Role of fatty liver in the association between obesity and reduced hepatic insulin clearance

Y Matsubayashi; A Yoshida; H Suganami; H Ishiguro; M Yamamoto; K Fujihara; S Kodama; S Tanaka; K Kaku; H Sone

doi:10.1016/j.diabet.2017.12.003

Role of fatty liver in the association between obesity and reduced hepatic insulin clearance

Diabetes Metab. 2018 Mar;44(2):135-142. doi: 10.1016/j.diabet.2017.12.003. Epub 2017 Dec 11.

Authors

Y Matsubayashi¹, A Yoshida², H Suganami³, H Ishiguro¹, M Yamamoto¹, K Fujihara¹, S Kodama¹, S Tanaka⁴, K Kaku⁵, H Sone⁶

Affiliations

¹ Department of hematology, endocrinology and metabolism, faculty of medicine, Niigata university, Niigata, Japan.
² Department of hematology, endocrinology and metabolism, faculty of medicine, Niigata university, Niigata, Japan; Medical information and product advancement department, Kowa Pharmaceutical Co. Ltd, Tokyo, Japan.
³ Clinical data science department, Kowa Co. Ltd, 3-4-10 Nihonbashi-Honcho, Chuo-ku, 103-0023 TokyoJapan.
⁴ Department of clinical biostatistics, Graduate School of Medicine, Kyoto university.
⁵ Kawasaki Medical School, Yoshida-konoe-cho, Sakyo-ku, 606-8501 KyotoOkayama, Japan.
⁶ Department of hematology, endocrinology and metabolism, faculty of medicine, Niigata university, Niigata, Japan. Electronic address: sone@med.niigata-u.ac.jp.

PMID: 29395810
DOI: 10.1016/j.diabet.2017.12.003

Abstract

Aim: Hepatic insulin clearance (HIC) is important in regulating plasma insulin levels. Diminished HIC causes inappropriate hyperinsulinaemia, and both obesity and fatty liver (FL), which are known to decrease HIC, can be found either together in the same patient or on their own. The mechanism by which obesity reduces HIC is presumed to be mediated by FL. However, few reports have examined the role of FL in the relationship between obesity and HIC in type 2 diabetes (T2D) patients. Therefore, our study investigated the association of HIC with clinical factors, including insulin sensitivity indices, focusing on the presence or absence of FL and obesity in T2D patients.

Method: Baseline data from 419 patients with T2D (279 men, 140 women; mean age: 57.6 years; body mass index: 25.5kg/m²) controlled by diet and exercise were analyzed. HIC was calculated from the ratio of fasting c-peptide to fasting insulin levels (HIC_CIR). Correlation analyses between HIC_CIR and clinical variables were performed using Pearson's product-moment correlation coefficients and single regression analysis in all participants and in those with obesity and FL either alone or in combination.

Results: HIC_CIR was significantly correlated with whole-body insulin sensitivity indices and influenced by FL, but only in the FL group was obesity independently influenced HIC level. HIC_CIR decreased in those with both FL and obesity compared with those with only one such complication.

Conclusion: HIC_CIR may be used to evaluate whole-body insulin sensitivity in T2D. Also, compared with obesity, the influence of FL strongly contributed to a reduced HIC.

Trial registration number: These trials were registered by the Japan Pharmaceutical Information Centre clinical trials information (JapicCTI) as 101349 and 101351.

Keywords: Fatty liver; Hyperinsulinaemia; Insulin hypersecretion; Insulin resistance; Insulin sensitivity; Insulin sensitivity assessment.

MeSH terms

Aged
Fatty Liver* / complications
Fatty Liver* / epidemiology
Fatty Liver* / physiopathology
Female
Humans
Insulin Resistance / physiology*
Male
Middle Aged
Obesity* / complications
Obesity* / epidemiology
Obesity* / physiopathology