scholarly journals Liver Fat Content and Hepatic Insulin Sensitivity in Overweight Patients With Type 1 Diabetes

2015 ◽  
Vol 100 (2) ◽  
pp. 607-616 ◽  
Author(s):  
Gemma Llauradó ◽  
Ksenia Sevastianova ◽  
Sanja Sädevirta ◽  
Antti Hakkarainen ◽  
Nina Lundbom ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Sensitivity ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Hepatic Insulin Sensitivity

Effect of liver fat on insulin clearance

2007 ◽  
Vol 293 (6) ◽  
pp. E1709-E1715 ◽  
Author(s):  
Anna Kotronen ◽  
Satu Vehkavaara ◽  
Anneli Seppälä-Lindroos ◽  
Robert Bergholm ◽  
Hannele Yki-Järvinen
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Fat Content ◽  
Insulin Clearance ◽  
Liver Fat ◽  
Hepatic Insulin Resistance ◽  
Model Assessment ◽  
Liver Fat Content ◽  
Hepatic Insulin Sensitivity ◽  
Impaired Insulin

A fatty liver is associated with fasting hyperinsulinemia, which could reflect either impaired insulin clearance or hepatic insulin action. We determined the effect of liver fat on insulin clearance and hepatic insulin sensitivity in 80 nondiabetic subjects [age 43 ± 1 yr, body mass index (BMI) 26.3 ± 0.5 kg/m2]. Insulin clearance and hepatic insulin resistance were measured by the euglycemic hyperinsulinemic (insulin infusion rate 0.3 mU·kg−1·min−1for 240 min) clamp technique combined with the infusion of [3-3H]glucose and liver fat by proton magnetic resonance spectroscopy. During hyperinsulinemia, both serum insulin concentrations and increments above basal remained ∼40% higher ( P < 0.0001) in the high (15.0 ± 1.5%) compared with the low (1.8 ± 0.2%) liver fat group, independent of age, sex, and BMI. Insulin clearance (ml·kg fat free mass−1·min−1) was inversely related to liver fat content ( r = −0.52, P < 0.0001), independent of age, sex, and BMI ( r = −0.37, P = 0.001). The variation in insulin clearance due to that in liver fat (range 0–41%) explained on the average 27% of the variation in fasting serum (fS)-insulin concentrations. The contribution of impaired insulin clearance to fS-insulin concentrations increased as a function of liver fat. This implies that indirect indexes of insulin sensitivity, such as homeostatic model assessment, overestimate insulin resistance in subjects with high liver fat content. Liver fat content correlated significantly with fS-insulin concentrations adjusted for insulin clearance ( r = 0.43, P < 0.0001) and with directly measured hepatic insulin sensitivity ( r = −0.40, P = 0.0002). We conclude that increased liver fat is associated with both impaired insulin clearance and hepatic insulin resistance. Hepatic insulin sensitivity associates with liver fat content, independent of insulin clearance.

Effects of insulin therapy on liver fat content and hepatic insulin sensitivity in patients with type 2 diabetes

2007 ◽  
Vol 292 (3) ◽  
pp. E829-E835 ◽  
Author(s):  
Leena Juurinen ◽  
Mirja Tiikkainen ◽  
Anna-Maija Häkkinen ◽  
Antti Hakkarainen ◽  
Hannele Yki-Järvinen
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Insulin Therapy ◽  
Fat Content ◽  
Fat Free Mass ◽  
Liver Fat ◽  
Whole Body ◽  
Liver Fat Content ◽  
Hepatic Insulin Sensitivity

We determined whether insulin therapy changes liver fat content (LFAT) or hepatic insulin sensitivity in type 2 diabetes. Fourteen patients with type 2 diabetes (age 51 ± 2 yr, body mass index 33.1 ± 1.4 kg/m2) treated with metformin alone received additional basal insulin for 7 mo. Liver fat (proton magnetic resonance spectroscopy), fat distribution (MRI), fat-free and fat mass, and whole body and hepatic insulin sensitivity (6-h euglycemic hyperinsulinemic clamp combined with infusion of [3-3H]glucose) were measured. The insulin dose averaged 75 ± 10 IU/day (0.69 ± 0.08 IU/kg, range 24–132 IU/day). Glycosylated hemoglobin A1c (Hb A1c) decreased from 8.9 ± 0.3 to 7.4 ± 0.2% ( P < 0.001). Whole body insulin sensitivity increased from 2.21 ± 0.38 to 3.08 ± 0.40 mg/kg fat-free mass (FFM)·min ( P < 0.05). This improvement could be attributed to enhanced suppression of hepatic glucose production (HGP) by insulin (HGP 1.04 ± 0.28 vs. 0.21 ± 0.19 mg/kg FFM·min, P < 0.01). The percent suppression of HGP by insulin increased from 72 ± 8 to 105 ± 11% ( P < 0.01). LFAT decreased from 17 ± 3 to 14 ± 3% ( P < 0.05). The change in LFAT was significantly correlated with that in hepatic insulin sensitivity ( r = 0.56, P < 0.05). Body weight increased by 3.0 ± 1.1 kg ( P < 0.05). Of this, 83% was due to an increase in fat-free mass ( P < 0.01). Fat distribution and serum adiponectin concentrations remained unchanged while serum free fatty acids decreased significantly. Conclusions: insulin therapy improves hepatic insulin sensitivity and slightly but significantly reduces liver fat content, independent of serum adiponectin.

