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Little is known of the interaction between diabetes and other vascular risk factors in affecting the risk of CLTI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated the association of diabetes, and its interaction with hypertension, body mass index (BMI) and smoking, with the risk of LEA due to CLTI in the population-based Singapore Chinese Health Study. Participants were interviewed at recruitment (1993\u20131998) and 656 incident LEA cases were identified via linkage with nationwide hospital database through 2017. Multivariate-adjusted Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% CIs for the associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The HR (95% CI) for LEA risk was 13.41 (11.38\u201315.79) in participants with diabetes compared to their counterparts without diabetes, and the risk increased in a stepwise manner with duration of diabetes (\n                      <jats:italic>P<\/jats:italic>\n                      for trend &lt;\u20090.0001). Hypertension and increased BMI independently increased LEA risk in those without diabetes but did not increase the risk in those with diabetes (\n                      <jats:italic>P<\/jats:italic>\n                      for interaction with diabetes \u2264\u20090.0006). Conversely, current smoking conferred a risk increment of about 40% regardless of diabetes status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although diabetes conferred more than tenfold increase in risk of LEA, hypertension and increased BMI did not further increase LEA risk among those with diabetes, suggesting a common mechanistic pathway for these risk factors. In contrast, smoking may act via an alternative pathway and thus confer additional risk regardless of diabetes status.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12933-021-01441-0","type":"journal-article","created":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T04:02:47Z","timestamp":1641614567000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Diabetes and other vascular risk factors in association with the risk of lower extremity amputation in chronic limb-threatening ischemia: a prospective cohort study"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7403-7517","authenticated-orcid":false,"given":"Ariel Fangting","family":"Ying","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8524-7912","authenticated-orcid":false,"given":"Tjun Yip","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aizhen","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tze Tec","family":"Chong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek John","family":"Hausenloy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woon-Puay","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,8]]},"reference":[{"issue":"9901","key":"1441_CR1","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1016\/S0140-6736(13)61249-0","volume":"382","author":"FG Fowkes","year":"2013","unstructured":"Fowkes FG, Rudan D, Rudan I, et al. 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