Postloading insulinemia is independently associated with arterial stiffness in young Japanese persons

Norimitsu Murai,Yasuyoshi Kigawa,Shoichiro Nagasaka,Rie Tadokoro,Fumiko Otsuka,Eriko Kodama,Kei Endo,Shun Ishibashi,Asami Suzuki,Naoko Saito,Tatsuya Iida,Chiho Sugisawa,Yuto Nishikawa,Hideyuki Imai,Kentaro Mikura,Toru Iizaka,Mai Hashizume,Sayuri Nii

doi:10.1038/s41440-021-00749-4

Norimitsu Murai, Yasuyoshi Kigawa + Show 16 more

Open Access

https://doi.org/10.1038/s41440-021-00749-4

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Abstract

Associations of arterial stiffness with glucose, insulin, and proinsulin dynamics during the oral glucose tolerance test (OGTT) remain under debate. The aim of this study was to investigate whether plasma glucose (PG), insulin, and proinsulin (Pro) contribute to arterial stiffness, measured by pulse wave velocity (PWV), in young Japanese persons. PG, immunoreactive insulin (IRI), and Pro levels were determined in 1193 young Japanese subjects (<40 years of age) with normal glucose tolerance or nondiabetic hyperglycemia before and at 30, 60, and 120 min during a 75-g OGTT. Participants were divided into two groups according to the median PWV. Background factors, PG, IRI, and Pro levels during the OGTT, and insulin sensitivity (SI) indices in each group were compared. Several multiple regression analysis models were used to evaluate factors contributing to PWV. All IRI and Pro levels before and after glucose loading and the area under the curve (AUC) values for IRI and Pro increased with higher PWV. 1/HOMA-IR and ISI-Matsuda as measures of SI decreased with higher PWV. The IRI AUC and Pro level before glucose loading (Pro0) were independently associated with PWV, in addition to male sex, heart rate, and mean blood pressure. The IRI AUC had a stronger relationship with PWV than Pro0. The IRI AUC had an independent relationship with PWV, whereas both SI indices did not. Postloading insulinemia, but not reduced SI, was independently associated with arterial stiffness in young Japanese persons.

Highlights

Hyperglycemia, such as that seen in nondiabetic hyperglycemia (NDH) and diabetes mellitus (DM), is a well-known risk factor for cerebrocardiovascular diseases [1,2,3]
The participants were young, and no significant differences in Low-density lipoprotein cholesterol (LDL), Total cholesterol (T-C), frequency of NDH, or high-sensitivity C-reactive protein (hsCRP) levels were seen between Brachial-ankle PWV (baPWV) groups
Number of males, body mass index (BMI), Waist circumference (WC), Heart rate (HR), SBP, DBP, Mean blood pressure (MBP), and TG levels increased with higher baPWV, but high-density lipoprotein cholesterol (HDL) and adiponectin levels decreased with higher baPWV

Summary

Introduction

Hyperglycemia, such as that seen in nondiabetic hyperglycemia (NDH) and diabetes mellitus (DM), is a well-known risk factor for cerebrocardiovascular diseases [1,2,3]. Evaluation of cerebrocardiovascular complications is important for predicting patient outcomes. OGTT 1-h glucose levels are associated with arterial stiffness [17,18,19], and associations are reported between 1-h OGTT glucose levels and the risk of diabetes onset, cardiovascular risk factors, and death [20,21,22,23]. These studies, failed to sufficiently evaluate postloading insulin or Pro levels. The above studies failed to fully show whether postloading glucose, previously cited measures such as insulin or Pro levels, or insulin resistance is most relevant to arterial stiffness

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