Ghada Anwar

The association of metabolic syndrome, insulin resistance and non-alcoholic fatty liver disease in overweight/obese children.

Background/Aim: To study the prevalence of metabolic syndrome (MS), insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase (ALT). Patients and Methods: Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and liver biochemical profile, in addition to liver ultrasound and liver biopsy. Results: Twenty patients (60.6%) were labeled with MS. IR was present in 16 (48.4%). Fifteen (44%) patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy (P=0.001). Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology (P< 0.05) and fitted more with the criteria of MS (80% vs. 44%). IR was significantly more common among NAFLD patients (73% vs. 28%). Conclusion: There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD.

Genetic polymorphisms in non-alcoholic fatty liver disease in obese Egyptian children

Background/Aim: Polymorphisms in the promoter of microsomal triglyceride transfer protein (MTP) lead to decreased MTP transcription, less export of triglyceride from hepatocytes, and greater intracellular triglyceride accumulation. Therefore, functional polymorphisms in MTP may be involved in determining susceptibility to nonalcoholic steatohepatitis (NASH). The aim of this study is to examine the effect of some genetic influences among a group of obese Egyptian children. Patients and Methods: A cross-sectional study was conducted on 76 overweight and obese children presenting to the Pediatric Endocrinology Unit, Cairo University Childrens Hospital, Egypt, as well as on 20 healthy controls. Anthropometric measurements were taken for all the patients and they underwent clinical examination, ultrasonographic examination of the liver, and liver biopsy when appropriate. Liver functions, blood glucose, serum insulin, C-peptide, and lipid profile were assessed and HOMA-IR calculated. Blood samples from biopsy-proven NASH patients and controls were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism for the –493 G/T polymorphism in the promoter of MTP and the 1183 T/C polymorphism in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD). Results: Eight had biopsy-proven simple steatosis and 7 had NASH. NASH patients had a much higher incidence of the MTP G/G genotype (P = 0.002, CI: 2.9–392) compared with the controls. NASH patients also had a 100% prevalence of the MnSOD T/T genotype. Conclusion: Certain genotypes in MTP and MnSOD are significantly more prevalent among obese children with NASH and may be responsible for such a phenotype.

Ultrasonography as a non-invasive tool for detection of nonalcoholic fatty liver disease in overweight/obese Egyptian children.

INTRODUCTION Liver biopsy, although a gold standard in diagnosis of nonalcoholic fatty liver disease (NAFLD), is an invasive and expensive tool. AIM To assess the diagnostic accuracy of abdominal ultrasound in detecting NAFLD among a group of overweight/obese children having one or more liver abnormality (clinical hepatomegaly, raised ALT or echogenic liver parenchyma by ultrasound). METHODS Seventy-eight overweight/obese children were referred to the Pediatric Hepatology Unit, Cairo University Pediatric Hospital, Egypt, for assessment for hepatic abnormalities. Out of the 78 children, 34 had one or more abnormality in the form of clinical hepatomegaly, raised alanine aminotransferase (ALT) and/or echogenic liver parenchyma by ultrasound. All 34 cases underwent liver biopsy for evaluation for NAFLD. RESULTS Histological NAFLD was detected in 15 cases; 8 simple steatosis and 7 nonalcoholic steatohepatitis (NASH). Sonographic evaluation of hepatic parenchymal echogenicity revealed: 11 with grade 1 echogenicity, 12 with grade 2 and 9 with grade 3 while only 2 had normal liver echopattern. Ultrasonography was 100% sensitive and 100% specific in detecting histological NAFLD, while the positive predictive value (PPV) was 47% and negative predictive value (NPV) was 11%. After consolidating the included children into 2 groups: the first including normal and grade 1 echogenicity and the second including grades 2 and 3, the sensitivity of ultrasonography in detecting histological NAFLD was still 100%, while negative predictive value increased to 100% with an accuracy of 82%. CONCLUSION We conclude that ultrasonography is an important non invasive tool in assessment for NAFLD. Normal or grade 1 hepatic echogenicity can soundly exclude histological NAFLD and obviates the need for liver biopsy.

Nesfatin-1 in childhood and adolescent obesity and its association with food intake, body composition and insulin resistance.

