Auxological, Clinical, and MRI Abnormalities in Pediatric Patients With Isolated Growth Hormone Deficiency.

OBJECTIVE:  This study aimed to assess the auxological, clinical, and MRI features of pediatric patients with isolated growth hormone deficiency (GHD) by analyzing the demographic and clinical characteristics of the study cohort. METHODS: A cohort of 115 pediatric patients diagnosed with isolated GHD was included. The patients were evaluated at a tertiary center in Jeddah, Saudi Arabia. Collected data included demographic information and auxological evaluations, such as height standard deviation (SD), height centile, weight SD, weight centile, and bone age SD. Neuroradiological assessments, particularly magnetic resonance imaging (MRI) of the hypothalamic-pituitary region, were collected to identify any structural abnormalities contributing to GHD. RESULTS: A total of 67 (SD 58.3) were males. The mean age was 9.55 years (SD 3.45). The mean bone age was 7.37 years (SD 3.24), indicating delayed bone development. Height measurements reflected a significant growth impairment, with a mean height SD of -2.45 (SD 1.12). Out of the 115 pediatric patients in the study cohort, 84 (73%) underwent neuroradiological assessments using brain MRI. Among these, 12% were found to have MRI abnormalities. The prevalence of MRI abnormality in the subgroup with severe growth hormone deficiency was higher, reaching 21%. The peak growth hormone (GH) in the growth hormone stimulation test was 6.38 ng/mL (SD 3.24). There was a significant difference in the peak GH levels between the subgroup of patients with normal MRI findings (mean 6.02 ng/mL, SD 2.47) and those with abnormal MRI findings (mean 3.2 ng/mL, SD 2.8) (p=0.01). CONCLUSION: Children with isolated GHD exhibited significant growth impairment and clinical characteristics consistent with the disorder. Neuroradiological abnormalities are common among patients with severe growth hormone deficiency; therefore, radiological assessment including MRI of the pituitary gland is recommended in patients with severe isolated growth hormone deficiency.

Effects of intermittent fasting regimens on glycemic, hepatic, anthropometric, and clinical markers in patients with non-alcoholic fatty liver disease: Systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Intermittent fasting (IF) regimens have been hypothesized to influence several markers of cardiometabolic and liver function. The objective of our meta-analysis was to investigate the impact of IF regimens on cardiometabolic and liver markers in subjects diagnosed with non-alcoholic fatty liver disease (NAFLD). METHODS: We searched several online databases (PubMed/Medline, Web of Science, Scopus and Embase) in order to identify suitable publications for inclusion in the meta-analysis. Results were expressed as weighted mean differences (WMD). RESULTS: From 12343 articles identified in different databases, a total of 7 RCT arms were entered into the quantitative synthesis. The manuscripts were published between 2019 and 2023. IF regimens (the 5:2 diet, 16/8 time-restricting feeding, and alternate day fasting) varied from 2 months to 3 months. IF regimens reduced steatosis scores (WMD: -33.22 CAP dB/m, 95 % CI: -50.72 to -15.72), anthropometric characteristics of obesity (WMD: -0.77 kg/m2, 95 % CI: -1.38 to -0.17 for body mass index; WMD: -3.16 kg, 95 % CI: -4.71 to -1.61 for body weight; WMD: -1.90 kg, 95 % CI: -3.51 to -0.29 for waist circumference), as well as ALT (WMD: -9.10 U/L, 95 % CI: -12.45 to -5.75), triglyceride (WMD: -20.83 mg/dl, 95 % CI: -39.01 to -2.66), total cholesterol (WMD: -7.80 mg/dl, 95 % CI: -15.18), HbA1c (WMD: -0.14 %, 95 % CI: -0.20 to -0.08) and HOMA-IR (WMD: -1.21, 95 % CI: -2.08 to -0.34) levels versus controls. Nevertheless, no between-group differences were detected for other biomarkers, e.g., fasting blood glucose, insulin, AST, HDL-C or LDL-C values, and fibrosis scores. CONCLUSION: IF regimens can improve some markers of cardiometabolic and liver function in patients with NAFLD. However, the available evidence to support the benefits of IF regimens is limited and derived from a small number of studies, thus further research is needed to clarify the impact of IF on the cardiometabolic health of NAFLD patients.

Indices of insulin resistance and adiposity can detect obesity-related morbidity in pediatrics.