scholarly journals Variants in Genes Controlling Oxidative Metabolism Contribute to Lower Hepatic ATP Independent of Liver Fat Content in Type 1 Diabetes

Diabetes ◽  
2016 ◽  
Vol 65 (7) ◽  
pp. 1849-1857 ◽  
Author(s):  
Sofiya Gancheva ◽  
Alessandra Bierwagen ◽  
Kirti Kaul ◽  
Christian Herder ◽  
Peter Nowotny ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Oxidative Metabolism ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content

scholarly journals Insulin-Like Growth Factor Binding Protein 1 as a Novel Specific Marker of Hepatic Insulin Sensitivity

2008 ◽  
Vol 93 (12) ◽  
pp. 4867-4872 ◽  
Author(s):  
Anna Kotronen ◽  
Moira Lewitt ◽  
Kerstin Hall ◽  
Kerstin Brismar ◽  
Hannele Yki-Järvinen
Keyword(s):  
Body Mass Index ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
Binding Protein ◽  
Fat Content ◽  
Liver Fat ◽  
Specific Marker ◽  
Liver Fat Content ◽  
C Peptide ◽  
Hepatic Insulin Sensitivity

Background and Aims: The liver is the main source and insulin the main regulator of IGF binding protein 1 (IGFBP-1) in humans. Here we examined how serum IGFBP-1 concentrations are related to directly measured hepatic insulin sensitivity and liver fat content in humans. Methods: We measured fasting serum (fS) IGFBP-1 concentrations and liver fat content by proton magnetic resonance spectroscopy in 113 nondiabetic subjects. In addition, hepatic insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp (insulin 0.3 mU/kg·min) technique in combination with the infusion of [3-(3)H]glucose in 78 subjects. Results: fS-IGFBP-1 concentrations were inversely related to liver fat content (r = −0.38, P &lt; 0.0001). Of circulating parameters, fS-IGFBP-1 was better correlated to hepatic insulin sensitivity (r = 0.48, P &lt; 0.0001) than fS-insulin (r = −0.42, P = 0.0001), fS-C-peptide (r = −0.41, P = 0.0002), fS-triglyceride (r = −0.33, P = 0.003), or fS-high-density lipoprotein cholesterol (r = 0.30, P = 0.007). In multiple linear regression analyses, body mass index (P &lt; 0.0001) and fS-IGFBP-1 (P = 0.008), but neither age nor gender, were independently associated with hepatic insulin sensitivity (P &lt; 0.0001 for ANOVA). Neither fS-insulin nor fS-C-peptide were independent determinants of hepatic insulin sensitivity after adjusting for age, gender, and body mass index. Conclusions: fS-IGFBP-1 is inversely correlated with liver fat and is an obesity-independent and liver-specific circulating marker of hepatic insulin sensitivity.

scholarly journals No Independent Association of Circulating Fetuin-A with Insulin Sensitivity in Young Women

2020 ◽  
Vol 52 (11) ◽  
pp. 809-814
Author(s):  
Sabrina Reif ◽  
Sarah Moschko ◽  
Christina Gar ◽  
Uta Ferrari ◽  
Nina Hesse ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Young Women ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Fetuin A ◽  
The Metabolic Syndrome ◽  
Independent Association

AbstractAnimal data link high circulating fetuin-A to low insulin sensitivity and observational studies identify the hepatokine as a marker of future incident type 2 diabetes mellitus in humans. However, a recent, well-powered Mendelian randomization study finds no causal role. We therefore tested in a deeply-phenotyped human cohort if circulating fetuin-A correlates independently with insulin sensitivity and how it relates to the metabolic syndrome and ectopic fat deposition. We analyzed data from 290 young women with and without recent gestational diabetes mellitus. We found that circulating fetuin-A correlates inversely with insulin sensitivity in univariate analyses, but that this correlation is lost after adjustment for markers of the metabolic syndrome and of fatty liver. Additionally, we investigated which fat compartment associates most strongly with circulating fetuin-A. In whole body MRI data from a subcohort of 152 women, this was liver fat content. We conclude that high circulating fetuin-A occurs as part of the metabolic syndrome in young women and associates most strongly with liver fat content. Its close link to the metabolic syndrome may also cause the inverse correlation of circulating fetuin-A with insulin sensitivity as we found no independent association.

