{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:12:45Z","timestamp":1792642365779,"version":"4.5.0"},"reference-count":72,"publisher":"American Diabetes Association","issue":"2","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,2,1]]},"abstract":"<jats:p>Alzheimer disease and type 2 diabetes are characterized by increased prevalence with aging, a genetic predisposition, and comparable pathological features in the islet and brain (amyloid derived from amyloid \u03b2 protein in the brain in Alzheimer disease and islet amyloid derived from islet amyloid polypeptide in the pancreas in type 2 diabetes). Evidence is growing to link precursors of amyloid deposition in the brain and pancreas with the pathogenesis of Alzheimer disease and type 2 diabetes, respectively. Given these similarities, we questioned whether there may be a common underlying mechanism predisposing to islet and cerebral amyloid. To address this, we first examined the prevalence of type 2 diabetes in a community-based controlled study, the Mayo Clinic Alzheimer Disease Patient Registry (ADPR), which follows patients with Alzheimer disease versus control subjects without Alzheimer disease. In addition to this clinical study, we performed a pathological study of autopsy cases from this same community to determine whether there is an increased prevalence of islet amyloid in patients with Alzheimer disease and increased prevalence of cerebral amyloid in patients with type 2 diabetes. Patients who were enrolled in the ADPR (Alzheimer disease n = 100, non-Alzheimer disease control subjects n = 138) were classified according to fasting glucose concentration (FPG) as nondiabetic (FPG &amp;lt;110 mg\/dl), impaired fasting glucose (IFG, FPG 110\u2013125 mg\/dl), and type 2 diabetes (FPG &amp;gt;126 mg\/dl). The mean slope of FPG over 10 years in each case was also compared between Alzheimer disease and non-Alzheimer disease control subjects. Pancreas and brain were examined from autopsy specimens obtained from 105 humans (first, 28 cases of Alzheimer disease disease vs. 21 non-Alzheimer disease control subjects and, second, 35 subjects with type 2 diabetes vs. 21 non-type 2 diabetes control subjects) for the presence of islet and brain amyloid. Both type 2 diabetes (35% vs. 18%; P &amp;lt; 0.05) and IFG (46% vs. 24%; P &amp;lt; 0.01) were more prevalent in Alzheimer disease versus non-Alzheimer disease control subjects, so 81% of cases of Alzheimer disease had either type 2 diabetes or IFG. The slope of increase of FPG with age over 10 years was also greater in Alzheimer disease than non-Alzheimer disease control subjects (P &amp;lt; 0.01). Islet amyloid was more frequent (P &amp;lt; 0.05) and extensive (P &amp;lt; 0.05) in patients with Alzheimer disease than in non-Alzheimer disease control subjects. However, diffuse and neuritic plaques were not more common in type 2 diabetes than in control subjects. In cases of type 2 diabetes when they were present, the duration of type 2 diabetes correlated with the density of diffuse (P &amp;lt; 0.001) and neuritic plaques (P &amp;lt; 0.01). In this community cohort from southeast Minnesota, type 2 diabetes and IFG are more common in patients with Alzheimer disease than in control subjects, as is the pathological hallmark of type 2 diabetes, islet amyloid. However, there was no increase in brain plaque formation in cases of type 2 diabetes, although when it was present, it correlated in extent with duration of diabetes. These data support the hypothesis that patients with Alzheimer disease are more vulnerable to type 2 diabetes and the possibility of linkage between the processes responsible for loss of brain cells and \u03b2-cells in these diseases.