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Fatty Liver Disease in Patients with Prediabetes and Overweight or Obesity.

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is a global health problem associated with liver morbimortality, obesity, and type 2 diabetes mellitus. This study aimed to analyze the prevalence of NAFLD (defined as a fatty liver index [FLI] ≥ 60) and its association with other cardiovascular risk (CVR) factors in patients with prediabetes and overweight/obesity. The present cross-sectional analysis uses baseline data from an ongoing randomized clinical trial. Sociodemographic and anthropometric characteristics, CVR (assessed by the REGICOR-Framingham risk equation), metabolic syndrome (MetS), and FLI-defined NAFLD (cut-off value of ≥60) were assessed. The prevalence of FLI-defined NAFLD was 78% overall. Men exhibited a worse cardiometabolic profile as compared to women, specifically, with higher values of systolic blood pressure (137.02 ± 13.48 vs. 131.22 ± 14.77 mmHg), diastolic blood pressure (85.33 ± 9.27 vs. 82.3 ± 9.12 mmHg), aspartate aminotransferase (AST) (27.23 ± 12.15 vs. 21.23 ± 10.05 IU/L), alanine aminotransferase (ALT) (34.03 ± 23.31 vs. 21.73 ± 10.80 IU/L), and higher CVR (5.58 ± 3.16 vs. 3.60 ± 1.68). FLI-defined NAFLD was associated with elevated AST, ALT, and the presence of MetS (73.7%) and CVR for the whole sample. People with prediabetes present a high burden of comorbidities related to CVR, despite clinical follow-up, and it is recommended to actively begin working with them to reduce their risks.

SUBMITTER: Arias-Fernandez M

PROVIDER: S-EPMC10146012 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Fatty Liver Disease in Patients with Prediabetes and Overweight or Obesity.

Arias-Fernández María M Fresneda Sergio S Abbate Manuela M Torres-Carballo Marina M Huguet-Torres Aina A Sánchez-Rodríguez Cristian C Bennasar-Veny Miquel M Yañez Aina M AM Busquets-Cortés Carla C

Metabolites 20230407 4

Non-alcoholic fatty liver disease (NAFLD) is a global health problem associated with liver morbimortality, obesity, and type 2 diabetes mellitus. This study aimed to analyze the prevalence of NAFLD (defined as a fatty liver index [FLI] ≥ 60) and its association with other cardiovascular risk (CVR) factors in patients with prediabetes and overweight/obesity. The present cross-sectional analysis uses baseline data from an ongoing randomized clinical trial. Sociodemographic and anthropometric chara ...[more]

PMID: 37110189

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Project description:AimsTo investigate the association between overweight/obesity and fatty liver index (FLI) on the odds of incident prediabetes/type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in 2020 participants after 10 years follow up.MethodsAt baseline (in 2001) 2020 participants, males and females, aged 24-39 years, were stratified according to body mass index (BMI), normal weight (<25 kg/m2), overweight (≥25-<30 kg/m2), or obese (≥30 kg/m2) and FLI (as high FLI ≥60 or low FLI <60). We examined the incidence of prediabetes/type 2 diabetes and NAFLD (ultrasound assessed) over 10 years to 2011 to determine the relative impact of FLI and BMI.Results514 and 52 individuals developed prediabetes and type 2 diabetes during follow-up. Such individuals were older, with higher BMI, serum glucose, insulin, alanine aminotransferase (ALT) and triglyceride (TG) concentrations than those who did not develop prediabetes or type 2 diabetes (n = 1454). The additional presence of high FLI significantly increased the risk of developing prediabetes and type 2 diabetes above the risk of being overweight/obese. Compared with normal weight, low FLI participants, the odds of prediabetes were ∼2-fold higher and the odds of type 2 diabetes were 9-10-fold higher respectively in the overweight/obese, high FLI group. No difference was observed between normal weight, low FLI and overweight/obese and low FLI groups.ConclusionsAn increased FLI significantly increases the odds of incident prediabetes, type 2 diabetes and NAFLD in individuals with overweight/obese highlighting the contributory role of liver fat accumulation in the pathophysiology of prediabetes/type 2 diabetes.Key messagesObesity is a risk factor for non-alcoholic fatty liver disease (NAFLD), prediabetes and type 2 diabetes.Additionally, NAFLD is more prevalent in people with prediabetes and type 2 diabetes when compared to age- and BMI-matched individuals.The presence of a raised fatty liver index (FLI) confers a significantly increased risk of developing prediabetes, type 2 diabetes and NAFLD above that conferred by being overweight/obese.The degree of elevation of FLI can risk stratify for incident prediabetes and type 2 diabetes in people with obesity.

