A Preliminary Study Showing the Impact of Genetic and Dietary Factors on GC-MS-Based Plasma Metabolome of Patients with and without PROX1-Genetic Predisposition to T2DM up to 5 Years Prior to Prediabetes Appearance.

Patrycja Mojsak,Katarzyna Miniewska,Adrian Godlewski,Michal Ciborowski,Paulina Samczuk,Edyta Adamska-Patruno,Adam Kretowski,Coral Barbas,Fernanda Rey-Stolle,Witold Bauer

doi:10.3390/cimb43020039

Patrycja Mojsak, Katarzyna Miniewska + Show 8 more

Open Access

https://doi.org/10.3390/cimb43020039

Copy DOI

Abstract

Risk factors for type 2 diabetes mellitus (T2DM) consist of a combination of an unhealthy, imbalanced diet and genetic factors that may interact with each other. Single nucleotide polymorphism (SNP) in the prospero homeobox 1 (PROX1) gene is a strong genetic susceptibility factor for this metabolic disorder and impaired β-cell function. As the role of this gene in T2DM development remains unclear, novel approaches are needed to advance the understanding of the mechanisms of T2DM development. Therefore, in this study, for the first time, postprandial changes in plasma metabolites were analysed by GC–MS in nondiabetic men with different PROX1 genotypes up to 5 years prior to prediabetes appearance. Eighteen contestants (12 with high risk (HR) and 6 with low risk (LR) genotype) participated in high-carbohydrate (HC) and normo-carbohydrate (NC) meal-challenge tests. Our study concluded that both meal-challenge tests provoked changes in 15 plasma metabolites (amino acids, carbohydrates, fatty acids and others) in HR, but not LR genotype carriers. Postprandial changes in the levels of some of the detected metabolites may be a source of potential specific early disturbances possibly associated with the future development of T2DM. Thus, accurate determination of these metabolites can be important for the early diagnosis of this metabolic disease.

Highlights

Type 2 diabetes mellitus (T2DM) is a complex polygenic disorder [1] characterised by the incapability of pancreatic β-ells to increase insulin secretion to compensate for insulin resistance (IR) in peripheral tissues [2]
This study revealed that plasma metabolites postprandially changing in the high-risk prospero homeobox 1 (PROX1) genotype carriers belong to T2DM-related metabolic pathways [11]
The groups were well matched without any between-group differences in age, anthropometric measurements (body mass index (BMI), body fat and fat-free mass content), fasting glucose and insulin level, as well as HOMA-IR, HOMA-B and glycated haemoglobin (HbA1c)

Summary

Introduction

Type 2 diabetes mellitus (T2DM) is a complex polygenic disorder [1] characterised by the incapability of pancreatic β-ells to increase insulin secretion to compensate for insulin resistance (IR) in peripheral tissues [2]. A proper diet and systematic physical activity are essential lifestyle determinants of potential T2DM development. The role of these modifiable factors in the prevention of T2DM strongly depends on genetic susceptibility. An indication of T2DM risk subgroups with genetic characteristics known to promote disease development, especially sensitive to specific foods, nutrients or physical activity, may help design and implement individualised and targeted intervention and/or prevention strategies [6]. It was indicated that mechanisms by which the PROX1 gene affects the susceptibility to T2DM seem to be more complex [9]. Identifying individuals with high risk for T2DM and elucidating the underlying mechanisms is crucial for developing effective strategies to prevent this disease [5]

Methods

Results

Discussion

Conclusion