INTESTINAL GLUCONEOGENESIS IS DOWNREGULATED IN PAEDIATRIC PATIENTS WITH COELIAC DISEASE

ABSTRACTObjectiveUntreated coeliac disease (CD) patients have increased levels of blood glutamine and a lower duodenal expression of glutaminase (GLS). Intestinal gluconeogenesis (IGN) is a process through which glutamine is turned into glucose in the small intestine, for which GLS is crucial. Animal studies suggest impaired IGN may have long-term effects on metabolic control and be associated with development of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to thoroughly investigate IGN at the gene expression level in children with untreated coeliac disease.DesignQuantitative polymerase chain reaction (qPCR) was used to quantify expression of 11 target genes related to IGN using the delta-delta Ct method with three reference genes (GUSB, IPO8 and YWHAZ) in duodenal biopsies collected from 84 children with untreated coeliac disease and 58 disease controls.ResultsSignificantly lower expression of nine target genes involved in IGN was seen in duodenal biopsies from CD patients compared with controls: FBP1, G6PC, GLS, GPT1, PCK1, PPARGC1A, SLC2A2, SLC5A1, and SLC6A19. No significant differences in expression were seen for G6PC3 and GOT1.ConclusionChildren with untreated coeliac disease have lower expression of genes important for IGN. Further studies are warranted to disentangle whether this is a consequence of intestinal inflammation or due to an impaired metabolic pathway shared with other chronic metabolic diseases. Impaired IGN could be a mechanism behind the increased risk of NAFLD seen in CD patients.SIGNIFICANCE OF THIS STUDYWhat is already known about this subject?Genome-wide association studies have shown an association between coeliac disease (CD) and glutaminase (GLS).Intestinal gluconeogenesis (IGN) is a process with a recently described important function in energy homeostasis and metabolic disease. GLS is critical for IGN by enabling it to use glutamine, its main substrate.CD patients are at an increased risk of non-alcoholic fatty liver disease (NAFLD) as adults.What are the new findings?Nine genes involved in IGN are downregulated at the gene expression level in the small intestine of children with untreated CD, suggesting impairment of IGN.How might it impact on clinical practice in the foreseeable future?Impaired IGN might be a mechanism behind the increased risk of NAFLD seen in CD patients as adults.Early diagnosis and treatment of CD may restore IGN and prevent CD patients from NAFLD later in adulthood.

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Gestational Diabetes Mellitus is associated with increased risk of Non-Alcoholic Fatty Liver Disease: A population-based cohort study

Endocrine Abstracts ◽

10.1530/endoabs.56.gp92 ◽

2018 ◽

Author(s):

Aikaterini Lavrentaki ◽

Anuradhaa Subramanian ◽

G Neil Thomas ◽

George Valsamakis ◽

Konstantinos Toulis ◽

...

Keyword(s):

Diabetes Mellitus ◽

Cohort Study ◽

Liver Disease ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Fatty Liver Disease ◽

Population Based ◽

Alcoholic Fatty Liver ◽

Increased Risk ◽

Alcoholic Fatty Liver Disease

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Non-alcoholic fatty liver disease: the hepatic consequence of obesity and the metabolic syndrome

Proceedings of The Nutrition Society ◽

10.1017/s0029665110000030 ◽

2010 ◽

Vol 69 (2) ◽

pp. 211-220 ◽

Cited By ~ 132

Author(s):

J. Bernadette Moore

Keyword(s):

Metabolic Syndrome ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Response To Treatment ◽

Health Concern ◽

Alcoholic Fatty Liver ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in both adults and children worldwide. As a disease spectrum, NAFLD may progress from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. An estimated 20–35% of the general population has steatosis, 10% of whom will develop the more progressive non-alcoholic steatohepatitis associated with markedly increased risk of cardiovascular- and liver-related mortality. Development of NAFLD is strongly linked to components of the metabolic syndrome including obesity, insulin resistance, dyslipidaemia and type 2 diabetes. The recognition that NAFLD is an independent risk factor for CVD is a major public health concern. There is a great need for a sensitive non-invasive test for the early detection and assessment of the stage of NAFLD that could also be used to monitor response to treatment. The cellular and molecular aetiology of NAFLD is multi-factorial; genetic polymorphisms influencing NAFLD have been identified and nutrition is a modifiable environmental factor influencing NAFLD progression. Weight loss through diet and exercise is the primary recommendation in the clinical management of NAFLD. The application of systems biology to the identification of NAFLD biomarkers and factors involved in NAFLD progression is an area of promising research.

