{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:18:51Z","timestamp":1791667131044,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["220283\/Z\/20\/Z"],"award-info":[{"award-number":["220283\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000273","name":"Diabetes Research and Wellness Foundation","doi-asserted-by":"publisher","award":["SCA\/01\/NCF\/22"],"award-info":[{"award-number":["SCA\/01\/NCF\/22"]}],"id":[{"id":"10.13039\/501100000273","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["NIHR303160"],"award-info":[{"award-number":["NIHR303160"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glycaemic traits are associated with poorer brain health and dementia risk. Recent advances in genetic instruments for specific glycaemic markers enable an in\u2010depth investigation of the likely nature of associations and underlying mechanisms between diabetes\u2010related mechanisms and brain health and dementia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used two\u2010sample Mendelian randomisation (MR) in the UK Biobank (UKB) (maximum\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009357\u2009883 White British, mean age 56.9\u2009years, 54% female) applying inverse\u2010variance weighted MR as our main estimator alongside MR\u2010Egger, weighted median estimator (WME) and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR\u2010PRESSO) as sensitivity tests. Instruments were 53 insulin resistance, 109 fasting glucose, 48 fasting insulin and 15 2\u2010h post\u2010load glucose genetic variants with variant\u2013outcome effects estimated adjusting for 10 PCs. We checked core MR assumptions and sought to replicate results in an independent Alzheimer's dementia genome\u2010wide association study (GWAS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In UKB, higher 2\u2010h post\u2010load glucose was associated with a 69% increased Alzheimer's dementia risk (odds ratio 1.69 [95% confidence interval 1.38\u20132.07]), though this did not replicate in an independent GWAS. Fasting insulin, fasting glucose and postprandial glucose did not influence total brain, hippocampal or white\u2010matter hyperintensity volumes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The association between elevated 2\u2010h post\u2010load glucose and increased Alzheimer's risk supports a potential role for postprandial hyperglycaemia in dementia. The lack of associations between fasting or postprandial glucose and hippocampal, total\u2010brain or white matter hyperintensity volumes suggests this risk may operate independently of gross structural atrophy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Genetically proxied postprandial hyperglycaemia contributes to increased Alzheimer's risk in mid\u2010life, warranting replication in other populations and ancestries to confirm and clarify underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70353","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T05:43:18Z","timestamp":1765604598000},"page":"1741-1749","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Disentangling the relationship between glucose, insulin and brain health: A\n     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