Association between prediabetes and risk of all cause mortality and cardiovascular disease: updated meta-analysis

Abstract

Objective: To evaluate the associations between prediabetes and the risk of all cause mortality and incident cardiovascular disease in the general population and in patients with a history of atherosclerotic cardiovascular disease.

Design: Updated meta-analysis.

Data sources: Electronic databases (PubMed, Embase, and Google Scholar) up to 25 April 2020.

Review methods: Prospective cohort studies or post hoc analysis of clinical trials were included for analysis if they reported adjusted relative risks, odds ratios, or hazard ratios of all cause mortality or cardiovascular disease for prediabetes compared with normoglycaemia. Data were extracted independently by two investigators. Random effects models were used to calculate the relative risks and 95% confidence intervals. The primary outcomes were all cause mortality and composite cardiovascular disease. The secondary outcomes were the risk of coronary heart disease and stroke.

Results: A total of 129 studies were included, involving 10 069 955 individuals for analysis. In the general population, prediabetes was associated with an increased risk of all cause mortality (relative risk 1.13, 95% confidence interval 1.10 to 1.17), composite cardiovascular disease (1.15, 1.11 to 1.18), coronary heart disease (1.16, 1.11 to 1.21), and stroke (1.14, 1.08 to 1.20) in a median follow-up time of 9.8 years. Compared with normoglycaemia, the absolute risk difference in prediabetes for all cause mortality, composite cardiovascular disease, coronary heart disease, and stroke was 7.36 (95% confidence interval 9.59 to 12.51), 8.75 (6.41 to 10.49), 6.59 (4.53 to 8.65), and 3.68 (2.10 to 5.26) per 10 000 person years, respectively. Impaired glucose tolerance carried a higher risk of all cause mortality, coronary heart disease, and stroke than impaired fasting glucose. In patients with atherosclerotic cardiovascular disease, prediabetes was associated with an increased risk of all cause mortality (relative risk 1.36, 95% confidence interval 1.21 to 1.54), composite cardiovascular disease (1.37, 1.23 to 1.53), and coronary heart disease (1.15, 1.02 to 1.29) in a median follow-up time of 3.2 years, but no difference was seen for the risk of stroke (1.05, 0.81 to 1.36). Compared with normoglycaemia, in patients with atherosclerotic cardiovascular disease, the absolute risk difference in prediabetes for all cause mortality, composite cardiovascular disease, coronary heart disease, and stroke was 66.19 (95% confidence interval 38.60 to 99.25), 189.77 (117.97 to 271.84), 40.62 (5.42 to 78.53), and 8.54 (32.43 to 61.45) per 10 000 person years, respectively. No significant heterogeneity was found for the risk of all outcomes seen for the different definitions of prediabetes in patients with atherosclerotic cardiovascular disease (all P>0.10).

Conclusions: Results indicated that prediabetes was associated with an increased risk of all cause mortality and cardiovascular disease in the general population and in patients with atherosclerotic cardiovascular disease. Screening and appropriate management of prediabetes might contribute to primary and secondary prevention of cardiovascular disease.

Fig 1

Flow of papers through review

Fig 2

Association between prediabetes and the risk of all cause mortality, composite cardiovascular disease, coronary heart disease, and stroke in the general population. HbA_1c-ADA=raised glycated haemoglobin according to the definition of the American Diabetes Association; HbA_1c-IEC=raised glycated haemoglobin according to the recommendation of the International Expert Committee; IFG-ADA=impaired fasting glucose according to the definition of the American Diabetes Association; IFG-WHO=impaired fasting glucose according to the definition of the World Health Organization; IGT=impaired glucose tolerance

Fig 3

Risk of all cause mortality and cardiovascular disease for different ranges of fasting plasma glucose concentrations, based on prediabetes defined as impaired fasting glucose according to the definition of the American Diabetes Association (reference group was fasting plasma glucose concentration <5.6 mmol/L)

Fig 4

Association between prediabetes and the risk of all cause mortality, composite cardiovascular disease, coronary heart disease, and stroke in patients with atherosclerotic cardiovascular disease. HbA_1c-ADA=raised glycated haemoglobin according to the definition of the American Diabetes Association; HbA_1c-IEC=raised glycated haemoglobin according to the recommendation of the International Expert Committee; IFG-ADA=impaired fasting glucose according to the definition of the American Diabetes Association; IFG-WHO=impaired fasting glucose according to the definition of the World Health Organization; IGT=impaired glucose tolerance