<\/jats:p>","DOI":"10.2337\/diabetes.53.2.474","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"474-481","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":826,"title":["Increased Risk of Type 2 Diabetes in Alzheimer Disease"],"prefix":"10.2337","volume":"53","author":[{"given":"Juliette","family":"Janson","sequence":"first","affiliation":[{"name":"Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota"},{"name":"Department of Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Laedtke","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E.","family":"Parisi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald C.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Neurology and Health Sciences Research, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Butler","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031207294071400_R1","doi-asserted-by":"crossref","unstructured":"Westermark P, Wilander E: The influence of amyloid deposits on the islet volume in maturity onset diabetes mellitus. Diabetologia\u200815:417\u2013421,1978","DOI":"10.1007\/BF01219652"},{"key":"2022031207294071400_R2","unstructured":"Clark A, Wells CA, Buley ID, Cruickshank JK, Vanhegan RI, Matthews DR, Cooper GJ, Holman RR, Turner RC: Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes. Diabetes Res\u20089:151\u2013159,1988"},{"key":"2022031207294071400_R3","doi-asserted-by":"crossref","unstructured":"Cooper GJ, Willis AC, Clark A, Turner RC, Sim RB, Reid KB: Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients. Proc Natl Acad Sci U S A\u200884:8628\u20138632,1987","DOI":"10.1073\/pnas.84.23.8628"},{"key":"2022031207294071400_R4","doi-asserted-by":"crossref","unstructured":"Westermark P, Wernstedt C, Wilander E, Hayden DW, O\u2019Brien TD, Johnson KH: Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells. Proc Natl Acad Sci U S A\u200884:3881\u20133885,1987","DOI":"10.1073\/pnas.84.11.3881"},{"key":"2022031207294071400_R5","unstructured":"Johnson KH, O\u2019Brien TD, Hayden DW, Jordan K, Ghobrial HK, Mahoney WC, Westermark P: Immunolocalization of islet amyloid polypeptide (IAPP) in pancreatic beta cells by means of peroxidase-antiperoxidase (PAP) and protein A-gold techniques. Am J Pathol\u2008130:1\u20138,1988"},{"key":"2022031207294071400_R6","doi-asserted-by":"crossref","unstructured":"Braak H, Braak E: The human entorhinal cortex: normal morphology and lamina-specific pathology in various diseases. Neurosci Res\u200815:6\u201331,1992","DOI":"10.1016\/0168-0102(92)90014-4"},{"key":"2022031207294071400_R7","doi-asserted-by":"crossref","unstructured":"Glenner GG, Wong CW: Alzheimer disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun\u2008120:885\u2013890,1984","DOI":"10.1016\/S0006-291X(84)80190-4"},{"key":"2022031207294071400_R8","doi-asserted-by":"crossref","unstructured":"Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K: Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A\u200882:4245\u20134249,1985","DOI":"10.1073\/pnas.82.12.4245"},{"key":"2022031207294071400_R9","doi-asserted-by":"crossref","unstructured":"Masters CL, Multhaup G, Simms G, Pottgiesser J, Martins RN, Beyreuther K: Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J\u20084:2757\u20132763,1985","DOI":"10.1002\/j.1460-2075.1985.tb04000.x"},{"key":"2022031207294071400_R10","doi-asserted-by":"crossref","unstructured":"Bahmanyar S, Higgins GA, Goldgaber D, Lewis DA, Morrison JH, Wilson MC, Shankar SK, Gajdusek DC: Localization of amyloid beta protein messenger RNA in brains from patients with Alzheimer disease. Science\u2008237:77\u201380,1987","DOI":"10.1126\/science.3299701"},{"key":"2022031207294071400_R11","doi-asserted-by":"crossref","unstructured":"Goedert M: Neuronal localization of amyloid beta protein precursor mRNA in normal human brain and in Alzheimer disease. EMBO J\u20086:3627\u20133632,1987","DOI":"10.1002\/j.1460-2075.1987.tb02694.x"},{"key":"2022031207294071400_R12","doi-asserted-by":"crossref","unstructured":"Card