Abstract
Aims/hypothesisPrevious studies have suggested that the haemoglobin glycation index (HGI) can be used as a predictor of diabetes-related complications in individuals with type 1 and type 2 diabetes. We investigated whether HGI was a predictor of adverse outcomes of intensive glucose lowering and of diabetes-related complications in general, using data from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial.MethodsWe studied participants in the ADVANCE trial with data available for baseline HbA1c and fasting plasma glucose (FPG) (n = 11,083). HGI is the difference between observed HbA1c and HbA1c predicted from a simple linear regression of HbA1c on FPG. Using Cox regression, we investigated the association between HGI, both categorised and continuous, and adverse outcomes, considering treatment allocation (intensive or standard glucose control) and compared prediction of HGI and HbA1c.ResultsIntensive glucose control lowered mortality risk in individuals with high HGI only (HR 0.74 [95% CI 0.61, 0.91]; p = 0.003), while there was no difference in the effect of intensive treatment on mortality in those with high HbA1c. Irrespective of treatment allocation, every SD increase in HGI was associated with a significant risk increase of 14–17% for macrovascular and microvascular disease and mortality. However, when adjusted for identical covariates, HbA1c was a stronger predictor of these outcomes than HGI.Conclusions/interpretationHGI predicts risk for complications in ADVANCE participants, irrespective of treatment allocation, but no better than HbA1c. Individuals with high HGI have a lower risk for mortality when on intensive treatment. Given the discordant results and uncertain relevance beyond HbA1c, clinical use of HGI in type 2 diabetes cannot currently be recommended.
Highlights
HbA1c is an established means of monitoring average blood glucose levels and a surrogate marker of the effect of glucoselowering interventions [1]
The high HbA1c group had a higher risk for macro- and microvascular complications and mortality compared with the low HbA1c group
With this analysis of the ADVANCE trial we showed that haemoglobin glycation index (HGI) predicts diabetes-related complications, but no better than HbA1c
Summary
HbA1c is an established means of monitoring average blood glucose levels and a surrogate marker of the effect of glucoselowering interventions [1]. It is highly associated with the risk for diabetes-related complications, in particular those of microvascular origin [2,3,4,5]. HbA1c is almost universally accepted to guide and monitor diabetes treatment, its use in clinical practice has arguable limitations. ‘the lower the better’ may not universally hold for HbA1c, and additional (bio)markers might be useful to individualise treatment targets and risk prediction [15]
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