Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds

Abstract

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>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<0.0001).To convert values for HbA 1c in % into mmol/mol subtract 2.15 and multiply by 10.929. Electronic supplementary material The online version of this article

ADVANCE and glycaemia thresholds: a need to clarify the statistical approach

“…To the Editor: The recent study published by the ADVANCE Collaborative Group confirming that there is a lower threshold of optimal HbA 1c [1] is a welcome confirmation of the original work published in The Lancet [2]. However, there is at least one important analytical failing that simply must be addressed for this study to be considered valid.…”

“…However, Zoungas and colleagues report two consistently differing patterns of association dependent upon whether participants were randomised to their intensive treatment arm or to standard care (see Fig. 1 in Zoungas et al [1]). Explained simply, the association between the hazard of major macrovascular events and HbA 1c was higher at lower HbA 1c levels in the intensive treatment arm.…”

Renal dysfunction in patients with myocardial infarction concurrent with type 2 diabetes mellitus

“…Нарушения углеводного обмена (НУО) представляют собой самостоятельный фактор риска (ФР) не только развития, но и не-благоприятного течения ССЗ [3]. Особую актуальность этот фак-тор приобретает в связи с продолжающимся значительным ро-стом заболеваемости сахарным диабетом 2-го типа (СД-2) в мире.…”

ADVANCE and glycaemia thresholds: a need to clarify the statistical approach. Reply to Currie CJ [letter]

“…

To the Editor: We thank Professor Currie for his interesting interpretation [1] of the complex analyses undertaken to examine the relationship between HbA 1c and outcomes in the ADVANCE trial cohort [2].With respect to the use of time-weighted average HbA 1c levels, we used several different approaches for assessing HbA 1c levels including baseline values and time-dependent covariates. Each gave similar findings to those presented.

…”

“…To the Editor: We thank Professor Currie for his interesting interpretation [1] of the complex analyses undertaken to examine the relationship between HbA 1c and outcomes in the ADVANCE trial cohort [2].…”