Unraveling the link between insulin resistance and Non-alcoholic fatty liver disease (or metabolic dysfunction-associated steatotic liver disease): A Narrative Review.

Objective: Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming a significant global health concern, representing the leading cause of chronic liver disease and posing a substantial public health challenge. NAFLD is associated with higher insulin resistance (IR) levels, a key pathophysiological mechanism contributing to its development and progression. To counter this growing trend, it is crucial to raise awareness about NAFLD and promote healthy lifestyles to mitigate the impact of this disease. Methods: Relevant studies regarding IR and NAFLD published until May 30, 2023, were extracted from Google PubMed, Scopus, and Web Of Science web databases. The following keywords were used: IR, diabetes mellitus, Non-alcoholic fatty liver disease, and metabolic syndrome. Results: IR leads to an accumulation of fatty acids within liver cells, resulting from increased glycolysis and decreased apolipoprotein B-100. Furthermore, the manifestations of NAFLD extend beyond liver-related morbidity and mortality, affecting multiple organs and giving rise to various non-communicable disorders such as diabetes mellitus, metabolic syndrome, polycystic ovary syndrome, obstructive sleep apnea, and cardiovascular disease. Although lifestyle modification remains the primary treatment approach for NAFLD, alternative therapies, including pharmacological, herbal, and surgical interventions, may be considered. By implementing early and simple measures, cirrhosis, end-stage liver disease, and hepatocellular carcinoma can be prevented. Conclusions: There is a clear association between NAFLD and elevated levels of IR. Several metabolic conditions, such as obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome, are closely interrelated with NAFLD and IR. Raising awareness about NAFLD and promoting a healthy lifestyle are crucial steps to reverse the impact of this disease.

Determinants of Self-monitoring of Blood Glucose in Iranian Children and Adolescents with Type 1 Diabetes.

Background: Type 1 diabetes mellitus (T1DM) is a prevalent chronic disease among children and adolescents, necessitating effective self-monitoring of blood glucose (SMBG) levels. Understanding the determinants and factors influencing SMBG behavior is crucial for optimizing diabetes management in this population. Objectives: This study aimed to investigate the frequency of SMBG and identify the determinants influencing factors in children and adolescents with T1DM. Methods: This cross-sectional study was conducted in Tehran, Iran, and included 275 participants selected through simple random sampling from the Gabric Diabetes Education Association. The inclusion criteria comprised children and adolescents aged 3 - 18 years diagnosed with T1DM for at least 6 months who were using analog or neutral protamine Hagedorn (NPH) and regular insulin subcutaneously. Patients using insulin pumps were excluded. Data collection involved an online questionnaire covering demographic information (e.g., age, gender, educational status, and parental occupations) as well as clinical information (number of hypoglycemic episodes, hemoglobin A1C (HbA1C) levels, diabetes duration, insulin regimen, diabetes complications, glucose monitoring practices, hospitalizations, and behavioral characteristics). Statistical analyses, including descriptive statistics, correlation tests, and Poisson regressions, were performed using SPSS software (version 21). A significance level of P-value < 0.05 was considered statistically significant. Results: The participants had a mean age of 10.00 ± 3.77 years, with 54.2% being males. Most of the participants (87.3%) were schoolchildren, and the mean age of diagnosis was 6.56 ± 3.73 years, with a mean duration of 44.72 ± 36.32 months. Anthropometric investigations revealed mean height, weight, and body mass index (BMI) values of 136.69 ± 21.11 cm, 37.45 ± 15.51 kg, and 18.31 ± 3.55 kg/m2, respectively. The majority of participants (93.5%) used insulin pens, and the mean daily insulin dosage was 35.34 ± 22.20 IU. Parents reported consistent glucose level monitoring in 64.7% of cases. The mean HbA1c level was 7.91 ± 1.58%. Factors such as the price and availability of glucometer strips influenced glucose level monitoring. In univariate analysis, only age and HbA1C levels showed a negative correlation; however, parents' consistent checking showed a positive correlation with the frequency of daily, weekly, or monthly glucose checking. Conclusions: This study underscores the significance of SMBG in children and adolescents with T1DM. The findings emphasize the critical role of price and availability of glucometers and strips in achieving standard care for T1DM patients.

