Outpatient clinic-wide psychological screening for children and adolescents with type 1 diabetes in Qatar: An initiative for integrative healthcare in the Gulf region.

OBJECTIVE: To identify culturally appropriate psychological screening measures for children and adolescents with type 1 diabetes in Qatar, determine rates of depressive and anxiety symptoms in a clinical sample, and examine associations between screening measures, demographic variables, medical characteristics, and diabetes treatment outcomes, specifically HbA1c. METHODS: A total of 150 participants with type 1 diabetes aged 10-17 were recruited. Participants were Arabic or English speaking and of Qatari and non-Qatari nationality. Participants completed the Mood and Feelings Questionnaire (child and parent proxy form), the Spence Children's Anxiety Scale, and the Pediatric Quality of Life, Diabetes version (child and parent proxy form). Glycosylated hemoglobin (HbA1c) on the date of the testing was recorded. RESULTS: Approximately ten percent (10.2%) of children and adolescents scored above the cutoff score of 27 indicating clinically significant depressive symptoms, and 12.8% of parents rated their child above the respective cutoff score of 21 for the parent proxy form. Further, 36% of the sample reported clinically significant anxiety symptoms, scoring above the cutoff score of 50. Parent report on their child's quality of life predicted HbA1c (F[6, 140] = 5.42, p = 0.000); B = -0.05, p = 0.002). CONCLUSIONS: Rates of depressive and anxiety symptoms are comparable to those observed in western countries. Thus, systematic screening for depression and anxiety in children and adolescents with type 1 diabetes should be implemented in Qatar. This will help inform decisions to refer to mental health services and thus provide more integrated care, possibly improving treatment outcomes.

The clinical and genetic characteristics of permanent neonatal diabetes (PNDM) in the state of Qatar.

BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare condition that occurs within the first six months of life. Permanent NDM (PNDM) is caused by mutations in specific genes that are known for their expression at early and/or late stages of pancreatic beta- cell development, and are either involved in beta-cell survival, insulin processing, regulation, and release. The native population in Qatar continues to practice consanguineous marriages that lead to a high level of homozygosity. To our knowledge, there is no previous report on the genomics of NDM among the Qatari population. The aims of the current study are to identify patients with NDM diagnosed between 2001 and 2016, and examine their clinical and genetic characteristics. METHODS: To calculate the incidence of PNDM, all patients with PNDM diagnosed between 2001 and 2016 were compared to the total number of live births over the 16-year-period. Whole Genome Sequencing (WGS) was used to investigate the genetic etiology in the PNDM cohort. RESULTS: PNDM was diagnosed in nine (n = 9) patients with an estimated incidence rate of 1:22,938 live births among the indigenous Qatari. Seven different mutations in six genes (PTF1A, GCK, SLC2A2, EIF2AK3, INS, and HNF1B) were identified. In the majority of cases, the genetic etiology was part of a previously identified autosomal recessive disorder. Two novel de novo mutations were identified in INS and HNF1B. CONCLUSION: Qatar has the second highest reported incidence of PNDM worldwide. A majority of PNDM cases present as rare familial autosomal recessive disorders. Pancreas associated transcription factor 1a (PTF1A) enhancer deletions are the most common cause of PNDM in Qatar, with only a few previous cases reported in the literature.

Continuous Subcutaneous Insulin Infusion Characteristics in Type 1 Diabetes Children and Adolescents in Qatar.

AIM: To describe continuous subcutaneous insulin infusion (CSII) characteristics in type 1 diabetes mellitus (T1DM) children and adolescents using a standardized protocol in routine clinical settings in Qatar. METHODS: A total of 138 T1DM patients (62 males; 76 females; mean age 9.8 ± 3.4 years) with a mean diabetes duration of 2.4 ± 1.9 years initiated CSII (MiniMed® Veo®™ and MiniMed® 640 G insulin pumps; Medtronic, Northridge, CA, USA) in 2016 and 2017. CSII characteristics and glycated hemoglobin (HbA1c) were evaluated 1 year after treatment initiation. RESULTS: At 1 year after treatment initiation, the insulin dose had significantly increased (from 0.59 ± 0.23 to 0.74 ± 0.26 U/kg body weight per 24; P < 0.05), and the HbA1c level had significantly decreased (from 9.7 ± 1.3 to 8.1 ± 0.6%; P < 0.05). More than 92% of patients used the Bolus Wizard feature of the insulin pump at the following settings: insulin-to-carbohydrate ratio 19.2 ± 9.3 g; insulin sensitivity factor 131 ± 68 mg/dl; target range 91 ± 9.3-135 ± 14.2 mg/dl; active insulin time 3.8 ± 0.8 h. CONCLUSION: Our results show that CSII may significantly improve glucose control in T1D children and adolescents who use a standardized protocol. A reduction of HbA1c by - 1.6% was achieved at 1 year after CSII initiation. These results need to be confirmed in a study with a longer duration.

