Background: A bidirectional relationship between hypothyroidism and nonalcoholic fatty liver disease (NAFLD) has been proposed. Fasting hyperglucagonemia in patients with hypothyroidism induced NAFLD needs to be further clarified. The aim of the present study was to determine fasting serum glucagon levels in hypothyroid adults with and without NAFLD. The possible association between fasting glucagon and NAFLD in patients with hypothyroidism was also evaluated.
Methods: This study was comprised 60 patients with uncontrolled hypothyroidism and 30 healthy controls matched for age and sex. Patients with hypothyroidism were divided into 2 groups: 30 patients with NAFLD and 30 patients without NAFLD. Diagnosis of NAFLD was based on the combination of hepatic steatosis index (HSI) at a cutoff value of 36 and measurements of steatosis using fibroScan. Anthropometric measurements, lipids profile, homeostasis model assessment of insulin resistance (HOMA-IR), free thyroxine (FT4), triiodothyronine (FT3), thyroid stimulating hormone (TSH) and serum fasting glucagon were assessed.
Results: Serum fasting glucagon concentration was significantly higher in hypothyroid patients with and without NAFLD than in healthy controls; glucagon was also significantly higher in the hypothyroid patients with NAFLD than in those without NAFLD. Fasting glucagon was significantly correlated with waist circumference (WC), body mass index (BMI), TSH, HSI and fibroScan parameters in hypothyroid patients with NAFLD. Fasting glucagon predicts NAFLD in patients with hypothyroidism at a cutoff value 85 ng/L with 90% sensitivity, 100% specificity and p < 0.001. With multivariable analysis, age, BMI and TSH were significant positive predictors of NAFLD in patients with hypothyroidism.
Conclusion: Fasting glucagon concentration may play a role in the development of NAFLD in patients with hypothyroidism. However, the exact underlying mechanism needs further studies.
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http://dx.doi.org/10.1186/s12986-025-00899-z | DOI Listing |
Nutr Metab (Lond)
March 2025
Internal Medicine Department, Mansoura Specialized Medical Hospital, Faculty of Medicine, Egyptian Liver Research Institute, Mansoura University, Sherben, Egypt.
Background: A bidirectional relationship between hypothyroidism and nonalcoholic fatty liver disease (NAFLD) has been proposed. Fasting hyperglucagonemia in patients with hypothyroidism induced NAFLD needs to be further clarified. The aim of the present study was to determine fasting serum glucagon levels in hypothyroid adults with and without NAFLD.
View Article and Find Full Text PDFNat Rev Endocrinol
March 2025
Division of Endocrinology, Department of Medicine, Duke University, Durham, NC, USA.
The pancreatic islets of Langerhans are central to fine-tuning metabolism to ensure metabolic homeostasis during the transition between fasting and feeding. Insulin and glucagon, the principal hormones generated and secreted by islets, exert powerful control in various metabolic tissues to drive nutrient uptake, storage and metabolism. Their canonical actions on glycaemia have positioned these hormones in opposition, however, their metabolic actions extend beyond controlling blood levels of glucose.
View Article and Find Full Text PDFCell Metab
March 2025
Life Sciences Institute and Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA. Electronic address:
Starvation triggers an organismal adaptive response that is orchestrated by endocrine factors. In this issue of Cell Metabolism, Long et al. uncover a famsin-glucagon axis that relays gut-derived hormonal cues to systemic glucose homeostasis during fasting.
View Article and Find Full Text PDFMol Metab
March 2025
The August Krogh Section for Human & Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark. Electronic address:
Background: Low-carbohydrate, high-fat diets under eucaloric conditions are associated with several health-beneficial metabolic effects in humans, particularly in the liver. We recently observed that apolipoprotein A-IV (apoA-IV), a highly abundant apolipoprotein, was among the most upregulated proteins in circulation after six weeks of consuming a high-fat diet in humans. However, the impact of dietary changes in regulating apoA-IV, and the potential effects of apoA-IV on regulation of glucose- and lipid metabolism remain to be fully established.
View Article and Find Full Text PDFIntroduction: Oral semaglutide, a glucagon-like peptide 1 receptor agonist, requires administration on an empty stomach with up to 120 mL of water, followed by no intake of food, beverages, or other oral medications for at least 30 min to ensure optimal absorption. These instructions can be challenging to adhere to during Ramadan when patients fast for extended periods. The O-SEMA-FAST study assessed the impact of fasting on adherence to oral semaglutide dosing instructions and its subsequent effects on glycaemic control and body weight.
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