Dysgerminoma in a 15 years old phenotypically female Swyer syndrome with 46, XY pure gonadal dysgenesis: A case report.

Swyer syndrome is a 46, XY karyotype, with pure gonadal dysgenesis and primary amenorrhea. These females have primordial Mullerian structures and seek medical attention as they experience primary amenorrhea. Here, we report a 15-year-old girl, diagnosed as Swyer syndrome associated with left ovarian dysgerminoma.

Benefits of metformin add-on insulin therapy (MAIT) for HbA1c and lipid profile in adolescents with type 1 diabetes mellitus: preliminary report from a double-blinded, placebo-controlled, randomized clinical trial.

OBJECTIVES: Metabolic control during puberty is impaired in Type 1 Diabetes Mellitus (T1DM) patients due to increased insulin resistance. Metformin is one of the oral medications typically used in type 2 diabetes mellitus to reduce insulin resistance. We aimed to examine the effect of metformin on glycemic indices and insulin daily dosage in adolescents with T1DM. METHODS: The present clinical trial was carried out on 50 adolescents aged 10-20 years with T1DM referred to the Endocrinology Clinic of Mofid Children's Hospital in Tehran for nine months. The patients were randomly divided into two groups. In the first group, metformin was added to insulin therapy, while the second group continued routine insulin therapy combined with placebo. Hemoglobin A1c (HbA1c), weight, BMI, insulin dosage, and blood pressure were measured at the beginning of the study and repeated every three months. Serum lipid profile, creatinine, blood urea nitrogen, and liver enzymes were also measured twice: At the beginning and end of the study (after nine months). RESULTS: The HbA1c level (p<0.001) and insulin dosage (p=0.04) were lower in the metformin group than in the placebo group after nine months. Daily insulin dosage variability was significantly lower in the metformin recipient group (p=0.041). Serum triglyceride, cholesterol, and creatinine were significantly lower in the metformin arm than in the placebo arm (p<0.05). However, metformin did not affect LDL, HDL, liver enzymes, and BUN. CONCLUSIONS: Adjunctive metformin therapy reduces insulin dosage by inhibiting insulin resistance and weight gain. It helps decrease daily insulin dosage variability, which may prevent hypoglycemia. Also, metformin reduces creatinine, preventing renal failure in the long term.

3-Hydroxyisobutyryl-CoA hydrolase deficiency in an infant with developmental delay and high anion gap acidosis.

Due to the rarity of this disorder, paying attention to diagnostic clues is important. Low valine formula seems to be effective in improvement of patient's symptoms. Prevention of consanguineous marriage is the best way to prevent this disease.

Clinical and Paraclinical Characteristics of Non-Classic Phenylketonuria.

OBJECTIVE: Phenylketonuria (PKU) is one of the most common inherited metabolic diseases, which is classified into classic and non-classic types. It is estimated that 2% of children with PKU develop a severe and progressive neurological disease, called non-classic (malignant) PKU. This study aimed to demonstrate the clinical features, laboratory findings, and diagnostic/therapeutic characteristics of non-classic PKU patients referred to a tertiary referral center for children in Tehran, Iran. MATERIALS & METHODS: In this study, background information, such as gender and age, clinical manifestations, laboratory findings, and response rate to conventional treatment, was investigated in patients with non-classic PKU, who were referred to Mofid Children's Hospital in Tehran, Iran, through neonatal screening. RESULTS: Twenty patients with a diagnosis of non-classic PKU were included in this study. The mean age of the patients was 6.00±2.81 years (range: 2-12 years), and 45.0% were male. In patients with a late diagnosis, the most common presentations were motor developmental delay (15.0%), skin and cutaneous manifestations (15.0%), seizure (5.0%), and restlessness (5.0%). The overall response rate to treatment was 85.0%. Factors that predict good response to treatment included female gender, higher neopterin level, and lower age at diagnosis and management. CONCLUSION: In conclusion, about half of patients with non-classic PKU remain asymptomatic, which is due to early diagnosis via neonatal screening. Also, higher age at diagnosis and treatment, besides low neopterin levels, may be useful as prognostic factors.

Assessment of Anthropometric Indices in Patients with Phenylketonuria.

