Liver Fat Content in People with Pituitary Diseases: Influence of Serum IGF1 Levels

AbstractNon-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, metabolic syndrome, and type 2 diabetes. NAFLD is also seen in patients with endocrinopathies. However, the relationship between endocrine diseases and the development of NAFLD is not well known. In this study, we set out to determine whether liver fat content (LFC) was associated with IGF1 levels in people with pituitary diseases (PD). Eighty-nine patients with pituitary diseases and 74 healthy controls were included in this study. LFC was measured using MRI. Hepatic steatosis was defined as LFC>5.5%. Patients with PD were older, and had a higher BMI than healthy controls. LFC was significantly higher in people with PD than in controls (6.5% vs. 3.2%; p<0.001). LFC was negatively associated with the IGF1 level. The prevalence of steatosis was higher in PD patients than in controls (36.3% vs. 14.8%; p=0.002). In multivariate analysis, which included patients and controls, the predictive variables for steatosis were age, BMI and IGF1 levels, whereas the presence of pituitary diseases and gender were not associated with steatosis. Our data showed that LFC was strongly associated with IGF1 levels. These results suggest that steatosis associated with PD is probably a consequence of a low IGF1 level in these patients.

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Effects of a multifactorial ecosustainable isocaloric diet on liver fat in patients with type 2 diabetes: randomized clinical trial

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001342 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001342 ◽

Cited By ~ 1

Author(s):

Giuseppe Della Pepa ◽

Claudia Vetrani ◽

Valentina Brancato ◽

Marilena Vitale ◽

Serena Monti ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fatty Acids ◽

Fat Content ◽

Liver Fat ◽

Liver Fat Content ◽

Alcoholic Fatty Liver ◽

Significant Difference ◽

Dietary Components ◽

Mufa Diet

IntroductionTreatment options for non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2D) are still a matter of debate. We compared the effects of a diet including different components versus a proven beneficial diet rich in monounsaturated fatty acids (MUFAs) on liver fat in T2D.Research design and methodsAccording to a parallel design, 49 individuals with T2D, overweight/obese, with high waist circumference, 35–75 years-old, in satisfactory blood glucose control with diet or drugs not affecting liver fat content, were randomly assigned to an 8-week isocaloric intervention with a MUFA diet (n=26) or a multifactorial diet rich in fiber, MUFA, n-6 and n-3 polyunsaturated fatty acids, polyphenols, and vitamins D, E, and C (n=23). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS complete data were available for n=21 (MUFA diet) and n=18 (multifactorial diet) participants.ResultsAdherence to dietary interventions was optimal. No significant differences between groups in body weight reduction, plasma glycated hemoglobin, insulin, glucose, lipids and liver enzymes were observed. Liver fat significantly decreased after both the multifactorial diet (9.18%±7.78% vs 5.22%±4.80%, p=0.003) and the MUFA diet (9.47%±8.89% vs 8.07%±8.52%, p=0.027) with a statistically significant difference between changes either in absolute terms (−4.0%±4.5% vs −1.4%±2.7%, p=0.035) or percent (−40%±33% vs −19%±25%, p=0.030).ConclusionsAn isocaloric multifactorial diet including several beneficial dietary components induced a clinically relevant reduction of liver fat in patients with T2D, more pronounced than that induced by simply replacing saturated fat with MUFA. This suggests that the ‘optimal diet’ for NAFLD treatment in T2D should be based on synergic actions of different dietary components on multiple pathophysiological pathways.Trial registration numberNCT03380416.

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GLP-1 receptor agonists for NAFLD treatment in patients with and without type 2 diabetes: an updated meta-analysis

Exploration of Medicine ◽

10.37349/emed.2020.00008 ◽

2020 ◽

Vol 1 (3) ◽

pp. 108-123 ◽

Cited By ~ 1

Author(s):

Alessandro Mantovani ◽

Giorgia Beatrice ◽

Graziana Petracca ◽

Filippo Pampagnin ◽

Damiano Sandri ◽

...

