Racial/ethnic and gender disparity in the severity of NAFLD among people with diabetes or prediabetes

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Abstract

Aim: Non-alcoholic fatty liver disease (NAFLD) exhibits a racial disparity. We examined the prevalence and the association between race, gender, and NAFLD among prediabetes and diabetes populations among adults in the United States.

Methods: We analyzed data for 3,190 individuals ≥18 years old from the National Health and Nutrition Examination Survey (NHANES) 2017–2018. NAFLD was diagnosed by FibroScan ^® using controlled attenuation parameter (CAP) values: S0 (none) < 238, S1 (mild) = 238–259, S2 (moderate) = 260–290, S3 (severe) > 290. Data were analyzed using Chi-square test and multinomial logistic regression, adjusting for confounding variables and considering the design and sample weights.

Results: Of the 3,190 subjects, the prevalence of NAFLD was 82.6%, 56.4%, and 30.5% ( p < 0.0001) among diabetes, prediabetes and normoglycemia populations respectively. Mexican American males with prediabetes or diabetes had the highest prevalence of severe NAFLD relative to other racial/ethnic groups ( p < 0.05). In the adjusted model, among the total, prediabetes, and diabetes populations, a one unit increase in HbA1c was associated with higher odds of severe NAFLD [adjusted odds ratio (AOR) = 1.8, 95% confidence level (CI) = 1.4–2.3, p < 0.0001; AOR = 2.2, 95% CI = 1.1–4.4, p = 0.033; and AOR = 1.5, 95% CI = 1.1–1.9, p = 0.003 respectively].

Conclusion: We found that prediabetes and diabetes populations had a high prevalence and higher odds of NAFLD relative to the normoglycemic population and HbA1c is an independent predictor of NAFLD severity in prediabetes and diabetes populations. Healthcare providers should screen prediabetes and diabetes populations for early detection of NAFLD and initiate treatments including lifestyle modification to prevent the progression to non-alcoholic steatohepatitis or liver cancer.

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Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.

Paul Nathan, Elizabeth Barrett, John M. Lachin … (2002)

Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors--elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle--are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes. We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups. The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin. Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.

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Mechanisms of NAFLD development and therapeutic strategies

Mary Rinella, Arun Sanyal, Scott Friedman … (2018)

There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosis and liver cancer. Here we review the pathogenic and clinical features of NAFLD, its major comorbidities, clinical progression and risk of complications and in vitro and animal models of NAFLD enabling refinement of therapeutic targets that can accelerate drug development. We also discuss evolving principles of clinical trial design to evaluate drug efficacy and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression.

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Modulation of Insulin Resistance in Nonalcoholic Fatty Liver Disease

Reenam Khan, Fernando Bril, Kenneth Cusi … (2019)

Nonalcoholic fatty liver disease (NAFLD) has an estimated prevalence of 25% in the general population, and cirrhosis secondary to nonalcoholic steatohepatitis (NASH) is predicted to become the leading cause of liver transplantation, yet there is a lack of effective licensed treatments for these conditions. There is a close relationship between insulin resistance (IR) and NAFLD, with prevalence of NAFLD being 5-fold higher in patients with diabetes compared to those without. IR is implicated both in pathogenesis of NAFLD and in disease progression from steatosis to NASH. Thus, modulation of IR represents a potential strategy for NAFLD treatment. This review highlights key proposed mechanisms linking IR and NAFLD, such as changes in rates of adipose tissue lipolysis and de novo lipogenesis, impaired mitochondrial fatty acid β-oxidation (FAO), changes in fat distribution, alterations in the gut microbiome, and alterations in levels of adipokines and cytokines. Furthermore, this review will discuss the main pharmacological strategies used to treat IR in patients with NAFLD and their efficacy based on recently published experimental and clinical data. These include biguanides, glucagon-like peptide 1 receptor (GLP-1) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, peroxisome proliferator-activated receptor (PPAR-γ/α/δ) agonists, sodium glucose cotransporter 2 (SGLT2) inhibitors, and farnesoid X receptor (FXR) agonists, with further novel treatments on the horizon. Ideally, treatment would improve IR, reduce cardiovascular risk, and produce demonstrable improvements in NASH histology-this is likely to be achieved with a combinatorial approach.

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Author and article information

Contributors

Magda Shaheen: URI : https://loop.frontiersin.org/people/1313997/overview

Katrina M. Schrode: URI : https://loop.frontiersin.org/people/2118270/overview

Marielle Tedlos: URI : https://loop.frontiersin.org/people/2065288/overview

Deyu Pan: URI : https://loop.frontiersin.org/people/2203814/overview

Sonia M. Najjar: URI : https://loop.frontiersin.org/people/405929/overview

Theodore C. Friedman: URI : https://loop.frontiersin.org/people/685267/overview

Journal

Journal ID (nlm-ta): Front Physiol

Journal ID (iso-abbrev): Front Physiol

Journal ID (publisher-id): Front. Physiol.

Title: Frontiers in Physiology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-042X

Publication date (Electronic): 20 February 2023

Publication date Collection: 2023

Volume: 14

Electronic Location Identifier: 1076730

Affiliations

[1] ¹ Charles R. Drew University , Los Angeles, CA, United States

[2] ² Heritage College of Osteopathic Medicine , Ohio University , Athens, OH, United States

Author notes

Edited by: Germán Perdomo, Instituto de Biología y Genética Molecular (IBGM) (CSIC), Spain

Reviewed by: Marta García-Arévalo, Rey Juan Carlos University, Spain

Beatriz Merino, University of Valladolid, Spain

*Correspondence: Magda Shaheen, magdashaheen@ 123456cdrewu.edu

This article was submittedto Metabolic Physiology, a section of the journal Frontiers in Physiology

Article

Publisher ID: 1076730

DOI: 10.3389/fphys.2023.1076730

PMC ID: 9986441

PubMed ID: 36891143

SO-VID: b846253f-c6af-4b67-8621-fdda2368a275

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 21 October 2022

Date accepted : 03 February 2023

Funding

This study was supported by the National Institutes of Health grants NIMHD R01MD012579, U54MD007598, S21MD000103, NIDA R25 DA050723-01A1, and NCATS UL1TR000124.

Racial/ethnic and gender disparity in the severity of NAFLD among people with diabetes or prediabetes

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Most cited references 38

Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.

Mechanisms of NAFLD development and therapeutic strategies

Modulation of Insulin Resistance in Nonalcoholic Fatty Liver Disease

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