{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T07:53:22Z","timestamp":1792482802071,"version":"4.5.0"},"reference-count":32,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>With prolonged life expectancy, we often encounter patients with elderly-onset type 2 diabetes mellitus (eT2DM). Although the clinical features of eT2DM are suggested to be different from those in patients with middle-age\u2013onset type 2 diabetes mellitus (mT2DM), the islet pathologic features in eT2DM have not been addressed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We attempted to characterize the pancreatic pathology in eT2DM and sought its clinical implications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Pancreata from 13 young nondiabetic (age, 20 to 29 years), 27 patients with mT2DM (age, 45 to 87 years), 22 middle-age subjects without T2DM, 15 subjects with eT2DM (age, 85 to 100 years), and 30 elderly subjects without T2DM were investigated. Together with conventional microscopic observations, morphometric analysis on the islet, islet endocrine cells, and amyloid deposition was conducted on immunostained sections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The estimated age of diabetes onset was 80.8 \u00b1 1.4 years (mean \u00b1 standard error) in the eT2DM group and that of the mT2DM group was 48.3 \u00b1 2.4 years. The pancreatic weight was nearly 50% less in the eT2DM group than in the other groups, showing duct obstruction with epithelial hyperplasia, marked acinar atrophy, fibrosis, and amyloid deposition in the islet. The islet mass was significantly reduced in the eT2DM group. The amyloid volume density correlated inversely with the \u03b2-cell volume density but not with the body mass index in the eT2DM group. Laboratory data showed mild elevation of serum amylase in the eT2DM group, although clinical signs and symptoms of pancreatitis were not apparent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>eT2DM is distinct from mT2DM and characterized by pancreas atrophy, ductal lesions, and amyloid deposition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/jc.2016-3735","type":"journal-article","created":{"date-parts":[[2017,5,12]],"date-time":"2017-05-12T14:45:27Z","timestamp":1494600327000},"page":"3162-3171","source":"Crossref","is-referenced-by-count":32,"title":["Pancreas Atrophy and Islet Amyloid Deposition in Patients With Elderly-Onset Type 2 Diabetes"],"prefix":"10.1210","volume":"102","author":[{"given":"An","family":"Xin","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Mizukami","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Inaba","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-ki","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soroku","family":"Yagihashi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2017,5,12]]},"reference":[{"key":"2020071622254893400_B1","first-page":"7","volume-title":"The Aging of Populations and Its Economic and Social Implications","author":"United Nations, The Department of Economic and Social Affairs","year":"1956"},{"issue":"6","key":"2020071622254893400_B2","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1111\/ggi.12450","article-title":"Japan as the front-runner of super-aged societies: perspectives from medicine and medical care in Japan","volume":"15","author":"Arai","year":"2015","journal-title":"Geriatr Gerontol Int"},{"issue":"6865","key":"2020071622254893400_B3","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/414782a","article-title":"Global and societal implications of the diabetes epidemic","volume":"414","author":"Zimmet","year":"2001","journal-title":"Nature"},{"issue":"12","key":"2020071622254893400_B4","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.2337\/dc12-1801","article-title":"Diabetes in older adults","volume":"35","author":"Kirkman","year":"2012","journal-title":"Diabetes Care"},{"issue":"4","key":"2020071622254893400_B5","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1177\/0145721708321022","article-title":"Hospitalization and discharge education of emergency department patients with hypoglycemia","volume":"34","author":"Ginde","year":"2008","journal-title":"Diabetes Educ"},{"issue":"11","key":"2020071622254893400_B6","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.2337\/dc06-1058","article-title":"The burden and treatment of diabetes in elderly individuals in the U.S","volume":"29","author":"Selvin","year":"2006","journal-title":"Diabetes Care"},{"issue":"1","key":"2020071622254893400_B7","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s125-002-8248-z","article-title":"Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese type II diabetic patients","volume":"45","author":"Sakuraba","year":"2002","journal-title":"Diabetologia"},{"issue":"1","key":"2020071622254893400_B8","doi-asserted-by":"crossref","first-page":"102","DOI":"10.2337\/diabetes.52.1.102","article-title":"Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes","volume":"52","author":"Butler","year":"2003","journal-title":"Diabetes"},{"issue":"7","key":"2020071622254893400_B9","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.2337\/dc13-2018","article-title":"Involvement of oxidative stress-induced DNA damage, endoplasmic reticulum stress, and autophagy deficits in the decline of \u03b2-cell mass in Japanese type 2 diabetic patients","volume":"37","author":"Mizukami","year":"2014","journal-title":"Diabetes Care"},{"key":"2020071622254893400_B10","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1463-1326.2008.00969.x","article-title":"Pancreatic beta-cell mass in European subjects with type 2 diabetes","volume":"10","author":"Rahier","year":"2008","journal-title":"Diabetes Obes Metab"},{"issue":"7","key":"2020071622254893400_B11","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1007\/s00125-011-2118-4","article-title":"Pancreatic alpha cell mass in European subjects with type 2 diabetes","volume":"54","author":"Henquin","year":"2011","journal-title":"Diabetologia"},{"issue":"5","key":"2020071622254893400_B12","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1111\/j.2040-1124.2010.00074.x","article-title":"Report of the committee on the classification and diagnostic criteria of diabetes mellitus","volume":"1","author":"Seino","year":"2010","journal-title":"J Diabetes Investig"},{"issue":"6","key":"2020071622254893400_B13","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/s001250050960","article-title":"Extra-insular beta cells associated with ductules are frequent in adult human