JP, Meade RP, Davis LG: Immunocytochemical localization of the precursor protein for beta-amyloid in the rat central nervous system. Neuron\u20081:835\u2013846,1988","DOI":"10.1016\/0896-6273(88)90131-6"},{"key":"2022031207294071400_R13","doi-asserted-by":"crossref","unstructured":"Shivers BD, Hilbich C, Multhaup G, Salbaum M, Beyreuther K, Seeburg PH: Alzheimer disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell contact. EMBO J\u20087:1365\u20131370,1988","DOI":"10.1002\/j.1460-2075.1988.tb02952.x"},{"key":"2022031207294071400_R14","doi-asserted-by":"crossref","unstructured":"Van Broeckhoven C, Genthe AM, Vandenberghe A, Horsthemke B, Backhovens H, Raeymaekers P, Van Hul W, Wehnert A, Gheuens J, Cras P, et al: Failure of familial Alzheimer disease to segregate with the A4-amyloid gene in several European families. Nature\u2008329:153\u2013155,1987","DOI":"10.1038\/329153a0"},{"key":"2022031207294071400_R15","doi-asserted-by":"crossref","unstructured":"Tanzi RE, St George-Hyslop PH, Haines JL, Polinsky RJ, Nee L, Foncin JF, Neve RL, McClatchey AI, Conneally PM, Gusella JF: The genetic defect in familial Alzheimer disease is not tightly linked to the amyloid beta-protein gene. Nature\u2008329:156\u2013157,1987","DOI":"10.1038\/329156a0"},{"key":"2022031207294071400_R16","doi-asserted-by":"crossref","unstructured":"St George-Hyslop PH, Haines JL, Farrer LA, Polinsky R, Van Broeckhoven C, Goate A, McLachlan DR, Orr H, Bruni AC, Sorbi S, et al: Genetic linkage studies suggest that Alzheimer disease is not a single homogeneous disorder: FAD Collaborative Study Group. Nature\u2008347:194\u2013197,1990","DOI":"10.1038\/347194a0"},{"key":"2022031207294071400_R17","doi-asserted-by":"crossref","unstructured":"Wilson PW, Anderson KM, Kannel WB: Epidemiology of diabetes mellitus in the elderly: the Framingham Study. Am J Med\u200880(5A):3\u20139,1986","DOI":"10.1016\/0002-9343(86)90532-2"},{"key":"2022031207294071400_R18","doi-asserted-by":"crossref","unstructured":"Barnett AH, Eff C, Leslie RD, Pyke DA: Diabetes in identical twins: a study of 200 pairs. Diabetologia\u200820:87\u201393,1981","DOI":"10.1007\/BF00262007"},{"key":"2022031207294071400_R19","doi-asserted-by":"crossref","unstructured":"Newman B, Selby JV, King MC, Slemenda C, Fabsitz R, Friedman GD: Concordance for type 2 (non-insulin-dependent) diabetes mellitus in male twins. Diabetologia\u200830:763\u2013768,1987","DOI":"10.1007\/BF00275741"},{"key":"2022031207294071400_R20","doi-asserted-by":"crossref","unstructured":"Hilbich C, Kisters-Woike B, Reed J, Masters CL, Beyreuther K: Aggregation and secondary structure of synthetic amyloid beta A4 peptides of Alzheimer disease. J Mol Biol\u2008218:149\u2013163,1991","DOI":"10.1016\/0022-2836(91)90881-6"},{"key":"2022031207294071400_R21","doi-asserted-by":"crossref","unstructured":"Glenner GG, Eanes ED, Wiley CA: Amyloid fibrils formed from a segment of the pancreatic islet amyloid protein. Biochem Biophys Res Commun\u2008155:608\u2013614,1988","DOI":"10.1016\/S0006-291X(88)80538-2"},{"key":"2022031207294071400_R22","doi-asserted-by":"crossref","unstructured":"Lorenzo A, Razzaboni B, Weir GC, Yankner BA: Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus. Nature\u2008368:756\u2013760,1994","DOI":"10.1038\/368756a0"},{"key":"2022031207294071400_R23","doi-asserted-by":"crossref","unstructured":"Schubert D, Behl C, Lesley R, Brack A, Dargusch R, Sagara Y, Kimura H: Amyloid peptides are toxic via a common oxidative mechanism. Proc Natl Acad Sci U S A\u200892:1989\u20131993,1995","DOI":"10.1073\/pnas.92.6.1989"},{"key":"2022031207294071400_R24","unstructured":"O\u2019Brien TD, Butler PC, Kreutter DK, Kane LA, Eberhardt NL: Human islet amyloid polypeptide expression in COS-1 