Keyword(s):

Meta Analysis ◽

Fat Content ◽

Liver Fat ◽

Liver Fat Content ◽

Alcoholic Fatty Liver ◽

Receptor Agonists ◽

Promising Treatment ◽

Glucagon Like Peptide 1 ◽

Mean Differences

Aim: Recent randomized controlled trials (RCTs) have tested the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RA) to specifically treat non-alcoholic fatty liver disease (NAFLD). We performed a meta-analysis of RCTs to investigate the efficacy of GLP-1 RAs for treatment of NAFLD or non-alcoholic steatohepatitis (NASH). Methods: We systematically searched PubMed and ClinicalTrials.Gov databases utilizing specific terms to identify placebo-controlled or head-to-head RCTs (last research on March 1, 2020) involving NAFLD patients with the aim to evaluate the efficacy of GLP-1 RAs to treat NAFLD/NASH. Primary outcomes were changes in serum liver enzymes, liver fat content, or histologic resolution of NASH. Weighted mean differences (WMD) were used to test the differences between the treatment arms. Results: Overall, we found 7 placebo-controlled or head-to-head RCTs involving 472 middle-aged individuals (66% men; 77% with established diabetes) followed for a median of 16 weeks that have used liraglutide or exenatide to treat NAFLD on imaging (n = 6) or biopsy (n = 1). Compared to placebo or reference therapy, treatment with GLP-1 RAs decreased serum alanine aminotransferase [n = 7 studies; WMD: -8.77 IU/L, 95% confidence intervals (CI) -17.69 to 0.14 IU/L; I2 = 87.3%] and gamma-glutamyltransferase levels (n = 4 studies; WMD: -10.17 IU/L, 95% CI -14.27 IU/L to -6.07 IU/L; I2 = 0%) and imaging-defined liver fat content (n = 4 studies; WMD: -6.23%, 95% CI -8.95% to -3.51%; I2 = 85.9%). In one RCT involving 55 patients with biopsy-proven NASH, a 48-week treatment with liraglutide also led to a greater histological resolution of NASH than placebo. Conclusions: GLP-1 RAs (mostly liraglutide) seem to be a promising treatment option for NAFLD or NASH.

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The association between cardiorespiratory fitness, liver fat and insulin resistance in adults with or without type 2 diabetes: a cross sectional-analysis

BMC Sports Science Medicine and Rehabilitation ◽

10.1186/s13102-021-00261-9 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Angelo Sabag ◽

Shelley E. Keating ◽

Kimberley L. Way ◽

Rachelle N. Sultana ◽

Sean M. Lanting ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Cardiorespiratory Fitness ◽

Fat Content ◽

Liver Fat ◽

Liver Fat Content ◽

Cross Sectional ◽

Sectional Analysis ◽

The Relationship

Abstract Background Exercise-induced improvements in cardiorespiratory fitness (CRF) often coincide with improvements in insulin sensitivity and reductions in liver fat content. However, there are limited data concerning the relationship between CRF and liver fat content in adults with varying degrees of metabolic dysfunction. Methods The aim of this study was to examine the association between CRF, liver fat content, and insulin resistance in inactive adults with obesity and with or without type 2 diabetes (T2D), via cross-sectional analysis. CRF was determined via a graded exercise test. Liver fat content was assessed via proton magnetic resonance spectroscopy and insulin resistance was assessed via homeostatic model of insulin resistance (HOMA-IR). A partial correlation analysis, controlling for age and gender, was performed to determine the association between CRF, demographic, cardiometabolic, and anthropometric variables. Independent t tests were performed to compare cardiometabolic outcomes between participants with T2D and participants without T2D. Results Seventy-two adults (46% male) with a mean age of 49.28 ± 10.8 years, BMI of 34.69 ± 4.87 kg/m2, liver fat content of 8.37 ± 6.90%, HOMA-IR of 3.07 ± 2.33 and CRF of 21.52 ± 3.77 mL/kg/min participated in this study. CRF was inversely associated with liver fat content (r = − 0.28, p = 0.019) and HOMA-IR (r = − 0.40, p < 0.001). Participants with T2D had significantly higher liver fat content (+ 3.66%, p = 0.024) and HOMA-IR (+ 2.44, p < 0.001) than participants without T2D. Participants with T2D tended to have lower CRF than participants without T2D (− 1.5 ml/kg/min, p = 0.094). Conclusion CRF was inversely associated with liver fat content and insulin resistance. Participants with T2D had lower CRF than those without T2D, however, the difference was not statistically significant. Further longitudinal studies are required to elucidate the relationship between CRF and the progression of obesity-related diseases such as T2D. Registration: ACTRN12614001220651 (retrospectively registered on the 19th November 2014) and ACTRN12614000723684 (prospectively registered on the 8th July 2014).

