bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monounsaturated Fatty Acids Prevent Saturated Fatty Acid–Induced Impairment of Mitochondrial Trafficking in Dorsal Root Ganglion Sensory Neurons
Authors: RUMORA AMY , LOGRASSO GIOVANNI , HAIDAR JULIA A. , DOLKOWSKI JUSTIN , LENTZ STEPHEN I. , FELDMAN EVA L. 
Published: June 2018

Diabetic neuropathy (DN) is a common complication of type 2 diabetes characterized by peripheral nerve damage and sensory loss. Dorsal root ganglion (DRG) sensory neurons require axonal mitochondrial transport to produce axonal ATP for neuronal function. In DN, DRG neurons exhibit axonal mitochondrial dysfunction and bioenergetic failure. A correlation between DN progression and dyslipidemia suggests that increased plasma saturated fatty acids (FAs) and decreased unsaturated FAs may play a role in the progression of DN. In this study, we evaluated the effect of saturated FA palmitate and monounsaturated FA oleate on mitochondrial trafficking and mitochondrial function in DRG neurons. Primary DRG neurons were treated with physiological concentrations of palmitate, oleate, and oleate/palmitate mixtures. The impact of these treatments was assessed by measuring mitochondrial motility and mitochondrial membrane depolarization using TMRM staining. Treatment with 62.5 μM to 250 μM palmitate induced a significant and dose-dependent decrease in axonal mitochondrial transport whereas oleate treatments from 31.25 to 250 μM did not alter the percentage of motile mitochondria. Palmitate treatments also resulted in a reduction of mitochondrial membrane potential in DRG neurons treated with 125 to 250 μM palmitate. Conversely, DRG neurons treated with 125 to 250 μM oleate maintained their mitochondrial membrane potential. Based on the differential effects of oleate and palmitate, we next evaluated whether oleate supplementation could prevent palmitate-induced inhibition of mitochondrial trafficking. Mixtures of oleate/palmitate at 1:1 or 2:1 molar ratios prevented palmitate-induced decreases in mitochondrial trafficking and mitochondrial membrane depolarization. These results indicate that monounsaturated FAs prevent saturated FA induced mitochondrial dysfunction in DRG neurons associated with dyslipidemia and DN.

Disclosure
A. Rumora: None. G. LoGrasso: None. J.A. Haidar: None. J. Dolkowski: None. S.I. Lentz: None. E.L. Feldman: None.
Muscarinic Receptor Antagonist Improves Nerve Fiber Function in Subjects with Type 2 Diabetes and Peripheral Neuropathy
Authors: VINIK AARON I. , CALCUTT NIGEL A. , EDWARDS JOSHUA F. , WEAVER JESSICA R. , BAILEY MICHAEL D. , FERNYHOUGH PAUL , CUNDRA LINDSEY B. , FRIZZI KATIE E. , PARSON HENRI , CASELLINI CAROLINA M. 
Published: June 2018

Degeneration of nerve fibers due to diabetic peripheral neuropathy (DPN) has been linked to mitochondrial dysfunction. Manipulation of mitochondrial dysfunction through antagonism of muscarinic receptors (MR) promotes neurite outgrowth in adult sensory neurons in vitro and provides neuroprotection in rodent models of DPN. The aim of the study was to assess the efficacy of MR antagonist topical 3% oxybutynin in structural and functional measures of nerve fiber function in subjects with type 2 diabetes (T2DM) and DPN. Pilot, randomized, placebo-controlled, double-blinded study in 40 subjects assessed at baseline and after 20 weeks of treatment with oxybutynin or placebo with the following: intraepidermal nerve fiber density (IENFD) on proximal and distal leg; neuropathy scores and quality of life (Norfolk QoL DN) questionnaire. Baseline demographic characteristics were similar between the treatment groups. IENFD improved significantly after 20 weeks for the treatment group. Neuropathy scores and Norfolk QoL DN also improved significantly in the treatment group (Table 1). No improvements were seen in the placebo group. In this study, oxybutynin proves to be efficacious in improving structural and functional measures of small fiber function, and quality of life in T2DM subjects. These results offer a promising novel therapeutic approach for DPN that needs to be explored further.

