Abstract

AimThis study aimed to assess whether a higher insulin response increased the long-term risk of mortality in a non-diabetic population.MethodsA total of 446 people with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) who participated in the Da Qing Diabetes Study, were stratified into quartiles subgroups according to their baseline insulin area under the curve (AUC) during oral glucose tolerance test, defined as Q1, Q2, Q3 and Q4. The participants were followed from 1986 to 2016 to assess the risk of death in association with the magnitude of post-load insulin response.ResultsOver 30 years, the rates of all cause death were 9.94, 14.81, 15.02, and 17.58 per 1000 person-years across the four groups respectively. The rate for cardiovascular disease (CVD) death was 5.14, 6.50, 6.80 and 10.47 per 1000 person-years. Compared with Q1, the risk of all-cause death was significantly higher in participants in Q4 (HR = 2.14, 95% CI 1.34–3.42), Q3 (HR = 1.94, 95% CI 1.20–3.14), and Q2 group (HR = 1.70, 95% CI 1.06–2.74). In the Fine-Gray model with non-CVD death as competing risk, the increased insulin AUC were also significantly associated with the CVD death (Q4 vs Q1, HR = 2.04, 95% CI 1.10–3.79). In the fractional polynomial regression analysis, a nonlinear association between insulin AUC and all-cause and CVD death was demonstrated. In addition, insulin AUC was associated with a progressively higher risk of all-cause death and CVD death (fractional power 3, P < 0.001).ConclusionA higher post-load insulin response was significantly associated with a long-term increased risk of all-cause and CVD deaths in the Chinese non-diabetic population. It suggests that people featured by this phenotype is a potential important target for further intervention.

Highlights

  • Several studies had suggested that a higher blood insulin concentration in non-diabetic people may have contributed to the increased risk of death

  • After adjusted for age, sex and smoking status, Cox proportional hazards analysis showed that compared with Q1, the risk of all-cause death was significantly higher in participants in Q4 (HR=2.14, 95% Confidence intervals (CIs) 1.34–3.42), Q3 (HR=1.94, 95% CI 1.20–3.14), and Q2 (HR=1.70,95% CI 1.06–2.74)

  • As for cardiovascular disease (CVD) death risk, participants in Q4 showed a higher risk than those in Q1 (HR=2.56, 95% CI 1.35–4.82) (Fig. 1)

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Summary

Introduction

Several studies had suggested that a higher blood insulin concentration in non-diabetic people may have contributed to the increased risk of death. In line with that result, an 11-year follow-up investigation of the Paris Prospective Study demonstrated that fasting plasma insulin level was an independent predictor of cardiovascular disease death after adjusting for overt diabetes [2]. The results varied in the 15-year follow-up investigation of the same study, wherein the 2-h post-load plasma insulin level was a significant predictor of CVD-related death, while levels of blood glucose were not a significant predictor after the adjustment of plasma insulin levels. The author addressed that insulin response to oral glucose tolerance test (OGTT) requires further investigation as a potential risk factor for coronary artery disease and a potential target for further intervention [3]

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