Type 2 Diabetes Is Associated with a Different Pattern of Serum Polyamines: A Case⁻Control Study from the PREDIMED-Plus Trial.

Jose Fernandez-Garcia,Daniel Castellano-Castillo,Bruno Ramos-Molina,Antoni Delpino-Rius,Fernando Cardona,Maria Queipo-Ortuño,Maria Bernal-Lopez,Iris Samarra,Araceli Muñoz-Garach,Francisco Tinahones

doi:10.3390/jcm8010071

Abstract

Objective: Polyamines are naturally occurring cationic molecules present in all living cells. Dysregulation of circulating polyamines has been reported in several conditions, but little is known about the levels of serum polyamines in chronic metabolic disorders such as type 2 diabetes (T2D). Therefore, the aim of this study was to evaluate the polyamine-related metabolome in a cohort of metabolic syndrome individuals with and without T2D. Design and methods: This was a nested case–control study within the PREDIMED-Plus trial that included 44 patients with T2D and 70 patients without T2D. We measured serum levels of arginine, ornithine, polyamines, and acetyl polyamines with an ultra-high performance liquid chromatography tandem mass spectrometry platform. Results: Our results showed that serum putrescine, directly generated from ornithine by the catalytic action of the biosynthetic enzyme ornithine decarboxylase, was significantly elevated in patients with T2D compared to those without T2D, and that it significantly correlated with the levels of glycosylated hemoglobin (HbA1c). Correlation analysis revealed a significantly positive association between fasting insulin levels and spermine. Multiple logistic regression analysis (adjusted for age, gender and body weight index) revealed that serum putrescine and spermine levels were associated with a higher risk of T2D. Conclusions: Our study suggests that polyamine metabolism is dysregulated in T2D, and that serum levels of putrescine and spermine are associated with glycemic control and circulating insulin levels, respectively.

Highlights

Polyamines, cationic compounds widely distributed in living organisms, participate in a myriad of cellular functions, including cell proliferation, apoptosis, and differentiation [1,2,3]
While there were no significant differences in age, blood pressure, HDL-cholesterol or triglyceride levels between study groups, patients with type 2 diabetes (T2D) showed significantly higher BMI, waist circumference, HbA1c levels, fasting glucose, insulin, and HOMA-IR
Whereas the serum levels of arginine and ornithine were lower in T2D subjects, putrescine, which is directly produced from ornithine by the enzymatic activity of ornithine decarboxylase (ODC)

Summary

Introduction

Polyamines, cationic compounds widely distributed in living organisms, participate in a myriad of cellular functions, including cell proliferation, apoptosis, and differentiation [1,2,3]. Putrescine, spermidine, and spermine are the predominant polyamines in mammalian cells. Polyamine metabolism can be dysregulated in certain pathological conditions such as cancer, inflammation, stroke, neurological disorders and renal failure [5,6,7,8]. The dysregulation of polyamine metabolism has been shown to impact glucose, lipid and energy homeostasis [9,10,11,12,13,14]. A number of studies using animal models of obesity have reported impaired levels of polyamines in adipose tissue [15], liver [16,17], pancreatic islets [18], and urine [19]

Methods

Results

Conclusion