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Diabetes Remission Clinical Trial (DiRECT)—Plasma Liver Function Tests Reflect Change in Liver Fat Content in Early Type 2 Diabetes

Diabetes ◽

10.2337/db18-1834-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 1834-P

Author(s):

SVIATLANA V. ZHYZHNEUSKAYA ◽

AHMAD AL-MRABEH ◽

CARL PETERS ◽

ALISON C. BARNES ◽

KIEREN G. HOLLINGSWORTH ◽

...

Keyword(s):

Type 2 Diabetes ◽

Clinical Trial ◽

Liver Function ◽

Liver Function Tests ◽

Fat Content ◽

Diabetes Remission ◽

Liver Fat ◽

Early Type ◽

Liver Fat Content

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A carbohydrate-reduced high-protein diet improves HbA1c and liver fat content in weight stable participants with type 2 diabetes: a randomised controlled trial

Diabetologia ◽

10.1007/s00125-019-4956-4 ◽

2019 ◽

Vol 62 (11) ◽

pp. 2066-2078 ◽

Cited By ~ 20

Author(s):

Mads J. Skytte ◽

Amirsalar Samkani ◽

Amy D. Petersen ◽

Mads N. Thomsen ◽

Arne Astrup ◽

...

Keyword(s):

Type 2 Diabetes ◽

Randomised Controlled Trial ◽

Controlled Trial ◽

High Protein Diet ◽

Fat Content ◽

Protein Diet ◽

Liver Fat ◽

Liver Fat Content ◽

Randomised Controlled

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Liver steatosis coexists with myocardial insulin resistance and coronary dysfunction in patients with type 2 diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00604.2005 ◽

2006 ◽

Vol 291 (2) ◽

pp. E282-E290 ◽

Cited By ~ 97

Author(s):

Riikka Lautamäki ◽

Ronald Borra ◽

Patricia Iozzo ◽

Markku Komu ◽

Terho Lehtimäki ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Liver Steatosis ◽

Fat Content ◽

Liver Fat ◽

Liver Fat Content ◽

Artery Disease ◽

Myocardial Insulin Resistance ◽

High Liver

Nonalcoholic fatty liver (NAFL) is a common comorbidity in patients with type 2 diabetes and links to the risk of coronary syndromes. The aim was to determine the manifestations of metabolic syndrome in different organs in patients with liver steatosis. We studied 55 type 2 diabetic patients with coronary artery disease using positron emission tomography. Myocardial perfusion was measured with [15O]H2O and myocardial and skeletal muscle glucose uptake with 2-deoxy-2-[18F]fluoro-d-glucose during hyperinsulinemic euglycemia. Liver fat content was determined by magnetic resonance proton spectroscopy. Patients were divided on the basis of their median (8%) into two groups with low (4.6 ± 2.0%) and high (17.4 ± 8.0%) liver fat content. The groups were well matched for age, BMI, and fasting plasma glucose. In addition to insulin resistance at the whole body level ( P = 0.012) and muscle ( P = 0.002), the high liver fat group had lower insulin-stimulated myocardial glucose uptake ( P = 0.040) and glucose extraction rate ( P = 0.0006) compared with the low liver fat group. In multiple regression analysis, liver fat content was the most significant explanatory variable for myocardial insulin resistance. In addition, the high liver fat group had increased concentrations of high sensitivity C-reactive protein, soluble forms of E-selectin, vascular adhesion protein-1, and intercellular adhesion molecule-1 ( P < 0.05) and lower coronary flow reserve ( P = 0.02) compared with the low liver fat group. In conclusion, in patients with type 2 diabetes and coronary artery disease, liver fat content is a novel independent indicator of myocardial insulin resistance and reduced coronary functional capacity. Further studies will reveal the effect of hepatic fat reduction on myocardial metabolism and coronary function.

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Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial

Diabetes Care ◽

10.2337/dc19-0641 ◽

2019 ◽

Vol 43 (2) ◽

pp. 298-305 ◽

Cited By ~ 23

Author(s):

Sabine Kahl ◽

Sofiya Gancheva ◽

Klaus Straßburger ◽

Christian Herder ◽

Jürgen Machann ◽

...

