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Acta Diabetologica

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27-01-2024 | Insulins | Original Article

Association between a polygenic lipodystrophy genetic risk score and diabetes risk in the high prevalence Maltese population

Authors: Maria Zammit, Rachel Agius, Stephen Fava, Josanne Vassallo, Nikolai Paul Pace

Published in: Acta Diabetologica | Issue 5/2024

Abstract

Background

Type 2 diabetes (T2DM) is genetically heterogenous, driven by beta cell dysfunction and insulin resistance. Insulin resistance drives the development of cardiometabolic complications and is typically associated with obesity. A group of common variants at eleven loci are associated with insulin resistance and risk of both type 2 diabetes and coronary artery disease. These variants describe a polygenic correlate of lipodystrophy, with a high metabolic disease risk despite a low BMI.

Objectives

In this cross-sectional study, we sought to investigate the association of a polygenic risk score composed of eleven lipodystrophy variants with anthropometric, glycaemic and metabolic traits in an island population characterised by a high prevalence of both obesity and type 2 diabetes.

Methods

814 unrelated adults (n = 477 controls and n = 337 T2DM cases) of Maltese-Caucasian ethnicity were genotyped and associations with phenotypes explored.

Results

A higher polygenic lipodystrophy risk score was correlated with lower adiposity indices (lower waist circumference and body mass index measurements) and higher HOMA-IR, atherogenic dyslipidaemia and visceral fat dysfunction as assessed by the visceral adiposity index in the DM group. In crude and covariate-adjusted models, individuals in the top quartile of polygenic risk had a higher T2DM risk relative to individuals in the first quartile of the risk score distribution.

Conclusion

This study consolidates the association between polygenic lipodystrophy risk alleles, metabolic syndrome parameters and T2DM risk particularly in normal-weight individuals. Our findings demonstrate that polygenic lipodystrophy risk alleles drive insulin resistance and diabetes risk independent of an increased BMI.

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Title: Association between a polygenic lipodystrophy genetic risk score and diabetes risk in the high prevalence Maltese population
Authors: Maria Zammit
Rachel Agius
Stephen Fava
Josanne Vassallo
Nikolai Paul Pace
Publication date: 27-01-2024
Publisher: Springer Milan
Keywords: Insulins
Insulins
Type 2 Diabetes
Obesity
Obesity
Published in: Acta Diabetologica / Issue 5/2024
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-023-02230-9

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Abstract

Background

Objectives

Methods

Results

Conclusion

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