Impact of glucose tolerance on the severity of non-alcoholic steatohepatitis

Nakamura, Akinobu; Yoneda, Masato; Fujita, Koji; Tajima, Kazuki; Kikuchi, Kaori; Nakajima, Atsushi; Maeda, Shin; Terauchi, Yasuo

doi:10.1111/j.2040-1124.2011.00134.x

Cited by 13 publications

(11 citation statements)

References 32 publications

(33 reference statements)

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“…The overall study, summarized in a schematic diagram ( Figure 6), demonstrate potential markers and their significance in early detection and prognosis of NAFLD and associated pathology. Dyslipidemia is characterized by altered level of lipids, lipoproteins and impaired glucose tolerance, evidenced by the increased level of FBG, predisposes patients to various metabolic disorders including NAFLD [61,62]. Our results are in concordance, as the system lipid profile was severely altered in our obese and diabetic patients with or without fatty infiltration of liver.…”

Section: Discussionsupporting

confidence: 86%

Predicting Nonalcoholic Fatty Liver Disease through a Panel of Plasma Biomarkers and MicroRNAs in Female West Virginia Population

Pillai

Lakhani

Zehra

et al. 2020

IJMS

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(1) Background: Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the presence of fatty liver, hepatic inflammation and fibrogenesis eventually leading to nonalcoholic steatohepatitis (NASH) or cirrhosis. Obesity and diabetes are common risk factors associated with the development and progression of NAFLD, with one of the highest prevalence of these diseased conditions in the West Virginia population. Currently, the diagnosis of NAFLD is limited to radiologic studies and biopsies, which are not cost-effective and highly invasive. Hence, this study aimed to develop a panel and assess the progressive levels of circulatory biomarkers and miRNA expression in patients at risk for progression to NASH to allow early intervention strategies. (2) Methods: In total, 62 female patients were enrolled and blood samples were collected after 8–10 h of fasting. Computed tomography was performed on abdomen/pelvis following IV contrast administration. The patients were divided into the following groups: Healthy subjects with normal BMI and normal fasting blood glucose (Control, n = 20), Obese with high BMI and normal fasting blood glucose (Obese, n = 20) and Obese with high fasting blood glucose (Obese + DM, n = 22). Based on findings from CT, another subset was created from Obese + DM group with patients who showed signs of fatty liver infiltration (Obese + DM(FI), n = 10). ELISA was performed for measurement of plasma biomarkers and RT-PCR was performed for circulating miRNA expression. (3) Results: Our results show significantly increased levels of plasma IL-6, Leptin and FABP-1, while significantly decreased level of adiponectin in Obese, Obese + DM and Obese + DM(FI) group, as compared to healthy controls. The level of CK-18 was significantly increased in Obese + DM(FI) group as compared to control. Subsequently, the expression of miR-122, miR-34a, miR-375, miR-16 and miR-21 was significantly increased in Obese + DM and Obese + DM(FI) group as compared to healthy control. Our results also show distinct correlation of IL-6, FABP-1 and adiponectin levels with the expression of miRNAs in relation to the extent of NAFLD progression. (4) Conclusion: Our results support the clinical application of these biomarkers and miRNAs in monitoring the progression of NAFLD, suggesting a more advanced diagnostic potential of this panel than conventional methods. This panel may provide an appropriate method for early prognosis and management of NAFLD and subsequent adverse hepatic pathophysiology, potentially reducing the disease burden on the West Virginia population.

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Section: Discussionsupporting

confidence: 86%

Predicting Nonalcoholic Fatty Liver Disease through a Panel of Plasma Biomarkers and MicroRNAs in Female West Virginia Population

Pillai

Lakhani

Zehra

et al. 2020

IJMS

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“…We previously investigated the association between factors related to glucose tolerance and the severity of NASH in Japanese patients with NAFLD. Although we found no correlations between the fasting plasma glucose and either the total NAFLD activity score or the stage of NASH, the fasting serum insulin level was significantly correlated with both, even after adjustments for age, sex and body mass index (BMI).…”

Section: Introductionmentioning

confidence: 65%

“…Hyperinsulinemia and increased insulin resistance could have important roles in the pathogenesis of NASH in both Western and Asian countries, and improvement of the insulin sensitivity has been reported to reverse some of the clinical manifestations and histological changes in NASH. We have also shown the possible important role of hyperinsulinemia in the pathogenesis of NASH in humans. Furthermore, we recently showed that long‐term high‐fat (HF) diet loading was sufficient to induce NASH in C57bl/6J mice, and that the amelioration of obesity and hyperinsulinemia, by switching from the HF diet to a standard chow diet, protected against the development of NASH in the same mice without any changes of the blood glucose levels.…”

Section: Discussionmentioning

confidence: 98%

Modification of a simple clinical scoring system as a diagnostic screening tool for non‐alcoholic steatohepatitis in Japanese patients with non‐alcoholic fatty liver disease

