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
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OBJECTIVE: To examine the relationship between glycated haemoglobin A1c (HbA1c) levels and the risk of cardiovascular outcomes and all-cause mortality based on data from observational studies and to determine the optimal levels of HbA1c for preventing cardiovascular events and/or mortality in diabetic and non-diabetic populations. REVIEW METHODS: We systematically searched Medline, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews and Web of Science databases, from inception to July 2016, for observational studies addressing the association of HbA1c levels with mortality and cardiovascular outcomes. Random effects models were used to compute pooled estimates of HR and respective 95% CI for all-cause mortality, cardiovascular mortality and risk of cardiovascular events, separately for people with and without diabetes. RESULTS: Seventy-four published studies were included in the systematic review, but only 46 studies could be incorporated in the meta-analysis. In both diabetic and non-diabetic populations, there was an increase in the risk of all-cause mortality when HbA1c levels were over 8.0% and 6.0%, respectively. The highest all-cause mortality in people with diabetes was HbA1c above 9.0% (HR=1.69; 95% CI 1.09 to 2.66) and in those without diabetes was HbA1c above 6.0% (HR=1.74; 95% CI 1.38 to 2.20). However, both diabetic and non-diabetic populations with lower HbA1c levels (below 6.0% HR=1.57; 95% CI 1.14 to 2.17 and below 5.0% HR=1.19; 95% CI 1.04 to 1.36, respectively) had higher all-cause mortality. Similar pooled estimates were found when cardiovascular mortality was the outcome variable. CONCLUSION: HbA1c is a reliable risk factor of all-cause and cardiovascular mortality in both diabetics and non-diabetics. Our findings establish optimal HbA1c levels, for the lowest all-cause and cardiovascular mortality, ranging from 6.0% to 8.0% in people with diabetes and from 5.0% to 6.0% in those without diabetes.
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A1C has lower sensitivity than fasting plasma glucose or 2-hour oral glucose tolerance test for diagnosing diabetes.
“analyses of the fidelity of DM diagnosis using A1C have reported a lower sensitivity than FPG or 2-hour OGTT.4,5,7-10”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [7]
The Introduction discusses HbA1c as a diagnostic criterion, and the Discussion describes changes to fasting-plasma-glucose and HbA1c thresholds. Neither passage compares their diagnostic sensitivity. Searches for lower sensitivity and OGTT found no passage addressing the claimed comparison with fasting plasma glucose or a 2-hour oral glucose tolerance test. (LLM, conf=0.76)
Experimental — accuracy not yet measuredA meta-analysis of 46 observational studies reported that patients with diabetes with HbA1c ranging from 6.0% to 8.0% had the lowest all-cause and cardiovascular mortality.
“A meta-analysis of 46 observational studies reported that patients with diabetes with HbA1c ranging from 6.0% to 8.0% had the lowest all-cause and CVD mortality (27).”
From Time in Range in Relation to All-Cause and Cardiovascular Mortality in Patients With Type 2 Diabetes: A Prospective Cohort Study (2021) · cites this paper as [27]
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- Authors
- Cavero-Redondo, I., Peleteiro, B., Álvarez-Bueno, C., Rodriguez-Artalejo, F., & Martínez-Vizcaíno, V.
- Affiliations
- Universidad de Castilla—La Mancha, Health and Social Research Center, Cuenca, Spain
- EPI Unit, Instituto de Saúde Pública,Universidade do Porto, Porto, Portugal
- Department of Preventive Medicine and Public Health, Universidad Autónoma de Madrid/ IdiPaz, CIBERESP, and IMDEA-Food Institute. CEI UAM+CSIC, Madrid, Spain
- Venue
- BMJ Open
- Publisher
- BMJ
- Published
- 2017-07
- Volume
- 7
- Issue
- 7
- Pages
- e015949
- ISSN
- 2044-6055 (ISSN-L)
- PMC
- PMC5642750
- OpenAlex
- W2739699420
- Cited by
- 260
- References
- 46
- Citations by year
- 2026: 13 · 2025: 26 · 2024: 27 · 2023: 46 · 2022: 45 · 2021: 44 · 2020: 26 · 2019: 24 · 2018: 8 · 2017: 1
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- BMJ Open (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- HighWire Press Open Archive (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Funders
- Universidad de Castilla-La Mancha (FPU13/01582, FPU13/03137)
- Fundação para a Ciência e a Tecnologia (SFRH/BPD/108751/2015)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- glycated haemoglobin A1c, HbA1c targets, all-cause mortality, cardiovascular mortality, cardiovascular events, diabetes mellitus, glycemic control, cardiovascular risk factors, non-diabetic population, HbA1c thresholds, cardiovascular disease prevention
- MeSH terms
- Cardiovascular Diseases, Diabetes Mellitus, Type 2, Glycated Hemoglobin, Humans, Risk Factors, Observational Studies as Topic
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