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Vasco J, Tavares M, Mansilha HF. Association Between Hyperuricemia, Body Composition, and Comorbidities in an Obese Pediatric Population. J Nutr Metab 2025; 2025:2768062. [PMID: 40225283 PMCID: PMC11986183 DOI: 10.1155/jnme/2768062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 01/29/2025] [Indexed: 04/15/2025] Open
Abstract
Background: Childhood obesity is a global issue with multifactorial causes, leading to chronic and complex disease affecting all organs and systems with high morbidity and mortality, later in life. Elevated serum uric acid (SUA) levels are linked to several comorbidities in adults. In children, however, SUA levels vary by age, sex, and pubertal stage, and therefore, this relation is not well documented. While higher body mass index (BMI) has been associated with SUA levels, other nutritional assessment methods have not been thoroughly investigated and the link between SUA levels and obesity comorbidities in children is underexplored. Objective: This study aims to determine if hyperuricemia is related to body composition and obesity-related comorbidities in children. Methods: A retrospective analysis examined records from 505 obese children aged 5 to 18. The study evaluated the relationship between three nutritional assessment methods: BMI, waist-to-height ratio (WHtR), and body fat mass (BFM) percentage determined by bioimpedance (using InBody 270 scale), SUA levels, and blood markers associated with target organ damage. Results: A significant correlation was found between all three nutritional assessment methods (p < 0.001). WHtR showed a stronger correlation with the assessed comorbidities than the BMI z-score. SUA level correlated with HOMA-IR, ALT level, and lipid profile (p < 0.001). Multiple linear regression indicated an association between SUA level, BFM percentage, and WHtR (p < 0.001). Significant differences in body composition, SUA, and comorbidity markers were observed between children with and without hepatic steatosis (p < 0.05). Conclusion: Our results indicated a strong correlation among all nutritional assessment methods; however, WHtR and BFM percentage had a better correlation with obesity complications. SUA is a potential marker for insulin resistance, inflammation, and metabolic dysfunction-associated fatty liver disease (MAFLD) in obese children.
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Affiliation(s)
- João Vasco
- Pediatric Department, Hospital do Divino Espírito Santo, Ponta Delgada, Azores, Portugal
| | - Mónica Tavares
- Nutrition Unit, Pediatric Department, Centro Materno-Infantil do Norte, ULSSA, Porto, Portugal
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Shi D, Tan Q, Zhang Y, Qi X, Xu X, Xu G, Bai R, Deng J, Chen M, Jiang T, Mei Y. Serum uric acid trajectories and risk of metabolic dysfunction-associated steatotic liver disease in China: a 2019-2021 cohort health survey. BMC Public Health 2025; 25:653. [PMID: 39962427 PMCID: PMC11834244 DOI: 10.1186/s12889-024-21214-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 12/26/2024] [Indexed: 02/20/2025] Open
Abstract
OBJECTIVE To investigate the associations between serum uric acid (UA) trajectories and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in large cohort survey 2019-2021. METHODS This cohort health survey included 11,644 participants without MASLD before January 1, 2021. Among them, 5578 (47.90%) were men and 6066 (52.10%) were women. The group-based trajectory model method was applied to identify serum UA trajectories from January 1, 2019, to December 30, 2021. New-onset MASLD events in 2021 were treated as outcomes. A logistic regression model was used to assess associations between UA trajectories and incidence of MASLD. RESULTS Four distinct serum UA trajectories among both sexes were identified: "low-stable" trajectory 1 (n = 783 men; n = 1143 women), "moderate-moderate increasing" trajectory 2 (n = 2794 men; n = 3266 women), "moderate high-moderate increasing" trajectory 3 (n = 1660 men; n = 1464 women), and "high-increasing" trajectory 4 (n = 341 men; n = 193 women). During the 3-year follow-up period, 840 (15.06%) men and 408 (6.72%) women developed MASLD, respectively. Compared with the trajectory 1 group, the trajectory 4 group had the highest risk (odds ration [OR] 2.99 [95% confidence interval {CI} 1.70, 5.24] for men; OR 2.37 [95% CI 1.04, 5.33] for women), followed by the trajectory 3 (OR 2.23 [95% CI 1.52, 3.30] for men; OR 2.37 [95% CI 1.45, 3.92] for women) and trajectory 2 (OR 1.43 [95% CI 1.07, 1.94] for men; OR 1.37 [95% CI 0.93, 2.03] for women) groups. CONCLUSIONS High serum UA trajectories were independent risk factors for MASLD in both sexes, which is critical for informing prevention and treatment strategies in public health initiatives and clinical practice.
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Affiliation(s)
- Dan Shi
- School of Public Health, Chongqing Medical University, Chongqing, 400016, China
| | - Qilong Tan
- School of Public Health, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China
- School of Public Health, Harbin Medical University, Harbin, 150081, Heilongjiang, China
| | - Yong Zhang
- School of Public Health, Chongqing Medical University, Chongqing, 400016, China
- Department of Health Management, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, 400011, China
| | - Xiaoya Qi
- Department of Health Management, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, 400011, China
| | - Xiaoyang Xu
- Department of Health Management, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, 400011, China
| | - Guoqiong Xu
- Department of Health Management, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, 400011, China
| | - Ruixue Bai
- Department of Health Management, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, 400011, China
| | - Jing Deng
- Department of Health Management, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, 400011, China
| | - Mengxue Chen
- Department of Health Management, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, 400011, China
| | - Tao Jiang
- Department of Health Management, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, 400011, China.
| | - Ying Mei
- Department of Health Management, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, 400011, China.
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Valerio G, Di Bonito P, Calcaterra V, Cherubini V, Corica D, De Sanctis L, Di Sessa A, Faienza MF, Fornari E, Iughetti L, Licenziati MR, Manco M, Del Giudice EM, Morandi A, Salerno M, Street ME, Umano GR, Wasniewska M, Maffeis C. Cardiometabolic risk in children and adolescents with obesity: a position paper of the Italian Society for Pediatric Endocrinology and Diabetology. Ital J Pediatr 2024; 50:205. [PMID: 39380079 PMCID: PMC11463079 DOI: 10.1186/s13052-024-01767-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Accepted: 09/20/2024] [Indexed: 10/10/2024] Open
Abstract
Despite the implementation of preventive measures to counteract the obesity epidemics, the prevalence of childhood obesity is still alarming all over the world. Childhood obesity is the most common risk factor for both cardiovascular and metabolic diseases. In fact, an earlier onset of obesity can cause a greater risk of adiposity tracking across the lifespan and consequently a longer exposure to cardiometabolic risk factors. Accumulating evidence provided by prospective and intervention studies demonstrated the link between pediatric obesity and selected subclinical signs of cardiovascular damage (atherosclerosis and left ventricular hypertrophy), or fatal and not fatal cardiovascular events as early as 40 years of age.The numerous guidelines and scientific documents published in the last years demonstrate the relevance of assessing cardiometabolic risk factors in children and adolescents with OB.This Position paper, released by experts of the "Childhood Obesity study group" within the Italian Society for Pediatric Endocrinology and Diabetology, aims to review the assessment of cardiometabolic risk factors and comorbidities in children and adolescents with OW/OB on the light of the most recent scientific evidence.The main recommendations are: (a) early detection of comorbidities, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, polycystic ovary syndrome, inactivity, obstructive sleep apnea and decline in kidney function; (b) weight loss treatment, which is associated with a reduction of all cardiometabolic risk factors; (c) specific treatment of comorbidities, through lifestyle modifications or pharmacological treatment added to lifestyle for suitable individuals; d). monitoring comorbidities for mitigating future morbidity and mortality.
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Affiliation(s)
- Giuliana Valerio
- Department of Medical, Movement and Wellbeing Sciences, University of Napoli "Parthenope", Napoli, 80133, Italy.
| | - Procolo Di Bonito
- Department of Internal Medicine, "S. Maria delle Grazie" Hospital, Pozzuoli, 80078, Italy
| | - Valeria Calcaterra
- Pediatric Department, "V. Buzzi" Children's Hospital, 20154, Milano, Italy
- Department of Internal Medicine, University of Pavia, Pavia, 27100, Italy
| | - Valentino Cherubini
- Department of Women's and Children's Health, Azienda Ospedaliero-Universitaria delle Marche, Ospedali Riuniti di Ancona, "G. Salesi Hospital,", Ancona, Italy
| | - Domenico Corica
- Department of Human Pathology in Adulthood and Childhood, University of Messina, Messina, 98122, Italy
| | - Luisa De Sanctis
- Department of Public Health and Pediatric Sciences, University of Turin, Turin, 10126, Italy
| | - Anna Di Sessa
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, 80138, Italy
| | - Maria Felicia Faienza
- Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari "Aldo Moro", Bari, 70124, Italy
| | - Elena Fornari
- Department of Surgery, Dentistry, Pediatrics and Gynecology, Section of Pediatric Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, 37126, Italy
| | - Lorenzo Iughetti
- Paediatric Unit Department of Medical and Surgical Sciences of Mothers, Children and Adults, University of Modena and Reggio Emilia, Modena, 41121, Italy
| | - Maria Rosaria Licenziati
- Neuro-Endocrine Diseases and Obesity Unit, Department of Neurosciences, Santobono- Pausilipon Children's Hospital, Naples, 80129, Italy
| | - Melania Manco
- Preventive and Predictive Medicine Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, 00165, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, 80138, Italy
| | - Anita Morandi
- Department of Surgery, Dentistry, Pediatrics and Gynecology, Section of Pediatric Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, 37126, Italy
| | - Mariacarolina Salerno
- Department of Translational Medical Science, University of Naples "Federico II", Napoli, 80131, Italy
| | | | - Giuseppina Rosaria Umano
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, 80138, Italy
| | - Malgorzata Wasniewska
- Department of Human Pathology in Adulthood and Childhood, University of Messina, Messina, 98122, Italy
| | - Claudio Maffeis
- Department of Surgery, Dentistry, Pediatrics and Gynecology, Section of Pediatric Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, 37126, Italy
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Barlabà A, Grella C, Tammaro M, Petrone D, Guarino S, Miraglia Del Giudice E, Marzuillo P, Di Sessa A. Kidney function evaluation in children and adolescents with obesity: a not-negligible need. Eur J Pediatr 2024; 183:3655-3664. [PMID: 38871979 DOI: 10.1007/s00431-024-05641-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Revised: 05/03/2024] [Accepted: 06/02/2024] [Indexed: 06/15/2024]
Abstract
UNLABELLED The role of obesity as risk factor for chronic kidney disease (CKD) has been well-recognized. As previously demonstrated in adults, emerging data highlighted the relevant impact of obesity on renal function since childhood. As a matter of fact, obesity also affects renal health through a complex pathogenic mechanism in which insulin resistance (IR) plays a pivotal role. Worthy of note, the vicious interplay among obesity, IR, and renal hemodynamics clinically translates into a plethora of kidney function impairments potentially leading to CKD development. Therefore, renal injury needs to be added to the well-known spectrum of cardiometabolic obesity comorbidities (e.g., type 2 diabetes, IR, metabolic syndrome, cardiovascular disease). CONCLUSION Taking this into account, a careful and timely monitoring of kidney function should not be neglected in the global assessment of children with obesity. We aimed to provide a comprehensive overview on the relevance of kidney evaluation in children with obesity by shedding lights on the intriguing relationship of obesity with renal health in this at-risk population. WHAT IS KNOWN • Obesity has been found to be a risk factor for chronic kidney disease. • Unlike adults, pediatric data supporting the association between obesity and renal function are still limited. WHAT IS NEW • As observed in adults, obesity might affect renal function since childhood. • Kidney function should be carefully evaluated in children with obesity.
