Autopsy Case of Slowly Progressive Type 1 Diabetes with Concomitant Acute Myocardial and Mesenteric Ischemia
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1 CASE REPORT Autopsy Cse of Slowly Progressive Type 1 Dietes with Conomitnt Aute Myoril n Mesenteri Ishemi Yoko Mtsu 1, Atsushi Arki 2, Ysuhito Skno 3, Yuko Chi 2, Yusuke Tsuoko 4, Tkshi Nishimur 3, Tomio Ari 1 Deprtment of 1 Pthology, Division of 2 Dietes, Metolism n Enorinology, 3 Cri surgery, n 4 Criovsulr internl meiine, Tokyo Metropolitn Geritri Hospitl, 35-2 Ske-ho, Itshi-ku, Tokyo , Jpn ABSTRACT An Eighty-three-yer-ol womn ignose with slowly progressive insulin-epenent (type 1) ietes mellitus ue to high serum level of nti-glutmi i eroxylse ntioy unerwent oronry rtery ypss grfting. She h ominl pin n ie 5 ys fter the opertion. At utopsy, we foun issetion of the right oronry rtery, ute myoril ishemi t the posterior septl wll, n severe nerosis from the uoenum to the sening olon. In the pnres, severl islets showe lrge, eforme, n iminishing insulin- n glugon-positive ells. The β-ell mss ws reue. We foun infiltrtion of luster of ifferentition 8-positive lymphoytes in the inr ells n islets. Sustine nti-glutmi i eroxylse ntioy positivity in the present ptient might e ssoite with the prolonge oxitive n proinflmmtory sttes n the susequent inution of myoril n mesenteri ishemi. INTRODUCTION Slowly progressive insulin-epenent (type 1) ietes mellitus (SPIDDM) is sutype of type 1 ietes [1]. The hrteristis of SPIDDM inlue long-term positive nti-glutmi i eroxylse (GAD), nti-islet ell, nti-insulin, n/or nti-insulinom-ssoite tyrosine phosphtse-like protein-2 ntioies; similr insulin seretion to tht of type 2 ietes uring the erly stges of the isese; possiility to hieve goo ontrol of ietes mellitus (DM) y using iet therpy n orl hypoglyemi gents t the erly stge of isese onset; n the insulin seretion eventully isppers, thus requiring the ptient to reeive insulin injetions. Generlly, ptients with SPIDDM re ge etween 30 n 50 yers t ignosis. The β-ell funtion of ptients with SPIDDM is preserve for long time n slowly elines over time; in generl, insulin intervention is effetive for preventing β-ell filure in SPIDDM ptients [2, 3]. As SPIDDM ws first reporte, mny stuies hve emonstrte tht this sutype of type Reeive Mrh 01st, Aepte April 10th, 2016 Keywors Autopsy; Mesenteri Ishemi Arevitions CD luster of ifferentition; DM ietes mellitus; GAD nti-glutmi i eroxylse; NOMI nonolusive mesenteri Ishemi; SPIDDM slowly progressive insulin-epenent ietes mellitus Corresponene Yoko Mtsu Deprtment of Pthology Tokyo Metropolitn Geritri Hospitl 35-2 Ske-ho, Itshi-ku Tokyo , Jpn Phone (ext. 2413) Fx E-mil yoko_mtsu@tmghig.jp 1 ietes is prevlent in severl ifferent ethni groups, n it ws lter lso terme ltent utoimmune ietes in ults (LADA) [4]. However, some ifferenes hve een reporte etween SPIDDM n LADA in terms of geneti preispositions, inluing the humn leukoyte ntigen lss II n I genes, n the pthologil mehnisms of these iseses re still ontroversil. We report n 83-yer-ol womn with SPIDDM ompnie y onomitnt ute myoril n mesenteri ishemi. CLINICAL PRESENTATION Sujet An Eighty-three-yer-ol womn ws mitte to our hospitl euse of hest pin. She ws ignose with ietes t the ge of 48 yers n with SPIDDM t the ge of 81 yers ue to high serum levels of nti-gad ntioy (44.9 U/mL; referene vlue, <1.4 U/mL). She ws trete with insulin, ut her HA1 level ws 9.0%. She h poorly ontrolle glyemi, repetely showing oth hyperglyemi n hypoglyemi. She ws trete with ntihypertensive gents, n her loo pressure ws 129/69 mmhg. She i not show ieti retinopthy, renl filure, or neuropthy. After mission, she unerwent oronry rtery ypss grfting for triple-vessel isese euse she showe high levels of retine phosphokinse (2450 IU/L) n troponin (6.33 ng/ml) n n elevtion of ST in II, III, n V F. After the opertion, n intr-orti lloon pump ws inserte euse of poor irultion sttus. Her loo gluose level ws kept stle with insulin. Three ys 444