OBJECTIVES: Dietary phenylalanine restriction is the main treatment of phenylketonuria (PKU, OMIM 261600). There are a number of studies which have demonstrated growth retardation in these patients, and some are in contrast. This study was performed to assess the growth parameters of treated PKU patients. MATERIALS & METHODS: This cross-sectional study was performed between 2015 and 2017 to compare growth indices in PKU patients in our clinics with normal age and sex matched controls. Weight, height, head circumference (HC), weight for height and BMI (weight/height2) were measured and converted into Z-scores. We assessed differences between patients and controls' anthropometric indexes in all patients and separately in patients who were diagnosed by newborn screening program and patients who were diagnosed after presentation of clinical manifestations in comparison with age and sex-matched controls. Also, this difference was assessed separately in patients aged two years and less. Correlations between pretreatment plasma phenylalanine concentrations mean plasma phenylalanine concentrations and anthropometric parameters were analyzed in the patients. RESULTS: Overall, 209 under-treatment PKU patients (103 males, 106 females; mean age 9.29 ± 8.7 years) and 216 controls (109 males and 107 females; mean age 8.98 ± 8.62 years) matched in terms of age, sex and birth weight were enrolled in this study. In general, 130 patients were diagnosed by newborn screening and 79 were diagnosed when they became symptomatic before the screening program. A significant difference (p=0.000) was found only in HC z-score and weight for height z-score in comparison with the control group, when we assessed all patients. We did not find any significant differences in any of the anthropometric indexes between cases and controls who were aged 2 years old and less. Head circumference SDS and weight for height SDS were significantly different when patients and controls who were more than 2 years old were compared. Mean HC was significantly lower in patients, while BMI SDS, weight SDS, and weight for height SDS were significantly higher in PKU patients in comparison with the control group when patients who were diagnosed in newborn screening were assessed. Head circumference SDS, BMI, height SDS and difference between patients' height SDS and mid parental height SDS had significantly lower mean scores in comparison with those of the control group, while mean weight SDS was significantly higher compared to controls when patients who were diagnosed after clinical presentation were assessed. Mean phenylalanine was not correlated with anthropometric indices, while there was a correlation between pretreatment phenylalanine and HC. CONCLUSION: Disparities in anthropometric indexes changes observed in different studies may be due to diverse diet protocols, availability of various specific products and micronutrient substitutes.

Non-progressive Nonimmune Hydrops Fetalis Caused by a Novel Mutation in GUSB Gene.

Objectives: Mucopolysaccharidosis type VII (MPS VII) or Sly syndrome is a rare autosomal recessive disorder caused by deficiency of ß-glucuronidase enzyme, which is involved in degradation of glycosaminoglycans. The lack of ß-glucuronidase in this lysosomal storage disorder is characterized by various manifestations such as nonimmune hydrops fetalis, spinal deformity, organomegaly, dysostosis multiplex, intellectual disability, and eye involvement. It is caused by a mutation in GUSB gene located on chromosome 7 q11. The current study reported an Iranian female with MPS VII and a novel mutation (c.542G>T, p.Arg181Leu) in GUSB gene.

Utility of Seizure Pattern and Related Clinical Features in the Diagnosis of Neurometabolic Disorders.

OBJECTIVES: The current study aimed at identifying the role of seizure types and related clinical features in differentiation between neurometabolic disorders and other causes of seizure. MATERIALS & METHODS: The current cross sectional study was conducted at two referral children hospitals in Tehran, Iran, from 2011 to 2018. The study population included 120 patients presenting with seizure due to neurometabolic disorders and 120 cases due to other causes. The types of seizure and related clinical findings were assessed in both groups. RESULTS: There was a significant difference in the frequency of seizure types in the two groups. Tonic and myoclonic seizures as well as infantile spasm were observed more commonly in the patients with neurometabolic disorders, while atonic, partial and generalized tonic-clonic seizures were more common in the control group. In addition, frequency of refractory seizure, age at onset of seizure, and pattern of involvement in brain imaging were helpful for differentiation. CONCLUSION: The pattern of seizure and related findings varied in patients with metabolic disorders, and was helpful for diagnosis. Thus, these factors can contribute to early diagnosis and treatment.

A Rare Case of Ovarian Hyperstimulation Syndrome in a Preterm Infant.