Project description:BackgroundThe early detection and management of children with metabolic associated fatty liver disease (MAFLD) is challenging.ObjectiveTo develop a non-invasive and accurate prediction protocol for the identification of MAFLD among children with overweight/obesity candidates to confirmatory diagnosis.MethodsA total of 115 children aged 8-12 years with overweight/obesity, recruited at a primary care, were enrolled in this cross-sectional study. The external validation was performed using a cohort of children with overweight/obesity (N = 46) aged 8.5-14.0 years. MAFLD (≥5.5% hepatic fat) was diagnosed by magnetic resonance imaging (MRI). Fasting blood biochemical parameters were measured, and 25 candidates' single nucleotide polymorphisms (SNPs) were determined. Variables potentially associated with the presence of MAFLD were included in a multivariate logistic regression.ResultsChildren with MAFLD (36%) showed higher plasma triglycerides (TG), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate transaminase (AST), glutamyl-transferase (GGT) and ferritin (p < 0.05). The distribution of the risk-alleles of PPARGrs13081389, PPARGrs1801282, HFErs1800562 and PNLPLA3rs4823173 was significantly different between children with and without MAFLD (p < 0.05). Three biochemical- and/or SNPs-based predictive models were developed, showing strong discriminatory capacity (AUC-ROC: 0.708-0.888) but limited diagnostic performance (sensitivity 67%-82% and specificity 63%-69%). A prediction protocol with elevated sensitivity (72%) and specificity (84%) based on two consecutive steps was developed. The external validation showed similar results: sensitivity of 70% and specificity of 85%.ConclusionsThe HEPAKID prediction protocol is an accurate, easy to implant, minimally invasive and low economic cost tool useful for the early identification and management of paediatric MAFLD in primary care.

Project description:Abstract Background Overweight/obesity are associated with relative growth hormone (GH) deficiency, and GH deficiency has been implicated in the development of nonalcoholic fatty liver disease (NAFLD). NAFLD and its progressive form, nonalcoholic steatohepatitis (NASH), are associated with significant morbidity and mortality, and no approved therapies currently exist. We hypothesized that GH administration would reduce hepatic steatosis, inflammation and fibrosis in individuals with overweight/obesity and NAFLD. Methods A randomized, double-blind, placebo-controlled trial of GH administration in adults with overweight/obesity and NAFLD was conducted (NCT02217345). Fifty-three adults ages 18-70 years with BMI ≥25 kg/m2 and NAFLD were randomly assigned to receive daily subcutaneous GH or placebo for 6 months. Target IGF-1 was upper quartile of normal. Primary endpoints included intrahepatic lipid content (IHL) by proton magnetic resonance spectroscopy (1H-MRS) and radiographic inflammation and fibrosis by LiverMultiScan corrected T1 score (cT1). Secondary endpoints included alanine transaminase (ALT), visceral adipose tissue (VAT) by dual-energy x-ray absorptiometry (DEXA), hsCRP and HOMA-IR. Data are reported as mean ± SD. Results Forty-one subjects completed the 6-month study. Mean age (45±12 years), BMI (33±5 kg/m2), sex distribution (50% female) and baseline IHL (21.4±14.5%) did not differ between the GH and placebo groups. Over the 6-month study period, there was no difference in change in weight between the groups (GH -0.7±3.8% and placebo -0.6±4.0%, p=0.7). Change in absolute percent IHL was significantly greater in the GH vs placebo group (-5.1±10.5% vs 3.8±6.9%, p=0.003), resulting in a net treatment effect of an 8.9% reduction in IHL (95% CI 3.3-14.6%). Improvements in serum ALT (-10±13 IU/L vs -2±12 IU/L, p=0.009) and cT1 score (-11±63 ms vs 27±57 ms, p=0.037) were greater in the GH vs placebo group. There were also significant reductions in DEXA VAT area (-10±9 cm2 vs 0±20 cm2, p=0.050) and hsCRP (-0.8±0.9 mg/dL vs -0.3±1.7 mg/dL, p=0.017) in the GH vs placebo group. In multivariable models controlling for age, sex, change in weight and change in HOMA-IR, significant effects of GH vs placebo were observed on IHL (p=0.012) and ALT (p=0.015) with a trend towards improvement in cT1 score (p=0.088). In a secondary analysis excluding all subjects with >3% weight loss, which has been shown to independently impact NAFLD outcomes, there were significant improvements in IHL (p=0.001), ALT (p=0.040) and cT1 score (p=0.050) in the GH vs placebo group. No subjects were discontinued due to hyperglycemia (fasting glucose ≥126 mg/dL or HbA1c ≥6.5%). Mild edema was the only treatment-emergent side effect that had a significantly greater incidence in the GH vs placebo group (19% vs 0%, p=0.048). Conclusion GH administration reduces hepatic steatosis and markers of hepatic inflammation and fibrosis in adults with overweight/obesity and NAFLD. The GH/IGF-1 axis may offer targetable therapeutic options for NAFLD/NASH. Presentation: Tuesday, June 14, 2022 10:00 a.m. - 10:15 a.m.

Dataset Information

Fatty Liver Disease in Patients with Prediabetes and Overweight or Obesity.

Publications

Fatty Liver Disease in Patients with Prediabetes and Overweight or Obesity.

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