Disclosure
A.I. Vinik: None. N.A. Calcutt: Stock/Shareholder; Self; WinSanTor, Inc.. J.F. Edwards: None. J.R. Weaver: None. M.D. Bailey: None. P. Fernyhough: Stock/Shareholder; Self; WinSanTor, Inc.. L.B. Cundra: None. K.E. Frizzi: None. H. Parson: None. C.M. Casellini: None.
Insulin Resistance, Cardiovascular Autonomic Neuropathy, and Left Ventricular Hypertrophy in Patients with Congenital Generalized Lipodystrophy
Authors: FERNANDES VIRGINIA O. , PONTE CLARISSE M.M. , GURGEL MARIA HELANE C. , MONTENEGRO ANA PAULA D.R. , BATISTA LIVIA A.A. , LIBERATO CRISTIANE B.R. , D'ALVA CATARINA B. , MONTENEGRO RENAN M. ,   BRAZILIAN LIPODYSTROPHY STUDY GROUP (BRAZLIPO)
Published: June 2018

Congenital generalized lipodystrophy (CGL) subjects have a high prevalence of cardiovascular autonomic neuropathy (CAN) and cardiac complications, including left ventricular hypertrophy (LVH). This study aimed to analyze insulin resistance (IR), CAN severity and LVH association. A cross sectional study with 10 CGL patients and 20 healthy controls. We evaluated clinical and laboratory data, echocardiogram parameters, 3 spectral analysis components - high frequency (HF), low frequency (LF), and very low frequency (VLF) - of heart rate variability (HRV), sympathetic-vagal balance, time domains of HRV, corrected QT interval (cQT), and 4 cardiovascular reflexes tests (postural hypotension test, orthostatic, respiratory, and valsalva coefficients - 2 abnormal tests: clinic CAN, 1 abnormal test: incipient CAN, and postural hypotension: advanced CAN). In CGL group 50% had CAN (40% clinic and 10% incipient) and 40% LVH. There was inverse correlation between LVMI and HF (p=0,007), IVS and HF (p=0,013), and positive correlation between IVS and HOMA-IR (p=0,042), and BP drop (p=0,010). These suggest that IR may be involved in the severity of CAN and cardiac autonomic dysfunction in the pathophysiology of cardiovascular complications in these disease.

Disclosure
V.O. Fernandes: None. C.M.M. Ponte: None. M.C. Gurgel: None. A.D.R. Montenegro: None. L.A.A. Batista: None. C.B.R. Liberato: None. C.B. D'Alva: None. R.M. Montenegro: None.
Statins Decrease VEGF Expression in Retinal Pigment Epithelial Cells by Downregulation of Receptor for AGE (RAGE)
Authors: TSUJINAKA HIROKI , ITAYA-HIRONAKA ASAKO , YAMAUCHI AKIYO , SAKURAMOTO-TSUCHIDA SUMIYO , MAKINO MAI , SHOBATAKE RYOGO , MASUDA NAONORI , HIRAI HIROMASA , OGATA NAHOKO , TAKASAWA SHIN 
Published: June 2018

Age-related macular degeneration (AMD) is one of the most important causes of blindness in the elderly patients. Statins, inhibitors for HMG-CoA reductase, are recently reported to be useful for decreasing the risk of wet-type AMD. However, the molecular mechanisms how statins reduce the risk of AMD remain unclear. In this study, we examined the effects of statins (atorvastatin and lovastatin) on the expression of VEGF and RAGE in human retinal pigment epithelial (RPE) cells. We used h1RPE7, human RPE cells, damaged by 20 µM hydroquinone (HQ)+300 µg/mL advanced glycation end-product (AGE) as an experimental AMD model. These cells were treated with atorvastatin (100 nM) or lovastatin (2 µM) for 24 hours. After the treatment, the expression of VEGF and RAGE was evaluated by real-time RT-PCR, and we found that the mRNA levels of VEGF and RAGE in the HQ+AGE treated cells were increased. The additions of statins significantly attenuated the HQ+AGE-induced VEGF and RAGE mRNA expression. We also measured the VEGF concentration in the cell culture medium by ELISA and found that it was markedly decreased by the addition of statins. In order to know the impact of RAGE on the VEGF expression, small interfering RNA (siRNA) for RAGE (siRAGE) was introduced into h1RPE7 cells by lipofection method and the VEGF expression was measured by real-time RT-PCR. The RT-PCR results show that siRAGE attenuated the up-regulation of VEGF in the HQ+AGE treated cells. The luciferase reporter assays for RAGE and VEGF transcription showed that the RAGE expression in the statin-treated cells was regulated at the transcriptional level, and that the VEGF expression in these cells was regulated by a post-transcriptional mechanism. These results indicate that statins attenuated the HQ+AGE-induced VEGF expression via decreasing RAGE expression. As VEGF is an important factor for the development of wet-type AMD, statins could decrease the risk of wet-type AMD and be a preventive medicine for diabetic patients.