Ovarian hyperstimulation syndrome is a rare disease among preterm infants. This syndrome was first described in 1985 in four infants with a gestational age of <30 weeks. Several explanations for this syndrome have been suggested namely the immaturity of Hypothalamic-Pituitary-Gonadal (HPG) axis, lack of negative feedback, increased sensitivity of Follicle Stimulating Hormone (FSH) receptors due to mutation and high level of estradiol. In this report, a case of hyperstimulation syndrome in a newborn with gestational age of 30 weeks is presented and the probable mechanisms in the literature are discussed.

Assessment of Sexual Maturation Among Girls With Special Needs in Tehran, Iran.

BACKGROUND: There is limited data on sexual maturation among girls with intellectual, sensory, or physical disabilities. OBJECTIVES: The present cross-sectional study was conducted to assess the sexual maturation of girls with these disabilities in special schools. METHODS: In this cross-sectional study, we evaluated the onset and progression of sexual maturation in 642 six to 18-year-old girls with intellectual, sensory, or physical disabilities from special schools in Tehran. The participants were selected by multi-stage random sampling. Pubertal stages were assessed by visual inspection and palpation based on the rating scales of Tanner. Stage two (breast budding and pubic hair growth) and stage five were considered the onset and end of puberty, respectively. RESULTS: The mean ages of onset of puberty indicated by breast budding (B2 stage) and by pubic hair growth (P2 stage) were 10.8 ± 1.48 and 10.79 ± 1.64 years, respectively. The process of puberty based on breast budding and pubic hair growth was completed at 15.58 ± 1.85 and 15.59 ± 1.8 years, respectively. The average height at the onset of puberty (stage B2) among participants was 128 ± 28.79 cm and the average weight was 8.31 ± 36.47 kg. CONCLUSIONS: Among our patients, the mean ages of onset of puberty indicated by breast budding (B2 stage) and by pubic hair growth (P2 stage) were 10.8 ± 1.48 and 10.79 ± 1.64 years, respectively. Compared to the data from healthy Iranian girls, our findings indicate that the mean age of pubertal onset among schoolgirls with disabilities is slightly higher than that of their healthy counterparts.

Vitamin D deficiency in chronic idiopathic urticaria.

Chronic urticaria is the most common skin diseases, characterized by chronic cutaneous lesions which severely debilitates patients in several aspects of their everyday life. Vitamin D is known to exert several actions in the immune system and to influence function and differentiation of mast cells, central role players in the pathogenesis of chronic idiopathic urticaria. This study was performed to evaluate the relationship between vitamin D levels and susceptibility to chronic idiopathic urticaria. One hundred and fourteen patients with chronic idiopathic urticaria were recruited in this study along with one hundred and eighty seven sex-matched and age-matched healthy volunteers as the control group. For each patient, urticaria activity score was calculated and autologous serum skin test was done. Vitamin D metabolic statue was measured in serum as 25 hydroxyvitamin D using enzyme immunoassay method. Patients with chronic idiopathic urticaria significantly showed lower levels of vitamin D. Vitamin D deficiency was significantly associated with increased susceptibility to chronic idiopathic urticaria. There was a significant positive correlation between vitamin D levels and urticaria activity score. This study showed that patients with chronic idiopathic urticaria had reduced levels of vitamin D, while vitamin D deficiency could increase susceptibility to chronic idiopathic urticaria.

Segregation of a novel homozygous 6 nucleotide deletion in GLUT2 gene in a Fanconi-Bickel syndrome family.

Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, impaired utilization of glucose and galactose, rickets, and severe short stature. It has been shown to be caused by mutations in GLUT2 gene, a member of the facilitative glucose transporter family. Here, we report an Iranian family with 2 affected siblings. The clinical findings in the patients include developmental delay, failure to thrive, hepatomegaly, enlarged kidneys and rickets. A novel 6 nucleotide deletion (c.1061_1066del6, p.V355_S356del2) is shown to be segregated with the disease in this family.

Proptosis, Micrognathia, Low Set Ear and Chest Deformity in a Patient with Extra Marker Chromosome 22.

There is a number of syndromes, associated with proptosis, micrognathia, low-set ear and chest deformity. Herein, we report a 9-year-old female with such phenotype who was presented with a vaginal neuroma. The result of karyotype showed 47XX, with extra marker chromosome 22. Although such a manifestation had not been reported in the literature, it should be considered as a very rare manifestation of the disease.