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Cited by 175Diabetes, Cardiovascular Risks, and LipoproteinsDiet, Metabolism, and DiseaseDiabetes Management and Research

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Markers of Dysglycaemia and Risk of Coronary Heart Disease in People without Diabetes: Reykjavik Prospective Study and Systematic Review

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Sarwar, Nadeem, Aspelund, Thor, Eiriksdottir, Gudny, Gobin, Reeta, Seshasai, Sreenivasa Rao Kondapally, Forouhi, Nita G., Sigurdsson, Gunnar, Danesh, John, Gudnason, Vilmundur·2010·PLoS Medicine
DOI 10.1371/journal.pmed.1000278PMC PMC2876150
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Abstract

BACKGROUND: Associations between circulating markers of dysglycaemia and coronary heart disease (CHD) risk in people without diabetes have not been reliably characterised. We report new data from a prospective study and a systematic review to help quantify these associations. METHODS AND FINDINGS: Fasting and post-load glucose levels were measured in 18,569 participants in the population-based Reykjavik study, yielding 4,664 incident CHD outcomes during 23.5 y of mean follow-up. In people with no known history of diabetes at the baseline survey, the hazard ratio (HR) for CHD, adjusted for several conventional risk factors, was 2.37 (95% CI 1.79-3.14) in individuals with fasting glucose > or = 7.0 mmol/l compared to those < 7 mmol/l. At fasting glucose values below 7 mmol/l, adjusted HRs were 0.95 (0.89-1.01) per 1 mmol/l higher fasting glucose and 1.03 (1.01-1.05) per 1 mmol/l higher post-load glucose. HRs for CHD risk were generally modest and nonsignificant across tenths of glucose values below 7 mmol/l. We did a meta-analysis of 26 additional relevant prospective studies identified in a systematic review of Western cohort studies that recorded fasting glucose, post-load glucose, or glycated haemoglobin (HbA(1c)) levels. In this combined analysis, in which participants with a self-reported history of diabetes and/or fasting blood glucose > or = 7 mmol/l at baseline were excluded, relative risks for CHD, adjusted for several conventional risk factors, were: 1.06 (1.00-1.12) per 1 mmol/l higher fasting glucose (23 cohorts, 10,808 cases, 255,171 participants); 1.05 (1.03-1.07) per 1 mmol/l higher post-load glucose (15 cohorts, 12,652 cases, 102,382 participants); and 1.20 (1.10-1.31) per 1% higher HbA(1c) (9 cohorts, 1639 cases, 49,099 participants). CONCLUSIONS: In the Reykjavik Study and a meta-analysis of other Western prospective studies, fasting and post-load glucose levels were modestly associated with CHD risk in people without diabetes. The meta-analysis suggested a somewhat stronger association between HbA(1c) levels and CHD risk.

