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Review
. 2016 Nov 23;355:i5953.
doi: 10.1136/bmj.i5953.

Association Between Prediabetes and Risk of Cardiovascular Disease and All Cause Mortality: Systematic Review and Meta-Analysis

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Free PMC article
Review

Association Between Prediabetes and Risk of Cardiovascular Disease and All Cause Mortality: Systematic Review and Meta-Analysis

Yuli Huang et al. BMJ. .
Free PMC article

Abstract

Objectives: To evaluate associations between different definitions of prediabetes and the risk of cardiovascular disease and all cause mortality.

Design: Meta-analysis of prospective cohort studies.

Data sources: Electronic databases (PubMed, Embase, and Google Scholar).

Selection criteria: Prospective cohort studies from general populations were included for meta-analysis if they reported adjusted relative risks with 95% confidence intervals for associations between the risk of composite cardiovascular disease, coronary heart disease, stroke, all cause mortality, and prediabetes.

Review methods: Two authors independently reviewed and selected eligible studies, based on predetermined selection criteria. Prediabetes was defined as impaired fasting glucose according to the criteria of the American Diabetes Association (IFG-ADA; fasting glucose 5.6-6.9 mmol/L), the WHO expert group (IFG-WHO; fasting glucose 6.1-6.9 mmol/L), impaired glucose tolerance (2 hour plasma glucose concentration 7.8-11.0 mmol/L during an oral glucose tolerance test), or raised haemoglobin A1c (HbA1c) of 39-47 mmol/mol : (5.7-6.4%) according to ADA criteria or 42-47 mmol/mol (6.0-6.4%) according to the National Institute for Health and Care Excellence (NICE) guideline. The relative risks of all cause mortality and cardiovascular events were calculated and reported with 95% confidence intervals.

Results: 53 prospective cohort studies with 1 611 339 individuals were included for analysis. The median follow-up duration was 9.5 years. Compared with normoglycaemia, prediabetes (impaired glucose tolerance or impaired fasting glucose according to IFG-ADA or IFG-WHO criteria) was associated with an increased risk of composite cardiovascular disease (relative risk 1.13, 1.26, and 1.30 for IFG-ADA, IFG-WHO, and impaired glucose tolerance, respectively), coronary heart disease (1.10, 1.18, and 1.20, respectively), stroke (1.06, 1.17, and 1.20, respectively), and all cause mortality (1.13, 1.13 and 1.32, respectively). Increases in HBA1c to 39-47 mmol/mol or 42-47 mmol/mol were both associated with an increased risk of composite cardiovascular disease (1.21 and 1.25, respectively) and coronary heart disease (1.15 and 1.28, respectively), but not with an increased risk of stroke and all cause mortality.

Conclusions: Prediabetes, defined as impaired glucose tolerance, impaired fasting glucose, or raised HbA1c, was associated with an increased risk of cardiovascular disease. The health risk might be increased in people with a fasting glucose concentration as low as 5.6 mmol/L or HbA1c of 39 mmol/mol.

Conflict of interest statement

All author shave completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Flow of papers through review of prediabetes and risk of cardiovascular disease and all cause mortality. CVD=cardiovascular disease, CHD=coronary heart disease, IFG=impaired fasting glucose, IGT= impaired glucose tolerance
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Fig 2 Association between prediabetes and risk of all cause mortality. D+L=DerSimonian and Laird random effects models; HbA1c-ADA=prediabetes defined as raised HbA1c according to American Diabetes Association (ADA) criteria (39-47 mmol/mol); HbA1c-NICE=prediabetes defined as raised HbA1c according to NICE guidance (42-47 mmol/mol); IFG-ADA=impaired fasting glucose (IFG) according to ADA criteria (fasting plasma glucose of 5.6-6.9 mmol/L); IFG-WHO=IFG according to WHO criteria (6.1-6.9 mmol/L); IGT=impaired glucose tolerance; I-V=inverse variance fixed effects models
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Fig 3 Association between prediabetes and composite cardiovascular events. D+L=DerSimonian and Laird random effects models; HbA1c-ADA=prediabetes defined as raised HbA1c according to American Diabetes Association (ADA) criteria (39-47 mmol/mol); HbA1c-NICE=prediabetes defined as raised HbA1c according to NICE guidance (42-47 mmol/mol); IFG-ADA=impaired fasting glucose (IFG) according to ADA criteria (fasting plasma glucose of 5.6-6.9 mmol/L); IFG-WHO=IFG according to WHO criteria (6.1-6.9 mmol/L); IGT=impaired glucose tolerance; I-V=inverse variance fixed effects models
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Fig 4 Association between prediabetes and risk of coronary heart disease. D+L=DerSimonian and Laird random effects models; HbA1c-ADA=prediabetes defined as raised HbA1c according to American Diabetes Association (ADA) criteria (39-47 mmol/mol); HbA1c-NICE=prediabetes defined as raised HbA1c according to NICE guidance (42-47 mmol/mol); IFG-ADA=impaired fasting glucose (IFG) according to ADA criteria (fasting plasma glucose of 5.6-6.9 mmol/L); IFG-WHO=IFG according to WHO criteria (6.1-6.9 mmol/L); IGT=impaired glucose tolerance; I-V=inverse variance fixed effects models
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Fig 5 Association between prediabetes and risk of stroke. D+L=DerSimonian and Laird random effects models; HbA1c-ADA=prediabetes defined as raised HbA1c according to American Diabetes Association (ADA) criteria (39-47 mmol/mol); HbA1c-NICE=prediabetes defined as raised HbA1c according to NICE guidance (42-47 mmol/mol); IFG-ADA=impaired fasting glucose (IFG) according to ADA criteria (fasting plasma glucose of 5.6-6.9 mmol/L); IFG-WHO=IFG according to WHO criteria (6.1-6.9 mmol/L); IGT=impaired glucose tolerance; I-V=inverse variance fixed effects models

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