Early effective intervention can significantly reduce all-cause mortality in prediabetic patients: a systematic review and meta-analysis based on high-quality clinical studies

Background Reducing the occurrence of diabetes is considered a primary criterion for evaluating the effectiveness of interventions for prediabetes. There is existing evidence that early lifestyle-based interventions can significantly decrease the incidence of diabetes. However, whether effective interventions can reduce long-term outcomes in patients, including all-cause mortality, cardiovascular risks, and the occurrence of microvascular complications, which are the most concerning issues for both patients and clinicians, remains a subject of inconsistent research findings. And there is no direct evidence to answer whether effective intervention has long-term benefits for prediabetic patients. Therefore, we conducted a systematic review and meta-analysis to assess the relationship between early effective intervention and macrovascular and microvascular complications in prediabetic patients. Methods PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched for the randomized controlled trials of lifestyle or/and drugs intervention in prediabetes from inception to 2023.9.15. Two investigators independently reviewed the included studies and extracted relevant data. Random or fixed effects model meta-analysis to derive overall relative risk (RR) with 95% CI for all-cause mortality, cardiovascular events, and microvascular complications. Results As of September 15, 2023, a total of 7 effective intervention studies were included, comprising 26 articles out of 25,671 articles. These studies involved 26,389 patients with a total follow-up duration of 178,038.6 person-years. The results indicate that effective intervention can significantly reduce all-cause mortality in prediabetic patients without a history of cardiovascular disease by 17% (RR 0.83, 95% CI 0.70-0.98). Additionally, effective intervention reduced the incidence of retinopathy by 38% (RR 0.62, 95% CI 0.70-0.98). Furthermore, the study results suggest that women and younger individuals have lower all-cause mortality and cardiovascular mortality. Subsequently, we conducted an in-depth analysis of patients without a history of cardiovascular disease. The results revealed that prediabetic patients with a 10-year cardiovascular risk 10% experienced more significant benefits in terms of all-cause mortality ( P =0.01). When comparing the results of all-cause mortality and cardiovascular mortality from the Da Qing Diabetes Prevention Outcome Study longitudinally, it was evident that the duration of follow-up is a key factor influencing long-term benefits. In other words, the beneficial effects become more pronounced as the intervention duration reaches a certain threshold. Conclusion Early effective intervention, which significantly reduces the incidence of diabetes, can effectively lower all-cause mortality in prediabetic patients without a history of cardiovascular disease (especially those with a 10-year cardiovascular risk 10%), with women and younger individuals benefiting more significantly. Additionally, the duration of follow-up is a key factor influencing outcomes. The conclusions of this study can provide evidence-based guidance for the clinical treatment of prediabetic patients to prevent cardiovascular and microvascular complications. Systematic review registration https://www.crd.york.ac.uk/prospero , identifier CRD42020160985.