Nesfatin-1 is an anorexigenic peptide that controls feeding behavior and glucose homeostasis. However, there is little data that exists regarding nesfatin-1 secretion in obese children and young adolescents. The aim of this study is to investigate serum nesfatin-1 in childhood and adolescent obesity and to study potential correlations with food intake, anthropometric indices, body composition and insulin resistance. Forty obese children and adolescents and 40 healthy control subjects were studied. Anthropometric measurements were assessed, dietary food intake was evaluated based on 3-days food record and body composition indices were evaluated using bioelectrical impedance analysis. Lipid profile, fasting blood sugar, fasting insulin and HOMA-IR were measured. Fasting serum nesfatin-1 was quantitatively assayed by ELISA. Serum nesfatin-1 was significantly higher in obese group (2.49±1.96 ng/ml) than in control group (0.70±0.81 ng/ml), P=0.001. Positive correlations with serum insulin (P=0.001), HOMA-IR (P=0.000), BMI-SDS (P=0.04), body fat % (P=0.000), fat mass (P=0.000), fat free mass (P=0.03), CHO % (P=0.000), and saturated fat % (P=0.01) were found. While significant negative correlation with protein % (P=0.000) was observed. In conclusion, our results denote that nesfatin-1 might have an important role in regulation of food intake and pathogenesis of insulin resistance in obese children and young adolescents.

Prevalence of hepatic abnormalities in a cohort of Egyptian children with type 1 diabetes mellitus

El‐Karaksy HM, Anwar G, Esmat G, Mansour S, Sabry M, Helmy H, El‐Hennawy A, Fouad H. Prevalence of hepatic abnormalities in a cohort of Egyptian children with type 1 diabetes mellitus.

Predictors of non-alcoholic fatty liver disease in obese and overweight Egyptian children: single center study.

Background/Aim: Pediatric non-alcoholic fatty liver disease (NAFLD) is a global problem which has been increasingly recognized with the dramatic rise in pediatric obesity. The aim of the present study was to identify the clinical, sonographic, and biochemical predictors for NAFLD in obese children. Materials and Methods: Seventy-six children (2-15 years) were included after an informed consent. All were subjected to full anthropometric assessment (including height, weight, body mass index, subscapular skin fold thickness, waist and hip circumference and calculation of waist: hip ratio), biochemical assessment of liver function tests, lipid profile and insulin resistance and sonographic assessment of hepatic echogenicity. Liver biopsy when indicated, was done in 33 patients. Results: Sixteen patients (21%) had elevated ALT and 6 (7.9%) had elevated AST. Significant dyslipidemia (low HDL-c, high total cholesterol, high LDL-c and triglycerides) and higher insulin resistance were found in obese patients (P<0.01). The main sonographic findings were hepatomegaly in 20 patients (26.3%) and echogenic liver in 41 patients (53.9%). Liver biopsy showed simple steatosis in eight cases (24.2%) and non-alcoholic steatohepatitis (NASH) in seven cases (21.2%). Anthropometric measurements, increased hepatic echogenicty by ultrasound, insulin resistance and lipid profile were good predictors of NAFLD in obese children if assessed together. However, LDL-c was the only sensitive predictor (independent variable) for NAFLD in both uni- and multivariate logistic regression analyses. Conclusion: Dyslipidemia per se is a strong predictor of NAFLD among obese Egyptian children.

The value of different insulin resistance indices in assessment of non-alcoholic fatty liver disease in overweight/obese children.

OBJECTIVE The aim of the present study was to determine the association between insulin resistance (IR) and both non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) in a group of Egyptian overweight/obese children and adolescents and to evaluate different IR indices in detection of NAFLD. PATIENTS AND METHODS The study included 76 overweight/obese children aged 2-15 years; 52.6% were males. Laboratory analysis included fasting blood glucose, serum insulin, lipid profile, liver biochemical profile, and liver ultrasound. IR was calculated using the following indices; the homeostasis model assessment method (HOMA-IR), the quantitative insulin-sensitivity check index (QUICKI) and hepatic insulin sensitivity. The National Cholesterol Education Program Adult Treatment Panel III criteria were used to estimate prevalence of MetS. Liver biopsy was done when medically indicated and accepted by parents. RESULTS IR was detected in 43.4% and 34.2% by using QUICKI and HOMA, respectively. MetS was detected in 36.8% and NAFLD was detected in 45.5% among those performing liver biopsy. Cases with NAFLD had more frequent IR than children with normal histology. QUICKI showed significant difference between normal subjects and both steatosis and non-alcoholic steatohepatitis; while HOMA-IR was sensitive in cases with NASH only. MetS was present in 100% of patients with NASH and in 75% of those with steatosis and they were all obese. Patients with NASH had significantly higher ALT than those with normal histology. CONCLUSION IR was significantly associated with NAFLD. QUICKI is considered more sensitive than HOMA-IR in differentiating simple steatosis from normal liver histology.

The effect of tailoring of cornstarch intake on stature in children with glycogen storage disease type III.