Nakamura

Yoneda

Sumida

et al. 2013

J of Diabetes Invest

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Aims/Introduction: We reinvestigated the clinical usefulness of the modified NAFIC scoring system, modified by changing the weightage assigned to the fasting serum insulin level based on the importance of hyperinsulinemia in the pathogenesis of non-alcoholic steatohepatitis (NASH), in Japanese patients with non-alcoholic fatty liver disease (NAFLD) who had undergone liver biopsy. Materials and Methods: The NAFIC score is conventionally calculated as follows: serum ferritin ≥200 ng/mL (female) or ≥300 ng/mL (male), 1 point; serum fasting insulin ≥10 lU/mL, 1 point; and serum type IV collagen 7 s ≥5.0 ng/mL, 2 points. A total of 147 patients with NAFLD who had undergone liver biopsies were included in the estimation group. To validate the modified scoring system, 355 patients from nine hepatology centers in Japan were also enrolled. Results: In the estimation group, 74 (50.3%) patients were histologically diagnosed as having NASH, whereas the remaining 73 (49.7%) were diagnosed as not having NASH. As the percentage of NASH patients increased not only among participants with serum insulin levels greater than 10 lU/mL, but also in those with serum levels greater than 15 lU/mL, we advocated use of the modified NAFIC score, as follows: serum fasting insulin 10-15 lU/mL, 1 point and ≥15 lU/mL, 2 points. The modified NAFIC score showed improved sensitivity and negative predictive value for the diagnosis of NASH. This finding was also confirmed in the validation group. Conclusions: The modified NAFIC scoring system could be a clinically useful diagnostic screening tool for NASH. (J Diabetes Invest,

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“…This suggests that factors other than adiposity may contribute to insulin resistance in NAFLD, which is compatible with our present finding that the severity of histological findings affects insulin sensitivity in NAFLD independently of BMI in multiple regression analysis. In previous reports, histological severity in NAFLD was significantly correlated with insulin sensitivity/resistance indices, but these results were not necessarily adjusted with BMI [ 33 – 35 ]. Our present results also accord with a recent report that severity of histological findings correlates with insulin sensitivity after adjustment for BMI [ 36 ].…”

Section: Discussionmentioning

confidence: 95%

Analysis of factors influencing glucose tolerance in Japanese patients with non-alcoholic fatty liver disease

Ohmi

Ono

Takata

et al. 2017

Diabetol Metab Syndr

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BackgroundWhile the association of the prevalence of non-alcoholic fatty liver disease (NAFLD) with impaired glucose metabolism has been reported, the factors influencing glucose tolerance in NAFLD remain to be clarified.MethodsGlucose tolerance of 131 Japanese patients diagnosed as NAFLD by histological findings of liver biopsy specimen was examined using 75 g-OGTT. According to Matteoni’s classification, patients were divided to 4 groups [M1 ~ 4, M1, 2: non-alcoholic fatty liver (NAFL); and M3, 4: non-alcoholic steatohepatitis (NASH)]. Based on the OGTT data, insulinogenic index (IGI) and QUICKI were calculated as indices of insulin secretion and insulin sensitivity, respectively. Plasma glucose 120 min after glucose loading (G120) was used as the index for glucose intolerance.ResultsStepwise multiple regression analysis using G120 as a dependent variable and loge-IGI, QUICKI, sex, BMI, age, NAFL/NASH as independent variables revealed that loge-IGI (β = −0.595) and QUICKI (β = −0.323) are significant factors predicting glucose intolerance (R2 = 0.403), indicating an important role of insulin secretion in glucose tolerance. These findings accord with glucose intolerance as high as 89.7% in patients with impaired insulin secretion defined by ≤43.2 pmol/mmol (40 μU/mg) IGI. Stepwise multiple regression analysis using QUICKI as a dependent variable and NAFL/NAFLD, sex, BMI, and age as independent variables revealed that BMI (β = −0.469) and NAFL/NAFLD (β = −0.204) are significant factors predicting insulin sensitivity (R2 = 0.248).ConclusionImpairment of insulin secretion is the most important factor to predict glucose intolerance in NAFLD; severity of histological findings is associated with insulin sensitivity independent of adiposity in NAFLD.

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Impact of glucose tolerance on the severity of non-alcoholic steatohepatitis

Cited by 13 publications

References 32 publications

Predicting Nonalcoholic Fatty Liver Disease through a Panel of Plasma Biomarkers and MicroRNAs in Female West Virginia Population

Predicting Nonalcoholic Fatty Liver Disease through a Panel of Plasma Biomarkers and MicroRNAs in Female West Virginia Population

Modification of a simple clinical scoring system as a diagnostic screening tool for non‐alcoholic steatohepatitis in Japanese patients with non‐alcoholic fatty liver disease

Analysis of factors influencing glucose tolerance in Japanese patients with non-alcoholic fatty liver disease

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