02985nas a2200361   4500000000100000008004100001260001700042100001300059700001600072700001500088700001500103700002200118700001800140700001900158700005000177700001300227700001500240700001400255700001700269700001300286700001400299700001400313700001600327700001500343700001800358700001500376245013900391250001500530300001200545490000700557520201300564020004602577       2012                            d  c2041695162521 aLi Qiang1 aNinomiya T.1 aFulcher G.1 aTravert F.1 ade Galan Bastiaan1 aWoodward Mark1 aZoungas Sophia1 aADVANCE Collaborative Group Writing Committee1 aMarre M.1 aPoulter N.1 aHarrap S.1 aColagiuri S.1 aHamet P.1 aHeller S.1 aCooper M.1 aChalmers J.1 aNeal Bruce1 aPatel Anushka1 aMacmahon S00aAssociation of HbA(1c) levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds  a2011/12/22  a636-6430 v553 a<p>
AIMS/HYPOTHESIS: There is conflicting evidence regarding appropriate glycaemic targets for patients with type 2 diabetes. Here, we investigate the relationship between HbA(1c) and the risks of vascular complications and death in such patients. METHODS: Eleven thousand one hundred and forty patients were randomised to intensive or standard glucose control in the Action in Diabetes and Vascular disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Glycaemic exposure was assessed as the mean of HbA(1c) measurements during follow-up and prior to the first event. Adjusted risks for each HbA(1c) decile were estimated using Cox models. Possible differences in the association between HbA(1c) and risks at different levels of HbA(1c) were explored using linear spline models. RESULTS: There was a non-linear relationship between mean HbA(1c) during follow-up and the risks of macrovascular events, microvascular events and death. Within the range of HbA(1c) studied (5.5-10.5%), there was evidence of 'thresholds', such that below HbA(1c) levels of 7.0% for macrovascular events and death, and 6.5% for microvascular events, there was no significant change in risks (all p &gt; 0.8). Above these thresholds, the risks increased significantly: every 1% higher HbA(1c) level was associated with a 38% higher risk of a macrovascular event, a 40% higher risk of a microvascular event and a 38% higher risk of death (all p &lt; 0.0001). CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes, HbA(1c) levels were associated with lower risks of macrovascular events and death down to a threshold of 7.0% and microvascular events down to a threshold of 6.5%. There was no evidence of lower risks below these levels but neither was there clear evidence of harm. TRIAL REGISTRATION: ClinicalTrial.gov NCT00145925 FUNDING: Servier and the National Health and Medical Research Council of Australia (project grant ID 211086 and programme grant IDs 358395 and 571281).
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