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Affiliation(s)
- Annalisa Barlabà
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Carolina Grella
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Mariagrazia Tammaro
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Delfina Petrone
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.
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Lin JH, Lin CH, Kuo YW, Liao CA, Chen JF, Tsai SY, Li CM, Hsu YC, Huang YY, Hsia KC, Yeh YT, Ho HH. Probiotic Lactobacillus fermentum TSF331, Lactobacillus reuteri TSR332, and Lactobacillus plantarum TSP05 improved liver function and uric acid management-A pilot study. PLoS One 2024; 19:e0307181. [PMID: 39046973 PMCID: PMC11268587 DOI: 10.1371/journal.pone.0307181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 06/30/2024] [Indexed: 07/27/2024] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD) is predominantly associated with metabolic disturbances representing aberrant liver function and increased uric acid (UA) levels. Growing evidences have suggested a close relationship between metabolic disturbances and the gut microbiota. A placebo-controlled, double-blinded, randomized clinical trial was therefore conducted to explore the impacts of daily supplements with various combinations of the probiotics, Lactobacillus fermentum TSF331, Lactobacillus reuteri TSR332, and Lactobacillus plantarum TSP05 with a focus on liver function and serum UA levels. Test subjects with abnormal levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and UA were recruited and randomly allocated into six groups. Eighty-two participants successfully completed the 60-day intervention without any dropouts or occurrence of adverse events. The serum AST, ALT, and UA levels were significantly reduced in all treatment groups (P < 0.05). The fecal microbiota analysis revealed the intervention led to an increase in the population of commensal bacteria and a decrease in pathobiont bacteria, especially Bilophila wadsworthia. The in vitro study indicated the probiotic treatments reduced lipid accumulation and inflammatory factor expressions in HepG2 cells, and also promoted UA excretion in Caco-2 cells. The supplementation of multi-strain probiotics (TSF331, TSR332, and TSP05) together can improve liver function and UA management and may have good potential in treating asymptomatic MAFLD. Trial registration. The trial was registered in the US Library of Medicine (clinicaltrials.gov) with the number NCT06183801 on December 28, 2023.
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Affiliation(s)
- Jia-Hung Lin
- Functional R&D Department, Research and Design Center, Glac Biotech Co., Ltd., Tainan City, Taiwan
| | - Chi-Huei Lin
- Functional R&D Department, Research and Design Center, Glac Biotech Co., Ltd., Tainan City, Taiwan
| | - Yi-Wei Kuo
- Functional R&D Department, Research and Design Center, Glac Biotech Co., Ltd., Tainan City, Taiwan
| | - Chorng-An Liao
- Aging and Disease Prevention Research Center, Fooyin University, Kaohsiung City, Taiwan
| | - Jui-Fen Chen
- Research Product Department, Research and Design Center, Glac Biotech Co., Ltd., Tainan City, Taiwan
| | - Shin-Yu Tsai
- Research Product Department, Research and Design Center, Glac Biotech Co., Ltd., Tainan City, Taiwan
| | - Ching-Min Li
- Research Product Department, Research and Design Center, Glac Biotech Co., Ltd., Tainan City, Taiwan
| | - Yu-Chieh Hsu
- Research Product Department, Research and Design Center, Glac Biotech Co., Ltd., Tainan City, Taiwan
| | - Yen-Yu Huang
- Research Product Department, Research and Design Center, Glac Biotech Co., Ltd., Tainan City, Taiwan
| | - Ko-Chiang Hsia
- Research Product Department, Research and Design Center, Glac Biotech Co., Ltd., Tainan City, Taiwan
| | - Yao-Tsung Yeh
- Aging and Disease Prevention Research Center, Fooyin University, Kaohsiung City, Taiwan
- Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung City, Taiwan
| | - Hsieh-Hsun Ho
- Functional R&D Department, Research and Design Center, Glac Biotech Co., Ltd., Tainan City, Taiwan
- Research Product Department, Research and Design Center, Glac Biotech Co., Ltd., Tainan City, Taiwan
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Di Sessa A, Guarino S, Umano GR, Miraglia Del Giudice E, Marzuillo P. Uric acid in pediatric MASLD definition: Is it time to implement diagnostic criteria? J Hepatol 2024; 80:e254-e255. [PMID: 38458323 DOI: 10.1016/j.jhep.2024.02.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 02/27/2024] [Indexed: 03/10/2024]
Affiliation(s)
- Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.
| | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Giuseppina Rosaria Umano
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
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Wang HP, Xu YY, Xu BL, Lu J, Xia J, Shen T, Fang J, Lei T. Correlation Between Abdominal Fat Distribution and Serum Uric Acid in Patients Recently Diagnosed with Type 2 Diabetes. Diabetes Metab Syndr Obes 2023; 16:3751-3762. [PMID: 38028991 PMCID: PMC10676110 DOI: 10.2147/dmso.s430235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 09/26/2023] [Indexed: 12/01/2023] Open
Abstract
Objective To investigated the link between the distribution of abdominal fat and the concentration of serum uric acid (SUA) in individuals recently diagnosed with type 2 diabetes. Methods Studied 364 individuals had been diagnosed with type 2 diabetes within one month, and evaluated factors such as the distribution of fat in the abdomen, indicators related to glucose and lipid metabolism. The participants' SUA concentrations were divided into a normal control group (CG) and a hyperuricemia group (HG). Results The HG group had elevated abdominal subcutaneous fat area (SFA), visceral fat content (VFA), body mass index (BMI), fasting blood glucose (FBG), 2-hour postprandial blood glucose (PBG), glycosylated albumin (GA), serum creatinine (SCr), triacylglycerol (TG), and lower values in glomerular filtration rate (eGFR), high-density lipoprotein cholesterol (HDL-C) when compared to the CG group (P < 0.05). Among the obese individuals, the hyperuricemia subgroup exhibited higher measurements in waistline, hipline, VFA, SFA, BMI, PBG, SCr, TG, and lower HDL-C (P < 0.05) compared to the subgroup with normal uric acid levels. In the non-obese group, the hyperuricemia subgroup showed higher VFA, SCr, and FBG levels, and lower HDL-C (P < 0.05). There was a positive correlation between VFA and serum uric acid (SUA) levels (r = 0.329, P < 0.0001). Logistic regression analysis indicated a 24% increased risk of hyperuricemia with every 10cm2 increase in abdominal VFA. Generate the Receiver Operating Characteristic (ROC) curve analysis revealed that VFA was the most effective predictor of hyperuricemia and insulin resistance (P < 0.05). Conclusion Newly diagnosed type 2 diabetes patients exhibit a strong correlation between abdominal visceral fat and SUA concentration, the former is identified as an autonomous risk factor for hyperuricemia and an effective indicator for assessing the presence of hyperuricemia and predicting insulin resistance.
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Affiliation(s)
- Hong-Ping Wang
- Department of Endocrinology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, Shanghai, 200333, People’s Republic of China
| | - Yuan-Ying Xu
- Department of Endocrinology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, Shanghai, 200333, People’s Republic of China
| | - Bi-Lin Xu
- Department of Endocrinology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, Shanghai, 200333, People’s Republic of China
| | - Jun Lu
- Department of Endocrinology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, Shanghai, 200333, People’s Republic of China
| | - Juan Xia
- Department of Endocrinology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, Shanghai, 200333, People’s Republic of China
| | - Tian Shen
- Department of Endocrinology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, Shanghai, 200333, People’s Republic of China
| | - Ji Fang
- Department of Endocrinology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, Shanghai, 200333, People’s Republic of China
- Department of Nephrology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, Shanghai, 200333, People’s Republic of China
| | - Tao Lei
- Department of Endocrinology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, Shanghai, 200333, People’s Republic of China
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Wu Y, Chen Q, Zhang Q, Wu Y, Zheng X. A 5-Year Follow-Up Study to Explore Factors Associated with Rapid Kidney Function Decline Among Bus Drivers. Int J Gen Med 2023; 16:3193-3201. [PMID: 37533838 PMCID: PMC10392821 DOI: 10.2147/ijgm.s419098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 07/21/2023] [Indexed: 08/04/2023] Open
Abstract
Background Owing to the stressful occupational characteristics, bus drivers have been reported to have a higher risk of renal dysfunction. However, the related factors associated with rapid kidney function decline among bus drivers have not been explored in the existing literature. Therefore, our research aimed to investigate factors related with rapid kidney function decline, and to explore the correlation of baseline SUA (serum uric acid), longitudinal changes in SUA, and rapid eGFR (estimated glomerular filtration rate) decline for bus drivers. Methods This was a five-year cohort study in Shenzhen, China, between 2017 and 2021. We included 832 bus drivers with normal kidney function at baseline. Study subjects were stratified into four quartiles of change in eGFR, and rapid eGFR decline was regarded as the highest (4th) quartile of ΔeGFR (eGFR in 2017-eGFR in 2021). Univariable and multivariable logistic regressions were conducted to explore factors affecting rapid eGFR decline. Results The incidence of hyperuricemia among bus drivers was 37.7% in 2017 and 40.5% in 2021. The overall subjects had a median 5-year decrease in eGFR of 6.72 mL/min/1.73 m2, and individuals with increased SUA from normal to hyperuricemia group had the greatest decline of eGFR. Multivariate analysis showed bus drivers' age (Odds radio: OR, 1.04), elevated baseline eGFR (OR, 1.08), and SUA increase (OR, 1.38) were significantly associated with rapid eGFR changes. Conclusion The high prevalence of hyperuricemia among bus drivers should warrant more attention from health professionals. Subjects' age, elevated baseline eGFR, and SUA increase were risk factors for rapid eGFR decline over 5-year. The findings can provide significant evidence for timely prevention and intervention to decrease the incidence of rapid renal function decline among bus drivers.
