Glycated haemoglobin A1c as a risk factor of cardiovascular outcomes and all-cause mortality in diabetic and non-diabetic populations: a systematic review and meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational studies
PubMed 28760792 · doi:10.1136/bmjopen-2017-015949
What was done
The authors systematically searched Medline, Embase, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, and Web of Science through July 2016 for observational studies evaluating the link between HbA1c levels and all-cause mortality, cardiovascular mortality, or cardiovascular events. Random-effects models were used to calculate pooled hazard ratios (HR) and 95% confidence intervals separately for diabetic and non-diabetic cohorts.
What was found
Seventy-four studies were identified, with 46 included in the meta-analysis. In diabetic individuals, all-cause mortality increased at HbA1c > 8.0%, peaking at > 9.0% (HR 1.69; 95% CI 1.09 to 2.66), but was also increased at levels < 6.0% (HR 1.57; 95% CI 1.14 to 2.17). In non-diabetic individuals, all-cause mortality was higher at HbA1c > 6.0% (HR 1.74; 95% CI 1.38 to 2.20) and at levels < 5.0% (HR 1.19; 95% CI 1.04 to 1.36). Similar patterns occurred for cardiovascular mortality. Lowest mortality was observed at HbA1c 6.0% to 8.0% in diabetics and 5.0% to 6.0% in non-diabetics.
Why it matters
These findings highlight a U-shaped relationship between glycemia and mortality, suggesting that overly aggressive glycemic targets below 6.0% in diabetes may confer excess risk comparable to poor glycemic control.
Limits
The review included only observational studies, which cannot establish causality and remain vulnerable to residual confounding or reverse causation from severe comorbidities. Twenty-eight included studies could not be pooled in the meta-analysis. The abstract does not provide the total participant count or details on duration of follow-up and patient medical therapy.
Cited by
- contradicts All-cause mortality data show better outcomes for individuals with a hemoglobin A1c of 5.0% compared to 5.5%.