Although 9.4 T magnetic resonance imaging (MRI) has been tested in healthy volunteers, its safety in diabetic patients is unclear. Furthermore, the effects of high static magnetic fields (SMFs), especially gradient vs. uniform fields, have not been investigated in diabetics. Here, we investigated the consequences of exposure to 1.0-9.4 T high SMFs of different gradients (>10 T/m vs. 0-10 T/m) on type 1 diabetic (T1D) and type 2 diabetic (T2D) mice. We found that 14 h of prolonged treatment of gradient (as high as 55.5 T/m) high SMFs (1.0-8.6 T) had negative effects on T1D and T2D mice, including spleen, hepatic, and renal tissue impairment and elevated glycosylated serum protein, blood glucose, inflammation, and anxiety, while 9.4 T quasi-uniform SMFs at 0-10 T/m did not induce the same effects. In regular T1D mice (blood glucose ≥16.7 mmol/L), the >10 T/m gradient high SMFs increased malondialdehyde ( P<0.01) and decreased superoxide dismutase ( P<0.05). However, in the severe T1D mice (blood glucose ≥30.0 mmol/L), the >10 T/m gradient high SMFs significantly increased tissue damage and reduced survival rate. In vitro cellular studies showed that gradient high SMFs increased cellular reactive oxygen species and apoptosis and reduced MS-1 cell number and proliferation. Therefore, this study showed that prolonged exposure to high-field (1.0-8.6 T) >10 T/m gradient SMFs (35-1 380 times higher than that of current clinical MRI) can have negative effects on diabetic mice, especially mice with severe T1D, whereas 9.4 T high SMFs at 0-10 T/m did not produce the same effects, providing important information for the future development and clinical application of SMFs, especially high-field MRI.

9.4 T 核磁共振成像（MRI）已经在健康志愿者中进行了检测，但其对糖尿病患者的影响尚不清楚。稳态强磁场（SMFs），尤其是梯度和/或均匀稳态强磁场对糖尿病的影响也未进行研究。该研究旨在探究不同梯度（>10 T/m 和 0–10 T/m）的1.0–9.4 T高场SMFs对1型糖尿病（T1D）和2型糖尿病（T2D）小鼠的影响。我们发现持续14小时的梯度（高达55.5 T/m）高场（1.0–8.6 T）SMFs处理后，对T1D和T2D小鼠均可产生有害影响，包括：脾脏、肝脏和肾脏组织损伤，以及糖基化血清蛋白、血糖、炎症和焦虑水平升高等；而近均匀SMFs（0–10 T/m，~9.4 T）却没有出现以上现象。在普通的T1D小鼠（血糖≥16.7 mmol/L）肾脏组织中，>10 T/m的梯度高场SMFs增加了组织丙二醛水平（ P<0.01），减少超氧化物歧化酶的含量（ P<0.05）。然而，在严重的T1D小鼠（血糖≥30.0mmol/L）中，>10 T/m梯度高场SMFs不仅明显增加多组织损伤，还降低了严重的T1D小鼠的存活率。体外细胞研究表明，梯度高场SMFs增加了MS-1细胞的活性氧水平，并促进细胞凋亡，减少了MS-1细胞数量和细胞增殖。因此，我们的研究表明，长期暴露于>10 T/m梯度SMFs（比目前临床MRI高35–1380倍）高场（1.0–8.6 T）对糖尿病小鼠，尤其是对严重的T1D小鼠产生有害影响。相反，0–10 T/m的~9.4 T近均匀高场SMFs却没有负面影响，这为SMFs特别是高场MRI的未来发展和临床应用提供了重要信息。.

Department of Oncology 1st Affiliated Hospital of Anhui Medical University Hefei Anhui 230022 China

High Magnetic Field Laboratory CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology Hefei Institutes of Physical Science Chinese Academy of Sciences Hefei Anhui 230031 China

Institute of Physics of the Czech Academy of Sciences Prague 18221 Czech Republic

Institutes of Physical Science and Information Technology Anhui University Hefei Anhui 230601 China

International Magnetobiology Frontier Research Center Science Island Hefei Anhui 230031 China

International Magnetobiology Frontier Research Center Science Island Hefei Anhui 230031 China E mail

Science Island Branch of Graduate School University of Science and Technology of China Hefei Anhui 230026 China

Zobrazit více v PubMed

Abbas Z, Gras V, Mollenhoff K, et al Quantitative water content mapping at clinically relevant field strengths: a comparative study at 1.5 T and 3 T. Neuroimage. 2015;106:404–413. doi: 10.1016/j.neuroimage.2014.11.017. PubMed DOI

American Diabetes Association Diagnosis and classification of diabetes mellitus. Diabetes Care. 2013;36(S1):S62–S69.