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Affiliation(s)
- Yanxia Wu
- Health Management Center, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, People’s Republic of China
| | - Qianqian Chen
- Medical School, Shenzhen University, Shenzhen, 518060, People’s Republic of China
| | - Qionghua Zhang
- Health Management Center, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, People’s Republic of China
| | - Yanli Wu
- Department of Operation Room, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, People’s Republic of China
| | - Xujuan Zheng
- Medical School, Shenzhen University, Shenzhen, 518060, People’s Republic of China
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Zakharova N, Luo C, Aringazina R, Samusenkov V. The efficacy of L-carnitine in patients with nonalcoholic steatohepatitis and concomitant obesity. Lipids Health Dis 2023; 22:101. [PMID: 37438785 DOI: 10.1186/s12944-023-01867-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 06/30/2023] [Indexed: 07/14/2023] Open
Abstract
BACKGROUND In light of the high prevalence of nonalcoholic fatty liver disease and obesity, treatment options for nonalcoholic steatohepatitis are of particular interest. The purpose of the study is to assess the efficacy of L-carnitine and its effects on the functional state of the liver, as well as on lipid and carbohydrate metabolism in patients with nonalcoholic steatohepatitis and concomitant obesity. METHODS People in the control group followed a hypocaloric diet and received 1 tablet of simvastatin 20 mg once a day and 2 capsules of essential phospholipids 600 mg three times a day for 90 days. People in the experimental group followed a hypocaloric diet and received 1 tablet of simvastatin 20 mg once a day and L-carnitine 10 mL orally two times a day for 90 days. RESULTS L-carnitine normalized the blood lipid profile of subjects, as demonstrated by a significant decrease in the blood levels of total cholesterol, triglycerides, low-density lipoproteins, atherogenic index, and insulin resistance. The use of L-carnitine in patients with nonalcoholic steatohepatitis and concomitant obesity contributes to the steady reduction of the main clinical and biochemical symptoms of nonalcoholic steatohepatitis. CONCLUSIONS L-carnitine produces positive effects on the blood lipid profile and carbohydrate metabolism.
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Affiliation(s)
- Natalia Zakharova
- Department of Chemistry, I.M. Sechenov First Moscow State Medical University (Sechenov University, Trubetskaya str., 8-2, Moscow, 119991, Russian Federation
| | - Chenguang Luo
- Department of Hospital Therapy named after Academician G.I. Storozhakov of the Medical Faculty, Pirogov Russian National Research Medical University, Ostrovityanova str., 1 , Moscow, 117997, Russian Federation
| | - Raisa Aringazina
- Department of Internal Diseases № 1, Non-Commercial Joint-Stock Society "West Kazakhstan Marat Ospanov Medical University", Aleksey Maresyev str, Aktobe, 030019, Kazakhstan.
| | - Vadim Samusenkov
- Department of Prosthetic Dentistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya str., 8-2, Moscow, 119991, Russian Federation
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10
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Di Sessa A, Russo MC, Arienzo MR, Umano GR, Cozzolino D, Cirillo G, Guarino S, Miraglia Del Giudice E, Marzuillo P. PNPLA3 I148M Polymorphism Influences Renal Function in Children With Obesity and Prediabetes. J Ren Nutr 2022; 32:670-676. [PMID: 35121131 DOI: 10.1053/j.jrn.2022.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 11/28/2021] [Accepted: 01/10/2022] [Indexed: 11/11/2022] Open
Abstract
OBJECTIVE Nonalcoholic fatty liver disease negatively impacts on renal function with the contribution of the I148 M variant in the patatin-like phospholipase-containing domain 3 (PNPLA3) gene. We hypothesized that children with prediabetes present with a lower estimated glomerular filtration rate (eGFR) than those with normal glucose tolerance (NGT) and that the 148M PNPLA3 allele could play a worsening role. We aimed evaluating the influence of the I148 M PNPLA3 polymorphism on the relationship between the eGFR and prediabetes in children with obesity. METHODS One thousand thirty-six children underwent to complete assessment and were genotyped for the I148 M PNPLA3 polymorphism. RESULTS Patients with prediabetes showed lower eGFR levels (171.03 ± 40.32 vs. 190.80 ± 41.71 mL/min/1.73 m2; P = .001) and higher prevalence of nonalcoholic fatty liver disease (80% vs. 59%; P = .003) than those with NGT. Children with prediabetes showed lower eGFR levels than those with NGT (150.97 ± 14.56 vs. 192.88 ± 40.09; P < .0001) among carriers of the PNPLA3 148M allele. This was not confirmed among patients homozygous for the PNPLA3 I148 allele. A general linear model for eGFR variance confirmed an inverse and significant association of the eGFR with prediabetes in patients carrying the 148M PNPLA3 allele but not in patients homozygous for the PNPLA3 I148 allele. CONCLUSIONS Prediabetes negatively affects renal function in children with obesity. This effect is heightened in patients carrying the PNPLA3 148M allele.
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Affiliation(s)
- Anna Di Sessa
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy.
| | - Maria Cecilia Russo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Maria Rosaria Arienzo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Giuseppina Rosaria Umano
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Domenico Cozzolino
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Grazia Cirillo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Stefano Guarino
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
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11
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Di Bonito P, Valerio G, Licenziati MR, Di Sessa A, Miraglia del Giudice E, Morandi A, Maffeis C, Baroni MG, Chiesa C, Pacifico L, Manco M. Uric acid versus metabolic syndrome as markers of fatty liver disease in young people with overweight/obesity. Diabetes Metab Res Rev 2022; 38:e3559. [PMID: 35728124 PMCID: PMC9787784 DOI: 10.1002/dmrr.3559] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 03/23/2022] [Accepted: 06/03/2022] [Indexed: 12/30/2022]
Abstract
AIMS To compare the association of high serum uric acid (HUA) or metabolic syndrome (MetS) with fatty liver disease (FLD) in youths with overweight/obesity (OW/OB). MATERIALS AND METHODS Cross-sectional study of anthropometrics, biochemical variables, and liver ultrasound of 3104 individuals with OW/OB (age 5-17 years). Metabolic syndrome was defined by ≥ 3 criteria among (1) high waist circumference; (2) high triglycerides; (3) low high-density lipoproteins; (4) fasting glucose ≥100 mg/dl; (5) blood pressure ≥95th percentile in children, and ≥130/80 mmHg in adolescents. High serum uric acid was defined as serum UA value ≥ 75th percentile adjusted for sex. Fatty liver disease was determined by echography. RESULTS The sample was stratified in four categories: (1) no HUA, no MetS (reference category); (2) MetS; (3) HUA; (4) HUA and MetS (HUA + MetS). The prevalence of FLD increased across the four categories from 29.9%, 44.0%, 52.2%, to 67.1%, respectively (p < 0.0001). The ORs for the categorical variables were 1.33 (1.06-1.68) for MetS (p = 0.02), 3.19 (2.51-4.05) for HUA (p < 0.0001) and 3.72 (2.65-5.21) for HUA + MetS (p < 0.0001), versus the reference category regardless of the body mass index. CONCLUSIONS HUA represents a useful marker of FLD in youths with OW/OB, given its greater ability to identify those at increased risk of the disease compared to MetS. The ability of both to predict incident FLD must be investigated in longitudinal study.
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Affiliation(s)
- Procolo Di Bonito
- Department of Internal Medicine"S. Maria delle Grazie" HospitalPozzuoliItaly
| | - Giuliana Valerio
- Department of Movement Sciences and WellbeingUniversity "Parthenope"NaplesItaly
| | - Maria Rosaria Licenziati
- Department of NeuroscienceObesity and Endocrine Disease UnitSantobono‐Pausilipon Children's HospitalNaplesItaly
| | - Anna Di Sessa
- Department of Woman, Child and General and Specialized SurgeryUniversity of Campania "Luigi Vanvitelli"NaplesItaly
| | | | - Anita Morandi
- Pediatric Diabetes and Metabolic Disorders UnitUniversity of VeronaVeronaItaly
| | - Claudio Maffeis
- Pediatric Diabetes and Metabolic Disorders UnitUniversity of VeronaVeronaItaly
| | - Marco Giorgio Baroni
- Department of Clinical Medicine, Life, Health & Environmental SciencesUniversity of L'AquilaItaly
- Neuroendocrinology and Metabolic DiseasesIRCCS NeuromedPozzilliItaly
| | - Claudio Chiesa
- Institute of Translational PharmacologyNational Research CouncilRomeItaly
| | - Lucia Pacifico
- Department of PediatricsPoliclinico Umberto I Hospital"Sapienza" University of RomeRomeItaly
| | - Melania Manco
- Research Area for Multifactorial Disease and Complex PhenotypesChildren's Hospital Bambino GesùIRCCSRomeItaly
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12
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Xiong J, Zheng X, Luo J, Luo X, Zhang Y, Xu L, Wang Y. A follow-up study to explore factors associated with rapid kidney function decline and new-onset kidney disease among Chinese elderly population. Geriatr Gerontol Int 2022; 22:968-975. [PMID: 36116914 DOI: 10.1111/ggi.14480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 07/28/2022] [Accepted: 08/21/2022] [Indexed: 11/30/2022]
Abstract
AIM To explore potential factors associated with rapid kidney function decline and new-onset kidney disease among a Chinese elderly population, and to examine the relationships between baseline serum uric acid (SUA), longitudinal change in SUA and rapid estimated glomerular filtration rate (eGFR) decline over 5 years for this Chinese elderly population. METHODS A 5-year follow-up study was conducted from 2016 to 2020 in Xiamen City, China; and 2436 elderly people with normal kidney function at baseline was included. The multivariable logistic regressions were used to explore risk factors for rapid eGFR decline and new-onset kidney disease. RESULTS The median age of subjects was 65 years, and 38.5% were men. These elderly people experienced a median 5-year decrease in eGFR of 14.50 mL/min/1.73 m2 , and 11.2% of them had developed new-onset kidney disease after 5-year follow-up. Participants with elevated SUA change from the normal group to the hyperuricemia group witnessed the highest decrease of eGFR after a 5-year follow-up than other groups. Multivariate analysis found advanced age, female, elevated baseline SUA, elevated SUA change, hypertension and triglyceride-glucose index were risk factors for rapid eGFR decline and new-onset kidney disease. CONCLUSION The Chinese elderly population was more likely to encounter rapid renal function decline and new-onset kidney disease. A regular test for kidney disease was strongly recommended for these elderly people who were female, with advanced age, with elevated baseline SUA and elevated SUA change; and had high levels of insulin resistance, and blood pressure. The derived findings can offer significant evidence for targeted prevention for the Chinese elderly population. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2022; ••: ••-••.
