Diabetes attenuates weight reduction-mediated liver fibrosis regression in persons with morbid obesity.
4 affiliations
- 1Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
- 2Department of Human Pathology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
- 3Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
- 4Department of Surgery, Kanazawa University Hospital, Kanazawa, Japan.
Abstract
Aims
Weight loss by laparoscopic sleeve gastrectomy (LSG) compared to medical weight loss (low-calorie diet: LCD) ameliorates diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to evaluate changes in liver pathology 1-year after LSG and their associations with metabolic factors in Japanese participants with severe obesity.Materials and methods
We recruited 27 Japanese participants with severe obesity (BMI > 35 kg/m²) and metabolic disorders who showed inadequate weight loss after at least 6 months of medical treatment. LSG was performed after 4 weeks of LCD. Liver biopsy samples were obtained intraoperatively and at 1-year after surgery. The primary endpoint was the change in liver histopathological scores.Results
LSG significantly reduced histological scores in hepatic steatosis, hepatocellular ballooning, lobular inflammation, and hepatic fibrosis, together with fasting plasma glucose, hemoglobin A1c, body weight, body mass index, and liver enzymes. Reduction in steatosis was associated with a reduction in glycemic parameters and γ-glutamyl transpeptidase. Reduction in lobular inflammation was associated with reductions in liver enzyme levels and hemoglobin A1c. Changes in hepatic fibrosis were not associated with metabolic or biochemical changes but were related to baseline fibrosis severity and the presence of diabetes. Unexpectedly, weight reduction significantly lowered platelet counts and elevated the fibrosis-4 index.Conclusion
LSG improves liver histopathology of MASLD in Japanese participants with severe obesity. The comorbidity of diabetes was associated with attenuated improvement in liver fibrosis after LSG, suggesting that glycemic status and diabetes-related factors may be key modifiers of fibrosis reversibility in MASLD.
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BibTeX
@article{matsubara2026diabetes,
title = {{Diabetes attenuates weight reduction-mediated liver fibrosis regression in persons with morbid obesity.}},
author = {Daiki Matsubara and Yumie Takeshita and Masahiro Mori and Yujiro Nakano and Kenichi Harada and Noboru Takata and Kengo Hayashi and Hideki Moriyama and Noriyuki Inaki and Masao Honda and Taro Yamashita and Toshinari Takamura},
journal = {Journal of diabetes investigation},
year = {2026},
month = oct,
doi = {10.1111/jdi.70465},
url = {https://europepmc.org/article/MED/42852796},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Diabetes attenuates weight reduction-mediated liver fibrosis regression in persons with morbid obesity.
AU - Daiki Matsubara
AU - Yumie Takeshita
AU - Masahiro Mori
AU - Yujiro Nakano
AU - Kenichi Harada
AU - Noboru Takata
AU - Kengo Hayashi
AU - Hideki Moriyama
AU - Noriyuki Inaki
AU - Masao Honda
AU - Taro Yamashita
AU - Toshinari Takamura
PY - 2026
DA - 2026/10/09
JO - Journal of diabetes investigation
DO - 10.1111/jdi.70465
UR - https://europepmc.org/article/MED/42852796
AB - Aims Weight loss by laparoscopic sleeve gastrectomy (LSG) compared to medical weight loss (low-calorie diet: LCD) ameliorates diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to evaluate changes in liver pathology 1-year after LSG and their associations with metabolic factors in Japanese participants with severe obesity.Materials and methods We recruited 27 Japanese participants with severe obesity (BMI > 35 kg/m²) and metabolic disorders who showed inadequate weight loss after at least 6 months of medical treatment. LSG was performed after 4 weeks of LCD. Liver biopsy samples were obtained intraoperatively and at 1-year after surgery. The primary endpoint was the change in liver histopathological scores.Results LSG significantly reduced histological scores in hepatic steatosis, hepatocellular ballooning, lobular inflammation, and hepatic fibrosis, together with fasting plasma glucose, hemoglobin A1c, body weight, body mass index, and liver enzymes. Reduction in steatosis was associated with a reduction in glycemic parameters and γ-glutamyl transpeptidase. Reduction in lobular inflammation was associated with reductions in liver enzyme levels and hemoglobin A1c. Changes in hepatic fibrosis were not associated with metabolic or biochemical changes but were related to baseline fibrosis severity and the presence of diabetes. Unexpectedly, weight reduction significantly lowered platelet counts and elevated the fibrosis-4 index.Conclusion LSG improves liver histopathology of MASLD in Japanese participants with severe obesity. The comorbidity of diabetes was associated with attenuated improvement in liver fibrosis after LSG, suggesting that glycemic status and diabetes-related factors may be key modifiers of fibrosis reversibility in MASLD.
SN - 2040-1116
SN - 2040-1124
ER -