cells: a model of intracellular amyloidogenesis. Am J Pathol\u2008147:609\u2013616,1995"},{"key":"2022031207294071400_R25","doi-asserted-by":"crossref","unstructured":"Janson J, Ashley RH, Harrison D, McIntyre S, Butler PC: The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particles. Diabetes\u200848:491\u2013498,1999","DOI":"10.2337\/diabetes.48.3.491"},{"key":"2022031207294071400_R26","doi-asserted-by":"crossref","unstructured":"Mirzabekov TA, Lin MC, Kagan BL: Pore formation by the cytotoxic islet amyloid peptide amylin. J Biol Chem\u2008271:1988\u20131992,1996","DOI":"10.1074\/jbc.271.4.1988"},{"key":"2022031207294071400_R27","doi-asserted-by":"crossref","unstructured":"Lashuel HA, Hartley D, Petre BM, Waltz T, Lansbury PT: Neurodegenerative disease: amyloid pores from pathogenic mutations. Nature\u2008418:291,2002","DOI":"10.1038\/418291a"},{"key":"2022031207294071400_R28","doi-asserted-by":"crossref","unstructured":"Couce M, Kane LA, O\u2019Brien TD, Charlesworth J, Soeller W, McNeish J, Kreutter D, Roche P, Butler PC: Treatment with growth hormone and dexamethasone in mice transgenic for human islet amyloid polypeptide causes islet amyloidosis and \u03b2-cell dysfunction. Diabetes\u200845:1094\u20131101,1996","DOI":"10.2337\/diab.45.8.1094"},{"key":"2022031207294071400_R29","doi-asserted-by":"crossref","unstructured":"O\u2019Brien TD, Butler AE, Roche PC, Johnson KH, Butler PC: Islet amyloid polypeptide in human insulinomas: evidence for intracellular amyloidogenesis. Diabetes\u200843:329\u2013336,1994","DOI":"10.2337\/diabetes.43.2.329"},{"key":"2022031207294071400_R30","doi-asserted-by":"crossref","unstructured":"Craig EA, Weissman JS, Horwich AL: Heat shock proteins and molecular chaperones: mediators of protein conformation and turnover in the cell. Cell\u200878:365\u2013372,1994","DOI":"10.1016\/0092-8674(94)90416-2"},{"key":"2022031207294071400_R31","doi-asserted-by":"crossref","unstructured":"Butler PC, Eberhardt NL, O\u2019Brien TD. Islet amyloid polypeptide (IAPP) and insulin secretion. In Molecular Biology of Diabetes. Draznin B, LeRoith D, Eds. Totowa, NJ, Humana Press,1994, p.381\u2013398","DOI":"10.1007\/978-1-4612-0241-7_16"},{"key":"2022031207294071400_R32","doi-asserted-by":"crossref","unstructured":"Schwartz P: Senile cerebral, pancreatic insular and cardiac amyloidosis. Trans N Y Acad Sci\u200827:393\u2013413,1965","DOI":"10.1111\/j.2164-0947.1965.tb02977.x"},{"key":"2022031207294071400_R33","doi-asserted-by":"crossref","unstructured":"Petersen RC, Kokmen E, Tangalos E, Ivnik RJ, Kurland LT: Mayo Clinic Alzheimer disease patient registry. Aging\u20082:408\u2013415,1990","DOI":"10.1007\/BF03323961"},{"key":"2022031207294071400_R34","doi-asserted-by":"crossref","unstructured":"Gearing M, Mirra SS, Hedreen JC, Sumi SM, Hansen LA, Heyman A: The Consortium to Establish a Registry for Alzheimer Disease (CERAD): Part X. Neuropathology confirmation of the clinical diagnosis of Alzheimer disease. Neurology\u200845:461\u2013466,1995","DOI":"10.1212\/WNL.45.3.461"},{"key":"2022031207294071400_R35","doi-asserted-by":"crossref","unstructured":"Betsholtz C, Christmansson L, Engstrom U, Rorsman F, Svensson V, Johnson KH, Westermark P: Sequence divergence in a specific region of islet amyloid polypeptide (IAPP) explains differences in islet amyloid formation between species. FEBS Lett\u2008251:261\u2013264,1989","DOI":"10.1016\/0014-5793(89)81467-X"},{"key":"2022031207294071400_R36","doi-asserted-by":"crossref","unstructured":"Westermark P, Engstrom U, Johnson KH, Westermark GT, Betsholtz C: Islet amyloid polypeptide: pinpointing amino acid residues linked to amyloid fibril formation. Proc Natl Acad Sci U S A\u200887:5036\u20135040,1990","DOI":"10.1073\/pnas.87.13.5036"},{"key":"2022031207294071400_R37","doi-asserted-by":"crossref","unstructured":"Zhang