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Affiliation(s)
- Juan Xiong
- Health Science Centre, Shenzhen University, Shenzhen, China
| | - Xujuan Zheng
- Health Science Centre, Shenzhen University, Shenzhen, China
| | - Jingang Luo
- Department of Laboratory Medicine, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Xiaohua Luo
- Department of Laboratory Medicine, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Yiqin Zhang
- Department of Nephrology, The No.2 Affliated Hospital of Xiamen Medical College, Xiamen, China
| | - Liping Xu
- Department of Nephrology, The No.2 Affliated Hospital of Xiamen Medical College, Xiamen, China
| | - Yuxin Wang
- Department of Nephrology, The No.2 Affliated Hospital of Xiamen Medical College, Xiamen, China
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13
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Di Bonito P, Rosanio FM, Marcovecchio ML, Cherubini V, Delvecchio M, Di Candia F, Iafusco D, Zanfardino A, Iovane B, Maffeis C, Maltoni G, Ripoli C, Piccinno E, Piona CA, Ricciardi MR, Schiaffini R, Franzese A, Mozzillo E. Uric acid and cardiometabolic risk by gender in youth with type 1 diabetes. Sci Rep 2022; 12:12153. [PMID: 35840585 PMCID: PMC9287370 DOI: 10.1038/s41598-022-15484-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 06/24/2022] [Indexed: 11/16/2022] Open
Abstract
The aim of this study was to investigate the association between uric acid (UA) and cardiometabolic risk factors (CMRFs) by sex in youth with type 1 diabetes (T1D). Retrospective data collected from 1323 children and adolescents (5–18 years; 716 boys) with T1D recruited in 9 Italian Pediatric Diabetes Centers were analyzed. CMRFs included UA, HbA1c, blood pressure (BP), cholesterol (TC), HDL, triglycerides (TG), neutrophils (N) and lymphocytes (L) count, glomerular filtration rate (eGFR) (calculated using Schwartz-Lyon equation). In boys, we found a higher age, daily insulin dose, TG, TG/HDL ratio, TC/HDL ratio, systolic BP, N/L ratio and lower HDL, and eGFR across UA tertiles (p = 0.01–0.0001). Similar results were found in girls but not for TG and systolic BP. In boys, the odds ratio (OR) of high levels of TG/HDL ratio, TC/HDL ratio, BP and mildly reduced eGFR (MRGFR) increased for 0.5 mg/dL of UA. Instead, in girls an increased levels of 0.5 mg/dL of UA were associated with high OR of TC/HDL ratio, N/L ratio and MRGFR. Uric acid may represent a useful marker for identifying youth with T1D at high cardiometabolic risk, and this association appears to vary by sex.
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Affiliation(s)
- Procolo Di Bonito
- Department of Internal Medicine, "S. Maria Delle Grazie", Pozzuoli Hospital, Naples, Italy
| | - Francesco Maria Rosanio
- Department of Translational Medical Science, Section of Pediatrics, Regional Center for Pediatric Diabetes, University of Naples Federico II, Via S. Pansini 5, 80131, Naples, Italy
| | | | - Valentino Cherubini
- Department of Women's and Children's Health, Azienda Ospedaliero-Universitaria, Ospedale Riuniti Di Ancona, "G. Salesi" Hospital, Ancona, Italy
| | - Maurizio Delvecchio
- Azienda Ospedaliero Universitaria Consorziale Policlinico Giovanni XXIII, Bari, Italy
| | - Francesca Di Candia
- Department of Translational Medical Science, Section of Pediatrics, Regional Center for Pediatric Diabetes, University of Naples Federico II, Via S. Pansini 5, 80131, Naples, Italy
| | - Dario Iafusco
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Angela Zanfardino
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Brunella Iovane
- Regional Diabetes Center, Children Hospital "Pietro Barilla", University Hospital of Parma, Parma, Italy
| | - Claudio Maffeis
- Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giulio Maltoni
- Department of Woman, Child and Urological Diseases, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Carlo Ripoli
- Pediatric Diabetology Unit, Pediatric and Microcytemia Department, AO Brotzu, Cagliari, Italy
| | - Elvira Piccinno
- Azienda Ospedaliero Universitaria Consorziale Policlinico Giovanni XXIII, Bari, Italy
| | - Claudia Anita Piona
- Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | | | | | - Adriana Franzese
- Department of Translational Medical Science, Section of Pediatrics, Regional Center for Pediatric Diabetes, University of Naples Federico II, Via S. Pansini 5, 80131, Naples, Italy
| | - Enza Mozzillo
- Department of Translational Medical Science, Section of Pediatrics, Regional Center for Pediatric Diabetes, University of Naples Federico II, Via S. Pansini 5, 80131, Naples, Italy.
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14
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Lanzaro F, Guarino S, D'Addio E, Salvatori A, D'Anna JA, Marzuillo P, Miraglia Del Giudice E, Di Sessa A. Metabolic-associated fatty liver disease from childhood to adulthood: State of art and future directions. World J Hepatol 2022; 14:1087-1098. [PMID: 35978659 PMCID: PMC9258256 DOI: 10.4254/wjh.v14.i6.1087] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 12/26/2021] [Accepted: 04/25/2022] [Indexed: 02/06/2023] Open
Abstract
In 2020, an international group of experts proposed to replace the term of nonalcoholic fatty liver disease with metabolic-associated fatty liver disease (MAFLD). This recent proposal reflects the close association of fatty liver with metabolic derangements, as demonstrated by previous robust data. Several factors [including genetics, inflammation, metabolic abnormalities, insulin resistance (IR), obesity, prenatal determinants, and gut-liver axis] have been found to be involved in MAFLD pathophysiology, but this tangled puzzle remains to be clearly understood. In particular, IR has been recognized as a key player in metabolic impairments development in children with fatty liver. On this ground, MAFLD definition focuses on the pathophysiological basis of the disease, by emphasizing the crucial role of metabolic impairments in this condition. Although primarily developed for adults, MAFLD diagnostic criteria have been recently updated with an age-appropriate definition for sex and age percentiles, because of the increasing attention to cardiometabolic risk in childhood. To date, accumulating evidence is available on the feasibility of MAFLD definition in clinical practice, but some data are still conflicting in highly selected populations. Considering the growing prevalence worldwide of fatty liver and its close relationship with metabolic dysfunction both in children and adults with subsequent increased cardiovascular risk, early strategies for MAFLD identification, treatment and prevention are needed. Novel therapeutic insights for MAFLD based on promising innovative biological techniques are also emerging. We aimed to summarize the most recent evidence in this intriguing research area both in children and adults.
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Affiliation(s)
- Francesca Lanzaro
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Elisabetta D'Addio
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Alessandra Salvatori
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Josè Alberto D'Anna
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy.
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
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15
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Riccio S, Melone R, Vitulano C, Guida P, Maddaluno I, Guarino S, Marzuillo P, Miraglia del Giudice E, Di Sessa A. Advances in pediatric non-alcoholic fatty liver disease: From genetics to lipidomics. World J Clin Pediatr 2022; 11:221-238. [PMID: 35663007 PMCID: PMC9134151 DOI: 10.5409/wjcp.v11.i3.221] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/05/2021] [Accepted: 04/02/2022] [Indexed: 02/06/2023] Open
Abstract
As a result of the obesity epidemic, non-alcoholic fatty liver disease (NAFLD) represents a global medical concern in childhood with a closely related increased cardiometabolic risk. Knowledge on NAFLD pathophysiology has been largely expanded over the last decades. Besides the well-known key NAFLD genes (including the I148M variant of the PNPLA3 gene, the E167K allele of the TM6SF2, the GCKR gene, the MBOAT7-TMC4 rs641738 variant, and the rs72613567:TA variant in the HSD17B13 gene), an intriguing pathogenic role has also been demonstrated for the gut microbiota. More interestingly, evidence has added new factors involved in the "multiple hits" theory. In particular, omics determinants have been highlighted as potential innovative markers for NAFLD diagnosis and treatment. In fact, different branches of omics including metabolomics, lipidomics (in particular sphingolipids and ceramides), transcriptomics (including micro RNAs), epigenomics (such as DNA methylation), proteomics, and glycomics represent the most attractive pathogenic elements in NAFLD development, by providing insightful perspectives in this field. In this perspective, we aimed to provide a comprehensive overview of NAFLD pathophysiology in children, from the oldest pathogenic elements (including genetics) to the newest intriguing perspectives (such as omics branches).
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Affiliation(s)
- Simona Riccio
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Rosa Melone
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Caterina Vitulano
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Pierfrancesco Guida
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Ivan Maddaluno
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Anna Di Sessa
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
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16
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Nicolucci A, Maffeis C. The adolescent with obesity: what perspectives for treatment? Ital J Pediatr 2022; 48:9. [PMID: 35033162 PMCID: PMC8761267 DOI: 10.1186/s13052-022-01205-w] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 01/02/2022] [Indexed: 12/14/2022] Open
Abstract
The dramatic increase in overweight and obesity among children and adolescents has become a major public health problem. Obesity in children and young adults is associated with an increased prevalence of cardiometabolic risk factors. Obesity during adolescence represents a strong predictor of obesity and higher mortality in adulthood. Due to the serious implications of obesity in adolescents, effective treatments are urgently needed. Lifestyle interventions represent the recommended therapy. Nevertheless, real world data show that the majority of adolescents do not achieve weight loss in the long term, and are reluctant to participate in lifestyle interventions. Pharmacological treatment is recommended if a formal lifestyle modification program fails to limit weight gain or to improve comorbidities. However, until 2020 the European Medicines Agency (EMA) had not approved any pharmacotherapeutic agents for obesity in pediatric patients. On April 2021, EMA has authorized the use of Liraglutide, a glucagon-like peptide (GLP)-1 analog, for the treatment of obesity in adolescents (12–17 years). The efficacy and safety of Liraglutide were demonstrated in a randomized, double-blind trial, enrolling 251 adolescents. After 56 weeks, a reduction in BMI of at least 5% was observed in 43.3% of participants in the liraglutide group vs. 18.7% in the placebo group, and a reduction in BMI of at least 10% was observed in 26.1 and 8.1%, respectively. Gastrointestinal events were the events most frequently reported with liraglutide. Bariatric surgery represents another effective treatment for adolescents with severe obesity, with sustained benefits on weight loss and cardiometabolic risk factors. However, long-term safety and effectiveness data in adolescents are still scarce. Risks of bariatric surgery include the need for additional abdominal surgical procedures and specific micronutrient deficiencies. Hopefully, new pharmacological treatments in addition to lifestyle interventions will offer more chances of success.