pancreas","volume":"41","author":"Bouwens","year":"1998","journal-title":"Diabetologia"},{"issue":"4","key":"2020071622254893400_B14","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1210\/en.2009-1277","article-title":"\u03b2-Cell mass dynamics and islet cell plasticity in human type 2 diabetes","volume":"151","author":"Hanley","year":"2010","journal-title":"Endocrinology"},{"issue":"1","key":"2020071622254893400_B15","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/jdi.12118","article-title":"Age-associated changes of islet endocrine cells and the effects of body mass index in Japanese","volume":"5","author":"Mizukami","year":"2014","journal-title":"J Diabetes Investig"},{"issue":"3","key":"2020071622254893400_B16","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3109\/13506129.2014.937857","article-title":"Islet amyloid with macrophage migration correlates with augmented \u03b2-cell deficits in type 2 diabetic patients","volume":"21","author":"Kamata","year":"2014","journal-title":"Amyloid"},{"issue":"10","key":"2020071622254893400_B17","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/BF00275740","article-title":"Residual insulin positivity and pancreatic atrophy in relation to duration of chronic type 1 (insulin-dependent) diabetes mellitus and microangiopathy","volume":"30","author":"L\u00f6hr","year":"1987","journal-title":"Diabetologia"},{"issue":"1","key":"2020071622254893400_B18","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s00125-015-3752-z","article-title":"The influence of type 1 diabetes on pancreatic weight","volume":"59","author":"Campbell-Thompson","year":"2016","journal-title":"Diabetologia"},{"issue":"4","key":"2020071622254893400_B19","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/s00125-016-3867-x","article-title":"Pancreatic ductal hyperplasia\/dysplasia with obstructive chronic pancreatitis: an association with reduced pancreatic weight in type 1 diabetes","volume":"59","author":"Kobayashi","year":"2016","journal-title":"Diabetologia"},{"issue":"8","key":"2020071622254893400_B20","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1111\/j.1464-5491.1993.tb00160.x","article-title":"The size of the pancreas in diabetes mellitus","volume":"10","author":"Alzaid","year":"1993","journal-title":"Diabet Med"},{"issue":"3","key":"2020071622254893400_B21","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s005920170012","article-title":"Pancreatic volume in type 1 and type 2 diabetes mellitus","volume":"38","author":"Goda","year":"2001","journal-title":"Acta Diabetol"},{"issue":"5","key":"2020071622254893400_B22","doi-asserted-by":"crossref","first-page":"e0126825","DOI":"10.1371\/journal.pone.0126825","article-title":"Altered volume, morphology and composition of the pancreas in type 2 diabetes","volume":"10","author":"Macauley","year":"2015","journal-title":"PLoS One"},{"issue":"1","key":"2020071622254893400_B23","first-page":"200","article-title":"Increased proliferation of the pancreatic duct gland compartment in type 1 diabetes","volume":"102","author":"Moin","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2020071622254893400_B24","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/BF00427003","article-title":"The endocrine pancreas in chronic pancreatitis: immunocytochemical and ultrastructural studies","volume":"377","author":"Kl\u00f6ppel","year":"1978","journal-title":"Virchows Arch A Pathol Anat Histol"},{"issue":"1","key":"2020071622254893400_B25","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0168-8227(00)00204-7","article-title":"Histopathology and immunohistochemistry of pancreatic islets in fibrocalculous pancreatic diabetes","volume":"51","author":"Govindarajan","year":"2001","journal-title":"Diabetes Res Clin Pract"},{"issue":"6","key":"2020071622254893400_B26","doi-asserted-by":"crossref","first-page":"2632","DOI":"10.1016\/j.ajpath.2011.02.036","article-title":"\u03b2-Cell loss and \u03b2-cell apoptosis in human type 2 diabetes are related to islet amyloid deposition","volume":"178","author":"Jurgens","year":"2011","journal-title":"Am J Pathol"},{"issue":"1","key":"2020071622254893400_B27","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2337\/dc12-0421","article-title":"\u03b2-Cell mass and turnover in humans: effects of obesity and aging","volume":"36","author":"Saisho","year":"2013","journal-title":"Diabetes Care"},{"issue":"9","key":"2020071622254893400_B28","doi-asserted-by":"crossref","first-page":"3724","DOI":"10.1210\/jc.2013-1373","article-title":"Change in \u03b2-cell mass in Japanese nondiabetic obese individuals","volume":"98","author":"Kou","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"8","key":"2020071622254893400_B29","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/ca.20543","article-title":"Pancreas volumes in humans from birth to age one hundred taking into account sex, obesity, and presence of type-2 diabetes","volume":"20","author":"Saisho","year":"2007","journal-title":"Clin Anat"},{"issue":"1-2","key":"2020071622254893400_B30","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0344-0338(81)80006-4","article-title":"Lipomatosis of the pancreas: a morphometrical investigation","volume":"173","author":"Schmitz-Moormann","year":"1981","journal-title":"Pathol Res Pract"},{"issue":"1","key":"2020071622254893400_B31","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1478-7954-2-4","article-title":"Using linked data to calculate summary measures of population health: health-adjusted life expectancy of people with diabetes mellitus","volume":"2","author":"Manuel","year":"2004","journal-title":"Popul Health Metr"},{"issue":"4","key":"2020071622254893400_B32","doi-asserted-by":"crossref","first-page":"e007736","DOI":"10.1136\/bmjopen-2015-007736","article-title":"Diagnosed diabetes and premature death among middle-aged Japanese: results from a large-scale population-based cohort study in Japan (JPHC study)","volume":"5","author":"Kato","year":"2015","journal-title":"BMJ Open"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/102\/9\/3162\/19703284\/jc.2016-3735.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/102\/9\/3162\/19703284\/jc.2016-3735.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T06:43:08Z","timestamp":1594968188000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/102\/9\/3162\/3819475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,12]]},"references-count":32,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2017,9,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2016-3735","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,9,1]]},"published":{"date-parts":[[2017,5,12]]}}}