S, Liu J, Saafi EL, Cooper GJ: Induction of apoptosis by human amylin in RINm5F islet beta-cells is associated with enhanced expression of p53 and p21WAF1\/CIP1. FEBS Lett\u2008455:315\u2013320,1999","DOI":"10.1016\/S0014-5793(99)00894-7"},{"key":"2022031207294071400_R38","doi-asserted-by":"crossref","unstructured":"Zhang S, Liu J, MacGibbon G, Dragunow M, Cooper GJ: Increased expression and activation of c-Jun contributes to human amylin-induced apoptosis in pancreatic islet beta-cells. J Mol Biol\u2008324:271\u2013285,2002","DOI":"10.1016\/S0022-2836(02)01044-6"},{"key":"2022031207294071400_R39","doi-asserted-by":"crossref","unstructured":"Bai JZ, Saafi EL, Shang S, Cooper GJ: Role of Ca2+ in apoptosis evoked by human amylin in pancreatic islet beta-cells. Biochem J\u2008343:53\u201361,1999","DOI":"10.1042\/bj3430053"},{"key":"2022031207294071400_R40","doi-asserted-by":"crossref","unstructured":"Tucker HM, Rydel RE, Wright S, Estus S: Human amylin induces \u201capoptotic\u201d pattern of gene expression concomitant with cortical neuronal apoptosis. J Neurochem\u200871:506\u2013516,1998","DOI":"10.1046\/j.1471-4159.1998.71020506.x"},{"key":"2022031207294071400_R41","doi-asserted-by":"crossref","unstructured":"Laczko I, Holly S, Konya Z, Soos K, Varga J, Hollosi M, Penke B: Conformational mapping of amyloid peptides from the putative neurotoxic 25\u201335 region. Biochem Biophys Res Commun\u2008205:120\u2013126,1994","DOI":"10.1006\/bbrc.1994.2638"},{"key":"2022031207294071400_R42","doi-asserted-by":"crossref","unstructured":"Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Glabe CG: Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science\u2008300:486\u2013489,2003","DOI":"10.1126\/science.1079469"},{"key":"2022031207294071400_R43","doi-asserted-by":"crossref","unstructured":"Blake MJ, Edelsman R, Feulner GJ, Nortone DD, Holbrook NJ: Stress-induced heat shock protein 70 expression in adrenal cortex: an adrenocorticotropic hormone-sensitive, age-dependent response. Proc Natl Acad Sci U S A\u200888:9873\u20139877,1991","DOI":"10.1073\/pnas.88.21.9873"},{"key":"2022031207294071400_R44","doi-asserted-by":"crossref","unstructured":"Finch CE, Cohen DM: Aging, metabolism, and Alzheimer disease: review and hypothesis. Exp Neurol\u2008143:82\u2013102,1997","DOI":"10.1006\/exnr.1996.6339"},{"key":"2022031207294071400_R45","doi-asserted-by":"crossref","unstructured":"Yan SD, Stern D, Schmidt AM: What\u2019s the rage? The receptor for advanced glycation and end products (RAGE) and the dark side of glucose. Eur J Clin Invest\u200827:179\u2013181,1997","DOI":"10.1046\/j.1365-2362.1996.00072.x"},{"key":"2022031207294071400_R46","doi-asserted-by":"crossref","unstructured":"Sasaki N, Toki S, Chowei H, Saito T, Nakao N, Hayashi Y, Takeuchi M, Makita Z: Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer disease. Brain Res\u2008888:256\u2013262,2001","DOI":"10.1016\/S0006-8993(00)03075-4"},{"key":"2022031207294071400_R47","doi-asserted-by":"crossref","unstructured":"Heitner J, Dickson D: Diabetics do not have increased Alzheimer-type pathology with age-matched control subjects: a retrospective postmortem immunocytochemical and histofluorescent study. Neurology\u200849:1306\u20131311,1997","DOI":"10.1212\/WNL.49.5.1306"},{"key":"2022031207294071400_R48","doi-asserted-by":"crossref","unstructured":"Curb JD, Rodriguez BL, Abbott RD, Petrovitch H, Ross GW, Masaki KH, Foley D, Blanchette PL, Harris T, Chen R, White LR: Longitudinal association of vascular and Alzheimer dementias, diabetes, and glucose tolerance. Neurology\u200852:971\u2013975,1999","DOI":"10.1212\/WNL.52.5.971"},{"key":"2022031207294071400_R49","doi-asserted-by":"crossref","unstructured":"MacKight C, Rockwood K, Awalt E, McDowell I: Diabetes mellitus and the risk of dementia, Alzheimer