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Affiliation(s)
- Antonio Nicolucci
- Center for Outcomes Research and Clinical Epidemiology, CORESEARCH SRL, Corso Umberto I, 65122, Pescara, Italy.
| | - Claudio Maffeis
- Department of Surgery, Dentistry, Pediatrics and Gynecology, Section of Pediatric Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126, Verona, Italy
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17
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Yang A, Jung N, Kim S, Lee JE. Association Between Non-invasive Diagnostic Methods of Liver Fibrosis and Type 2 Diabetes in Pediatric Patients With Non-alcoholic Fatty Liver Disease. Front Pediatr 2022; 10:825141. [PMID: 35223701 PMCID: PMC8866638 DOI: 10.3389/fped.2022.825141] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 01/10/2022] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND AND PURPOSE The prevalence of non-alcoholic fatty liver disease (NAFLD) in children has been increasing associated with insulin resistance. However, there is a scarcity of related studies in children with NAFLD with type 2 diabetes mellitus (T2DM) compared to adults. We conducted this study to investigate the association between non-invasive diagnostic methods of liver fibrosis and T2DM in pediatric patients with NAFLD. METHODS We enrolled a total of 152 patients aged <18 years with NAFLD, and compared their data according to the presence of T2DM. We evaluated fibrosis by transient elastography (TE, FibroScan®), and calculated the following fibrosis scores for each patient: NAFLD fibrosis score (NFS), AST: platelet ratio index (APRI), Fibrosis-4 (FIB-4) index, and pediatric NAFLD fibrosis index (PNFI). RESULTS In the NAFLD-T2DM group, the NFS and mean controlled attenuation parameter in FibroScan were significantly higher than those in the nondiabetic group. The receiver operating characteristic (ROC) curve values for predicting the presence of T2DM were 0.78 for NFS, 0.64 for FIB-4, 0.62 for PNFI, and 0.61 for APRI. The cutoff HbA1c levels for predicting fibrosis progression in APRI, NFS, and PNFI were 5.7% [area under the curve (AUC) 0.74], 6.4% (AUC 0.71), and 6.4% (AUC 0.55), respectively. In the multivariate analysis, hepatosteatosis on abdomen sonography, NFS, FibroScan F, and APRI were independently associated with T2DM risk. CONCLUSIONS We significantly characterized non-invasive fibrosis markers and elastography in pediatric NAFLD with T2DM compared with the nondiabetic group. We suggest evaluating the progression of fibrosis in the prediabetic stage in children using a combination of these non-invasive methods.
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Affiliation(s)
- Aram Yang
- Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Nayoung Jung
- Department of Pediatrics, Inha University Hospital, Inha University College of Medicine, Incheon, South Korea
| | - Sinae Kim
- Division of Biostatistics, Department of R&D Management, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Ji-Eun Lee
- Department of Pediatrics, Inha University Hospital, Inha University College of Medicine, Incheon, South Korea
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Du R, Li L, Li P, Wang Y. Impact of Insulin Resistance on Cardiometabolic Risk Factors and an Anthropometry-Based Predictive Nomogram for Insulin Resistance Among Adolescents in China. Front Endocrinol (Lausanne) 2022; 13:852395. [PMID: 35418950 PMCID: PMC8995502 DOI: 10.3389/fendo.2022.852395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 02/28/2022] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE We aimed to investigate the impact of insulin resistance (IR), as determined by the homeostasis model assessment of insulin resistance (HOMA-IR), on cardiometabolic risk factors (CMRFs), and develop an anthropometry-based predictive nomogram for IR among adolescents in China. DESIGN Data were acquired from a cross-sectional study with a stratified cluster sampling method, conducted among adolescents in Northeast China. PARTICIPANTS A total of 882 adolescents (aged 12-16 years, 468 boys) were included. MEASUREMENTS All participants underwent anthropometric and biochemical examinations. The thresholds of IR included the 90th percentile of the HOMA-IR for adolescents with a normal body mass index (BMI) and fasting plasma glucose (FPG) level within each sex group (Cutoff A), and the 75th percentile for all participants of the same sex (Cutoff B). RESULTS The HOMA-IR was associated with CMRFs. IR, as defined by both cutoffs A and B, was significantly associated with most CMRFs, except decreased HDL-C levels. Excellent concordance (κ = 0.825) was found between these two criteria in diagnosing IR. However, IR using cutoff A, was more closely associated with cardiometabolic risk. The incidence of IR, as defined by cutoff A, was 18.93% and increased from 10.99% to 43.87% based on the different BMI categories. Further, an anthropometry-based predictive model for IR, incorporating sex, age, waist-to-hip ratio, weight and BMI, was developed and presented as a nomogram. CONCLUSIONS IR among adolescents is strongly related to cardiometabolic risk. We developed an anthropometry-based predictive nomogram for IR among adolescents, which may facilitate health counselling and self-risk assessments.
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Corica D, Bottari A, Aversa T, Morabito LA, Curatola S, Alibrandi A, Ascenti G, Wasniewska M. Prospective assessment of liver stiffness by shear wave elastography in childhood obesity: a pilot study. Endocrine 2022; 75:59-69. [PMID: 34302259 DOI: 10.1007/s12020-021-02828-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 07/12/2021] [Indexed: 12/17/2022]
Abstract
PURPOSE The increased incidence of childhood obesity and related non-alcoholic fatty liver disease (NAFLD) has determined the need to identify a non-invasive technique to diagnose and monitor NAFLD. Two-dimensional shear wave elastography (2D-SWE) has emerged as a reliable, non-invasive, tool to evaluate liver tissue elasticity in clinical practice. Aims of this study were to longitudinally evaluate 2D-SWE changes in relation to weight loss, metabolic profile, and body composition modifications and to investigate the correlation between 2D-SWE variation and clinical and biochemical indices of cardio-metabolic risk in obese children. METHODS Thirty-three children underwent anthropometric, bioimpedenziometric, fasting biochemical assessments, ultrasound, and SWE evaluations, at baseline (V0) and after a 12-months of follow-up (V12). Diet and physical activity programs have been prescribed to all patients according to European Society of Endocrinology and Pediatric Endocrine Society recommendations. Adherence to the prescribed diet and physical activity program was checked every 3 months during the 12-month of follow-up. Variation of all parameters was evaluated in intragroup and intergroup comparison analysis in children, who had not lost weight (Group A) and those who had lost weight (Group B) at V12. Study population was also analyzed dividing it into two groups with respect to 2D-SWE liver elasticity value ≤10.6 kPa or >10.6 kPa. RESULTS A significant reduction of mean 2D-SWE value was demonstrated both in the entire cohort (p = 0.002) and in Group B children (p = 0.004). Intragroup comparison analysis, between V0 and V12, documented a significant decrease of 2D-SWE and BMI SDS and a significant improvement of metabolic profile (decrease of HOMA-IR, HbA1c, oral glucose tolerance test 120-min glucose and insulin, triglycerides, triglycerides/HDL-ratio, transaminases, uric acid, and increase of Matsuda-index and HDL) in children of Group B but not in those of Group A. Intergroup comparison analysis showed significant differences for BMI, BMI SDS, transaminases and several parameters of glucose and lipid metabolism, between Group A and Group B children after 12-months of follow-up. No significant differences were documented with regard to clinical and biochemical variables by dividing the population in accordance with the 2D-SWE cut-off of 10.6 kPa. CONCLUSIONS These results suggested a relation between weight loss, metabolic profile improvement and 2D-SWE value reduction. SWE could play a significant role in the non-invasive assessment of NAFLD in children and adolescents with obesity.
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Affiliation(s)
- Domenico Corica
- Department of Human Pathology of Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy.
| | - Antonio Bottari
- Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Messina, Italy
| | - Tommaso Aversa
- Department of Human Pathology of Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | - Letteria Anna Morabito
- Department of Human Pathology of Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | - Selenia Curatola
- Department of Human Pathology of Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | | | - Giorgio Ascenti
- Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Messina, Italy
| | - Malgorzata Wasniewska
- Department of Human Pathology of Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
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Assessment and management of obesity and metabolic syndrome in children with CKD stages 2-5 on dialysis and after kidney transplantation-clinical practice recommendations from the Pediatric Renal Nutrition Taskforce. Pediatr Nephrol 2022; 37:1-20. [PMID: 34374836 PMCID: PMC8674169 DOI: 10.1007/s00467-021-05148-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 05/04/2021] [Accepted: 05/18/2021] [Indexed: 12/12/2022]
Abstract
Obesity and metabolic syndrome (O&MS) due to the worldwide obesity epidemic affects children at all stages of chronic kidney disease (CKD) including dialysis and after kidney transplantation. The presence of O&MS in the pediatric CKD population may augment the already increased cardiovascular risk and contribute to the loss of kidney function. The Pediatric Renal Nutrition Taskforce (PRNT) is an international team of pediatric renal dietitians and pediatric nephrologists who develop clinical practice recommendations (CPRs) for the nutritional management of children with kidney diseases. We present CPRs for the assessment and management of O&MS in children with CKD stages 2-5, on dialysis and after kidney transplantation. We address the risk factors and diagnostic criteria for O&MS and discuss their management focusing on non-pharmacological treatment management, including diet, physical activity, and behavior modification in the context of age and CKD stage. The statements have been graded using the American Academy of Pediatrics grading matrix. Statements with a low grade or those that are opinion-based must be carefully considered and adapted to individual patient needs based on the clinical judgment of the treating physician and dietitian. Research recommendations are provided. The CPRs will be periodically audited and updated by the PRNT.
