Metabolic memory and all-cause death in community-based patients with type 2 diabetes: the Fremantle Diabetes Study

To validate the findings, in a usual care setting, of glycaemic intervention trials, which have shown that tight control in patients with recently diagnosed type 2 diabetes protects against death during post-study monitoring, but that it may be deleterious in long-duration diabetes with vascular complications.

A subset of 531 patients with type 2 diabetes from the community-based observational Fremantle Diabetes Study Phase 1, who attended ≥5 annual reviews (mean follow-up 15.9 years), were categorized by baseline diabetes duration [<1 year (Group 1); 1 to <5 years (Group 2); and ≥5 years (Group 3)]. Glycated haemoglobin (HbA1c) trajectories over the first 5 years were determined [low, medium and high; equivalent to mean HbA1c ≤6.6% (<49 mmol/mol), 6.7-8.0% (50-64 mmol/mol) and ≥8.0% (>64 mmol/mol), respectively]. Kaplan-Meier analysis was used to assess survival by duration and HbA1c trajectory. Cox proportional hazards modelling identified predictors of all-cause death.

There was greater mortality in patients with a medium versus those with a low trajectory in Group 1: hazard ratio (HR) 1.99 [95% confidence interval (CI) 1.003-3.94; p = 0.049], and in patients with a high versus a low trajectory in Group 2: HR 2.02 (95% CI 1.11-3.71; p = 0.022). In Group 3, both medium [HR 0.57 (95% CI 0.35-0.92; p = 0.022)] and high [HR 0.56 (95% CI 0.32-0.96); p = 0.035] trajectories were independently and inversely associated with death.

In community-based patients with newly or recently diagnosed type 2 diabetes, poor glycaemic control was an adverse prognostic indicator. Tight control was independently associated with death in patients with diabetes duration ≥5 years. These data parallel intervention trial findings and support individualization of HbA1c targets.