Association between varying cut-points of intermediate hyperglycemia and risk of mortality, cardiovascular events and chronic kidney disease: a systematic review and meta-analysis

Introduction: We conducted a systematic review and meta-analysis to evaluate the updated evidence regarding prediabetes for predicting mortality, macrovascular and microvascular outcomes.

Research design and methods: We identified English language studies from MEDLINE, PubMed, OVID and Cochrane database indexed from inception to January 31, 2020. Paired reviewers independently identified 106 prospective studies, comprising nearly 1.85 million people, from 27 countries. Primary outcomes were all-cause mortality (ACM), cardiovascular mortality (CVDM), cardiovascular disease (CVD), coronary heart disease (CHD) and stroke. Secondary outcomes were heart failure, chronic kidney disease (CKD) and retinopathy.

Results: Impaired glucose tolerance was associated with ACM; HR 1.19, 95% CI (1.15 to 1.24), CVDM; HR 1.21, 95% CI (1.10 to 1.32), CVD; HR 1.18, 95% CI (1.11 to 1.26), CHD; HR; 1.13, 95% CI (1.05 to 1.21) and stroke; HR 1.24, 95% CI (1.06 to 1.45). Impaired fasting glucose (IFG) 110-125 mg/dL was associated with ACM; HR 1.17, 95% CI (1.13 to 1.22), CVDM; HR 1.20, 95% CI (1.09 to 1.33), CVD; HR 1.21, 95% CI (1.09 to 1.33), CHD; HR; 1.14, 95% CI (1.06 to 1.22) and stroke; HR 1.22, 95% CI (1.07 to 1.40). IFG 100-125 mg/dL was associated with ACM; HR 1.11, 95% CI (1.04 to 1.19), CVDM; HR 1.14, 95% CI (1.03 to 1.25), CVD; HR 1.15, 95% CI (1.05 to 1.25), CHD HR; 1.10, 95% CI (1.02 to 1.19) and CKD; HR; 1.09, 95% CI (1.01 to 1.18). Glycosylated hemoglobin A1c (HbA1c) 6.0%-6.4% was associated with ACM; HR 1.30, 95% CI (1.03 to 1.66), CVD; HR 1.32, 95% CI (1.00 to 1.73) and CKD; HR 1.50, 95% CI (1.32 to 1.70). HbA1c 5.7%-6.4% was associated with CVD HR 1.15, 95% CI (1.02 to 1.30), CHD; HR 1.28, 95% CI (1.13 to 1.46), stroke; HR 1.23, 95% CI (1.04 to 1.46) and CKD; HR 1.32, 95% CI (1.16 to 1.50).

Conclusion: Prediabetes is an elevated risk state for macrovascular and microvascular outcomes. The prevention and management of prediabetes should be considered.