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Passaro AP, Marzuillo P, Guarino S, Scaglione F, Miraglia del Giudice E, Di Sessa A. Omics era in type 2 diabetes: From childhood to adulthood. World J Diabetes 2021; 12:2027-2035. [PMID: 35047117 PMCID: PMC8696648 DOI: 10.4239/wjd.v12.i12.2027] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 04/01/2021] [Accepted: 11/02/2021] [Indexed: 02/06/2023] Open
Abstract
Parallel to the dramatic rise of pediatric obesity, estimates reported an increased prevalence of type 2 diabetes (T2D) already in childhood. The close relationship between obesity and T2D in children is mainly sustained by insulin resistance (IR). In addition, the cardiometabolic burden of T2D including nonalcoholic fatty liver disease, cardiovascular disease and metabolic syndrome is also strictly related to IR. Although T2D pathophysiology has been largely studied in an attempt to improve therapeutic options, molecular mechanisms are still not fully elucidated. In this perspective, omics approaches (including lipidomics, metabolomics, proteomics and metagenomics) are providing the most attractive therapeutic options for T2D. In particular, distinct both lipids and metabolites are emerging as potential therapeutic tools. Of note, among lipid classes, the pathogenic role of ceramides in T2D context has been supported by several data. Thus, selective changes of ceramides expression might represent innovative therapeutic strategies for T2D treatment. More, distinct metabolomics pathways have been also found to be associated with higher T2D risk, by providing novel potential T2D biomarkers. Taken together, omics data are responsible for the expanding knowledge of T2D pathophysiology, by providing novel insights to improve therapeutic strategies for this tangled disease. We aimed to summarize the most recent evidence in the intriguing field of the omics approaches in T2D both in adults and children.
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Affiliation(s)
- Antonio Paride Passaro
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania “Luigi Vanvitelli”, Napoli 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania “Luigi Vanvitelli”, Napoli 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania “Luigi Vanvitelli”, Napoli 80138, Italy
| | - Federica Scaglione
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania “Luigi Vanvitelli”, Napoli 80138, Italy
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania “Luigi Vanvitelli”, Napoli 80138, Italy
| | - Anna Di Sessa
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania “Luigi Vanvitelli”, Napoli 80138, Italy
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22
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Cuthbertson DJ, Koskinen J, Brown E, Magnussen CG, Hutri-Kähönen N, Sabin M, Tossavainen P, Jokinen E, Laitinen T, Viikari J, Raitakari OT, Juonala M. Fatty liver index predicts incident risk of prediabetes, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Ann Med 2021; 53:1256-1264. [PMID: 34309471 PMCID: PMC8317942 DOI: 10.1080/07853890.2021.1956685] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 07/12/2021] [Indexed: 12/25/2022] Open
Abstract
AIMS To 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. METHODS At 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. RESULTS 514 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. CONCLUSIONS An 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.
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Affiliation(s)
- Daniel J. Cuthbertson
- Metabolism and Nutrition Research Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK
| | - Juha Koskinen
- Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
- Heart Center, Kotka Central Hospital, Kotka, Finland
| | - Emily Brown
- Metabolism and Nutrition Research Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK
| | - Costan G. Magnussen
- Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
| | - Nina Hutri-Kähönen
- Department of Pediatrics, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Matthew Sabin
- Murdoch Children’s Research Institute, The Royal Children’s Hospital and University of Melbourne, Melbourne, Australia
| | - Päivi Tossavainen
- Department of Pediatrics, PEDEGO Research Unit and Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Eero Jokinen
- Department of Pediatric Cardiology, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
| | - Tomi Laitinen
- Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland
| | - Jorma Viikari
- Department of Medicine, University of Turku, Turku, Finland
- Division of Medicine, Turku University Hospital, Turku, Finland
| | - Olli T. Raitakari
- Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
| | - Markus Juonala
- Department of Medicine, University of Turku, Turku, Finland
- Division of Medicine, Turku University Hospital, Turku, Finland
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Di Bonito P, Licenziati MR, Campana G, Chiesa C, Pacifico L, Manco M, Miraglia Del Giudice E, Di Sessa A, Baroni MG, Marzuillo P, Valerio G. Prevalence of Mildly Reduced Estimated GFR by Height- or Age-Related Equations in Young People With Obesity and Its Association with Cardiometabolic Risk Factors. J Ren Nutr 2021; 31:586-592. [PMID: 33642186 DOI: 10.1053/j.jrn.2020.11.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 10/24/2020] [Accepted: 11/01/2020] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE To compare the prevalence of mildly reduced estimated glomerular filtration rate (MRGFR) (eGFR >60 and < 90 mL/min/1.73 m2), calculated by two creatinine-based equations, and its association with cardiometabolic risk factors (CMRF) in youth with overweight (OW)/obesity (OB). METHODS This is a multicenter cross-sectional study involving university and non-university hospital pediatrics departments. We enrolled 3,118 youth with OW/OB (5-14 years) and 286 healthy normal weight (NW) youth. eGFR was calculated using bedside Schwartz equation (eGFRBSE) and Full Age Spectrum equation (eGFRFAS). In OW/OB group we analyzed the association between eGFR calculated by both equations and CMRF. Uric acid (UA) and birth weight were available in 2,135 and in 1,460 youth. RESULTS The prevalence of MRGFR was 3.8% in NW versus 7.8% in OW/OB (P = .016) by eGFRBSE, and 8.7% in NW versus 19.4% in OW/OB (P < .0001) by eGFRFAS. eGFRBSE and eGFRFAS identified 242 and 605 young people with OW/OB with MRGFR, respectively. Individuals with MRGFR according with both equations showed lower birth weight, younger age, higher BMI-SDS, non-high-density lipoprotein-cholesterol and UA as compared to those with normal eGFR. To examine whether the eGFRFAS was associated with a worse CMR profile also in the range of normal eGFRBSE, we reclassified young people with normal eGFRBSE (n = 2,876) according with eGFRFAS. Out of youth with normal eGFRBSE, 366 (12.7%) presented MRGFR by eGFRFAS and had lower age, higher BMI-SDS, BP and UA than the remaining youth reclassified as normal eGFRFAS. CONCLUSION MRGFR is associated with an altered CMR profile in a large sample of young people with overweight (OW)/obesity (OB). The eGFRFAS equation identifies a higher prevalence of youth with MRGFR, compared to eGFRBSE equation.
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Affiliation(s)
- Procolo Di Bonito
- Department of Internal Medicine, "S. Maria delle Grazie", Pozzuoli Hospital, Naples, Italy
| | - Maria Rosaria Licenziati
- Obesity and Endocrine Disease Unit, Department of Neuroscience, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Giuseppina Campana
- Obesity and Endocrine Disease Unit, Department of Neuroscience, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Claudio Chiesa
- Institute of Translational Pharmacology, National Research Council, Rome, Italy
| | - Lucia Pacifico
- Policlinico Umberto I Hospital, Sapienza University of Rome, Rome, Italy
| | - Melania Manco
- Research Area for Multifactorial Disease and Complex Phenotypes, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Anna Di Sessa
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Marco Giorgio Baroni
- Department of Clinical Medicine, Public Health, Life and Environmental Sciences (MeSVA), University of L'Aquila, Italy; Neuroendocrinology and Metabolic Diseases, IRCCS Neuromed, Pozzilli (IS), Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.
| | - Giuliana Valerio
- Department of Movement Sciences and Wellbeing, University of Naples Parthenope, Naples, Italy
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Di Sessa A, Guarino S, Passaro AP, Liguori L, Umano GR, Cirillo G, Miraglia Del Giudice E, Marzuillo P. NAFLD and renal function in children: is there a genetic link? Expert Rev Gastroenterol Hepatol 2021; 15:975-984. [PMID: 33851883 DOI: 10.1080/17474124.2021.1906649] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 03/18/2021] [Indexed: 02/06/2023]
Abstract
Introduction: Over the past decades, a large amount of both adult and pediatric data has shown relationship between Nonalcoholic Fatty Liver Disease (NAFLD) and chronic kidney disease (CKD), resulting in an overall increased cardiometabolic burden. In view of the remarkable role of the genetic background in the NAFLD pathophysiology, a potential influence of the major NAFLD polymorphisms (e.g. the I148M variant of the Patatin-like phospholipase containing domain 3 (PNPLA3) gene, the E167K allele of the Transmembrane 6 superfamily member 2 (TM6SF2), the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), and the Membrane bound O-acyltransferase domain containing 7-transmembrane channel-like 4 (MBOAT7-TMC4) genes) on renal function has been supposed. A shared metabolic and proinflammatory pathogenesis has been hypothesized, but the exact mechanism is still unknown.Areas covered: We provide a comprehensive review of the potential genetic link between NAFLD and CKD in children. Convincing both adult and pediatric evidence supports this association, but there is some dispute especially in childhood.Expert opinion: Evidence supporting a potential genetic link between NAFLD and CKD represents an intriguing aspect with a major clinical implication because of its putative role in improving strategy programs to counteract the higher cardiometabolic risk of these patients.
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Affiliation(s)
- Anna Di Sessa
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Stefano Guarino
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Antonio Paride Passaro
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Laura Liguori
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Giuseppina Rosaria Umano
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Grazia Cirillo
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Pierluigi Marzuillo
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
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Colucci A, Rocco MC, De Anseris AGE, Nazzaro L, Vajro P, Mandato C. Pediatric vs. adult NAFLD to MAFLD transition: a welcome but tangled path. EXPLORATION OF MEDICINE 2021. [DOI: 10.37349/emed.2021.00051] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The term non-alcoholic fatty liver disease (NAFLD) appears unfitting both in adults and in children. As obesity and metabolic syndrome play a relevant pathogenic role, an international group of adults’ liver disease experts has proposed to rename this condition metabolic (dysfunction)-associated fatty liver disease (MAFLD). While this new more appropriate and useful definition has mostly been met with good reactions in adults, it may present a tangled path in pediatrics. Here we further stress the recommendations of the North American and the European Societies for Pediatric Gastroenterology, Hepatology and Nutrition that a hyperechogenic liver in a child affected by obesity or overweight with chronically elevated liver enzymes should not be assumed to have NAFLD only. Especially in those patients who are not in the classic age range or who have particularly severe laboratory anomalies, other genetic, metabolic (inborn errors of metabolism, IEM), endocrine, intestinal and hepatic pediatric-onset conditions, should in fact be excluded, particularly when response to a weight loss trial is not available. The term pediatric fatty liver disease (PeFLD) with three subtypes (1. contextual diagnosis of an IEM; 2. Metabolic (dysfunction)-associated fatty liver; 3. unknown cause of fatty liver) has recently been proposed aiming to separate true MAFLD from IEM and/or the other above mentioned conditions, which may be rare when considered individually but represent a large group when considered collectively. Although the cost-effectiveness ratio of this attitude is still indeterminate, it is likely that the advantage of the early identification of a specifically treatable pediatric-onset liver disease associated to/mimicking MAFLD would be rewarding.
