Intensity of Glycemic Exposure in Early Adulthood and Target Organ Damage in Middle Age: The CARDIA Study.

Yifen Lin,Yiquan Huang,Daya Yang,Xingfeng Xu,Xiaomin Ye,Yuqi Li,Zhenyu Xiong,Huimin Zhou,Shaozhao Zhang,Yue Guo,Xiangbin Zhong,Xinxue Liao,Xiaodong Zhuang,Xiuting Sun,Yongqiang Fan,Menghui Liu

doi:10.3389/fphys.2021.614532

Abstract

AimTo determine whether long-term intensity of glycemic exposure (IGE) during young adulthood is associated with multiple target organs function at midlife independent of single fasting glucose (FG) measurement.MethodsWe included 2,859 participants, aged 18–30 years at Y0, in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. IGE was calculated as the sum of (average FG of two consecutive examinations × years between the examinations) over 25 years. Target organs function was indicated by cardiac structure, left ventricular (LV) systolic function, LV diastolic function, coronary artery calcium (CAC), and urine albumin-to-creatinine ratio (UACR) at Y25. We evaluated the associations between IGE with target organs function using linear regression models and estimated the associations between IGE with numbers of organs involved (0, 1, or ≥ 2 organs) using multinomial logistic regression models.ResultsA 1-SD increment of IGE was significantly associated with worse target organs function after multivariable adjustment: left ventricular mass (β [SE], 5.468 [1.175]); global longitudinal strain (β [SE], 0.161 [0.071]); E/e’ ratio (β[SE], 0.192 [0.071]); CAC score (β [SE], 27.948 [6.116]); and log UACR (β [SE], 0.076 [0.010]). Besides, IGE was independently associated with having ≥ 2 organs involved in both overall population (OR [95% CI], 1.48 [1.23, 1.41], P < 0.001) and subgroups stratified by diabetes at Y25.ConclusionHigher intensity of glycemic exposure during young adulthood was independently associated with subclinical alterations of target organs function at midlife. Our findings highlight the importance of early screening and management of IGE in youth.

Highlights

Individuals with long-term exposure to hyperglycemia underwent chronic injuries to multiple organ systems
We evaluated the association between intensity of glycemic exposure (IGE) and the number of target organs involved
It should be noted that the association were statistically significant in both DM and non-DM subgroups. In this prospective cohort of young adults followed up over 25 years, we demonstrated greater IGE during young adulthood was associated with unfavorable impairment of multiple target organs, including subclinical cardiac structural and functional impairment, subclinical atherosclerosis, and albuminuria independent of fasting glucose at Y25

Summary

Introduction

Individuals with long-term exposure to hyperglycemia underwent chronic injuries to multiple organ systems. Since chronic exposure to glycemia shows detrimental impacts on target organs, a life-course evaluation of glycemic exposure considering both the magnitude and duration of exposure to hyperglycemia should be established for comprehensive assessment of its toxicity. Attempts have been made to investigate the long-term impact of glycemic exposure based on the longterm blood glucose trajectory, which was associated with mortality and cardiovascular disease (Lee et al, 2018; Ogata et al, 2019). Long-term trajectories clustered the subjects into different groups based on the change tendency of blood glucose, leading to inaccurate assessment of glycemic exposure (Nagin and Odgers, 2010). The association between increased intensity of glycemic exposure (IGE) in young adulthood with target organ damages (TOD) in midlife deserves investigation

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