Variability in glycaemic control is associated with both microvascular and macrovascular events in patients with Type 2 diabetes, shows an analysis of the ADVANCE trial.
Several studies have shown an association between variable glycaemic control and microvascular diabetic complications, but this analysis is the first to extend the association to macrovascular events, say study author John Chalmers (The George Institute for Global Health, Sydney, Australia) and colleagues.
The researchers measured visit-to-visit variability of glycaemic control in 4399 patients assigned to receive intensive glucose treatment in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) trial. They assessed glycated haemoglobin and fasting glucose measurements taken five times between 3 and 24 months, and vascular events commencing from 24 months.
During the median 3-year follow-up, 234 patients had a major macrovascular event, defined as cardiovascular death, nonfatal myocardial infarction or nonfatal stroke, and 309 had a major microvascular event.
When divided into deciles, variability in glycated haemoglobin and fasting glucose, represented by their standard deviations (SDs), showed significant linear associations with both macrovascular and microvascular events, even after adjusting for average glycated haemoglobin and fasting glucose, respectively.
The associations were strongest for fasting glucose, with each decile increase in its SD resulting in a 12% increased risk of complications, whereas each decile increase in glycated haemoglobin SD conferred just a 5% increase.
Each decile increase in the SD of fasting glucose was significantly associated with an increased risk of both macrovascular events (8%) and microvascular events (15%), whereas glycated haemoglobin variability was significantly associated only with macrovascular events (6%).
Conversely, all-cause mortality was significantly associated with variability in glycated haemoglobin but not fasting glucose, the team reports in Diabetes Care.
The maximum fasting glucose measurement recorded was also significantly associated with vascular outcomes, with each decile increase associated with an 11% increase in all vascular outcomes and with 11% and 10% increases in macrovascular and microvascular events, respectively. By contrast, the maximum glycated haemoglobin measurement was not significantly associated with any outcome.
“Intensive and consistent glucose control that achieves target [glycated haemoglobin]/glucose levels recommended by current guidelines with minimum fluctuation may provide further protection against future development of both macro- and microvascular complications and subsequent death in type 2 diabetes”, conclude the researchers.
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