scholarly journals Insulin Sensitivity Is Correlated with Subcutaneous but Not Visceral Body Fat in Overweight and Obese Prepubertal Children

2008 ◽  
Vol 93 (6) ◽  
pp. 2122-2128 ◽  
Author(s):  
Claudio Maffeis ◽  
Riccardo Manfredi ◽  
Maddalena Trombetta ◽  
Silvia Sordelli ◽  
Monica Storti ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Body Fat ◽  
Fat Distribution ◽  
Fat Content ◽  
Liver Fat ◽  
P Value ◽  
Inflammation Markers ◽  
Liver Fat Content ◽  
Prepubertal Children

Abstract Aim: Our aim was to explore the relationship between insulin sensitivity, body fat distribution, ectopic (liver and skeletal muscle) fat deposition, adipokines (leptin and adiponectin), and inflammation markers (highly sensitive C-reactive protein, IL-6, IL-10, and TNF-α) in prepubertal children. Subjects and Methods: Thirty overweight and obese children (16 males and 14 females with body mass index z-score range of 1.1–3.2) were recruited. Body fat distribution and fat accumulation in liver and skeletal muscle were measured using magnetic resonance imaging. Insulin sensitivity was assessed by iv glucose tolerance test. Results: Insulin sensitivity was associated with sc abdominal adipose tissue (SAT) (r = −0.52; P &lt; 0.01) and liver fat content (r = −0.44; P &lt; 0.02) but not with visceral abdominal adipose tissue (VAT) (r = −0.193; P value not significant) and fat accumulation in skeletal muscle (r = −0.210; P value not significant). Adipokines, but not inflammation markers, were significantly correlated to insulin sensitivity. VAT correlated with C-reactive protein (r = 0.55; P &lt; 0.01) as well as adiponectin (r = −0.53; P &lt;0.01). Multiple regression analysis showed that only SAT and liver fat content were independently correlated to insulin sensitivity (P &lt; 0.01; 20 and 16% of explained variance, respectively). Conclusions: In overweight and moderately obese prepubertal children, insulin sensitivity was negatively correlated with SAT and liver fat content. Furthermore, contrary to adults, VAT and inflammation markers were not correlated with insulin sensitivity in children.

scholarly journals Estimating the Effect of Liver and Pancreas Volume and Fat Content on Risk of Diabetes: A Mendelian Randomization Study

Diabetes Care ◽  
2021 ◽  
Author(s):  
Susan Martin ◽  
Elena P. Sorokin ◽  
E. Louise Thomas ◽  
Naveed Sattar ◽  
Madeleine Cule ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Mendelian Randomization ◽  
Fat Content ◽  
Liver Fat ◽  
Liver And Pancreas ◽  
Pancreas Volume

OBJECTIVE Fat content and volume of liver and pancreas are associated with risk of diabetes in observational studies; whether these associations are causal is unknown. We conducted a Mendelian randomization (MR) study to examine causality of such associations. RESEARCH DESIGN AND METHODS We used genetic variants associated (P &lt; 5 × 10−8) with the exposures (liver and pancreas volume and fat content) using MRI scans of UK Biobank participants (n = 32,859). We obtained summary-level data for risk of type 1 (9,358 cases) and type 2 (55,005 cases) diabetes from the largest available genome-wide association studies. We performed inverse–variance weighted MR as main analysis and several sensitivity analyses to assess pleiotropy and to exclude variants with potential pleiotropic effects. RESULTS Observationally, liver fat and volume were associated with type 2 diabetes (odds ratio per 1 SD higher exposure 2.16 [2.02, 2.31] and 2.11 [1.96, 2.27], respectively). Pancreatic fat was associated with type 2 diabetes (1.42 [1.34, 1.51]) but not type 1 diabetes, and pancreas volume was negatively associated with type 1 diabetes (0.42 [0.36, 0.48]) and type 2 diabetes (0.73 [0.68, 0.78]). MR analysis provided evidence only for a causal role of liver fat and pancreas volume in risk of type 2 diabetes (1.27 [1.08, 1.49] or 27% increased risk and 0.76 [0.62, 0.94] or 24% decreased risk per 1SD, respectively) and no causal associations with type 1 diabetes. CONCLUSIONS Our findings assist in understanding the causal role of ectopic fat in the liver and pancreas and of organ volume in the pathophysiology of type 1 and 2 diabetes.

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