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Affiliation(s)
- Angelo Colucci
- Pediatrics Section, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi (Salerno), Italy
| | - Maria Chiara Rocco
- Pediatrics Section, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi (Salerno), Italy
| | | | - Lucia Nazzaro
- Pediatrics, AOU San Giovanni di Dio e Ruggi d’Aragona, 84131 Salerno, Italy
| | - Pietro Vajro
- Pediatrics Section, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi (Salerno), Italy
| | - Claudia Mandato
- Department of Pediatrics, Santobono-Pausilipon Children’s Hospital, 80129 Naples, Italy
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Di Sessa A, Riccio S, Pirozzi E, Verde M, Passaro AP, Umano GR, Guarino S, Miraglia del Giudice E, Marzuillo P. Advances in paediatric nonalcoholic fatty liver disease: Role of lipidomics. World J Gastroenterol 2021; 27:3815-3824. [PMID: 34321846 PMCID: PMC8291022 DOI: 10.3748/wjg.v27.i25.3815] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 04/06/2021] [Accepted: 06/04/2021] [Indexed: 02/06/2023] Open
Abstract
Due its close relationship with obesity, nonalcoholic fatty liver disease (NAFLD) has become a major worldwide health issue even in childhood. The most accepted pathophysiological hypothesis is represented by the "multiple hits" theory, in which both hepatic intracellular lipid accumulation and insulin resistance mainly contribute to liver injury through several factors. Among these, lipotoxicity has gained particular attention. In this view, the pathogenic role of different lipid classes in NAFLD (e.g., sphingolipids, fatty acids, ceramides, etc.) has been highlighted in recent lipidomics studies. Although there is some contrast between plasma and liver findings, lipidomic profile in the NAFLD context provides novel insights by expanding knowledge in the intricate field of NAFLD pathophysiology as well as by suggesting innovative therapeutic approaches in order to improve both NAFLD prevention and treatment strategies. Selective changes of distinct lipid species might be an attractive therapeutic target for treating NAFLD. Herein the most recent evidence in this attractive field has been summarized to provide a comprehensive overview of the lipidomic scenario in paediatric NAFLD.
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Affiliation(s)
- Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Simona Riccio
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Emilia Pirozzi
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Martina Verde
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Antonio Paride Passaro
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Giuseppina Rosaria Umano
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
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27
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Di Sessa A, Lanzaro F, Zarrilli S, Picone V, Guarino S, Miraglia del Giudice E, Marzuillo P. COVID-19 and pediatric fatty liver disease: Is there interplay? World J Gastroenterol 2021; 27:3064-3072. [PMID: 34168408 PMCID: PMC8192281 DOI: 10.3748/wjg.v27.i22.3064] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 03/27/2021] [Accepted: 05/07/2021] [Indexed: 02/06/2023] Open
Abstract
The rapid global spread of coronavirus disease 2019 (COVID-19) infection has become a major health issue with higher morbidity and mortality rates. Besides respiratory symptoms, a growing body of evidence indicates a variety of gastrointestinal manifestations including liver involvement. In this regard, several data supported an association between COVID-19 infection and liver injury in adults, while in children there is compelling but currently limited evidence. In particular, patients with COVID-19 have shown a higher risk of liver injury (mainly expressed as increased transaminase levels or hepatic steatosis). Conversely, a greater risk of more severe forms of COVID-19 infection has been observed in subjects with pre-existing chronic liver diseases. The dramatic interplay between COVID-19 and liver damage has been related to the inflammatory pathways chronically active in patients with nonalcoholic fatty liver disease and acutely in those affected by COVID-19, but other different pathogenic mechanisms have also been supposed. Of note, patients with previous metabolic comorbidities also had a higher risk of severe COVID-19 infection. This emphasizes the pathogenic interrelation of the inflammatory pathways with a dysregulated metabolic milieu in COVID-19 patients. Taking into account the prognostic role of fatty liver in COVID-19 patients and its intrinsic relationship with metabolic abnormalities even in childhood, a strict monitoring of this condition is recommended. We aimed to summarize the most recent evidence regarding the potential interplay between pediatric fatty liver and COVID-19.
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Affiliation(s)
- Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Francesca Lanzaro
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Sarah Zarrilli
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Vittorio Picone
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
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Di Sessa A, Guarino S, Umano GR, Arenella M, Alfiero S, Quaranta G, Miraglia del Giudice E, Marzuillo P. MAFLD in Obese Children: A Challenging Definition. CHILDREN (BASEL, SWITZERLAND) 2021; 8:247. [PMID: 33806784 PMCID: PMC8005020 DOI: 10.3390/children8030247] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/19/2021] [Accepted: 03/20/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Recently, the new definition of Metabolic (dysfunction) associated fatty liver disease (MAFLD) has gained remarkable scientific interest. We aimed to evaluate the effectiveness of MAFLD definition in selecting obese children at higher cardiovascular risk. METHODS A total of 954 obese children and adolescents was retrospectively enrolled. Clinical, biochemical, and metabolic evaluations were performed. Hepatic steatosis was assessed by liver ultrasound. According to the metabolic status, the population was divided in three groups. Group 1 included obese patients without both non-alcoholic fatty liver disease (NAFLD) and metabolic dysregulation; group 2 included patients with obesity and NAFLD (then encompassing one MAFLD criterion); group 3 included patients with obesity, NAFLD and evidence of metabolic dysregulation (then encompassing more than 1 MAFLD criteria). RESULTS Patients of Group 3 showed a worse cardiometabolic profile, as also proven by the higher percentage of prediabetes (defined as the presence of impaired fasting glucose or impaired glucose tolerance) compared to other groups (p = 0.001). CONCLUSIONS MAFLD criteria in obese children seem to be less accurate in identifying patients having an intrinsic higher cardiometabolic risk. This suggests the need for a more accurate definition in the context of pediatric obesity.
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Affiliation(s)
| | | | - Giuseppina Rosaria Umano
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 2, 80138 Napoli, Italy; (A.D.S.); (S.G.); (M.A.); (S.A.); (G.Q.); (E.M.d.G.); (P.M.)
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Di Bonito P, Valerio G, Licenziati MR, Campana G, Del Giudice EM, Di Sessa A, Morandi A, Maffeis C, Chiesa C, Pacifico L, Baroni MG, Manco M. Uric acid, impaired fasting glucose and impaired glucose tolerance in youth with overweight and obesity. Nutr Metab Cardiovasc Dis 2021; 31:675-680. [PMID: 33272808 DOI: 10.1016/j.numecd.2020.10.007] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 09/29/2020] [Accepted: 10/07/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND AIM The relationships between uric acid (UA) and prediabetes is poorly explored in youth. We investigated the association between UA, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), insulin resistance (IR) and low insulin sensitivity (IS) in youth with overweight/obesity (OW/OB). METHODS AND RESULTS A cross-sectional study was performed in 2248 youths with OW/OB (age 5-17 years). The sample was stratified in sex-specific quintiles (Q1 to Q5) of UA and the associations with fasting (FG), 2-h post-load glucose (2H-PG), IR and low IS were investigated. IR and low IS were estimated by assessment model of insulin resistance (HOMA-IR) and whole-body IS index (WBISI), respectively. IFG was defined as FG ≥ 100 < 126 mg/dL, IGT as 2H-PG ≥140 < 200 mg/dL, IR as HOMA-IR ≥75th percentile and low IS as WBISI ≤25th percentile by sex. Age, body mass index z-score, 2H-PG, HOMA-IR and WBISI, increased across sex-quintiles of UA while FG did not. The prevalence of IFG and IR were significantly increased in Q5 vs Q1 (reference quartile, P < 0.025). The prevalence of IGT increased from Q3 to Q5 vs Q1 (P < 0.025-0.0001) and that of low IS from Q2 to Q5 vs Q1 (P < 0.005-0.0001). CONCLUSIONS In youth with OW/OB, rates of IGT and low IS increased progressively across quintiles of UA. On the contrary, IFG and IR were associated only with the highest quintile of UA. Our data suggest that UA is a biomarker of impaired glucose metabolism prevalently in post-challenge condition rather than in fasting state.
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Affiliation(s)
- Procolo Di Bonito
- Department of Internal Medicine, "S. Maria delle Grazie" Hospital, Pozzuoli, Italy
| | - Giuliana Valerio
- Department of Movement Sciences and Wellbeing, University "Parthenope", Naples, Italy
| | - Maria R Licenziati
- Obesity and Endocrine Disease Unit, Department of Neuroscience, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Giuseppina Campana
- Obesity and Endocrine Disease Unit, Department of Neuroscience, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Emanuele M Del Giudice
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Anna Di Sessa
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Anita Morandi
- Pediatric Diabetes and Metabolic Disorders Unit, University of Verona, Verona, Italy
| | - Claudio Maffeis
- Pediatric Diabetes and Metabolic Disorders Unit, University of Verona, Verona, Italy
| | - Claudio Chiesa
- Institute of Translational Pharmacology, National Research Council, Rome, Italy
| | - Lucia Pacifico
- Department of Pediatrics, Policlinico Umberto I Hospital, "Sapienza" University of Rome, Rome, Italy
| | - Marco G Baroni
- Department of Clinical Medicine, Public Health, Life and Environmental Sciences (MeSVA), University of L'Aquila, Italy; IRCCS Neuromed, Pozzilli, IS, Italy
| | - Melania Manco
- Research Area for Multifactorial Disease and Complex Phenotypes, Children's Hospital Bambino Gesù, IRCCS, Rome, Italy.
