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We examined cancer risk across groups of individuals classified according to their time-weighted mean HbA\n                      <jats:sub>1c<\/jats:sub>\n                      over the entire follow-up period (\n                      <jats:italic>n<\/jats:italic>\n                      =49,978) or during specific early exposure periods (\n                      <jats:italic>n<\/jats:italic>\n                      =39,185). A weighted cumulative exposure model was used to determine the role of historical HbA\n                      <jats:sub>1c<\/jats:sub>\n                      exposures in cancer development (\n                      <jats:italic>n<\/jats:italic>\n                      =49,966).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 49,978 individuals with newly diagnosed type 2 diabetes, 1758 cancer events occurred. Each 11 mmol\/mol (1%) increase in time-weighted mean HbA\n                      <jats:sub>1c<\/jats:sub>\n                      was associated with a 27% relative higher risk of cancer at any site (HR 1.27; 95% CI 1.20, 1.33). Within the first 2 years after diagnosis, a time-weighted mean HbA\n                      <jats:sub>1c<\/jats:sub>\n                      \u226553 mmol\/mol (\u22657.0%) vs &lt;53 mmol\/mol (&lt;7.0%) was associated with a 30\u201375% relative higher risk of cancer at any site, depending on the specific HbA\n                      <jats:sub>1c<\/jats:sub>\n                      category, even after adjusting for subsequent HbA\n                      <jats:sub>1c<\/jats:sub>\n                      . Longer durations of early exposure were associated with higher risk, reaching 51\u2013213% in the first 5 years of exposure. Earlier high HbA\n                      <jats:sub>1c<\/jats:sub>\n                      exposures contributed more strongly to cancer risk than later exposures. A 11 mmol\/mol (1%) HbA\n                      <jats:sub>1c<\/jats:sub>\n                      reduction at 1\u20132 years was associated with a 6% relative lower cancer risk over a hypothetical 10\u00a0year window (HR 0.94; 95% CI 0.91, 0.98), whereas reductions after 5 years showed no significant risk differences.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>Overall, hyperglycaemic exposure was associated with an elevated long-term cancer risk in type 2 diabetes. Notably, individuals who showed better glycaemic management soon after diagnosis exhibited a lower cancer risk than those whose glycaemic management improved later, despite comparable overall glycaemic burdens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-026-06758-7","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T12:24:40Z","timestamp":1780662280000},"page":"2512-2522","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Early glycaemic exposure and cancer risk in people with newly diagnosed type 2 diabetes"],"prefix":"10.1007","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8529-7725","authenticated-orcid":false,"given":"Xinge","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2968-1762","authenticated-orcid":false,"given":"Aimin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2193-1114","authenticated-orcid":false,"given":"Hongjiang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1581-5643","authenticated-orcid":false,"given":"Eric S. 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Due to local regulations, the data are not available to the public. Requests for data access may be submitted via the Hong Kong Hospital Authority data-sharing portal, and will be considered on a case-by-case basis for research purposes, subject to institutional approval and relevant ethical and regulatory requirements. Data will be made available only to eligible researchers through the Hospital Authority\u2019s formal application mechanism and may be subject to restrictions on use. Further information is available at\n                      \n                      .","order":2,"name":"Ethics","label":"Data availability","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. RCWM acknowledges partial support from the Research Grants Council Area of Excellence Scheme (AoE\/M-401\/24-R).","order":3,"name":"Ethics","label":"Funding","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"AOYL has served as a member of advisory panels for Amgen, AstraZeneca, Boehringer Ingelheim and Sanofi, and has received research support from Amgen, the Asia Diabetes Foundation, Bayer, Boehringer Ingelheim, Lee\u2019s Pharmaceutical, MSD, Novo Nordisk, Roche, Sanofi, Sugardown Ltd and Takeda, outside the submitted work. APSK has received research grants and\/or speaker honoraria from Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Merck Serono, Nestle, Novo Nordisk, Pfizer and Sanofi, outside the submitted work. JCNC has received grants from Astra Zeneca, Lilly, Hua Medicine and Lee Powder, and grants and personal fees from Bayer, MSD, Merck and Sanofi, acts as the CEO of the Asia Diabetes Foundation and is a founding director of GemVCare, outside the submitted work. In addition, she has obtained a patent on genetic markers for diabetic kidney disease. RCWM is a member of the editorial board of\n                      Diabetologia\n                      , and has received grants from AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk and Roche Diagnostics (HK) Limited, and speaker honoraria or consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Medtronic, Merck, Novo Nordisk and Roche Diagnostics. All speaker honoraria or consultancy fees have been donated to support diabetes research. RCWM also reports support from the Hong Kong Government Innovation and Technology Commission and its Technology Start-Up Support Scheme for Universities (TSSSU), as co-founder of the technology start-up GemVCare, which provides genetic testing for diabetes and diabetes complications, outside the submitted work. The remaining authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","label":"Author relationships and activities","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"XZ contributed to conception of the article, statistical analysis and interpretation of results, drafted the manuscript, revised the manuscript critically and approved the final version. AOYL and RCWM contributed to conception of the article and interpretation of results, revised the manuscript critically and approved the final version. AY, HW, ESHL, MS and BF contributed to conception of the article and interpretation of results, revised the manuscript critically and approved the final version. EC, APSK and JCNC contributed to conception of the article, revised the manuscript critically and approved the final version. AOYL is the guarantor of this work, has full access to all the data in the study, and takes responsibility for the integrity of the data and the accuracy of the data analysis.","order":5,"name":"Ethics","label":"Contribution statement","group":{"name":"EthicsHeading","label":"Ethics"}}]}}