OBJECTIVES: To evaluated obesity-related morbidity prevalence among overweight/obese children and adolescents in Saudi Arabia, adiposity indicators and insulin resistance as obesity-related morbidity predictors. METHODS: We enrolled 318 overweight/obese children attending a Pediatric Endocrinology Clinic at King Abdulaziz University Hospital, Saudi Arabia, aged 2-20 years in this retrospective cross-sectional study from September 2019 to March 2021. All children had nutritional obesity, and their body mass index (BMI) standard deviation score was higher than one standard deviation score above the mean for their age and gender. Clinical adiposity indices including BMI, waist circumference (WC), waist-hip ratio (WHR), and bioimpedance analysis (BIA) of body composition were assessed. Biochemical testing of insulin resistance through homeostasis model assessment for insulin resistance and fasting insulin was performed, along with receiver operating curve analysis to obtain optimal cut-off points for obesity-related morbidity. RESULTS: Obesity related morbidity was found in 61.9%, whereas insulin resistance was detected among 64.7% of the patients. Body mass index standard deviation score, WC, BAI of body composition-derived body fat, homeostasis model assessment for insulin resistance, and fasting insulin are significant obesity-related morbidity predictors, and the cut-off points were established. CONCLUSION: Obesity-related morbidity is widely prevalent among obese children and insulin resistance is a key factor in its prediction. Clinical adiposity indices, given their accuracy and practicability, are important predictors of obesity-related morbidity.

Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The standard of care for treatment of celiac disease (CD) is a stringent lifetime gluten-free diet (GFD). Larazotide acetate (AT-1001) is an anti-zonulin which functions as a gut permeability regulator for treatment of CD. We endeavored to conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) which studied the efficacy and safety of AT-1001 in patients with CD. METHODS: We examined four databases from inception to 20-August-2020. We pooled continuous outcomes as mean difference and dichotomous outcomes as risk ratio with 95% confidence interval under the fixed-effects meta-analysis model. RESULTS: Four RCTs met our eligibility criteria, comprising 626 patients (AT-1001, n=465, placebo, n=161). Three and two RCTs reported outcomes of patients undergoing gluten challenge (intake of 2.4-2.7 grams of gluten/day) and GFD, respectively. For change in lactulose-to-mannitol ratio, the endpoint did not significantly differ between AT-1001 and placebo groups, irrespective of the gluten status. Subgroup analysis of patients undergoing gluten challenge showed AT-1001 treatment (compared with placebo) significantly correlated with better symptomatic improvement in the two endpoints of change in total gastrointestinal symptom rating scale (total GSRS) and CD-specific GSRS (CD-GSRS). However, no significant difference was noted among patients undergoing GFD for the abovementioned two efficacy endpoints. Compared with placebo, AT-1001 favorably reduced the adverse event (AE) of gluten-related diarrhea in patients who underwent gluten challenge. Other AEs were comparable between both AT-1001 and placebo groups. CONCLUSIONS: AT-1001 is largely well-endured and seems somehow superior to placebo in alleviating gastrointestinal symptoms among CD patients undergoing gluten challenge. Nevertheless, additional RCTs are warranted to validate these findings.

The association between vitamin D status and inflammatory bowel disease among children and adolescents: A systematic review and meta-analysis.

Aim: Vitamin D deficiency is very common among children with IBD. Since there are conflicting results regarding the association of vitamin D with IBD, we conducted this systematic review to confirm the association of vitamin D with IBD. Methods: We conducted a systematic search in Scopus, Cochrane Library, Web of Science, PubMed, and Google Scholar to find relevant studies. Articles with cross-sectional and case-control designs that reported the association between vitamin D and IBD among children were included. Results: Eventually, 9 studies (with 16 effect sizes) reported the mean and SD or the median and the interquartile range of serum vitamin D levels in both subjects with IBD and control subjects. The random effects meta-analysis revealed that subjects with IBD had -1.159 ng/ml (95% CI: -2.783, 0.464) lower serum vitamin D concentrations compared with their healthy counterparts, but this difference was not significant. A total of 14 studies (with 18 effect sizes) with 2,602 participants provided information for the prevalence of vitamin D deficiency or insufficiency in patients with IBD as 44% (95% CI: 0.34-0.54) with significant heterogeneity noted among studies (p < 0.001; I2 = 97.31%). Conclusion: This systematic and meta-analysis study revealed that vitamin D deficiency was associated with IBD. Longitudinal studies should be conducted in the future to confirm our findings. Large randomized controlled trials assessing the doses of supplementation of vitamin D would provide a better understanding of the association between vitamin D and IBD.

The Impact of Diabetes Distress on the Glycemic Control Among Adolescents and Youth With Type 1 Diabetes in Two Tertiary Centers, Jeddah, Saudi Arabia.