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Figure 1 Risk of CHD across tenths of baseline fasting glucose levels in the Reykjavik Study. All hazard ratios are adjusted for age, sex, recruitment period, smoking status, systolic blood pressure, total cholesterol, and BMI, and all are compared to individuals in the middle tenth of the distribution. The grey area denotes the 95% CI of the reference group. Analyses involved the full range of glucose values (i.e., including individuals with glucose levels in the diabetic range). To limit any bias related to having a diagnosis of diabetes (e.g., medication use, lifestyle changes), however, individuals with a known history of diabetes at the baseline survey were excluded.
Figure 1 Risk of CHD across tenths of baseline fasting glucose levels in the Reykjavik Study. All hazard ratios are adjusted for age, sex, recruitment period, smoking status, systolic blood pressure, total cholesterol, and BMI, and all are compared to individuals in the middle tenth of the distribution. The grey area denotes the 95% CI of the reference group. Analyses involved the full range of glucose values (i.e., including individuals with glucose levels in the diabetic range). To limit any bias related to having a diagnosis of diabetes (e.g., medication use, lifestyle changes), however, individuals with a known history of diabetes at the baseline survey were excluded.CC BY · PubMed Central
Figure 2 Risk of CHD across tenths of baseline 1 h post-load glucose levels in the Reykjavik Study. All hazard ratios are adjusted for age, sex, recruitment period, smoking status, systolic blood pressure, total cholesterol, and BMI, and all are compared to individuals in the middle tenth of the distribution. The grey area denotes the 95% CI of the reference group. Analyses involved the full range of glucose values (i.e., including individuals with glucose levels in the diabetic range). To limit any bias related to having a diagnosis of diabetes (e.g., medication use, lifestyle changes), however, individuals with a known history of diabetes at the baseline survey were excluded.
Figure 2 Risk of CHD across tenths of baseline 1 h post-load glucose levels in the Reykjavik Study. All hazard ratios are adjusted for age, sex, recruitment period, smoking status, systolic blood pressure, total cholesterol, and BMI, and all are compared to individuals in the middle tenth of the distribution. The grey area denotes the 95% CI of the reference group. Analyses involved the full range of glucose values (i.e., including individuals with glucose levels in the diabetic range). To limit any bias related to having a diagnosis of diabetes (e.g., medication use, lifestyle changes), however, individuals with a known history of diabetes at the baseline survey were excluded.CC BY · PubMed Central
Figure 3 Prospective studies of markers of dysglycaemia and CHD risk in individuals without diabetes in Western populations. Analyses were restricted to individuals who did not have a self-reported history of type 2 diabetes or had a fasting blood glucose <7.0 mmol/l at baseline. Risk estimates are presented per 1 mmol/l higher fasting and post-load glucose, and per 1% higher HbA1c. Abbreviations as listed in Table S2.
Figure 3 Prospective studies of markers of dysglycaemia and CHD risk in individuals without diabetes in Western populations. Analyses were restricted to individuals who did not have a self-reported history of type 2 diabetes or had a fasting blood glucose <7.0 mmol/l at baseline. Risk estimates are presented per 1 mmol/l higher fasting and post-load glucose, and per 1% higher HbA1c. Abbreviations as listed in Table S2.CC BY · PubMed Central
Figure 4 Prospective studies of fasting and post-load glucose and CHD risk in individuals without diabetes in Western population, grouped by study characteristics. Meta-regression analyses separately considered each characteristic presented. *Assessed as continuous factors.
Figure 4 Prospective studies of fasting and post-load glucose and CHD risk in individuals without diabetes in Western population, grouped by study characteristics. Meta-regression analyses separately considered each characteristic presented. *Assessed as continuous factors.CC BY · PubMed Central

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Research works printed but not linked: 2

  1. WHO consultation report. Definition, diagnosis and classification of diabetes mellitus and its complications., WHO/NCD/NCS/, 91.2
  2. RR Holman, 2007, A new era in the secondary prevention of CVD in prediabetes - the Acarbose Cardiovascular Evaluation (ACE) trial., Diab Vasc Dis Res, 4, S40

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Metadata

Authors
Sarwar, N., Aspelund, T., Eiriksdottir, G., Gobin, R., Seshasai, S. R. K., Forouhi, N. G., Sigurdsson, G., Danesh, J., & Gudnason, V.
Affiliations
  • University of Cambridge (GB)
  • University of Iceland (IS)
  • MRC Epidemiology Unit (GB)
Corresponding author
Sarwar, Nadeem
ORCID
Venue
PLoS Medicine
Publisher
Public Library of Science (PLoS)
Published
2010-05-25
Volume
7
Issue
5
Pages
e1000278
ISSN
  • 1549-1277 (ISSN-L)
  • 1549-1676
DOI
10.1371/journal.pmed.1000278
PMC
PMC2876150
OpenAlex
W1992852296
Cited by
175
References
54
Citations by year
2026: 1 · 2025: 7 · 2024: 2 · 2023: 11 · 2022: 9 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 12 · 2017: 10 · 2016: 12 · 2015: 15 · 2014: 16 · 2013: 18 · 2012: 15
FWCI
2.46
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • St George's Online Research Archive (St George's University of London) (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Pfizer
  • GlaxoSmithKline
  • Wellcome Trust
  • British Heart Foundation (RG/08/014/24067)
  • Bupa Foundation
  • European Commission
  • Cambridge Trust
  • Evelyn Trust
  • Gates Cambridge Trust
  • Medical Research Council
  • National Heart, Lung, and Blood Institute
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
dysglycemia, coronary artery disease, fasting blood glucose, post-load glucose, HbA1c, non-diabetic individuals, cardiovascular risk, hyperglycemia, prediabetes, Reykjavik Study, HbA1c thresholds
MeSH terms
Adult, Blood Glucose, Coronary Disease, Diabetes Mellitus, Fasting, Female, Glycated Hemoglobin, Humans, Hyperglycemia, Male, Middle Aged, Prospective Studies, Reference Values, Risk Factors, Biomarkers

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