Prediabetes and risk of mortality, diabetes-related complications and comorbidities: umbrella review of meta-analyses of prospective studies.
Level 3 - non-randomized controlled study
Umbrella review of systematic reviews and meta-analyses of prospective observational cohort studies
PubMed 34718834 · doi:10.1007/s00125-021-05592-3
What was done
Umbrella review of systematic reviews with meta-analyses of prospective observational studies assessing associations between prediabetes (defined by fasting glucose, 2-hour postload glucose, or HbA1c) and incident diabetes-related complications, comorbidities, and mortality in adults. Databases (PubMed, Web of Science, Cochrane Library, and Epistemonikos) were searched up to June 17, 2021. Summary risk estimates were recalculated using a random-effects model, and evidence certainty was evaluated with GRADE.
What was found
Ninety-five meta-analyses from 16 publications were identified. In the general population, prediabetes was associated with a 6-101% increased risk for all-cause mortality, cardiovascular outcomes, coronary heart disease, stroke, heart failure, atrial fibrillation, chronic kidney disease, total cancer, total liver cancer, hepatocellular carcinoma, breast cancer, and all-cause dementia (moderate certainty of evidence). Prediabetes was not associated with incident depressive symptoms or cognitive impairment (low or very low certainty). All-cause mortality risk was stronger when prediabetes was defined by impaired glucose tolerance than by HbA1c.
Why it matters
This umbrella review demonstrates that prediabetes is associated with broad adverse health risks—including cardiovascular disease, cancer, and dementia—prior to the onset of frank diabetes.
Limits
The findings are based entirely on observational prospective studies, which cannot establish causality. Specific complications like neuropathy were not evaluated, and associations varied depending on the diagnostic criteria used for prediabetes.