Association between Serum Zinc and Calcification Propensity (T50) in Patients with Type 2 Diabetes Mellitus and In Vitro Effect of Exogenous Zinc on T50.

Shinya Nakatani,Hideki Uedono,Tetsuo Shoji,Katsuhito Mori,Kozo Nishide,Akihiro Tsuda,Mika Sonoda,Masanori Emoto

doi:10.3390/biomedicines8090337

Shinya Nakatani, Hideki Uedono + Show 6 more

Open Access

https://doi.org/10.3390/biomedicines8090337

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Journal: Biomedicines	Publication Date: Sep 9, 2020
Citations: 10	License type: CC BY 4.0

Affiliation: Osaka City University, Inoue Hospital

Abstract

Zinc inhibits vascular calcification in vivo and in vitro. Patients with type 2 diabetes mellitus show hypozincemia and are at an elevated risk of cardiovascular events. Recently, an in vitro test (T50-test) was developed for determination of serum calcification propensity and a shorter T50 means a higher calcification propensity. This cross-sectional study investigated the association between serum zinc and T50 in 132 type 2 diabetes mellitus patients with various kidney functions. Furthermore, the effect of exogenous zinc on T50 was also investigated in vitro using separately pooled serum samples obtained from healthy volunteers and patients with hemodialysis. We measured T50 levels using the established nephelometric method. The median (interquartile range) levels of T50 and serum zinc were 306 (269 to 332) min, and 80.0 (70.1 to 89.8) µg/dL, respectively. Serum zinc level showed a weak, but positive correlation with T50 (rs = 0.219, p = 0.012). This association remained significant in multivariable-adjusted analysis, and was independent of known factors including phosphate, calcium, and magnesium. Kidney function and glycemic control were not significantly associated with T50. Finally, in vitro experiments showed that addition of a physiological concentration of exogenous zinc chloride significantly increased serum T50. Our results indicate that serum zinc is an independent factor with a potential role in suppressing calcification propensity in serum.

Highlights

Vascular calcification is common and contributes to cardiovascular mortality in patients with type 2 diabetes mellitus [1,2], as well as those with chronic kidney disease [3,4]
We examined the association between serum zinc and T50 levels in patients with type 2 diabetes mellitus
The first was a cross-sectional study using clinical data derived from our previous study of 143 patients with type 2 diabetes mellitus [39], while the second part was an in vitro study of the effect of increased zinc concentration on T50 assay findings, which was conducted using separately pooled serum samples obtained from healthy volunteers and patients with hemodialysis

Summary

Introduction

Vascular calcification is common and contributes to cardiovascular mortality in patients with type 2 diabetes mellitus [1,2], as well as those with chronic kidney disease [3,4]. Excess cardiovascular morbidity and mortality in those patients could be explained by redistribution and/or overload of calcium and phosphorus. The mechanism of vascular calcification is supposed to be due to ectopic deposition of hydroxyapatite [5,6] induced by increased calcium-phosphorus product (Ca × P). (BMP-2), oxidized lipids, and inflammation are known to accelerate vascular calcification [10]. It has been reported that matrix Gla protein (MGP), osteoprotegerin, and osteopontin act on the vascular wall as calcification inhibitors [11]

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