Association between ectopic pancreatic and hepatic fat and metabolic risk factors in children with non‐alcoholic fatty liver disease

Abstract

Background: Few studies have reported an association between ectopic pancreatic and hepatic fat and metabolic factors in children with non-alcoholic fatty liver disease (NAFLD).Objectives: We investigated this association and also the factors associated with pancreatic and hepatic fat deposition in children with NAFLD.Methods: This cross-sectional study investigated 65 children with NAFLD (49 boys, 13.0 ± 3.2 years, mean body mass index z-score 2.5 ± 1.2), who underwent liver biopsy and magnetic resonance imaging-based proton density fat fraction, as well as anthropometry, laboratory tests, body composition analysis, and hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) measurements.Results: HFF and PFF were 4.2%-49.9% (median 24.3) and 0.4%-26.9% (median 3.8), respectively. HFF was not significantly correlated with PFF. HFF was correlated with total body fat% (r = 0.329, p = 0.010) and γ-glutamyl transpeptidase (GGT) (r = 0.260, p = 0.040), while PFF was correlated with the diastolic blood pressure (r = 0.253, p = 0.045), GGT (r = 0.335, p = 0.007) and fasting plasma glucose (r = 0.417, p = 0.001). Multiple linear regression analysis showed that HFF was significantly associated with sex, age, body fat% and GGT, whereas PFF was associated with hypertension and fasting plasma glucose levels but not insulin resistance.Conclusions: HFF was associated with sex, age and body fat in children with NAFLD, while PFF was associated with hypertension and increased fasting plasma glucose, which suggests that the pathophysiology of ectopic fat accumulation varies across organs in children with NAFLD.

Uric acid and gamma‐glutamyl‐transferase in children and adolescents with obesity: Association to anthropometric measures and cardiometabolic risk markers depending on pubertal stage, sex, degree of weight loss and type of patient care: Evaluation of the adiposity patient follow‐up registry

“…As shown in a recent study, obesity in children with NAFLD is not only associated with increased accumulation of hepatic fat but also of pancreatic fat: Whereas hepatic fat fraction was closest associated to sex, age and body fat in children with NAFLD, pancreatic fat fraction was closest associated with arterial hypertension and increased fasting glucose, suggesting that the pathophysiology of ectopic fat accumulation varies across organs in children with NAFLD 28 …”

“…27 As shown in a recent study, obesity in children with NAFLD is not only associated with increased accumulation of hepatic fat but also of pancreatic fat: Whereas hepatic fat fraction was closest associated to sex, age and body fat in children with NAFLD, pancreatic fat fraction was closest associated with arterial hypertension and increased fasting glucose, suggesting that the pathophysiology of ectopic fat accumulation varies across organs in children with NAFLD. 28 Thus, the early detection and management of children or adolescents with obesity and metabolic associated fatty liver disease is challenging, and a non-invasive prediction protocol has recently been suggested. 29 There is strong evidence for an association between sUA and obesity to trigger proinflammatory processes and the development of MetS already in childhood 26 : Children and adolescents with extreme obesity have significantly higher levels of sUA compared to their peers of normal weight, and this early hyperuricemia is suggested to trigger cardiovascular disease at a young age.…”

Association of total and pancreatic serum amylase enzymatic activity with insulin resistance and the glucose and insulin responses to oral starch test in Mexican children

“…In this way, further lifestyle trial studies could be considering the serum enzymatic amylase level to investigate whether amylase mediates the association of the lifestyle patterns with IR, insulin sensitivity, and/or β‐cell function. Another important consideration for future amylase studies concerning glucose metabolism markers is the pancreatic fat accumulation, which was recently evidenced that is associated with increased FPG in children with non‐alcoholic fatty liver disease 48 . Furthermore, the evaluation of the relationship between amylase and the gut microbiome composition, which have demonstrated to be highly associated with obesity and fasting triglycerides and insulin levels in Mexican children, 49 could contribute with important insights about the possible clinical implications in the obesity and metabolic treatment.…”

“…Another important consideration for future amylase studies concerning glucose metabolism markers is the pancreatic fat accumulation, which was recently evidenced that is associated with increased FPG in children with non-alcoholic fatty liver disease. 48 Furthermore, the evaluation of the relationship between amylase and the gut microbiome composition, which have demonstrated to be highly associated with obesity and fasting triglycerides and insulin levels in Mexican children, 49…”

Fatty Pancreas-Centered Metabolic Basis of Pancreatic Adenocarcinoma: From Obesity, Diabetes and Pancreatitis to Oncogenesis

“…For example, positive associations were noted in a meta-analysis of 13 studies involving 49,329 subjects [60], a meta-analysis of 17 studies with 11,967 individuals [61], a cross-sectional study of 4419 Chinese individuals [62], and a pooled analysis of 12,675 individuals [24]. Positive correlations were also noted in studies involving the following participants: 121 consecutive children with echographic evidence of fatty liver [63]; 25 lean adolescents and 24 adolescents with obesity using MRI [64]; 198 participants without diabetes [65]; 78 Chinese T2DM subjects and 35 volunteers without diabetes [66]; 50 prepubertal children with obesity and 30 children with a lean status via ultrasonographic assessment [67]; 97 sedentary 40-55-year-old individuals [68]; 361 Caucasians at an increased risk of T2DM [69]; 105 patients with iron overload [70]; 45 patients with T2DM and 81 "at risk for T2DM" [71]; 56 patients with T2DM [35]; 65 children with NAFLD [72]; 39 Korean participants without a previous history of diabetes who underwent 1H-MRS [73]; 310 individuals with a body mass index (BMI) ≥ 25 kg/m 2 and serum triglycerides ≥ 1.7 mmol/l and/or T2DM [74]; 106 subjects at T2DM onset [75]; 14 T2DM patients, 13 age-and sex-matched healthy controls (HCs) and 11 young HCs using 3T Prisma MRI [76]; 132 consecutive T2DM patients [77]; 143 patients with NAFLD [78]; 79 patients undergoing total pancreatectomy with islet autotransplantation [79]; 27 subjects with morbid obesity and 15 HC subjects with bariatric surgery [80]; 50 age-and BMI-matched normal subjects, 51 with newly diagnosed type 2 diabetes (T2D-new), 53 with T2D < 5 years (T2D < 5Y), and 52 with T2D ≥ 5 years (T2D ≥ 5Y) [81]; 685 healthy volunteers with fat-water MRI and H-MRS [82]; 250 consecutive patients with endoscopic ultrasonography examination [83]; and 320 participants [84], 112 volunteers [85], 109 participants [59], 64 patients…”