Does a low level of glycated hemoglobin (HbA1c) increase mortality risk in a UK population without known diabetes or cardiovascular disease?
HbA1c Home Kit, studied in 17,196 men (Diabetologia 2011, PMID 21584793) — spline regression indicated no increased risk at the low end of the distribution, with the HR for all-cause mortality remaining constant in the low range and only beginning to rise at approximately 5.5%. The abstract mentions that differences in population characteristics might explain contrary results of earlier studies, suggesting a potential limitation in generalizability to other populations.
Source: Diabetologia 2011, PMID 21584793 ↗ · Research map · How Magellan grades evidence · evidence confidence: high
Diabetologia · 2011 · PMID 21584793 · DOI 10.1007/s00125-011-2162-0
Low glycated hemoglobin levels do not appear to increase mortality risk in a non-diabetic UK population; risk only rises above 5.5%.
The question
Does a low level of glycated hemoglobin (HbA1c) increase mortality risk in a UK population without known diabetes or cardiovascular disease?
What they tested
The study aimed to examine the shape of the risk relationship between glycated hemoglobin and mortality, particularly addressing the debate about increased mortality risk associated with low levels of glycaemia.
How they did it
The study included 17,196 men and women aged 39-82 years from the EPIC-Norfolk Study, all without known diabetes or cardiovascular disease. Hazard ratios (HRs) for total and cause-specific mortality were estimated using Cox regression, comparing categories of glycated hemoglobin (<4.5%, 4.5% to <5.0%, 5.0% to <5.5% [reference], 5.5% to <6.0%, 6.0% to <6.5%, and ">="6.5%).
What they found
During a mean follow-up of 11.2 years, 1,953 participants died. The HR for all-cause mortality increased with increasing glycated hemoglobin categories. Spline regression indicated no increased risk at the low end of the distribution, with the HR for all-cause mortality remaining constant in the low range and only beginning to rise at approximately 5.5%. Similar associations were observed for cause-specific mortality, with the strongest link to cardiovascular mortality.
| <4.5% | 0.94 | |
|---|---|---|
| 4.5% to <5.0% | 0.99 | |
| 5.0% to <5.5% | 1 | |
| 5.5% to <6.0% | 1.1 | |
| 6.0% to <6.5% | 1.29 | |
| ">="6.5% | 1.45 |
Hazard ratios for all-cause mortality increase with higher glycated hemoglobin levels, with the reference category being 5.0% to <5.5%.
What it means
The findings in this large non-diabetic population do not support the concern about increased mortality risk associated with low glycated hemoglobin levels. Differences in population characteristics might account for conflicting results from previous studies and warrant further investigation.
Limitations
The abstract mentions that differences in population characteristics might explain contrary results of earlier studies, suggesting a potential limitation in generalizability to other populations.
The paper at a glance
| Magellan’s evidence label | Glycated hemoglobin (3-month glucose) (our label for this citation — see PubMed for the paper’s own title and authors) |
|---|---|
| Journal | Diabetologia |
| Year | 2011 |
| PMID | 21584793 ↗ |
| DOI | 10.1007/s00125-011-2162-0 ↗ |
| Topic | Cardiovascular & vascular aging |
Read the source: PubMed record (authors, abstract, full citation) ↗ · Publisher via doi.org ↗
Where Magellan uses this paper
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HbA1c Home Kit
Higher HbA1c raises all-cause and cardiovascular mortality. Research relevant to this mechanism is indexed on PubMed and linked below; it describes the mechanism rather than this specific product.
Molecules & mechanisms in this paper
Each of these is named in the paper’s own words above. Open the monograph for the full mechanism and its other citations.
Cite this page
These citations point at this summary. To cite the original paper with its full author list, use the PubMed record or doi.org.
Magellan Longevity. (2026). Does a low level of glycated hemoglobin (HbA1c) increase mortality risk in a UK population without known diabetes or cardiovascular disease? [Plain-English summary of Diabetologia 2011, PMID 21584793, DOI 10.1007/s00125-011-2162-0]. Magellan Longevity. https://magellanlongevity.com/study/s144.html@misc{magellan_s144,
title = {Does a low level of glycated hemoglobin (HbA1c) increase mortality risk in a UK population without known diabetes or cardiovascular disease?},
author = {{Magellan Longevity}},
year = {2026},
howpublished = {\url{https://magellanlongevity.com/study/s144.html}},
note = {Plain-English summary of PubMed PMID 21584793; DOI 10.1007/s00125-011-2162-0; Diabetologia 2011. Reviewed by Gabriel Radu, DO},
urldate = {2026-08-11}
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