2 fter the opertion, she experiene ominl pin n stiffness. Aominl riogrphy i not revel mrke hnges. Therefore, ominl opertion ws performe, n nerosis of the smll intestine ws oserve. However, we i not perform smll intestine resetion. The ptient ie 5 ys fter the opertion. Pthologil Finings At utopsy, we foun severe erosion, hemorrhge, n nerosis from the uoenum to the sening olon (Figure 1, rrows). No thromus ws etete in the superior mesenteri rtery n vein (Figure 1). We lso foun issetion of the right oronry rtery, lot in the ypss grft (Figure 1), n ute myoril ishemi t the posterior septl wll (Figure 1). Arterioslerosis ws oserve in the oronry rteries, ort, n superior mesenteri rtery. We i not oserve mirongiopthy or glomerulr hnges in the kiney. Bse on these finings, we onsiere ute mesenteri n myoril ishemi s the mehnisms of eth. In the pnres, severl islets were enlrge n eforme (Figure 2, rrows n inset) with iminishment of insulin- (Figure 2, rrows n inset) n glugon-positive ells (Figure 2, rrows n inset). Suh norml islets were etete in the pnreti he n til. Most of the islets expresse insulin (Figure 2), ut the β-ell mss seeme to e reue. Furthermore, we foun infiltrtion of luster of ifferentition (CD) 8-positive lymphoytes in the trophi re of the inr ells (Figures 3, ), while no CD4-positive lymphoytes were etete. Moreover, slight infiltrtion of CD8-positive lymphoytes ws oserve in the islets (Figure 3), wheres insulitis ws not etete. The norml pnres otine from nother utopsy se i not show infiltrtion of CD8-positive ells (Figure 3). Beyon tht, hyliniztion of the islets ws oserve (Figure 3e), long with numerous pnreti intrepithelil neoplsis (gres 1 n 2) in the min n rnh pnreti uts (Figure 3f). The ptient h no other known utoimmune iseses. DISCUSSION We foun lrge norml islets with reution in not only the numer of insulin-prouing ells ut lso the glugon level s well s the size of the β-ell mss. Suh islets i not show ytologil typi; therefore, we onsiere them to e hyperplsti hnges of the islets. These finings support the notion tht ptients with SPIDDM iffer in hrteristis from ptients with type 2 n 1 DM. One previous report showe tht the β-ell mss in SPIDDM ses ws mintine s ompre with tht in type 1 DM, ut the reution in the size of the β-ell mss in the present se might e relte to the ft tht the ptient h poorly ontrolle glyemi. Furthermore, islet ntioy-positive long-term type 2 Figure 1. Non-olusive mesenteri ishemi n ute myoril ishemi. (). Nerosis of the smll intestine (rrows); r, 5 m. (). Superior mesenteri rtery; elsti vn Gieson stin; r, 500 μm. (). Bypss grft of the right oronry rtery; r, 500 μm. (). Nerosis of the myorium; r, 50 μm. 445
3 e f Figure 2. Morphologil hnges of islets in the pnres. (,, ). Hemtoxylin-n-eosin stin pttern. n. re the enlrge view of ; r, 100 μm. (). Insulin. (e.). Glugon. The rrows inite the norml islet with iminishment of insulin- n glugon-positive ells. Arrowhes inite the islet with insulin- n glugon-positive ells; r, 100 μm. (f). The size of the insulin-positive β-ell mss seeme to e reue; r, 200 μm. Insets show the high-power view. DM ptients hve een reporte to exhiit reue β-ell msses ue to immune-meite injury of the pnreti β-ells [5]. Insulitis hs een onsiere s hrteristi fining of the ute phse of type 1 DM [6], ut not SPIDDM. Aoringly, the present se h no insulitis ut h CD8- positive ell infiltrtion in the firoti lesion, without CD4- positive ell infiltrtion, suggesting ontinuous immunemeite injury of the pnres. Both