Associations between haemoglobin A_1c and mortality rate in the KORA S4 and the Heinz Nixdorf Recall population-based cohort studies

Background: There is limited knowledge about mortality risk in persons with increased haemoglobin A_1c (HbA_1c ) levels below the diabetes threshold. Moreover, little is known about how associations between increased HbA_1c and mortality depend on the length of follow-up. Therefore, we studied associations between HbA_1c and mortality over long-term follow-up in persons with and without known diabetes.

Methods: We used data from two German population-based cohort studies: KORA S4 Study (Southern Germany, n = 1458, baseline visits in 1999 to 2001, baseline age 55 to 74 years, mortality follow-up 16.8 years) and Heinz Nixdorf Recall (HNR) Study (Ruhr area, n = 4613, baseline visits in 2000 to 2003, baseline age 45 to 75 years, mortality follow-up 17.8 years). Adjusted log-linear models were fitted to estimate relative risks (RRs) with 95% confidence intervals (CI).

Results: In both cohorts, participants with HbA_1c 39 to 41 mmol/mol (5.7%-5.9%) and HbA_1c 42 to 46 mmol/mol (6.0% to 6.4%) did not have a larger overall mortality risk than participants with HbA_1c < 39 mmol/mol (5.7%): the corresponding adjusted RRs were 1.00 (95% CI: 0.83-1.21) and 1.01 (0.80-1.27) in KORA and 0.99 (0.82-1.21) and 0.83 (0.65-1.07) in the HNR Study. For the pooled cohorts, the RR for HbA_1c 39 to 46 mmol/mol (5.7%-6.4%) was 0.96 (0.85-1.07). Associations between newly detected diabetes (HbA_1c ≥ 6.5%) and mortality were weak after 4 and 8 years of follow-up, but were stronger after 12 years of follow-up, whereas associations between previously known diabetes (baseline) and mortality decreased.

Conclusions: HbA_1c -defined pre-diabetes is not associated with overall mortality. For newly detected and previously known diabetes, mortality risks vary with length of follow-up.