Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Feb;69(2):634-642.
doi: 10.1007/s10620-023-08214-7. Epub 2023 Dec 19.

Parental History of Type 2 Diabetes Mellitus and PNPLA3 Polymorphism Increase the Risk of Severe Stages of Nonalcoholic Fatty Liver Disease

Natalia Balassiano Wajsbrot  1 , Nathalie Carvalho Leite  2 , Paulo Henrique Condeixa Franca  3 , Claudia Regina Lopes Cardoso  4 , Gil Fernando Salles  4 , Cristiane A Villela-Nogueira  4
Affiliations

Parental History of Type 2 Diabetes Mellitus and PNPLA3 Polymorphism Increase the Risk of Severe Stages of Nonalcoholic Fatty Liver Disease

Natalia Balassiano Wajsbrot et al. Dig Dis Sci. 2024 Feb.

Abstract

Background & aims: In non-alcoholic fatty liver disease (NAFLD), the influence of parental history of type 2 diabetes (T2D) allied to single nucleotide polymorphisms (SNPs) in the offspring is not known. We aimed to investigate the impact of the parental history of T2D, PNPLA3 and TM6SF2 polymorphisms in liver steatosis and fibrosis.

Methods: This was a case-control study involving the offspring of T2D patients and controls without a parental history of T2D. Participants underwent clinical and laboratory evaluation, transient elastography (TE) by Fibroscan® (Echosens, Fr) and genotyping for PNPLA3 and TM6SF2. Multivariate logistic regression evaluated the influence of parental history of T2D on liver steatosis and fibrosis, controlled for age, gender, metabolic traits and SNPs.

Results: 161 T2D offspring and 78 controls, 10-46 years old, were included. The offspring of T2D had higher prevalences of obesity, T2D, arterial hypertension and sedentarism. Parental history of T2D was associated with fibrosis ≥ F2 (OR 8.89, CI 95% 1.09-72.01, p = 0.041) after adjustment for age, gender, metabolic traits and SNPs. PNPLA3 GG genotype was independently associated with steatosis ≥ S1 (OR 8.15, CI 95% 1.93-34.38, p = 0.004) and fibrosis ≥ F2 (OR 4.31, CI 95% 1.11-16.61, p = 0.034).

Conclusions: The offspring of T2D patients present a worse metabolic profile and the parental history of T2D confers an increased likelihood of hepatic fibrosis, independent of metabolic factors. PNPLA3 homozygous GG, but not TM6SF2 genotypes, also impacts on this phenotype.

Keywords: Hepatic fibrosis; NAFLD; Offspring; PNPLA3; TM6SF2; Type 2 diabetes mellitus.

PubMed Disclaimer

References

    1. Lazo M, Clark JM. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis. 2008;28:339–350. https://doi.org/10.1055/s-0028-1091978 . - DOI - PubMed
    1. Younossi ZM, Tampi R, Priyadarshini M, Nader F, Younossi IM, Racila A. Burden of illness and economic model for patients with nonalcoholic steatohepatitis in the United States. Hepatology. 2019;69:564–572. https://doi.org/10.1002/hep.30254 . - DOI - PubMed
    1. Pais R, Barritt AS, Calmus Y et al. NAFLD and liver transplantation: current burden and expected challenges. J Hepatol. 2016;65:1245–1257. https://doi.org/10.1016/j.jhep.2016.07.033 . - DOI - PubMed - PMC
    1. Younossi ZM, Golabi P, de Avila L et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis. J Hepatol. 2019;71:793–801. https://doi.org/10.1016/j.jhep.2019.06.021 . - DOI - PubMed
    1. Willner IR, Waters B, Patil SR, Reuben A, Morelli J, Riely CA. Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease. Am J Gastroenterol. 2001;96:2957–2961. https://doi.org/10.1111/j.1572-0241.2001.04667.x . - DOI - PubMed

Substances

LinkOut - more resources