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Food insecurity and lipid profile abnormalities are associated with an increased risk of non-alcoholic fatty liver disease (NAFLD): a case-control study

10.21203/rs.2.16412/v1 ◽

2019 ◽

Author(s):

Helda Tutunchi ◽

Maryam Saghafi-Asl ◽

Mohammad Asghari-Jafarabadi ◽

Alireza Ostadrahimi

Keyword(s):

Risk Factors ◽

Liver Disease ◽

Food Insecurity ◽

Fatty Liver Disease ◽

Case Control Study ◽

Case Control ◽

Alcoholic Fatty Liver ◽

Increased Risk ◽

Alcoholic Fatty Liver Disease ◽

Control Study

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is an important public health problem and a significant cause of morbidity and mortality. Little is known about the relation between food insecurity and NAFLD. This study aimed to assess the relationship between food insecurity, risk factors associated with food insecurity, and NAFLD prevalence in a sample of Iranian adults.Methods In this age-matched and gender-matched case–control study, 210 subjects were recruited. NAFLD diagnosis was performed by a single expert radiologist using ultrasonography. The demographic and socioeconomic characteristics, anthropometric indices, body composition, along with food insecurity and depression status were assessed. Blood samples were collected to determine the lipid profile parameters. Chi-square, independent samples t-test, and uni-and multi-variate logistic regression tests were used. Data were analysed using SPSS V.23.0.Results The prevalence of food insecurity was 56.8% and 26.1% in cases and controls ( P<0.001 ), respectively. According to final analysis model, food insecurity, depression, number of children≥4, overweight, and obesity were identified as significant independent risk factors for NAFLD. The chance of NAFLD in the food insecure, depressed, overweight, and obese subjects was 2.2 (95%CI:1.12-3.43), 1.9 (95%CI:1.02-3.62), 2.6 (95% CI:1.81-3.92), and 2.9 (95%CI:2.02- 5.34) times higher, respectively. Additionally, a higher waist circumference (men, OR = 2.9, P<0.001 ; women, OR= 2.6, P<0.001 ), an elevated waist-to-hip ratio (men, OR = 2.3, P<0.001 ; women, OR= 2.7, P<0.001 ), an increased waist-to-height ratio (OR = 2.9, P<0.001 ), and a higher body fat percentage (men, OR = 3.0, P<0.001 ; women, OR= 3.3, P<0.001 ) were independently associated with an increased risk of NAFLD. The odds of NAFLD increased by increment in serum triglyceride (TG) levels (OR = 2.6, P<0.001 ) and decreased by increase in serum high-density lipoprotein cholesterol (HDL-C) (OR = 0.34, P<0.001 ). Compared to controls, NAFLD patients were more likely to have higher TG/HDL-C ratio (OR = 3.3, P<0.001 ).Conclusions The prevalence of food insecurity in patients with NAFLD was significantly higher compared to controls. Food insecurity was associated with an increased risk of NAFLD, even after adjusting for potential confounding factors. Additionally, NAFLD was significantly related to some indicators of dyslipidemia.

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Food insecurity and lipid profile abnormalities are associated with an increased risk of non- alcoholic fatty liver disease (NAFLD): a case-control study in northwest of Iran

10.21203/rs.3.rs-15574/v1 ◽

2020 ◽

Author(s):

Helda Tutunchi ◽

Maryam Saghafi-Asl ◽

Mohammad-Javad Hosseinzadeh Attar ◽

Mohammad Asghari-Jafarabadi ◽

Alireza Ostadrahimi

Keyword(s):

Risk Factors ◽

Liver Disease ◽

Food Insecurity ◽

Fatty Liver Disease ◽

Case Control Study ◽

Case Control ◽

Alcoholic Fatty Liver ◽

Increased Risk ◽

Alcoholic Fatty Liver Disease ◽

Control Study

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is an important public health problem and a significant cause of morbidity and mortality. Little is known about the relation between food insecurity and NAFLD. This study aimed to assess the relationship between food insecurity, risk factors associated with food insecurity, and NAFLD prevalence in a sample of Iranian adults.Methods In this age-matched and gender-matched case–control study, 210 subjects were recruited. NAFLD diagnosis was performed by a single expert radiologist using ultrasonography. The demographic and socioeconomic characteristics, anthropometric indices, body composition, along with food insecurity and depression status were assessed. Blood samples were collected to determine the lipid profile parameters. Chi-square, independent samples t-test, and uni-and multi-variate logistic regression tests were used. Data were analysed using SPSS V.23.0.Results The prevalence of food insecurity was 56.8% and 26.1% in cases and controls ( P<0.001 ), respectively. According to final analysis model, food insecurity, depression, number of children ≥ 4, overweight, and obesity were identified as significant independent risk factors for NAFLD. The chance of NAFLD in the food insecure, depressed, overweight, and obese subjects was 2.2 (95%CI: 1.12-3.43), 1.9 (95%CI: 1.02-3.62), 2.6 (95%CI: 1.81-3.92), and 2.9 (95%CI: 2.02- 5.34) times higher, respectively. Additionally, a higher waist circumference (men, OR = 2.9, P < 0.001 ; women, OR= 2.6, P< 0.001 ), an elevated waist-to-hip ratio (men, OR=2.3, P<0.001 ; women, OR=2.7, P<0.001 ), an increased waist-to-height ratio (OR=2.9, P<0.001 ), and a higher body fat percentage (men, OR=3.0, P<0.001 ; women, OR=3.3, P<0.001 ) were independently associated with an increased risk of NAFLD. The odds of NAFLD increased by increment in serum triglyceride (TG) levels (OR=2.6, P<0.001 ) and decreased by increase in serum high-density lipoprotein cholesterol (HDL-C) (OR=0.34, P<0.001 ). Compared to controls, NAFLD patients were more likely to have higher TG/HDL-C ratio (OR =3.3, P<0.001 ).Conclusions The prevalence of food insecurity in patients with NAFLD was significantly higher compared to controls. Food insecurity was associated with an increased risk of NAFLD, even after adjusting for potential confounding factors. Additionally, NAFLD was significantly related to some indicators of dyslipidemia.

