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Background and objectives: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) have become public health problems in the pediatric population. However, the relationship between these two conditions is not well understood. The primary objective of this study was to assess whether treatment of hyperglycemia in obese, treatment-naive children with type 2 diabetes (T2DM) was associated with an improvement of surrogate markers of NAFLD. Materials and methods: This retrospective, longitudinal study included 151 obese children with a diagnosis of T2DM (Age: 14 ± 1 years, 72% female children, BMI: 98.6th percentile, and A1c: 10.3 ± 0.2%). Clinical/demographic information was collected before patients started any diabetes treatment and 1 and 3 years after starting metformin and/or insulin therapy. Results: Forty-eight patients (32%) had abnormal ALT/AST (i.e., >40 U/L), suggestive of NAFLD. After 1 year of therapy, there were no significant differences in plasma ALT among patients started on insulin, metformin, or combination: 5±4 vs. -10 ± 3 vs. -2±2 IU/L, respectively, P = .07. Of note, changes in plasma ALT were small, despite a significant reduction of A1c in patients prescribed insulin (alone or with metformin): -2.8 ± 1.0%, P = .01, and -2.7 ± 0.3%, P < .001, respectively. In line with this, no significant correlations were found between changes in A1c and plasma aminotransferases. In contrast, changes in plasma AST/ALT were more strongly associated with BMI changes (r = 0.32, P < .001, and r = 0.19, P = .04, respectively). Similar results were observed after 3 years of follow-up. Conclusions: Nonalcoholic fatty liver disease is highly prevalent in obese children with T2DM. Treatment of hyperglycemia with metformin and/or insulin did not result in any significant improvement in surrogate markers of NAFLD (i.e., plasma aminotransferases). While changes in ALT and/or AST may not perfectly reflect histological changes in NAFLD, our findings suggest that the treatment of hyperglycemia per se may not be associated with NAFLD improvement.
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BACKGROUND: Turner syndrome is a genetic disorder that affects women. It is caused by an absent or incomplete X chromosome, which can be presented in mosaicism or not. There are 12 cases of Turner syndrome patients who present structural alterations in autosomal chromosomes. CASE PRESENTATION: The present case report describes a patient with a reciprocal, maternally inherited translocation between chromosomes 2 and 12 with a mosaicism of X monosomy 45,X,t(2;12)(p13;q24)[95]/46,XX,t(2;12)(p13;q24)[5]. Through genetic mapping arrays, altered genes in the patient were determined within the 23 chromosome pairs. These genes were associated with the patient's clinical features using a bioinformatics tool. CONCLUSION: To our knowledge, this is the first case in which a translocation (2;12) is reported in a patient with Turner syndrome and confirmed by conventional cytogenetics, FISH and molecular genetics. Clinical features of our patient are closely related with the loss of one X chromosome, however mild intellectual disability can be likely explained by autosomal genes. The presence of familial translocations was a common finding, thus emphasizing the need for familiar testing for further genetic counselling.
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Exenatide (Exe) is a glucagon-like peptide (GLP)-1 receptor agonist that enhances insulin secretion and is associated with induction of satiety with weight loss. As mitochondrial dysfunction and lipotoxicity are central features of nonalcoholic steatohepatitis (NASH), we tested whether Exe improved mitochondrial function in this setting. We studied C57BL/6J mice fed for 24 weeks either a control- or high-fructose, high-trans-fat (TFD)-diet (i.e., a NASH model previously validated by our laboratory). For the final 8 weeks, mice were treated with Exe (30 µg/kg/day) or vehicle. Mitochondrial metabolism was assessed by infusion of [13C3]propionate, [3,4-13C2]glucose and NMR-based 13C-isotopomer analysis. Exenatide significantly decreased fasting plasma glucose, free fatty acids and triglycerides, as well as adipose tissue insulin resistance. Moreover, Exe reduced 23% hepatic glucose production, 15% tri-carboxylic acid (TCA) cycle flux, 20% anaplerosis and 17% pyruvate cycling resulting in a significant 31% decrease in intrahepatic triglyceride content (P = 0.02). Exenatide improved the lipidomic profile and decreased hepatic lipid byproducts associated with insulin resistance and lipotoxicity, such as diacylglycerols (TFD: 111 ± 13 vs Exe: 64 ± 13 µmol/g protein, P = 0.03) and ceramides (TFD: 1.6 ± 0.1 vs Exe: 1.3 ± 0.1 µmol/g protein, P = 0.03). Exenatide lowered expression of hepatic lipogenic genes (Srebp1C, Cd36) and genes involved in inflammation and fibrosis (Tnfa, Timp1). In conclusion, in a diet-induced mouse model of NASH, Exe ameliorates mitochondrial TCA cycle flux and significantly decreases insulin resistance, steatosis and hepatocyte lipotoxicity. This may have significant clinical implications to the potential mechanism of action of GLP-1 receptor agonists in patients with NASH. Future studies should elucidate the relative contribution of direct vs indirect mechanisms at play.