Disclosure
H. Tsujinaka: None. A. Itaya-Hironaka: None. A. Yamauchi: None. S. Sakuramoto-Tsuchida: None. M. Makino: None. R. Shobatake: None. N. Masuda: None. H. Hirai: None. N. Ogata: Research Support; Self; Alcon Japan, Bayer Yakuhin, Ltd., Santen Seyaku Co., Ltd., AMO, Otsuka Holdings Co., Ltd., HOYA Co., Ltd.. S. Takasawa: None.
Role of Xanthine Oxidoreductase from Mesenchymal Cells in Retinal Inflammation after Pericyte Breakdown
Authors: KUSHIYAMA AKIFUMI , KIKUCHI TAKAKO , YAMAZAKI HIROKI , YAMAMOTOYA TAKESHI , SAKODA HIDEYUKI , FUJISHIRO MIDORI , NAKATSU YUSUKE , UEMURA AKIYOSHI , SHIRAKURA TAKASHI , ASANO TOMOICHIRO , IWAMOTO YASUHIKO 
Published: June 2018

Glycemic control is important for diabetic retinopathy (DR), but not sufficient for the inhibition after proliferative DR (PDR). Uric acid in the vitreous is reportedly increased in patients with DR, especially in the PDR. Here, the involvement of xanthine oxidoreductase (XO), responsible for uric acid production, in worsening DR was examined in both mouse model and co-cultured angiogenesis model. First, retinal pericytes were abolished by anti-PDGFRβ antibody injection to C57/Bl6 neonatal mouse at P1. Pericyte dropout from endothelial cells is reportedly early histological change in DR, and induces bleeding, abnormal angiogenesis, inflammation, and retinal detachment with rapid progression at P9-11. The expression of XO level in retina was increasing after pericyte breakdown, and was proportional to VEGF, and preceding the increase of TNFalpha. When 3.6mg/kg Febuxostat (Fbx), an XO inhibitor was injected at P7, widespread edema and retinal detachment/funnel-like deformation were dramatically improved by Fbx treatment at P11. ICAM-1+ cells surrounding edema and CD11b+ cells were reduced. Next, we performed a 3D culture sprouting assay using HUVEC spheroids in collagen gel co-cultured with human lung fibroblast (hLF) in fibrin gel. By Fbx treatment within the physiological concentration, the branch sprouting, cellular migration to the distal side and mitosis in branch stems were inhibited. ICAM-1 increase in HUVEC was observed with hLF co-culture but was suppressed by Fbx treatment. Finally, these effects of Fbx were not shown on HUVEC in planar culture. On the other hand, dissolution of fibrin by hLF was delayed directly due to Fbx. VEGF and PAI-1 expression from hLF and MMP-9 activity in medium were decreased by Fbx treatment.
In summary, XO inhibition improved retinal inflammation and injury after pericyte loss. These results suggest the role of humoral inflammatory factors from mesenchymal cells surrounding retinal vessels in the hyperpermeable state such as DR.

Disclosure
A. Kushiyama: Research Support; Self; Teijin Pharma Limited, Sanwa Kagaku Kenkyusho Co., Ltd., Kowa Pharmaceutical Co., Ltd, StaGen. Consultant; Self; RIZAP. T. Kikuchi: None. H. Yamazaki: None. T. Yamamotoya: None. H. Sakoda: None. M. Fujishiro: Research Support; Self; Johnson & Johnson Services, Inc.. Y. Nakatsu: None. A. Uemura: Research Support; Self; Daiichi Sankyo Company, Limited, Boehringer Ingelheim GmbH, KAN Research Institute, Inc. T. Shirakura: Employee; Self; Teijin Pharma Limited. T. Asano: Research Support; Self; Teijin Pharma Limited, Sanwa Kagaku Kenkyusho Co., Ltd., Sanofi K.K. Y. Iwamoto: Board Member; Self; Japan Diabetes Foundation.
High-Fat Diet/Palmitate–Induced ER Stress Promotes Protein O-GlcNAcylation in Retina and Retinal Muller Cells
Authors: DAI WEIWEI , TORO ALLYSON , DIERSCHKE SADIE K. , DENNIS MICHAEL D. 
Published: June 2018