thromi n hyperperfusion, whih re iffiult to istinguish, re ommonly oserve fter ri surgery. The present se ws linilly suspete to e non-olusive mesenteri ishemi (NOMI), ut we oul not onfirm the ignosis euse we i not perform ngiogrphy. DM is signifint risk ftor of intestinl ishemi. The reporte iniene of NOMI in DM ptients is 5.9% [7]. One se of SPIDDM with NOMI ws reporte in n elerly womn showing right olon involvement [8]. Insulin efiieny, inluing SPIDDM, often uses hypoglyemi n poorly ontrolle glyemi. In turn, hypoglyemi my inue vsulr ostrution vi rrhythmi, oxygen stress, enothelil ell ysfuntion, ogultion normlity, n inflmmtion [9]. Moreover, glyemi vriility hs een shown to e ssoite with greter retive oxygen speies proution n vsulr mge thn hroni hyperglyemi [10]. The sustine nti-gad ntioy positivity in the present ptient might e ssoite with the prolonge oxitive n proinflmmtory sttes, n the susequent inution of mesenteri ishemi. Further nlysis is neee to lrify the reltionship etween SPIDDM n ishemi. 446
4 e f Figure 3. Infiltrtion of luster of ifferentition 8 (CD8)-positive T ells in the pnres. (, ). CD8-positive T ells infiltrting the firosis lesion; r, 200 μm. (). CD8-positive T ells infiltrting the islet; r, 50 μm. (). Norml pnres of nother utopsy se, showing no CD8-positive T ells. (e). Hyliniztion of the islet; r, 50 μm. (f). PnIN lesion; r, 100 μm. In onlusion, we report n utopsy se of SPIDDM with ute mesenteri n myoril ishemis. CONCLUSIONS Morphologil hnges in islets, inluing enlrge islets n CD8-positive T ell infiltrtion, re thought to e pthologil hnges ue to SPIDDM. Cliniins shoul py lose ttention to the omplitions of SPIDDM. Consent Informe written onsent for the use of tissues ws otine from ereve fmily. Conflit of interests There is no onflit of interests. Referenes 1. Koyshi T, Nishi Y, Tnk S, Ai K. Pthologil hnges in the pnres of fulminnt type 1 ietes n slowly progressive insulinepenent ietes mellitus (SPIDDM): innte immunity in fulminnt type 1 ietes n SPIDDM. Dietes Met Res Rev 2011; 27: [PMID: ] 2. Koyshi T, Mruym T, Shim A, Ksug A, Kntsuk A, Tkei I, Tnk S, et l. Insulin intervention to preserve et ells in slowly progressive insulin-epenent (type 1) ietes mellitus. Ann N Y A Si 2002; 958: [PMID: ] 3. Mruym T, Tnk S, Shim A, Fune O, Ksug A, Kntsuk A, Tkei I, et l. Insulin intervention in slowly progressive insulin-epenent (type 1) ietes mellitus. J Clin Enorinol Met 2008; 93: [PMID: ] 4. Koyshi T, Tnk S, Hrii N, Ai K, Shimur H, Ohmori M, Knesige M, et l. Immunopthologil n geneti fetures in slowly progressive insulin-epenent ietes mellitus n ltent utoimmune ietes in ults. Ann N Y A Si 2006; 1079:60-6. [PMID: ] 447
5 5. Suuste A, Ginni R, Chng AM, Plunkett C, Pietropolo SL, Zhng YJ, Brins-Mithell E, et l. Islet utoimmunity ientifies unique pttern of impire pnreti et-ell funtion, mrkely reue pnreti et ell mss n insulin resistne in linilly ignose type 2 ietes. PLoS One 2014; 9:e [PMID: ] 6. Gepts W, In't Vel PA. Islet morphologi hnges. Dietes Met Rev 1987; 3: [PMID: ] 7. Prk WM, Glovizki P, Cherry KJ Jr, Hllett JW Jr, Bower TC, Pnneton JM, Shlek C, et l. Contemporry mngement of ute mesenteri ishemi: Ftors ssoite with survivl. J Vs Surg 2002; 35: [PMID: ] 8. Hr K, Ysu H, Ari T, Miyoshi S, Kuokw O, Mori H, Akiski T, et l. A se of n elerly ptient with slowly progressive type 1 ietes who evelope severe nonolusive mesenteri ishemi without preisposing events. Intern Me 2012; 51: [PMID: ] 9. Ngi T, Tomizw T, Monen T, Mori M. Dietes mellitus ompnie y nonolusive oloni ishemi. Intern Me 1998; 37: [PMID: ] 10. Sisho Y. Glyemi vriility n oxitive stress: link etween ietes n riovsulr isese? Int J Mol Si 2014; 15: [PMID: ] 448
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