Alteration in glucose metabolism after an oral glucose load in patients with non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent hepatic disorder worldwide, and an unhealthy lifestyle is the leading risk factor for its occurrence. Vitamin C (VC) has been suggested to protect NAFLD, whereas evidence from randomized controlled trials (RCTs) is sparse. In this study, we aimed to investigate the potential benefits of VC supplementation daily on liver health and associated parameters in patients with NAFLD. In this double-blind, RCT, 84 patients with NAFLD, aged 18–60 years old, were assigned to 12 weeks of oral treatment with either low (250 mg/day, n = 26), medium (1,000 mg/day, n = 30), or high (2,000 mg/day, n = 28) doses of VC supplements. After the intervention, the Medium group had a more significant decrease in aspartate aminotransferase [Medium, −5.00 (−10.25, −1.75) vs. High, −2.50 (−7.75, 0.00), P = 0.02] and alanine aminotransferase [Medium, −8.00 (−18.00, −1.75) vs. High, −3.50 (−13.75, 4.25), P = 0.05; Medium vs. Low, −3.00 (−9.00, 5.50), P = 0.031]. The levels of other indicators of liver health, such as gamma-glutamyl transferase, alkaline phosphatase, total bilirubin, and direct bilirubin were decreased after the intervention but comparable among the three groups and so did the parameters of glucose metabolism, such as fasting insulin, fasting glucose, and homeostasis model assessment for insulin resistance. The plasma level of VC in patients and total adiponectin and high molecular weight (HMW) adiponectin levels were also elevated but not in a dose-dependent manner. Meanwhile, analysis of fecal microbiota composition showed an increase in the alpha diversity (Abundance-based Coverage Estimator (ACE), Shannon, chao1, and Simpson) both in the Low and the Medium groups. A total of 12 weeks of VC supplementation, especially 1,000 mg/day, improved liver health and glucose metabolism in patients with NAFLD. The elevated plasma levels of VC, total and HMW adiponectin, and the improvement of intestinal microbiota may have made some contributions.

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Interplay between Oxidative Stress and Metabolic Derangements in Non-Alcoholic Fatty Liver Disease: The Role of Selenoprotein P

International Journal of Molecular Sciences ◽

10.3390/ijms21228838 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8838

Author(s):

Gian Paolo Caviglia ◽

Chiara Rosso ◽

Angelo Armandi ◽

Melania Gaggini ◽

Fabrizia Carli ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Fatty Liver ◽

Hepatic Fibrosis ◽

Fatty Liver Disease ◽

Gas Chromatography Mass Spectrometry ◽

Oral Glucose ◽

Selenoprotein P ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Background: Pathogenetic mechanisms involved in the progression of non-alcoholic fatty liver disease (NAFLD) are complex and multifactorial. We investigated oxidative stress through the measurement of selenoprotein P (SeP) in serum and we explored its relation to metabolic derangements and liver damage in a group of non-diabetic NAFLD subjects. Methods: 57 NAFLD patients underwent a double-tracer oral glucose tolerance test (OGTT). Insulin resistance (IR) components were calculated at baseline as follows: hepatic-IR = (endogenous glucose production*insulin); peripheral-IR = (glucose rate of disappearance(Rd)); adipose-tissue(AT)-IR as Lipo-IR = (glycerol rate of appearance (Ra)*insulin) or AT-IR = (free fatty acids (FFAs)*insulin). The lipid and amino acid (AA) profiles were assessed by gas chromatography–mass spectrometry. SeP levels were measured by enzyme immunosorbent assay. Results: Circulating SeP correlated with insulin (rS = 0.28), FFAs (rS = 0.42), glucose Rd (rS = −0.33) and glycerol Ra (rS = −0.34); consistently, SeP levels correlated with Lipo-IR and AT-IR (rS > 0.4). Among the AA and lipid profiles, SeP inversely correlated with serine (rS = −0.31), glycine (rS = −0.44) and branched chain AA (rS = −0.32), and directly correlated with saturated (rS = 0.41) and monounsaturated FFAs (rS = 0.40). Hepatic steatosis and fibrosis increased in subjects with higher levels of SeP. In multivariable regression analysis, SeP was associated with the degree of hepatic fibrosis (t = 2.4, p = 0.022). Conclusions: SeP levels were associated with an altered metabolic profile and to the degree of hepatic fibrosis, suggesting a role in the pathogenesis of NAFLD.

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Relationship between non-alcoholic fatty liver disease during pregnancy and abnormal glucose metabolism during and after pregnancy

Journal of Investigative Medicine ◽

10.1136/jim-2019-001186 ◽

2019 ◽

Vol 68 (3) ◽

pp. 743-747

Author(s):

Maryam Sattari ◽

Fernando Bril ◽

Robert Egerman ◽

Srilaxmi Kalavalapalli ◽

Kenneth Cusi

Keyword(s):

Diabetes Mellitus ◽

Liver Disease ◽

Glucose Metabolism ◽

Glucose Tolerance ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Post Partum ◽

Alcoholic Fatty Liver ◽

Abnormal Glucose Metabolism ◽

Alcoholic Fatty Liver Disease

While non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of impaired glucose tolerance and type 2 diabetes mellitus (DM) in non-pregnant patients, the clinical significance of NAFLD during pregnancy is still unclear. We hypothesized that sonographic findings of NAFLD during pregnancy would be associated with gestational diabetes mellitus (GDM) and predict abnormal postpartum glucose metabolism. NAFLD was assessed by ultrasound during and after pregnancy. Standard 2-hour 75 g oral glucose tolerance test (OGTT) was used during pregnancy and post partum to establish GDM and the diagnosis of normal, impaired fasting glucose, or DM. We also measured plasma insulin, C peptide, and free fatty acids (FFA) concentration during an OGTT to evaluate glucose tolerance, insulin secretion and insulin resistance. Of the 84 subjects, 12 had sonographic evidence of NAFLD (5 of whom had OGTT post partum). There was a non-significant trend toward higher mean weight and body mass index during and after gestation in the NAFLD group, but no statistically significant differences in mean age, ethnicity, prepregnancy and postpregnancy hemoglobin A1C values, and postpartum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, insulin, or FFA. We did not find an association between sonographic evidence of NAFLD during the third trimester of pregnancy and abnormal glucose metabolism during or after pregnancy. This study also suggests that while AST and ALT are not reliable diagnostic tools for NAFLD during the postpartum period, ultrasound is a reasonably safe, practical, and cost-effective modality to assess maternal hepatic fat during pregnancy.