The incidence of type 2 diabetes, the most common cause of diabetic retinopathy (DR), is rapidly on the rise due to the overconsumption of calorie rich diets. Using an animal model of diet-induced obesity/pre-type 2 diabetes, we evaluated the mechanism responsible for increased O-GlcNAcylation of retinal proteins following consumption of a diet high in saturated fat (HFD), as dysregulated O-GlcNAcylation contributes to the development of DR. In the retina of mice fed a HFD for 4 weeks, increased O-GlcNAcylation was observed concomitant with markers of endoplasmic reticulum (ER) stress. Similarly, in TR-MUL retinal cells in culture, addition of the saturated fatty acid palmitate or the ceramide analog Cer6 to culture medium increased protein O-GlcNAcylation and ER stress. One potential mechanism whereby ER stress increases O-GlcNAcylation is by upregulating flux through the hexosamine biosynthetic pathway (HBP) via increased expression of the rate-limiting enzyme glutamine-fructose-6-phosphate amidotransferase (GFAT). In the retina of mice fed a HFD and in TR-MUL cells exposed to Cer6, mRNA and protein expression of GFAT2, but not GFAT1 were increased. Similarly, in TR-MUL cells treated with the ER stress inducer thapsigargin (TG) increased O-GlcNAcylation was observed concomitant with an increase in GFAT2. Alternatively, ER stress inhibitor prevented the effect. GFAT2 knockdown via siRNA attenuated O-GlcNAcylation induced by either TG or Cer6. The glial cell specific transcription factor OASIS (old astrocyte specifically-induced substance) plays a central role in coordinating the unfolded protein response. Unlike GFAT1, GFAT2 contains a putative binding site for OASIS. Both HFD and Cer6 increased OASIS expression, and OASIS was sufficient to promote GFAT2 expression and increase O-GlcNAcylation. Overall, the results support a model whereby HFD-induced ER stress acts to promote O-GlcNAcylation in retina through an OASIS/GFAT2-dependent mechanism.

Disclosure
W. Dai: None. A. Toro: None. S.K. Dierschke: None. M.D. Dennis: None.
FFAR1 Agonism Restores Insulin Secretion in Rodents, Human Islets, and Diabetic Monkeys
Authors: LIU JIANYING , LEE SEUNGHUN P. , MARTIN TONYA , RADY BRIAN , MEEGALLA SANATH , HUANG HUI , WINTERS MICHAEL P. , NORQUAY LISA D. , QI JENSON , DU FUYONG , NAWROCKI ANDREA R. , PLAYER MARK , POCAI ALESSANDRO 
Published: June 2018

The free fatty acid receptor 1 (FFAR1) mediates fatty acid-induced insulin secretion from pancreatic β-cells. Numerous ligands have been investigated for their antidiabetic actions. The most advanced, fasiglifam (TAK-875), is a site 1 binding agonist that stimulates IPone and improves glycemic control in diabetic patients via glucose-dependent insulin secretion (GSIS). Recently, FFAR1 agonists were discovered that bind to site 3, stimulate IPone and cAMP and result in both insulin and glucagon-like peptide-1 (GLP-1) secretion.
We hypothesized that this novel pharmacology would lead to superior glucose lowering relative to fasiglifam in diabetic monkeys. A selective FFAR1 agonist (CpdA) was discovered that activates rodent, cynomolgus and human FFAR1 receptors in vitro, triggering similar IPone and cAMP production. Incubation with CpdA but not fasiglifam restored insulin secretion in human islets from diabetic donors. Cpd A stimulates GLP-1 secretion in wild type but not GPR40 knockout mice, additionaly, as well as stimulates insulin secretion in ZDF rats. The ability of CpdA to control blood glucose was evaluated in diabetic cynomolgus monkeys during an oral glucose tolerance test after a single dose and repeated dosing for 7 days. Notably, the restoration of insulin secretion elicited by CpdA in diabetic human islets was recapitulated in vivo in diabetic monkeys and resulted in superior acute and chronic improvement in glucose tolerance relative to fasiglifam.
In conclusion, administration of CpdA restores insulin secretion and produces robust improvement in glucose metabolism in diabetic rodents and monkeys. Thus, FFAR1 agonists represent a potential treatment for type 2 diabetes.