Atkinson IC, Thulborn KR Feasibility of mapping the tissue mass corrected bioscale of cerebral metabolic rate of oxygen consumption using 17-oxygen and 23-sodium MR imaging in a human brain at 9.4 T. Neuroimage. 2010;51(2):723–733. doi: 10.1016/j.neuroimage.2010.02.056. PubMed DOI

Biessels GJ, Reijmer YD Brain changes underlying cognitive dysfunction in diabetes: What can we learn from MRI? Diabetes. 2014;63(7):2244–2252. doi: 10.2337/db14-0348. PubMed DOI

Carter CS, Huang SC, Searby CC, et al Exposure to static magnetic and electric fields treats type 2 diabetes. Cell Metabolism. 2020;32(4):561–574. doi: 10.1016/j.cmet.2020.09.012. PubMed DOI PMC

Chen HZ, Yang HY, Zhong K, et al Preliminary study on fine structures of subcortical nuclei in rhesus monkeys by ex vivo 9.4 T MRI. Zoological Research. 2020;41(2):199–202. doi: 10.24272/j.issn.2095-8137.2020.013. PubMed DOI PMC

Chen SQ, Han JY, Liu YQ Dual opposing roles of metallothionein overexpression in C57BL/6J mouse pancreatic β-cells. PLoS One. 2015;10(9):e0137583. doi: 10.1371/journal.pone.0137583. PubMed DOI PMC

Clotman K, Twickler MB Diabetes or endocrinopathy admitted in the COVID-19 ward. European Journal of Clinical Investigation. 2020;50(7):e13262. PubMed PMC

Crooks L, Arakawa M, Hoenninger J, et al Nuclear magnetic resonance whole-body imager operating at 3.5 Kgauss. Radiology. 1982;143(1):169–174. doi: 10.1148/radiology.143.1.7063722. PubMed DOI

de Jesus Gomes J, del Carlo RJ, da Silva MF, et al Swimming training potentiates the recovery of femoral neck strength in young diabetic rats under insulin therapy. Clinics. 2019;74:e829. doi: 10.6061/clinics/2019/e829. PubMed DOI PMC

Feng AL, Xiang YY, Gui L, et al Paracrine GABA and insulin regulate pancreatic alpha cell proliferation in a mouse model of type 1 diabetes. Diabetologia. 2017;60(6):1033–1042. doi: 10.1007/s00125-017-4239-x. PubMed DOI

Fujita I, Utoh R, Yamamoto M, et al The liver surface as a favorable site for islet cell sheet transplantation in type 1 diabetes model mice. Regenerative Therapy. 2018;8:65–72. doi: 10.1016/j.reth.2018.04.002. PubMed DOI PMC

Furman BL Streptozotocin-induced diabetic models in mice and rats. Current Protocols in Pharmacology. 2015;70:5.47.1–5.47.20. PubMed

Geijselaers SLC, Sep SJS, Stehouwer CDA, et al Glucose regulation, cognition, and brain MRI in type 2 diabetes: a systematic review. Lancet Diabetes & Endocrinology. 2015;3(1):75–89. PubMed

Hodgson S, Cheema S, Rani Z, et al Population stratification in type 2 diabetes mellitus: a systematic review. Diabetic Medicine. 2022;39(1):e14688. PubMed

Hogan MF, Liu AW, Peters MJ, et al Markers of islet endothelial dysfunction occur in male B6. BKS(D)- Leprdb/J mice and may contribute to reduced insulin release. Endocrinology. 2017;158(2):293–303. doi: 10.1210/en.2016-1393. PubMed DOI PMC

Khan H, Huang XF, Tian XF, et al Short- and long-term effects of 3.5–23.0 Tesla ultra-high magnetic fields on mice behaviour. European Radiology. 2022;32(8):5596–5605. doi: 10.1007/s00330-022-08677-8. PubMed DOI

Lammert E, Cleaver O, Melton D Induction of pancreatic differentiation by signals from blood vessels. Science. 2001;294(5542):564–567. doi: 10.1126/science.1064344. PubMed DOI