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Insulin resistance index (HOMA-IR) in the differentiation of patients with non-alcoholic fatty liver disease and healthy individuals

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032010000200009 ◽

2010 ◽

Vol 47 (2) ◽

pp. 165-169 ◽

Cited By ~ 84

Author(s):

Ana Lúcia Farias de Azevedo Salgado ◽

Luciana de Carvalho ◽

Ana Claudia Oliveira ◽

Virgínia Nascimento dos Santos ◽

Jose Gilberto Vieira ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Resistance Index ◽

Control Group ◽

Oral Glucose ◽

Healthy Individuals ◽

Alcoholic Fatty Liver ◽

Insulin Resistance Index ◽

Alcoholic Fatty Liver Disease

CONTEXT: Due to its good correlation to glycemic clamp, HOMA-IR has been widely utilized as insulin resistance index in clinical and epidemiological studies involving non-alcoholic fatty liver disease carriers. However, values used for this parameter have shown large variability. OBJECTIVE: To identify the HOMA-IR cut value that best distinguishes non-diabetic non-alcoholic fatty liver disease patients from a control group. METHODS: One hundred sixteen non-alcoholic fatty liver disease patients were studied, diagnosed by clinical, biochemical, and liver image or biopsy criteria, and 88 healthy individuals, without any liver disease and testing for oral glucose tolerance within normality. These groups did not differ in age and gender. All were submitted to oral glucose tolerance test and blood samples were collected for glucose and insulin measurements by immunofluorometric method. HOMA-IR was calculated according to the formula: fasting insulin (µU/L) x fasting glucose (nmol/L)/22.5. RESULTS: NAFLD patients showed higher insulin, glycemia, and HOMA-IR values than control group, even when excluding glucose intolerant and diabetes mellitus patients by their glycemic curves. HOMA-IR 75th percentile for control group was 1.78 and the best area under the curve index was obtained for HOMA-IR values of 2.0 [AUC= 0.840 (0.781-0.899 CI 95%), sensitivity (Se): 85%, specificity (Sp): 83%] while value 2.5 showed best specificity without important loss in sensitivity [AUC=0,831 (0.773-0.888) Se = 72%, Sp = 94%]. CONCLUSION: HOMA-IR values above or equal to 2.0 or 2.5 show enhanced diagnostic value in distinguishing non-alcoholic fatty liver disease carriers from control group individuals.

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The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial

Diabetologia ◽

10.1007/s00125-013-3149-9 ◽

2014 ◽

Vol 57 (5) ◽

pp. 878-890 ◽

Cited By ~ 68

Author(s):

Yumie Takeshita ◽

Toshinari Takamura ◽

Masao Honda ◽

Yuki Kita ◽

Yoh Zen ◽

...

Keyword(s):

Liver Disease ◽

Randomised Controlled Trial ◽

Glucose Metabolism ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Controlled Trial ◽

Alcoholic Fatty Liver ◽

Randomised Controlled ◽

Alcoholic Fatty Liver Disease

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Bicyclol Regulates Hepatic Gluconeogenesis in Rats with Type 2 Diabetes and Non-alcoholic Fatty Liver Disease by Inhibiting Inflammation

Frontiers in Pharmacology ◽

10.3389/fphar.2021.644129 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hongxue Li ◽

Qian Xu ◽

Chengye Xu ◽

Yuxin Hu ◽

Xingyang Yu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Liver Disease ◽

Glucose Metabolism ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Glucose Metabolism Disorders ◽

Liver Inflammation ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Hepatic gluconeogenesis plays an important role in maintaining the body’s glucose metabolism homeostasis. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases, when combined with type 2 diabetes mellitus (T2DM), it can cause severe glucose metabolism disorders. Studies have confirmed that chronic liver inflammatory lesions are the basis of T2DM combined with NAFLD (T2DM–NAFLD), inhibiting liver inflammation can improve glucose metabolism disorders. It is essential to explore safe and effective drugs to inhibit liver inflammation to improve the body’s glucose metabolism disorders. Bicyclol is a biphenyl derivative that has anti-oxidative and anti-inflammatory properties. In the present study, the hepatoprotective effects and underlying mechanisms of bicyclol in T2DM–NAFLD were investigated, and T2DM–NAFLD with/without bicyclol treatment models were established. The results revealed that bicyclol alleviated fasting blood glucose, serum transaminase levels, insulin resistance, hepatic adipogenesis, lipid accumulation and markedly reduced T2DM–NAFLD rat histological alterations of livers. Not only that, bicyclol markedly attenuated T2DM–NAFLD induced production of inflammation factors (IL-1β and TNF-α). Moreover, bicyclol suppressed the expression of insulin/gluconeogenesis signaling pathway (Akt, PGC-1α and PEPCK). These findings suggested that bicyclol might be a potentially effective drug for the treatment of T2DM–NAFLD and other metabolic disorders.

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