Disclosure
J. Liu: None. S.P. Lee: Employee; Self; Janssen Research & Development. T. Martin: Employee; Self; Janssen Research & Development. Stock/Shareholder; Self; Janssen Research & Development. B. Rady: Employee; Self; Janssen Research & Development. S. Meegalla: None. H. Huang: None. M.P. Winters: None. L.D. Norquay: Employee; Self; Janssen Research & Development. J. Qi: None. F. Du: None. A.R. Nawrocki: Employee; Self; Janssen Pharmaceuticals, Inc.. M. Player: None. A. Pocai: None.
Relationship between Nitrated High-Density Lipoproteins and Vascular Function in African-American Diabetic Patients
Authors: ADEDAYO AJIBOLA M. , ELUWOLE AYOBAMI , TEDLA FASIKA , KREMER ARYE , MASTROGIOVANNI NICOLE , ROSENBERG CARL , DREIZEN PAUL , LAROSA JOHN , SALCICCIOLI LOUIS , BOUTJDIR MOHAMED , BANERJI MARY ANN , BROWN CLINTON , SALIFU MORO , LAZAR JASON , BAKILLAH AHMED 
Published: June 2018

Previous studies have shown that HDL isolated from human atherosclerotic lesions and the blood of patients with established coronary artery disease contains elevated levels of nitrated apolipoprotein AI (NT-apoAI). The significance of NT-apoAI in the pathogenesis of vascular diabetic complications is not well understood. We aimed to evaluate the relationship between plasma NT-apoAI and vascular function in African-Americans diabetic patients. 125 patients with type 2 diabetes were enrolled over a 6 months period. Levels of plasma NT-apoAI was quantified by enzyme-linked immunosorbent assays (ELISA). Microvascular function was assessed by vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound image analysis. Patients population was divided in two groups (well-controlled: HbA1c ≤7.0%, N=54; poorly-controlled: HbA1c &gt;7.0%, N=71). Mean age 60±8 years; 64% female; 80% had hypertension; 90% had dyslipidemia and 15% had CKD. Mean HbA1c levels were 8.1±2.2% and duration of diabetes was 10.29±3.79 years. NT-apoAI was negatively correlated with levels of apoAI and VRI in well-controlled patients but not in poorly-controlled patients (r= -0.298, p=0.025 and r= -0.265, p=0.042; respectively). Multi-regression analysis revealed that NT-apoAI was independently associated with VRI, but neither with PWV nor CIMT, after adjustment for independent variables such as age, gender, weight, hypertension, stroke, smoking, duration of diabetes, dyslipidemia, total cholesterol, HDLc, triglycerides, and LDLc (β= 0.001, p= 0.025; r2= 0.325 for the model). NT-apoAI, independently of other clinical variables, can predict microvascular dysfunction particularly in well-controlled diabetic patients. NT-apoAI could be used as marker to identify diabetic patients at risk of developing early vascular complications.

Disclosure
A.M. Adedayo: None. A. Eluwole: None. F. Tedla: None. A. Kremer: None. N. Mastrogiovanni: None. C. Rosenberg: None. P. Dreizen: None. J. LaRosa: None. L. Salciccioli: None. M. Boutjdir: None. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc.. C. Brown: None. M. Salifu: None. J. Lazar: None. A. Bakillah: None.
Relationship between the Triglyceride Glucose Index and the Presence and Fibrosis of Nonalcoholic Fatty Liver Disease in Korean Adults
Authors: KIM MIN KYUNG , KIM JUNG HYE , PARK KAHUI , LEE SANG BAE , NAM JI SUN , KANG SHINAE , PARK JONG SUK , AHN CHUL WOO , KIM YU SIK 
Published: June 2018

