Low fasting glucose and future risks of major adverse outcomes in people without baseline diabetes or cardiovascular disease: a systematic review and meta-analysis

Abstract

Objective: To investigate the link between low fasting blood glucose levels and all-cause mortality and cardiovascular outcomes among people without baseline diabetes or cardiovascular disease.

Design: Systematic review and meta-analysis.

Data sources: PubMed and Embase (1966-February 2019).

Selection criteria: Prospective cohort studies were included for meta-analysis if they reported adjusted HRs with 95% CIs for associations between risk of all-cause mortality, stroke, major cardiovascular events, coronary heart disease and low fasting glucose levels (<4.6 mmol/L and/or 4.0 mmol/L, respectively) versus normal fasting glucose levels.

Data extraction and statistical analysis: Two independent reviewers extracted data from eligible studies. Heterogeneity was assessed by p value of χ² tests and I². We assessed four characteristics for each included study based on items developed by the US Preventive Task Force, as well as the modified checklist used in previous studies.

Results: Eleven articles (consisting of 129 prospective cohort studies) with 2 674 882 participants without diabetes and cardiovascular disease at baseline were included in this meta-analysis. Pooled results from the random effects model showed increased risks of all-cause mortality (HR: 1.56; 95% CI 1.09 to 2.23), total stroke (HR: 1.08, 95% CI 1.03 to 1.13) and ischaemic stroke (HR: 1.06, 95% CI 1.01 to 1.10), and major cardiovascular events (HR: 1.05, 95% CI 1.03 to 1.07) among people with a fasting glucose <4.0 mmol/L, as compared with people with normal fasting glucose. The less stringent low fasting glucose level, <4.6 mmol/L, was not associated with increased risk of any endpoints.

Discussion and conclusions: Among people without baseline diabetes or cardiovascular disease, a fasting blood glucose level of <4.0 mmol/L is associated with increased risk of all-cause mortality, major cardiovascular events and stroke.

Keywords: epidemiology; primary care; public health.

Figure 1

Flow chart of study selection.

Figure 2

Association of baseline low fasting glucose (<4.6 mmol/L and <4.0 mmol/L, respectively) and risk of all-cause mortality.

Figure 3

Association of baseline low fasting glucose (<4.6 mmol/L and <4.0 mmol/L, respectively) and risk of stroke, ischaemic stroke and haemorrhagic stroke.

Figure 4

Association of baseline low fasting glucose (<4.6 mmol/L and <4.0 mmol/L, respectively) and risk of major adverse cardiovascular events, coronary heart disease and cardiovascular mortality.