disease and vascular cognitive impairment in the Canadian study of health and aging. Dement Geriatr Cogn Disord\u200814:77\u201383,2002","DOI":"10.1159\/000064928"},{"key":"2022031207294071400_R50","doi-asserted-by":"crossref","unstructured":"Isomaa B, Almgren P, Tuomi T, Forse\u0301n B, Lahti K, Nisse\u0301n M, Taskinen M-R, Groop L: Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care\u200824:683\u2013689,2001","DOI":"10.2337\/diacare.24.4.683"},{"key":"2022031207294071400_R51","doi-asserted-by":"crossref","unstructured":"Sasaki N, Fukatsu R, Tsuzuki K, Hayashi Y, Yoshida T, Fujii N, Koike T, Wakayama I, Yanagihara R, Garruto R, Amano N, Makita Z: Advanced glycation end products in Alzheimer disease and other neurodegenerative diseases. Am J Pathol\u2008153:1149\u20131155,1998","DOI":"10.1016\/S0002-9440(10)65659-3"},{"key":"2022031207294071400_R52","doi-asserted-by":"crossref","unstructured":"Mast H, Thompson JL, Lee SH, Mohr JP, Sacco RL: Hypertension and diabetes mellitus as determinants of multiple lacunar infarcts. Stroke\u200826:30\u201333,1995","DOI":"10.1161\/01.STR.26.1.30"},{"key":"2022031207294071400_R53","doi-asserted-by":"crossref","unstructured":"Tatemichi TK, Desmond DW, Paik M, Figueroa M, Gropen TI, Stern Y, Sano M, Remien R, Williams JB, Mohr JP, et al.: Clinical determinants of dementia related to stroke. Ann Neurol\u200833:568\u2013575,1993","DOI":"10.1002\/ana.410330603"},{"key":"2022031207294071400_R54","doi-asserted-by":"crossref","unstructured":"Desmond DW, Tatemichi TK, Paik M, Stern Y: Risk factors for cerebrovascular disease as correlates of cognitive function in a stroke-free cohort. Arch Neurol\u200850:162\u2013166,1993","DOI":"10.1001\/archneur.1993.00540020040015"},{"key":"2022031207294071400_R55","doi-asserted-by":"crossref","unstructured":"McCall AL: The impact of diabetes on the NCS. Diabetes\u200841:557\u2013570,1992","DOI":"10.2337\/diabetes.41.5.557"},{"key":"2022031207294071400_R56","doi-asserted-by":"crossref","unstructured":"Biessels GJ, Kappelle AC, Bravenboer B, Erkelens DW, Gibsen WH: Cerebral function in diabetes mellitus. Diabetologia\u200837:643\u2013650,1994","DOI":"10.1007\/BF00417687"},{"key":"2022031207294071400_R57","doi-asserted-by":"crossref","unstructured":"Langen SJ, Deary IJ, Hepburn DA, Frier BM: Cumulative cognitive impairment following recurrent severe hypoglycaemia in adult patients with insulin-treated diabetes mellitus. Diabetologia\u200834:337\u2013344,1991","DOI":"10.1007\/BF00405006"},{"key":"2022031207294071400_R58","doi-asserted-by":"crossref","unstructured":"Ott A, Stolk RP, van Harskamp F, Pols H, Hofman A, Breteler M: Diabetes mellitus and the risk of dementia: the Rotterdam study. Neurology\u200853:1937\u20131942,1999","DOI":"10.1212\/WNL.53.9.1937"},{"key":"2022031207294071400_R59","doi-asserted-by":"crossref","unstructured":"Leibson CL, Rocca WA, Hanson VA, Cha R, Kokmen E, O\u2019Brien PC, Palumbo PJ: The risk of dementia among persons with diabetes mellitus: a population based cohort study. Am J Epidemiol\u2008145:301\u2013308,1997","DOI":"10.1093\/oxfordjournals.aje.a009106"},{"key":"2022031207294071400_R60","doi-asserted-by":"crossref","unstructured":"Luchsinger JA, Tang M-X, Yaakov S, Shea S, Mayeux R: Diabetes mellitus and risk of Alzheimer disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol\u2008154:635\u2013641,2001","DOI":"10.1093\/aje\/154.7.635"},{"key":"2022031207294071400_R61","doi-asserted-by":"crossref","unstructured":"Bucht G, Adolfsson R, Lithner F, Winblad B: Changes in blood glucose and insulin secretion in patients with senile dementia of Alzheimer type. Acta Med Scand\u2008213:387\u2013392,1983","DOI":"10.1111\/j.0954-6820.1983.tb03756.x"},{"key":"2022031207294071400_R62","doi-asserted-by":"crossref","unstructured":"Wolf-Klein GP, Silversone