Keyword(s):

Type 2 Diabetes ◽

Controlled Trial ◽

Fat Content ◽

Liver Fat ◽

Liver Fat Content ◽

Double Blind

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Dietary Factors in Relation to Liver Fat Content: A Cross-sectional Study

Nutrients ◽

10.3390/nu12030825 ◽

2020 ◽

Vol 12 (3) ◽

pp. 825 ◽

Cited By ~ 1

Author(s):

Cora Watzinger ◽

Tobias Nonnenmacher ◽

Mirja Grafetstätter ◽

Solomon A. Sowah ◽

Cornelia M. Ulrich ◽

...

Keyword(s):

Diet Quality ◽

Cross Sectional Study ◽

Fat Content ◽

Dietary Factors ◽

Liver Fat ◽

Inverse Association ◽

Sectional Study ◽

Liver Fat Content ◽

Cross Sectional ◽

Alcoholic Fatty Liver

Non-alcoholic fatty liver disease (NAFLD) can lead to functional liver impairment and severe comorbidities. Beyond energy balance, several dietary factors may increase NAFLD risk, but human studies are lacking. The aim of this cross-sectional study was to investigate the associations between food consumption (47 food groups, derived Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diet quality scores) and liver fat content (continuous scale and NAFLD, i.e., >5% liver fat content). Liver fat content was measured by magnetic resonance imaging (MRI) in 136 individuals (BMI: 25–40 kg/m2, age: 35–65, 50.7% women) and food intake was recorded by food frequency questionnaires (FFQs). Associations between food items and liver fat were evaluated by multi-variable regression models. Intakes of cake and cookies as well legumes were inversely associated with liver fat content, while positive associations with intakes of high-fat dairy and cheese were observed. Only cake and cookie intake also showed an inverse association with NAFLD. This inverse association was unexpected, but not affected by adjustment for reporting bias. Both diet quality scores were inversely associated with liver fat content and NAFLD. Thus, as smaller previous intervention studies, our results suggest that higher diet quality is related to lower liver fat, but larger trials with iso-caloric interventions are needed to corroborate these findings.

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Potential effects of reduced red meat compared with increased fiber intake on glucose metabolism and liver fat content: a randomized and controlled dietary intervention study

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy307 ◽

2019 ◽

Vol 109 (2) ◽

pp. 288-296 ◽

Cited By ~ 3

Author(s):

Caroline Willmann ◽

Martin Heni ◽

Katarzyna Linder ◽

Robert Wagner ◽

Norbert Stefan ◽

...

Keyword(s):

Body Fat ◽

Intervention Study ◽

Dietary Intervention ◽

Fat Content ◽

Red Meat ◽

Liver Fat ◽

Fiber Intake ◽

Liver Fat Content ◽

Meat Intake

ABSTRACT Background Epidemiological studies suggest that an increased red meat intake is associated with a higher risk of type 2 diabetes, whereas an increased fiber intake is associated with a lower risk. Objectives We conducted an intervention study to investigate the effects of these nutritional factors on glucose and lipid metabolism, body-fat distribution, and liver fat content in subjects at increased risk of type 2 diabetes. Methods This prospective, randomized, and controlled dietary intervention study was performed over 6 mo. All groups decreased their daily caloric intake by 400 kcal. The “control” group (N = 40) only had this requirement. The “no red meat” group (N = 48) in addition aimed to avoid the intake of red meat, and the “fiber” group (N = 44) increased intake of fibers to 40 g/d. Anthropometric parameters and frequently sampled oral glucose tolerance tests were performed before and after intervention. Body-fat mass and distribution, liver fat, and liver iron content were assessed by MRI and single voxel proton magnetic resonance spectroscopy. Results Participants in all groups lost weight (mean 3.3 ± 0.5 kg, P < 0.0001). Glucose tolerance and insulin sensitivity improved (P < 0.001), and body and visceral fat mass decreased in all groups (P < 0.001). These changes did not differ between groups. Liver fat content decreased significantly (P < 0.001) with no differences between the groups. The decrease in liver fat correlated with the decrease in ferritin during intervention (r2 = 0.08, P = 0.0021). This association was confirmed in an independent lifestyle intervention study (Tuebingen Lifestyle Intervention Program, N = 229, P = 0.0084). Conclusions Our data indicate that caloric restriction leads to a marked improvement in glucose metabolism and body-fat composition, including liver-fat content. The marked reduction in liver fat might be mediated via changes in ferritin levels. In the context of caloric restriction, there seems to be no additional beneficial impact of reduced red meat intake and increased fiber intake on the improvement in cardiometabolic risk parameters. This trial was registered at clinicaltrials.gov as NCT03231839.

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