Introduction Adolescents with type 1 diabetes (T1D) experience multiple symptoms of diabetes distress including fear of acute complications such as severe hypoglycemia which may lead to permanent brain damage or death. They also experience fear of acute hyperglycemia that can lead to diabetic ketoacidosis as well as chronic complication including diabetic nephropathy and retinopathy. No previous research was conducted in Saudi Arabia to assess diabetes distress among adolescents and youth with T1D. This study aimed to assess diabetes distress in adolescents and youth with T1D and its relation to clinical characteristics, glycemic control and diabetes co-morbidities. Methodology A cross-sectional study was conducted on 158 patients at King Abdulaziz University Hospital and Dr. Erfan and Bagedo General Hospital, Jeddah, Saudi Arabia. Data about participants' characters, episodes of DKA, last HbA1c level, diabetes co-morbidities were collected. Diabetes distress (DD) was assessed by the Problem Areas in Diabetes (PAID) and Diabetes Distress Scale (DDS) scores. Results The prevalence of diabetes distress among our population of adolescents with T1D was 24.1%. The mean scores of PAID and DDS were 43.56 ± 13.84 and 2.22 ± 1.05, respectively. Patients with suboptimal HbA1c had significantly higher mean PAID and DDS scores. There is also a significant positive correlation between HbA1c level and number of ketoacidosis episodes. A highly significant positive correlation was found between PAID and DDS scores. Conclusion This study found that participants with uncontrolled HbA1c had significantly higher mean PAID and DDS scores with a significant positive correlation between the last HbA1c measured level and number of ketoacidosis attacks and PAID and DDS scores. Future studies on larger samples are needed to implement interventions to minimize the burden of diabetes distress among adolescents with T1D.

Experience of Caring for a Child With Type 1 Diabetes Mellitus in a Food-Insecure Household: A Qualitative Evaluation.

OBJECTIVES: An earlier study from Nova Scotia showed that food insecurity (FI) is more prevalent (21.9%) in families of children with diabetes, yet little is known about its impact on these families. We aimed to describe the day-to-day experiences of families living with FI while caring for a child with type 1 diabetes (T1D). METHODS: This investigation was a qualitative study with thematic analyses using semistructured interviews to explore perceptions of caregivers living with pediatric T1D and FI (N=13 households). RESULTS: Three major themes emerged: 1) FI had a disproportionate impact on families after T1D diagnosis compared with before diagnosis. The cost of healthy food threatened food security before T1D; however, there is increased hardship once high-quality food and hypoglycemia supplies are required. 2) Sacrifices to combat FI have disproportionate impacts among family members. At times, caregivers sacrificed the needs (food, medicine) of other family members (including children) to prioritize the needs of the child with T1D. 3) Caregivers perceived T1D needs as posing unique barriers to traditional FI supports, such as school breakfast programs. CONCLUSIONS: This study provides insight into the realities of life with pediatric T1D and FI. Living with T1D and FI poses challenges, and caregivers often cope by making difficult choices when providing for their family. Caregivers struggled to meet dietary recommendations while finding that T1D needs are often not met by traditional FI supports. This suggests that T1D clinicians should assess FI and help families in problem solving to mitigate its impact.

Pituitary Dysfunction in Pediatric Patients with Optic Nerve Hypoplasia: A Retrospective Cohort Study (1975-2014).

BACKGROUND/AIMS: The risk factors for pituitary hormone dysfunction (PHD) in children with optic nerve hypoplasia (ONH) are not well understood. This study identified the type, timing, and predictors of PHD in children with ONH. METHODS: ONH patient charts were reviewed retrospectively. The incidence rate of PHD was calculated assuming a Poisson distribution. Predictors of PHD were identified through a multivariable Cox proportional hazards model. RESULTS: Among 144 subjects with ONH, 49.3% (n = 71) developed PHD over 614.7 person-years of follow-up. The incidence was 11.55 (95% confidence interval [CI]: 9.02-14.57/100 person-years). The median time to first PHD was 2.88 (interquartile range: 0.02-18.72) months. Eighty-two percent developed their first PHD by their 5th and 90% by their 10th birthday, and 89% within 5 years of ONH diagnosis. Prematurity (adjusted hazard ratio [aHR]: 0.33; 95% CI: 0.1-1.07), blindness (aHR: 1.72; 95% CI: 1.03-2.86), maternal substance abuse (aHR: 1.51; 95% CI: 0.91-2.48), abnormal posterior pituitary (aHR: 3.8; 95% CI: 2.01-7.18), and hypoplastic/absent anterior pituitary (aHR: 2.52; 95% CI: 1.29-4.91) were significant predictors of PHD. CONCLUSIONS: The clinical predictors of PHD included blindness, pituitary gland abnormalities, and maternal substance abuse. These predictors help clinical decision-making related to the need for and frequency of hormone testing in pediatric patients with ONH.