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Cardiovascular Risk in Non-Alcoholic Fatty Liver Disease: Mechanisms and Therapeutic Implications

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16173104 ◽

2019 ◽

Vol 16 (17) ◽

pp. 3104 ◽

Cited By ~ 25

Author(s):

Claudio Tana ◽

Stefano Ballestri ◽

Fabrizio Ricci ◽

Angelo Di Vincenzo ◽

Andrea Ticinesi ◽

...

Keyword(s):

Metabolic Syndrome ◽

Cardiovascular Risk ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Cardiovascular Events ◽

Alcoholic Fatty Liver ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Alcoholic Fatty Liver Disease

New evidence suggests that non-alcoholic fatty liver disease (NAFLD) has a strong multifaceted relationship with diabetes and metabolic syndrome, and is associated with increased risk of cardiovascular events, regardless of traditional risk factors, such as hypertension, diabetes, dyslipidemia, and obesity. Given the pandemic-level rise of NAFLD—in parallel with the increasing prevalence of obesity and other components of the metabolic syndrome—and its association with poor cardiovascular outcomes, the question of how to manage NAFLD properly, in order to reduce the burden of associated incident cardiovascular events, is both timely and highly relevant. This review aims to summarize the current knowledge of the association between NAFLD and cardiovascular disease, and also to discuss possible clinical strategies for cardiovascular risk assessment, as well as the spectrum of available therapeutic strategies for the prevention and treatment of NAFLD and its downstream events.

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Non alcoholic fatty liver disease is a predictor of subclinical Carotid Atherosclerosis in the presence of Metabolic Syndrome

Nepalese Heart Journal ◽

10.3126/njh.v16i1.23898 ◽

2019 ◽

Vol 16 (1) ◽

pp. 39-45

Author(s):

Cemal Kemaloglu ◽

Melek Didem Kemaloglu

Keyword(s):

Metabolic Syndrome ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Carotid Atherosclerosis ◽

Controlled Study ◽

Control Group ◽

Alcoholic Fatty Liver ◽

Increased Risk ◽

Alcoholic Fatty Liver Disease

Objective: The aim of this study is to identify the relationship between carotid intima-media thickness (c-imt) and non-alcoholic fatty liver disease (NAFLD), and to determine whether NAFLD is an independent predictor for the progression of atherosclerosis. Method: This is a prospective randomized controlled study. 103 NAFLD patients who have hepatosteatosis with grade II and above were enrolled in this study. Patients were divided into NAFLD with metabolic syndrome (MS) and NAFLD without MS groups and compared with 50 healthy people. Basal demographic characteristics and C-imt of all patients and control group were measured. Results: C-imt and carotid cross sectional area rates in the NAFLD groups were significantly higher than those in the control group. The mean and max. c-imt levels were significantly higher in the NAFLD group with metabolic syndrome (p<0,001). Homeostatic Model of Assessment-Insulin Resistance (HOMA-IR) levels were increased in the group with metabolic syndrome than those in the group without metabolic syndrome, with statistical significance (p<0.001). There was no difference in c-imt levels between HOMA-IR positive and negative groups (p=0.254) in patients with NAFLD and without metabolic syndrome. There was only a mild positive corelation between c-imt levels and high sensitive C-Reactive protein (hs-CRP) levels in metabolic syndrome positive group (p=0.026 r=0.30). Conclusion: NAFLD was a significant predictor to determine the increased risk of carotid atherosclerosis.

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Cardio-Metabolic Disorders in Non-Alcoholic Fatty Liver Disease

International Journal of Molecular Sciences ◽

10.3390/ijms20092215 ◽

2019 ◽

Vol 20 (9) ◽

pp. 2215 ◽

Cited By ~ 11

Author(s):

Hamza El Hadi ◽

Angelo Di Vincenzo ◽

Roberto Vettor ◽

Marco Rossato

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Metabolic Disorders ◽

Current Understanding ◽

Metabolic Complications ◽

Alcoholic Fatty Liver ◽

Increased Risk ◽

Stroke Type ◽

Alcoholic Fatty Liver Disease

With the progressive epidemics of obesity, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in adults and children. The increasing prevalence and incidence of NAFLD with advanced fibrosis is concerning because patients appear to experience higher non-liver-related morbidity and mortality than the general population. Recent clinical evidence suggests that NAFLD is directly associated with an increased risk of cardio-metabolic disorders. This mini review describes briefly the current understanding of the pathogenesis of NAFLD, summarizing the link between NAFLD and cardio-metabolic complications, focusing mainly upon ischemic stroke, type 2 diabetes mellitus (DM), hypertension, chronic kidney disease (CKD) and cardiac arrhythmias. In addition, it describes briefly the current understanding of the pathogenesis of NAFLD.

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