Abstract Aim: To determine the individual fasting tolerance for patients with glycogen storage disease type III (GSD III) and to assess their linear growth velocity after tailoring of dose intervals of oral uncooked cornstarch. Patients and methods: A prospective cohort study included 32 patients with GSD III aged 6 months–11.5 years (median: 3.3 years). The fasting tolerance of each patient was determined as the time interval between starch administration until the drop in blood glucose level was below 60 mg/dL. Results: Some 27 patients (84.4%) developed hypoglycemia. The intervals between oral cornstarch administration were tailored for each child according to his/her individual fasting tolerance. After a 6-month follow up there was a significant reduction in seizure attacks (p<0.01) and liver size (p<0.01), but there was no statistically significant difference in liver transaminase and serum lactate levels. There was a significant improvement in height (p<0.01) and linear growth velocity (p<0.05) of these patients after at least a 12-month follow up. Conclusion: Adjusting the intervals between the cornstarch doses for each patient with GSD III, according to individual fasting tolerance test was very beneficial and resulted in improvement of the linear growth velocity and reduction in the frequency of hypoglycemic seizures as well as the size of the liver. Individual scheduling of cornstarch doses prevents complications in those who develop hypoglycemia at short intervals; it also allows some relaxation in schedule for those who can tolerate longer fasting hours to improve their appetite and prolong their uninterrupted sleep hours.

A study of familial Mediterranean Fever (MEFV) gene mutations in Egyptian children with type 1 diabetes mellitus.

BACKGROUND/AIMS An association of type 1 DM and familial Mediterranean fever (FMF) has been newly reported in the medical literature. The aim of the present work was to investigate frequency of MEFV gene mutations in Egyptian children with type 1 diabetes mellitus. METHODS Forty five children with type 1 DM were screened for Mediterranean Fever (MEFV) gene mutation. Forty one healthy control subjects were included. Identification of FMF gene mutation was done based on polymerase chain reaction (PCR) and reverse hybridization. The assay covers 12 mutations in the FMF gene: E148Q - P369S - F479L - M680I (G/C) - M680I (G/A) - I692del - M694V - M694I - K695R-V726A - A744S and R761H. RESULTS Among the screened diabetics, the overall frequency of MEFV gene mutations was 42.2% and among the control group it was 34.1% with no significant difference. Fourteen out of 45 diabetic children (31.1%) were heterozygous (E148Q in 7 children, A744S in 3 children, V726A in 2 children, M680I (G/C) in 1 child and P369S in1 child), while 5 children (11.1%) were compound heterozygous (M694V/M694I in 2 children, E148Q/K695R mutations in 1 child, E148Q/M694I in 1 child and E148Q/V726A in 1 child). The control group showed heterozygous mutation in 34.1% of cases (E148Q mutation in 14.6%, V726A in 12.2%, M680I (G/C) in 4.9% and M694V in 2.4%). CONCLUSION No significant difference in mutation frequency between diabetic and non-diabetic children. We have high carrier rate of MEFV gene mutations among Egyptian population probably due to high consanguinity.

Glycogen storage disease type III in Egyptian children: A single centre clinico-laboratory study

BACKGROUND AND STUDY AIMS Glycogen storage disease type III (GSD III) is an autosomal recessive disorder caused by deficiency of glycogen debrancher enzyme and is characterised by clinical variability. PATIENTS AND METHODS We herein describe the clinical and laboratory findings in 31 Egyptian patients with GSD III presenting to the Paediatric Hepatology Unit, Cairo University, Egypt. RESULTS Eighteen patients (58%) were males. Their ages ranged between 6 months to 12 years. The main presenting complaint was progressive abdominal distention in 55%. Twelve patients (38.7%) had a history of recurrent attacks of convulsions; four had an erroneous diagnosis of hypocalcaemia and epilepsy. Doll-like facies was noted in 90%. Abdominal examination of all cases revealed abdominal distention and soft hepatomegaly which had bright echogenicity by ultrasound. Hypertriglyceridaemia was present in 93.6%, hyperlactacidaemia in 51.6% and hyperuricaemia in 19.4%. Liver biopsy showed markedly distended hepatocytes with well distinct cytoplasmic boundaries and 32% had macrovesicular fatty changes. Serum creatine kinase was elevated in 64.6% of patients and correlated positively and significantly with age (r=0.7 and P=<0.001), while serum triglycerides correlated negatively with age (r=-0.4 and P=0.05). CONCLUSION Blood glucose assessment and search for hepatomegaly in an infant with recurrent seizures may prevent delay in the diagnosis. A huge soft liver reaching the left midclavicular line that appears echogenic on ultrasonography is characteristic of GSD III. A distended hepatocyte with rarified cytoplasm is pathognomonic but not diagnostic. Hypertriglyceridaemia correlates negatively with age, in contrary to CK level.