FA, Brod MS, Levy A, Foley CJ, Termotto V, Breuer J: Are Alzheimer patients healthier?J Am Geriatr Soc\u200836:219\u2013224,1988","DOI":"10.1111\/j.1532-5415.1988.tb01804.x"},{"key":"2022031207294071400_R63","doi-asserted-by":"crossref","unstructured":"Ferini-Strambi L, Smirne S, Garanchini P, Pinto P, Franceschi M: Clinical and epidemiological aspects of Alzheimer disease with presenile onset: a case control study. Neuroepidemiology\u20089:39\u201349,1990","DOI":"10.1159\/000110750"},{"key":"2022031207294071400_R64","doi-asserted-by":"crossref","unstructured":"Landin K, Blennow K, Wallin A, Gottfries C-G: Low blood pressure and blood glucose levels in Alzheimer disease: evidence for a hypometabolic disorder?J Intern Med\u2008233:357\u2013363,1993","DOI":"10.1111\/j.1365-2796.1993.tb00684.x"},{"key":"2022031207294071400_R65","doi-asserted-by":"crossref","unstructured":"Mortel KF, Wood S, Pavol MA, Meyer JS, Rexer JL: Analysis of familial and individual risk factors among patients with ischemic vascular dementia and Alzheimer disease. Angiology\u200844:599\u2013605,1993","DOI":"10.1177\/000331979304400802"},{"key":"2022031207294071400_R66","doi-asserted-by":"crossref","unstructured":"Neilson KA, Nolan JH, Berchtold NC, Sandman CA, Mulnard RA, Cotman CW: Apolipoprotein-E genotyping of diabetic dementia patients: is diabetes rare in Alzheimer disease?J Am Geriatr Soc\u200844:1\u20138,1996","DOI":"10.1111\/j.1532-5415.1996.tb01857.x"},{"key":"2022031207294071400_R67","doi-asserted-by":"crossref","unstructured":"Heyman A, Wilkinson WE, Stafford JA, Helms MJ, Sigmon AH, Weinberg T: Alzheimer disease: a study of epidemiological aspects. Ann Neurol\u200815:335\u2013341,1984","DOI":"10.1002\/ana.410150406"},{"key":"2022031207294071400_R68","doi-asserted-by":"crossref","unstructured":"Broe GA, Henderson AS, Creasey H, McCusker E, Korten AE, Jorm AF, Longley W, Anthony JC: A case controlled study of Alzheimer disease in Australia. Neurology\u200840:1698\u20131707,1990","DOI":"10.1212\/WNL.40.11.1698"},{"key":"2022031207294071400_R69","doi-asserted-by":"crossref","unstructured":"Kokmen E, Beard CM, Chandra V, Offord KP, Schoenberg BS, Ballard DJ: Clinical risk factors for Alzheimer disease: a population based case-control study. Neurology\u200841:1393\u20131397,1991","DOI":"10.1212\/WNL.41.9.1393"},{"key":"2022031207294071400_R70","doi-asserted-by":"crossref","unstructured":"Thorpe J, Widman LP, Wallin A, Beiswanger J, Blumenthal HT: Comorbidity of other chronic age-dependent diseases in dementia. Aging Clin Exp Res\u20086:159\u2013166,1994","DOI":"10.1007\/BF03324233"},{"key":"2022031207294071400_R71","doi-asserted-by":"crossref","unstructured":"Curb JD, Roderiquez BL, Petrovich H, Masaki KH, Burchfiel CM, Ross W, Chen R, Harris T, White LR: The relationship of diabetes and glucose tolerance to Alzheimer disease and vascular dementia (Abstract 488). Neurobiol Aging\u200817 (Suppl.):S122,1996","DOI":"10.1016\/S0197-4580(96)80490-8"},{"key":"2022031207294071400_R72","doi-asserted-by":"crossref","unstructured":"The expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care\u200820:1183\u20131197,1997","DOI":"10.2337\/diacare.20.7.1183"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/53\/2\/474\/374615\/474.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/53\/2\/474\/374615\/474.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:20:54Z","timestamp":1667406054000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/53\/2\/474\/11453\/Increased-Risk-of-Type-2-Diabetes-in-Alzheimer"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,2,1]]},"references-count":72,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2004,2,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diabetes.53.2.474","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,2,1]]}}}