases postprandial insulin response in patients with type 2 diabetes: A randomized controlled trial[J]. Diabetes Care, 2022, 45(9):1935-1942. |
| [55] | MITSUSHIO K, BADEN M Y, KATO S,et al. Relationships between intra-pancreatic fat deposition and lifestyle factors: a cross-sectional study[J]. Front Endocrinol (Lausanne), 2023, 14:1219579. |
| [56] | LI M, ZHENG Q, MILLER J D,et al. Aerobic training reduces pancreatic fat content and improves β-cell function: A randomized controlled trial using IDEAL-IQ magnetic resonance imaging[J]. Diabetes Metab Res Rev, 2022, 38(4):e3516. |
| [57] | HEISKANEN M A, MOTIANI K K, MARI A,et al. Exercise training decreases pancreatic fat content and improves beta cell function regardless of baseline glucose tolerance: a randomised controlled trial[J]. Diabetologia, 2018, 61(8):1817-1828. |
| [58] | GHOSH A, DUTTA K, BHATT S P,et al. Dapagliflozin improves body fat patterning, and hepatic and pancreatic fat in patients with type 2 diabetes in north india[J]. J Clin Endocrinol Metab, 2022, 107(6):e2267-e2275. |
| [59] | OWOLABI A I, CORBETT R C, FLATT P R,et al. Positive interplay between FFAR4/GPR120, DPP-IV inhibition and GLP-1 in beta cell proliferation and glucose homeostasis in obese high fat fed mice[J]. Peptides, 2024, 177:171218. |
| [60] | JERMENDY G, KOLOSSVáRY M, DROBNI Z,et al. Environmental factors slightly outweigh genetic influences in the development of pancreatic lipid accumulation: a classical twin study[J]. Metab Syndr Relat Disord, 2020, 18(9):413-418. |
| [61] | SALMAN A A, SALMAN M A, SAID M,et al. Improvement of pancreatic steatosis and indices of insulin resistance after metabolic surgery[J]. Front Med (Lausanne), 2022, 9:894465. |
/
| 〈 |
|
〉 |
