BA1c increased the risk of all-cause mortality in a large cohort of patients routinely treated in UK primary care. Their primary analysis did not allow for changes in HbA1c over time and instead used the mean 1317923 1480666 of all HbA1c ML240 manufacturer values subsequent to the index date. Although further time dependent analysis were carried out using yearly mean HbA1c, missing data was dealt with using last observation carried forward which can result in bias. This is a potentially important limitation, as Currie et al. [12] did not report on the completeness of HbA1c records and these may not have been routinely recorded during the period they examined (1986 to 2008). Riveline et al. [13] also noted that Currie et al.’s population may have had substantial heterogeneity since the UKPDS trial has led to significant changes in the management of Type 2 diabetes (i.e. risk modeling, health economics). In addition, existing treatment targets for HbA1C set by the NICE (HbA1C,7 ) (2008) or the American Diabetes Association (HbA1C,7 ) (2008) are not age 548-04-9 site specific and Pani et al. [14]HbA1c Values and Mortality Riskunderlined the importance of establishing whether age-specific treatment criteria would be appropriate. This study aimed to evaluate short-term associations between HbA1c values recorded in clinical practice in primary care and subsequent risk of mortality in a post-UKPDS population. A case control study was implemented to establish an explicit temporal link between HbA1c values recorded in the previous 365 days and mortality risk, rather than utilizing HbA1c records that might cover a considerable length of time, as has been done previously [12]. We aimed to determine whether the risk of mortality was higher when the most recent HbA1c value in the preceding 365 days was either ,6.5 or .9.0 compared to HbA1c values that were between 6.5 and 9 . Considering the scarce evidence for a possible age-depended influence of HbA1C levels on mortality [14], an additional aim of the present study was to explore potential age-associated differences in mortality rates for both low and high HbA1C levels.statistical power by including more than one control per case [18]. Each control was assigned the index date of their matched case.MeasuresTo evaluate both recent HbA1c and recent change in HbA1c the latest two values in the 365 days preceding the index date were identified. HbA1c values below 2.5 or over 25 were discarded as these values were considered implausible. The most recent HbA1c test results in the 365 days before the index date was used as the primary exposure and was classified as `low’ (HbA1c less than 6.5 ), `normal’ (HbA1c between 6.5 and 9.0 mol/mol) or `high’ (HbA1c greater than 9.0 ). A value of 6.5 is a commonly employed cut-off point in studies exploring HbA1c levels and mortality association [19,20]. For instance, Zoungas et al. [20] suggested the 6.5 as the threshold above which there is an increase risk in microvascular events and death in diabetes patients. The same cut-point has also been recommended as a target for Type diabetes [2,3]. The 9 cut-off point has been suggested to represent an indicator for ineffective blood glucose management in type 2 diabetes [3,21]. Change in HbA1c represented the difference between the most recent value and the preceding HbA1c value if this was also recorded within 365 days of the index date. Change was classified as a decrease in HbA1c (decline in HbA1c of greater than 21 ), no or marginal change (change betwe.BA1c increased the risk of all-cause mortality in a large cohort of patients routinely treated in UK primary care. Their primary analysis did not allow for changes in HbA1c over time and instead used the mean 1317923 1480666 of all HbA1c values subsequent to the index date. Although further time dependent analysis were carried out using yearly mean HbA1c, missing data was dealt with using last observation carried forward which can result in bias. This is a potentially important limitation, as Currie et al. [12] did not report on the completeness of HbA1c records and these may not have been routinely recorded during the period they examined (1986 to 2008). Riveline et al. [13] also noted that Currie et al.’s population may have had substantial heterogeneity since the UKPDS trial has led to significant changes in the management of Type 2 diabetes (i.e. risk modeling, health economics). In addition, existing treatment targets for HbA1C set by the NICE (HbA1C,7 ) (2008) or the American Diabetes Association (HbA1C,7 ) (2008) are not age specific and Pani et al. [14]HbA1c Values and Mortality Riskunderlined the importance of establishing whether age-specific treatment criteria would be appropriate. This study aimed to evaluate short-term associations between HbA1c values recorded in clinical practice in primary care and subsequent risk of mortality in a post-UKPDS population. A case control study was implemented to establish an explicit temporal link between HbA1c values recorded in the previous 365 days and mortality risk, rather than utilizing HbA1c records that might cover a considerable length of time, as has been done previously [12]. We aimed to determine whether the risk of mortality was higher when the most recent HbA1c value in the preceding 365 days was either ,6.5 or .9.0 compared to HbA1c values that were between 6.5 and 9 . Considering the scarce evidence for a possible age-depended influence of HbA1C levels on mortality [14], an additional aim of the present study was to explore potential age-associated differences in mortality rates for both low and high HbA1C levels.statistical power by including more than one control per case [18]. Each control was assigned the index date of their matched case.MeasuresTo evaluate both recent HbA1c and recent change in HbA1c the latest two values in the 365 days preceding the index date were identified. HbA1c values below 2.5 or over 25 were discarded as these values were considered implausible. The most recent HbA1c test results in the 365 days before the index date was used as the primary exposure and was classified as `low’ (HbA1c less than 6.5 ), `normal’ (HbA1c between 6.5 and 9.0 mol/mol) or `high’ (HbA1c greater than 9.0 ). A value of 6.5 is a commonly employed cut-off point in studies exploring HbA1c levels and mortality association [19,20]. For instance, Zoungas et al. [20] suggested the 6.5 as the threshold above which there is an increase risk in microvascular events and death in diabetes patients. The same cut-point has also been recommended as a target for Type diabetes [2,3]. The 9 cut-off point has been suggested to represent an indicator for ineffective blood glucose management in type 2 diabetes [3,21]. Change in HbA1c represented the difference between the most recent value and the preceding HbA1c value if this was also recorded within 365 days of the index date. Change was classified as a decrease in HbA1c (decline in HbA1c of greater than 21 ), no or marginal change (change betwe.