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Zare Jeddi M, Dalla Zuanna T, Barbieri G, Fabricio ASC, Daprà F, Fletcher T, Russo F, Pitter G, Canova C. Associations of Perfluoroalkyl Substances with Prevalence of Metabolic Syndrome in Highly Exposed Young Adult Community Residents-A Cross-Sectional Study in Veneto Region, Italy. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:1194. [PMID: 33572770 PMCID: PMC7908308 DOI: 10.3390/ijerph18031194] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 01/21/2021] [Accepted: 01/23/2021] [Indexed: 01/06/2023]
Abstract
BACKGROUND Studies on the association between perfluoroalkyl substances (PFAS) and metabolic syndrome (MetS) are limited, and results are inconsistent. We aimed to examine the associations between PFAS serum levels and the prevalence of MetS among highly exposed young adults (ages 20-39) residents of a large area of the Veneto Region (North-Eastern Italy) primarily stemming from PFAS water contamination before September 2013. A total of 15,876 eligible young adult residents living in the investigated municipalities were enrolled in the study from January 2017 to July 2019. METHODS MetS was defined by using a modified harmonized definition requiring the presence of 3 of the following: obesity (body mass index ≥30), elevated triglyceride (TG), reduced high-density lipoprotein cholesterol, elevated blood pressure, and hemoglobin A1c ≥ 6.1% or self-reported diabetes mellitus or drug treatment for hyperglycemia. Multivariable generalized additive models were performed to identify the associations between four serum PFAS, including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), and risk of MetS controlling for potential confounders. RESULTS A total of 1282 participants (8.1%) met the criteria of MetS with a higher prevalence among men. PFOA, PFHxS, and PFNA were not associated with the risk of MetS, whereas PFOS showed a consistent protective effect against the risk of MetS (OR 0.76, (95% CI: 0.69, 0.85) per ln-PFOS). However, we found statistically significant positive associations between PFAS serum levels and individual components of MetS, mainly elevated blood pressure and elevated TG. CONCLUSION Our results did not support a consistent association between PFAS and MetS and conflicting findings were observed for individual components of MetS.
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Affiliation(s)
- Maryam Zare Jeddi
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardio-Thoraco-Vascular Sciences and Public Health, 35131 Padova, Italy; (M.Z.J.); (T.D.Z.); (G.B.)
| | - Teresa Dalla Zuanna
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardio-Thoraco-Vascular Sciences and Public Health, 35131 Padova, Italy; (M.Z.J.); (T.D.Z.); (G.B.)
| | - Giulia Barbieri
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardio-Thoraco-Vascular Sciences and Public Health, 35131 Padova, Italy; (M.Z.J.); (T.D.Z.); (G.B.)
| | | | - Francesca Daprà
- Laboratory Department-Regional Agency for Environmental Prevention and Protection-Veneto Region, 37135 Verona, Italy;
| | - Tony Fletcher
- London School of Hygiene and Tropical Medicine, London WC1H 9SH, UK;
| | - Francesca Russo
- Directorate of Prevention, Food Safety, and Veterinary Public Health-Veneto Region, 30123 Venice, Italy;
| | - Gisella Pitter
- Screening and Health Impact Assessment Unit, Azienda Zero-Veneto Region, 35131 Padova, Italy;
| | - Cristina Canova
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardio-Thoraco-Vascular Sciences and Public Health, 35131 Padova, Italy; (M.Z.J.); (T.D.Z.); (G.B.)
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Di Sessa A, Umano GR, Cirillo G, Passaro AP, Verde V, Cozzolino D, Guarino S, Marzuillo P, Miraglia del Giudice E. Pediatric non-alcoholic fatty liver disease and kidney function: Effect of HSD17B13 variant. World J Gastroenterol 2020; 26:5474-5483. [PMID: 33024398 PMCID: PMC7520609 DOI: 10.3748/wjg.v26.i36.5474] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 06/02/2020] [Accepted: 09/04/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Growing evidence supports a genetic link between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). Interesting data demonstrated that both the major NAFLD risk polymorphisms such as the I148M polymorphism in the patatin like phospholipase containing domain 3 (PNPLA3) and the E167K allele in the transmembrane 6 superfamily member 2 gene (TM6SF2) affect renal function. Recently the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene has been recognized as a novel genetic variant involved in NAFLD pathophysiology. In particular, it has been showed the protective effect of the rs72613567:TA variant of this gene against liver damage both in adults and children. AIM To investigate the impact of the rs72613567:TA variant of the HSD17B13 gene on estimated glomerular filtration rate (eGFR) in obese children. METHODS We enrolled 684 obese children (mean age 10.56 ± 2.94 years; mean BMI-SDS 2.98 ± 0.78) consecutively attending our Obesity Clinic. All the patients underwent a careful clinical assessment and a comprehensive biochemical evaluation. To detect hepatic steatosis, a liver ultrasound was performed. NAFLD was defined by ultrasound detected liver steatosis and/or alanine aminotransferase (ALT) levels > 40 IU/L. The study population was divided on the basis of the NAFLD presence. Genotyping for the rs72613567:TA variant of the HSD17B13 gene in all the enrolled subjects was also made. RESULTS Patients carrying the HSD17B13 rare A allele showed higher eGFR levels compared with homozygous patients both among subjects with and without NAFLD. A general linear model confirmed a direct and significant association of eGFR values with HSD17B13 genotype independently of PNPLA3 and TM6SF2 polymorphisms both in patients with and without NAFLD. A comparison of regression line confirmed the influence of HSD17B13 genotype on the relationship between eGFR and age both among patients with and without NAFLD. Homozygous patients for HSD17B13 genotype with NAFLD showed a significantly higher decline of eGFR with the increase of the age compared with the patients with NAFLD carrying the HSD17B13 rare A allele (P value for intercepts = 0.005; P value for slopes = 0.94). The same effect was observed among patients without NAFLD (P value for intercepts = 0.0012; P value for slopes = 0.87). CONCLUSION Carriers of the HSD17B13 rare A allele showed higher eGFR levels than homozygous subjects both among subjects with and without NAFLD and independently of PNPLA3 I148M and TM6SF6 E167K polymorphisms.
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Affiliation(s)
- Anna Di Sessa
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania Luigi Vanvitelli, Napoli 80138, Italy
| | - Giuseppina Rosaria Umano
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania Luigi Vanvitelli, Napoli 80138, Italy
| | - Grazia Cirillo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania Luigi Vanvitelli, Napoli 80138, Italy
| | - Antonio Paride Passaro
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania Luigi Vanvitelli, Napoli 80138, Italy
| | - Valentina Verde
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania Luigi Vanvitelli, Napoli 80138, Italy
| | - Domenico Cozzolino
- Department of Internal Medicine, Università degli Studi della Campania Luigi Vanvitelli, Napoli 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania Luigi Vanvitelli, Napoli 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania Luigi Vanvitelli, Napoli 80138, Italy
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania Luigi Vanvitelli, Napoli 80138, Italy
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Erdal İ, Yalçin SS, Aksan A, Gençal D, Kanbur N. How useful are anthropometric measurements as predictive markers for elevated blood pressure in adolescents in different gender? J Pediatr Endocrinol Metab 2020; 33:1203-1211. [PMID: 32829316 DOI: 10.1515/jpem-2020-0175] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 06/30/2020] [Indexed: 11/15/2022]
Abstract
Background Obesity and obesity-related diseases are one of the common health problems worldwide and have also been proposed to be important predictors of blood pressure and cardiovascular disease risk. The aim of our study is to determine the utility of different anthropometric measurements (body mass index [BMI], skinfold thickness [SFT], waist circumference [WC], mid-upper arm circumference [MUAC], arm circumference-height ratio [AHtR], and waist circumference-height ratio [WHtR]) as markers of hypertension (HT) risk in adolescents. Methods In this cross-sectional study, 544 participants aged between 12 and 13 years were included. Anthropometric measurements and blood pressure of participants were measured. The association of different anthropometric measurements with blood pressure was evaluated. Results The frequency of both elevated blood pressure and HT was 30.2%. Biceps, triceps, and suprailiac SFT have an impact on HT in girls but only suprailiac SFT in boys. WC measurements above the 85th percentile were strongly correlated with HT conditions, and this relationship was stronger in boys than in girls (3.3 vs. 2.6 fold). MUAC, WHtR, and AHtR measurements also have strong correlation with HT in boys but only WHtR has a poor relation in girls. In boys and girls with obesity, there was a positive association between obesity and blood pressures. Conclusions Not only age-related BMI z scores but also a number of other anthropometric measurements, such as WC, SFT, MUAC, WHtR, and AHtR, could have an influence on high blood pressure. The influence changes with gender during adolescence.
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Affiliation(s)
- İzzet Erdal
- Division of Social Pediatrics, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Songül S Yalçin
- Division of Social Pediatrics, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Ayşegül Aksan
- Obesity Center DGD Clinics Sachsenhausen, Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt, Germany
| | - Didem Gençal
- Şişli Hamidiye Etfal Training and Research Hospital, İstanbul, Turkey
| | - Nuray Kanbur
- Division of Adolescent Medicine, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey
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Differences among patients with and without nonalcoholic fatty liver disease having elevated alanine aminotransferase levels at various stages of metabolic syndrome. PLoS One 2020; 15:e0238388. [PMID: 32866186 PMCID: PMC7458345 DOI: 10.1371/journal.pone.0238388] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 08/14/2020] [Indexed: 12/20/2022] Open
Abstract
Background The prevalence of nonalcoholic fatty liver disease (NAFLD) in the non-obese population has increased and NAFLD is not always recognized in individuals with metabolic syndrome (MS). The risk of cirrhosis is higher in patients having NAFLD with elevated alanine aminotransferase (ALT) levels than in those having NAFLD with normal ALT levels. Objective To measure the differences in clinical factors associated with NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and to measure differences in metabolites between MS subjects with and without NAFLD having elevation of ALT. Methods Among 7,054 persons undergoing health check-ups, we included 3,025 subjects who met the selection criteria. We measured differences in clinical factors for NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and compared metabolites between subjects with and without NAFLD having elevation of ALT in 32 subjects with MS. Results The prevalence of NAFLD and NAFLD having elevation of ALT was significantly progressively greater in subjects with Non-MS, Pre-MS, and MS (p <0.001, respectively). In the Non-MS group, there were significant differences between subjects with and without NAFLD having elevation of ALT with respect to body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, hemoglobin A1c, uric acid, aspartate aminotransferase (AST); In the Pre-MS group, there were significant differences in BMI, hypertension, AST, and gamma-glutamyl transpeptidase (GGT); In the MS group, there were significant differences in HDL-C, impaired glucose tolerance, AST, and GGT. There were significant differences in levels of metabolites of nicotinamide, inosine, and acetyl-L-carnitine between MS subjects with and without NAFLD having elevation of ALT (all p <0.05). Conclusions Although NAFLD having elevation of ALT is important for development of NAFLD, differences in factors associated with NAFLD having elevation of ALT at various stages of MS should be considered. Additionally, several metabolites may play roles in the identification of risk for NAFLD in individuals with MS.
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