Hepatic Steatosis and High-Normal Fasting Glucose as Risk Factors for Incident Prediabetes

Toru Aizawa; Yasuto Nakasone; Norimitsu Murai; Rie Oka; Shoichiro Nagasaka; Koh Yamashita; Takahiro Sakuma; Kendo Kiyosawa

doi:10.1210/jendso/bvac110

Hepatic Steatosis and High-Normal Fasting Glucose as Risk Factors for Incident Prediabetes

J Endocr Soc. 2022 Jul 31;6(9):bvac110. doi: 10.1210/jendso/bvac110. eCollection 2022 Sep 1.

Authors

Toru Aizawa¹, Yasuto Nakasone¹, Norimitsu Murai², Rie Oka³, Shoichiro Nagasaka², Koh Yamashita¹, Takahiro Sakuma⁴, Kendo Kiyosawa⁵

Affiliations

¹ Diabetes Center, Aizawa Hospital, Matsumoto 390-8510, Japan.
² Division of Diabetes, Metabolism and Endocrinology, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan.
³ Department of Internal Medicine, Hokuriku Central Hospital, Toyama 932-8503, Japan.
⁴ Department of Internal Medicine, Ina Central Hospital, Ina 396-8555, Japan.
⁵ Department of Gastroenterology, Aizawa Hospital, Matsumoto 390-8510, Japan.

Abstract

Context: The role of hepatic steatosis (HS) in the initial stages of developing type 2 diabetes remains unclear.

Objective: We aimed to clarify the impact of HS indexed by Fatty Liver Index (FLI) and high-normal fasting plasma glucose (FPG) as risk factors for incident prediabetes in a nonobese cohort.

Methods: Data from 1125 participants with ADA-defined normal glucose metabolism (median age 52 years; BMI 23.1 kg/m²) were used for retrospective analysis. In the entire population, correlation between normal FPG and FLI was evaluated by multiple regression adjusted for age and sex. Follow-up data from 599 participants in whom 75-g OGTT was repeated 3.7 years later showed that 169 developed prediabetes. This was analyzed by the multivariate Cox proportional hazards model.

Results: In the entire population, FLI was positively correlated with FPG (P < 0.01): mean FLI increased from 15.8 at FPG 4.2 mmol/L to 31.6 at FPG 5.5 mmol/L. Analysis of the 599 participants (2061 person-years) by Cox model, adjusted for sex, age, family history of diabetes, ISI_MATSUDA, and Stumvoll-1, clarified an increased risk of prediabetes with high-normal FPG and FLI. Risk was increased 2.2 times with FLI ≥ 16.5 vs FLI < 16.5, P < 0.001, and increased 2.1 times in participants with FPG ≥ 5.3 mmol/L, P < 0.001. Cutoff values (unadjusted) were obtained by ROC at the point of the largest Youden's index using the entire range of the variables.

Conclusion: Even among nonobese individuals, HS indexed by FLI and a high-normal FPG (≥ 5.3 mmol/L) are risk factors for prediabetes, independently from insulin.

Keywords: fasting plasma glucose; hepatic steatosis; insulin secretion; insulin sensitivity; prediabetes.