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ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Clinical Diabetes
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1576431
This article is part of the Research TopicResearch in Obesity, Type 2 Diabetes, and Metabolic Syndrome: Cellular Pathways and Therapeutic InnovationsView all 4 articles
Energy landscape analysis of health checkup data clarified multiple pathways to diabetes development in obese and non-obese subjects
Provisionally accepted
Ryo Ito1
Makito Oku1*
Iwao Kimura1Takayuki Haruki1Masataka Shikata1Tsuyoshi Teramoto1Daisuke Chujo1Minoru Iwata1
Shiho Fujisaka1Yoshiki Nagata2Takashi Yamagami2
Makoto Kadowaki1Kazuyuki Tobe1
Shigeru Saito1
Keiichi Ueda1*- 1University of Toyama, Toyama, Toyama, Japan
- 2Hokuriku Health Service Association, Toyama, Japan
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Aims: To clarify the pathways from a healthy state to the diabetes onset via pre-disease states, we applied energy landscape analysis (ELA) to Specific Health Checkup data in Japan.This retrospective and observational cohort study analyzed data from 4,928 males aged 56.0 ± 3.2 years, including 242 individuals with diabetes, over a period of 5.26 ± 3.21 years. A total of 22,326 records were examined using six features: hemoglobin A1c, plasma glucose, high-density lipoprotein-cholesterol, body mass index (BMI), uric acid, and alanine aminotransferase. ELA was also applied to subdata from the 242 individuals with diabetes.Results: ELA revealed three stable states: healthy, intermediate, and unhealthy (pre-diabetes) states. The intermediate state was characterized by obesity. Obese individuals with BMI ≥ 25 kg/m^2 (n = 1,460) preferred a pathway via the intermediate state, whereas non-obese individuals with BMI < 25 kg/m^2 (n = 3,468) preferred to transit directly to the unhealthy state. There was a significant difference between the preferences of the two groups (p = 0.0085, chi-squared test). Two distinct pathways were also observed for obese and non-obese individuals with diabetes.We demonstrated that ELA could indicate different pathways of diabetes development in obese and non-obese individuals in a data-driven manner. These insights could inform more targeted diabetes prevention measures, such as reducing visceral fat in obese individuals and protecting beta-cells in non-obese individuals.
Keywords: Energy landscape analysis, Multiple pathways, pre-disease state, Specific Health Checkup data, diabetes, Obesity
Received: 14 Feb 2025; Accepted: 16 Apr 2025.
Copyright: © 2025 Ito, Oku, Kimura, Haruki, Shikata, Teramoto, Chujo, Iwata, Fujisaka, Nagata, Yamagami, Kadowaki, Tobe, Saito and Ueda. 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) or licensor 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.
* Correspondence:
Makito Oku, University of Toyama, Toyama, 930-0194, Toyama, Japan
Keiichi Ueda, University of Toyama, Toyama, 930-0194, Toyama, Japan
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