László JF, Szilvási J, Fényi A, et al Daily exposure to inhomogeneous static magnetic field significantly reduces blood glucose level in diabetic mice. International Journal of Radiation Biology. 2011;87(1):36–45. doi: 10.3109/09553002.2010.518200. PubMed DOI

Lin R, Brown F, James S, et al Continuous glucose monitoring: a review of the evidence in type 1 and 2 diabetes mellitus. Diabetic Medicine. 2021;38(5):e14528. PubMed

Lv Y, Fan YX, Tian XF, et al The anti-depressive effects of ultra-high static magnetic field. Journal of Magnetic Resonance Imaging. 2022;56(2):354–365. doi: 10.1002/jmri.28035. PubMed DOI

Patterson CC, Dahlquist G, Harjutsalo V, et al Early mortality in EURODIAB population-based cohorts of type 1 diabetes diagnosed in childhood since 1989. Diabetologia. 2007;50(12):2439–2442. doi: 10.1007/s00125-007-0824-8. PubMed DOI

Rose KJ, Scibilia R The COVID19 pandemic–Perspectives from people living with diabetes. Diabetes Research And Clinical Practice. 2021;173:108343. doi: 10.1016/j.diabres.2020.108343. PubMed DOI PMC

Sarkisian J, Klee P, Dirlewanger M, et al Benign COVID19 in a highly vulnerable adolescent with type 1 diabetes and leukemia. Swiss Medical Weekly. 2021;151:16–17.

Smith FW, Mallard JR, Reid A, et al Nuclear magnetic resonance tomographic imaging in liver disease. The Lancet. 1981;317(8227):963–966. doi: 10.1016/S0140-6736(81)91731-1. PubMed DOI

Sun H, Saeedi P, Karuranga S, et al IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Research and Clinical Practice. 2022;183:109119. doi: 10.1016/j.diabres.2021.109119. PubMed DOI PMC

Tian XF, Lv Y, Fan YX, et al Safety evaluation of mice exposed to 7.0–33.0 T high-static magnetic fields. Journal of Magnetic Resonance Imaging. 2021;53(6):1872–1884. doi: 10.1002/jmri.27496. PubMed DOI

Tian XF, Wang DM, Feng S, et al Effects of 3.5–23.0 T static magnetic fields on mice: a safety study. Neuroimage. 2019;199:273–280. doi: 10.1016/j.neuroimage.2019.05.070. PubMed DOI

Tian XF, Wang Z, Zhang L, et al Effects of 3.7 T-24.5 T high magnetic fields on tumor-bearing mice. Chinese Physics B. 2018;27(11):118703. doi: 10.1088/1674-1056/27/11/118703. DOI

Wang HZ, Zhang X Magnetic fields and reactive oxygen species. International Journal of Molecular Sciences. 2017;18(10):2175. doi: 10.3390/ijms18102175. PubMed DOI PMC

Wang SH, Luo J, Lv HH, et al Safety of exposure to high static magnetic fields (2 T-12 T): a study on mice. European Radiology. 2019;29(11):6029–6037. doi: 10.1007/s00330-019-06256-y. PubMed DOI

Yang XX, Song C, Zhang L, et al An upward 9.4 T static magnetic field inhibits DNA synthesis and increases ROS-P53 to suppress lung cancer growth. Translational Oncology. 2021;14(7):101103. doi: 10.1016/j.tranon.2021.101103. PubMed DOI PMC

Yu B, Liu JJ, Cheng J, et al A static magnetic field improves iron metabolism and prevents high-fat-diet/streptozocin-induced diabetes. The Innovation. 2021;2(1):100077. doi: 10.1016/j.xinn.2021.100077. PubMed DOI PMC

Zablotskii V, Lunov O, Kubinova S, et al Effects of high-gradient magnetic fields on living cell machinery. Journal of Physics D:Applied Physics. 2016;49(49):493003. doi: 10.1088/0022-3727/49/49/493003. DOI

Zablotskii V, Polyakova T, Dejneka A Cells in the non-uniform magnetic world: How cells respond to high-gradient magnetic fields. Bioessays. 2018;40(8):1800017. doi: 10.1002/bies.201800017. PubMed DOI

Zaiss M, Schuppert M, Deshmane A, et al Chemical exchange saturation transfer MRI contrast in the human brain at 9.4 T. Neuroimage. 2018;179:144–155. doi: 10.1016/j.neuroimage.2018.06.026. PubMed DOI