Background: Recently, the triglyceride glucose (TyG) index has been considered a surrogate marker of insulin resistance. Insulin resistance is a well known pathogenic factor in nonalcoholic fatty liver disease (NAFLD). However, few studies have investigated the relationship between the TyG index and liver fibrosis in subjects with NAFLD. Thus, we investigated the relationship between the TyG index and liver fibrosis in Korean adults.
Methods: In total, 5158 participants who underwent ultrasonography in a health promotion center were enrolled. Anthropometric profiles and multiple metabolic risk factors were measured. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated. NAFLD was diagnosed by ultrasonography, and degree of liver fibrosis was assessed by NAFLD fibrosis score (NFS). Significant liver fibrosis was defined as NFS ≥ -1.5.
Results: All subjects were stratified into four groups based on their TyG indices. Significant differences were observed in metabolic parameters among the groups, and the prevalence of NAFLD and liver fibrosis by NFS significantly increased with increasing TyG index. When classifying the severity of NAFLD into three groups, there was a significant correlation between the severity of NAFLD and the TyG index. In the logistic regression analysis after adjustment for multiple risk factors, the odds ratio for the prevalence of liver fibrosis, when comparing the highest and lowest quartiles of the TyG index was 1.92 (95% CI: 1.46-2.53; P for trend &lt; 0.01); the odds ratio for the prevalence of liver fibrosis, when comparing the highest and lowest quartiles of HOMA-IR was 2.92 (95% CI: 1.12-2.40; P for trend &lt;0.01).
Conclusion: There is a significant association between the TyG index and liver fibrosis of NAFLD, but HOMA-IR was superior to TyG index for predicting liver fibrosis in NAFLD patients.

Disclosure
M. Kim: None. J. Kim: None. K. Park: None. S. Lee: None. J. Nam: None. S. Kang: None. J. Park: None. C. Ahn: None. Y. Kim: None.
Prevalence of Lipid Abnormalities in Progressive Stages of Diabetes Mellitus
Authors: GUI BIN , SIAU EVAN , AMOROSA LOUIS F. 
Published: June 2018

Prediabetes (PD) often exists in patients with coronary artery disease (CAD). This cross-sectional study aimed to uncover a link between measures of fat metabolism and lipid profiles with increasing stages of glucose intolerance which could promote premature CAD in PD.
Methods: Subjects from NHANES 2005-2012 without history of DM, dyslipidemia or medication for these disorders were matched by age and gender and categorized into normal group (HbA1c&lt;5.7 and fasting plasma glucose&lt;100mg/dl), PD group (6.5&gt;HbA1c≥5.7 or 125mg/dl&gt;fasting plasma glucose≥100mg/dl) and DM group (HbA1c≥6.5 or fasting plasma glucose≥125mg/dl). Body mass measures, plasma insulin level, lipid panel and hepatic steatosis were compared among 3 groups, using Chi-square and Wilcoxon rank sum test.
Results: From 29314 subjects in NHANES: 128 normal, 132 PD and 130 DM subjects were selected. Weight, BMI, waist circumference significantly increased within groups (all P&lt;0.001) in parallel with hepatosteatosis, and consistent with increasing lipogenesis. LDL changes were distinctive being highest in PD group (P=0.0003).
Conclusions: Insulin values and progressive dyslipidemia correlated with increasing diabetes as expected, but the disparity between hepatic steatosis and LDL suggests an imbalance between lipogenesis and lipoprotein clearance resulting in higher LDL in PD; and a mechanism for early onset of diabetic induced atherogenesis.
Table 1Median and interquartile range or percentageNormal (1)PD (2)DM (3)P among groupsP (1) vs (2)P(2) vs (3)Total cholesterol204 (181-226)213 (194-249)2(182-245)0.010.0020.11LDL124 (99-141)146 (119-167)126 (100- 151)0.0003&lt;0.00010.007Triglyceride104 (82 -139)117 (83-175)179 (131-243)&lt;0.00010.13&lt;0.0001HDL55 (42-69)49 (43-60)40 (34-48)&lt;0.00010.16&lt;0.0001Non-HDL-Cholesterol147 (126-170)167 (140-198)167 (135-196)&lt;0.00010.00020.96Insulin7.24 (5.77-10.55)9.12 (7.28-12.59)15.22 (11.21-22.88)&lt;0.00010.0002&lt;0.0001Hepatic steatosis24.20%45.65%78.72%&lt;0.00010.002&lt;0.0001

Disclosure
B. Gui: None. E. Siau: None. L.F. Amorosa: None.