Background: 

Results of intervention studies in patients with type 2 diabetes have led to concerns about the safety of aiming for normal blood glucose concentrations. We assessed survival as a function of HbA_1c in people with type 2 diabetes.

Methods: 

Two cohorts of patients aged 50 years and older with type 2 diabetes were generated from the UK General Practice Research Database from November 1986 to November 2008. We identified 27 965 patients whose treatment had been intensified from oral monotherapy to combination therapy with oral blood-glucose lowering agents, and 20 005 who had changed to regimens that included insulin. Those with diabetes secondary to other causes were excluded. All-cause mortality was the primary outcome. Age, sex, smoking status, cholesterol, cardiovascular risk, and general morbidity were identified as important confounding factors, and Cox survival models were adjusted for these factors accordingly.

Findings: 

For combined cohorts, compared with the glycated haemoglobin (HbA_1c) decile with the lowest hazard (median HbA_1c 7·5%, IQR 7·5–7·6%), the adjusted hazard ratio (HR) of all-cause mortality in the lowest HbA_1c decile (6·4%, 6·1–6·6) was 1·52 (95% CI 1·32–1·76), and in the highest HbA_1c decile (median 10·5%, IQR 10·1-11·2%) was 1·79 (95% CI 1·56–2·06). Results showed a general U-shaped association, with the lowest HR at an HbA_1c of about 7·5%. HR for all-cause mortality in people given insulin-based regimens (2834 deaths) versus those given combination oral agents (2035) was 1·49 (95% CI 1·39–1·59).

Interpretation: 

Low and high mean HbA_1c values were associated with increased all-cause mortality and cardiac events. If confirmed, diabetes guidelines might need revision to include a minimum HbA_1c value.