The growth hormone-insulin-like growth factor-I axis in the diagnosis and treatment of growth disorders.

The growth hormone (GH)-insulin-like growth factor (IGF)-I axis is a key endocrine mechanism regulating linear growth in children. While paediatricians have a good knowledge of GH secretion and assessment, understanding and use of measurements of the components of the IGF system are less current in clinical practice. The physiological function of this axis is to increase the anabolic cellular processes of protein synthesis and mitosis, and reduction of apoptosis, with each being regulated in the appropriate target tissue. Measurement of serum IGF-I and IGF-binding protein (IGFBP)-3 concentrations can complement assessment of GH status in the investigation of short stature and contribute to prediction of growth response during GH therapy. IGF-I monitoring during GH therapy also informs the clinician about adherence and provides a safety reference to avoid over-dosing during long-term management.

Diagnosis and management of growth disorders in Gulf Cooperation Council (GCC) countries: Current procedures and key recommendations for best practice.

Diagnosis and management of growth disorders comprises an important area of pediatric practice. Current procedures in the different stages of the identification, referral, investigation, and treatment of growth disorders in the Gulf Cooperation Council (GCC) countries have been summarized. Evidence-based procedures, relating specifically to height screening for identification of short stature, auxological criteria for patient referral from primary to secondary pediatric care, and general and endocrine investigations and diagnosis have been discussed and outlined. The management issues related to key disorders that are licensed for growth hormone (hGH) therapy, namely GH deficiency, Turner syndrome, short stature related to birth size small for gestational age (SGA), and idiopathic short stature are discussed with recommendations described for best practice. Finally, two key components of short stature management, namely transitional care for the transfer of patients from pediatric to adult endocrinology services and adherence to recommended therapy with hGH, have been addressed with current practice outlines and recommendations presented.

Growth hormone therapy and treatment outcomes: current clinical practice of the Gulf Cooperation Council.

Over the last 20 years, recombinant human growth hormone (somatropin) has been the cornerstone of managing children with growth hormone deficiency (GHD). Although both international and national guidelines for growth hormone (GH) therapy exist, there is currently no consensus on the optimal use of GH therapy in Gulf Cooperation Council (GCC) countries. The goals of GH therapy are to normalize height during childhood, attain normal adult height and correct metabolic abnormalities related to GHD. However, extended use of GH >50 µg/kg/day may increase frequency of adverse events. Here, we report the proceedings from a meeting of nine GCC pediatric endocrinology experts, which took place in Beirut in November 2011. The meeting was also attended by three European counterparts and aimed to provide consensus on best practice in the management of children with GHD in the GCC based on current local medical and regulatory environments.

Detection of glycemic abnormalities in adolescents with beta thalassemia using continuous glucose monitoring and oral glucose tolerance in adolescents and young adults with ß-thalassemia major: Pilot study.

BACKGROUND: Both insulin deficiency and resistance are reported in patients with ß-thalassemia major (BTM). The use of continuous blood glucose monitoring (CGM), among the different methods for early detection of glycemic abnormalities, has not been studied thoroughly in these adolescents. MATERIALS AND METHODS: To assess the oralglucose tolerance (OGT) and 72-h continuous glucose concentration by the continuous glucose monitoring system (CGMS) and calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) was conducted in 16 adolescents with BTM who were receiving regular blood transfusions every 2-4 weeks and iron-chelation therapy since early childhood. RESULTS: SIXTEEN ADOLESCENTS WITH BTM (AGE: 19.75 ± 3 years) were investigated. Using OGTT, (25%) had impaired fasting blood (plasma) glucose concentration (BG) (>5.6 mmol/L). 2-h after the glucose load, one of them had BG = 16.2 mmol/L (diabetic) and two had impaired glucose tolerance (IGT) (BG > 7.8 and <11.1 mmol/L). Monitoring the maximum (postprandial) BG using CGMS,4 adolescents were diagnosed with diabetes (25%) (BG >11.1 mmol/L) and 9 with IGT (56%). HOMA and QUICKI revealed levels <2.6 (1.6 ± 0.8) and >0.33 (0.36 ± 0.03), respectively, ruling out significant insulin resistance in these adolescents. There was a significant negative correlation between the ß-cell function (B%) on one hand and the fasting and the 2-h BG (r=-0.6, and - 0.48, P < 0.01, respectively) on the other hand. Neither fasting serum insulin nor c-peptide concentrations were correlated with fasting BG or ferritin levels. The average and maximum blood glucose levels during CGM were significantly correlated with the fasting BG (r = 0.68 and 0.39, respectively, with P < 0.01) and with the BG at 2-hour after oral glucose intake (r = 0.87 and 0.86 respectively, with P < 0.001). Ferritin concentrations were correlated with the fasting BG and the 2-h blood glucose levels in the OGTT (r = 0.52, and r = 0.43, respectively, P < 0.01) as well as with the average BG recorded by CGM (r = 0.75, P < 0.01). CONCLUSION: CGM has proven to be superior to OGTT for the diagnosis of glycemic abnormalities in adolescents with BTM. Defective ß-cell function rather than insulin resistance appeared to be the cause for these abnormalities.

Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I-CET) position statement and guidelines.

The current management of thalassemia includes regular transfusion programs and chelation therapy. It is important that physicians be aware that endocrine abnormalities frequently develop mainly in those patients with significant iron overload due to poor compliance to treatment, particularly after the age of 10 years. Since the quality of life of thalassemia patients is a fundamental aim, it is vital to monitor carefully their growth and pubertal development in order to detect abnormalities and to initiate appropriate and early treatment. Abnormalities should be identified and treatment initiated in consultation with a pediatric or an adult endocrinologist and managed accordingly. Appropriate management shall put in consideration many factors such as age, severity of iron overload, presence of chronic liver disease, thrombophilia status, and the presence of psychological problems. All these issues must be discussed by the physician in charge of the patient's care, the endocrinologist and the patient himself. Because any progress in research in the field of early diagnosis and management of growth disorders and endocrine complications in thalassemia should be passed on to and applied adequately to all those suffering from the disease, on the 8 May 2009 in Ferrara, the International Network on Endocrine Complications in Thalassemia (I-CET) was founded in order to transmit the latest information on these disorders to the treating physicians. The I-CET position statement outlined in this document applies to patients with transfusion-dependent thalassemia major to help physicians to anticipate, diagnose, and manage these complications properly.

Does blood transfusion affect pituitary gonadal axis and sperm parameters in young males with sickle cell disease?

OBJECTIVE: We evaluated the effect of packed red cell transfusion (PCTx) on serum concentrations of gonadotropins luteinizing hormone and follicle-stimulating hormone (LH and FSH) and testosterone (T) levels and measured sperm parameters in young adults with sickle cell disease (SCD) on top-up transfusion (TTx) and those on exchange transfusion (ETx) regimen. MATERIALS AND METHODS: Basal serum concentrations of FSH, LH, and T and semen parameters were evaluated before and 7 days after PCTx in 18 young adults with transfusion-dependent SCD, aged 20.7 ± 2.88 years. They had full pubertal development (Tanner's stage 5), and capacity to ejaculate. They were regularly transfused since early childhood. Chelation therapy was started early during the first 2 years of life using desferrioxamine and was replaced by deferasirox for the last 4-5 years. Ten patients were on TTx and eight were on ETx regimen. RESULTS: PCTx significantly increased hemoglobin (Hb) from 8.5 ± 1.17 g/dl to 10.5 ± 0.4 g/dl, T from 12.3 ± 1.24 nmol/L to 14.23 ± 1.22 nmol/L and gonadotropins' concentrations. Sperm parameters improved significantly after PCTx including: total sperm count from 87.4 ± 24.6 million/ml to 146.2 ± 51.25 million/ml, total progressive sperm motility (TPM) from 40.8 ± 11.1 million/ml to 93.4 ± 38.3 million/ml, rapid progressive sperm motility (RPM) progressive motility from 29.26 ± 8.75 million/ml to 67.4 ± 29 million/ml. After PCTx the total sperm count, TPM and RPM were significantly better in the ETx group versus the TTx group. Before and after PCTx, T concentrations were correlated significantly with sperm total count, volume, TPM and RPM (r = 0.53, 0.55, 0.42, and 0.38, respectively, P < 0.01). Hb concentrations were correlated significantly with sperm count, TPM, RPM, and % of sperms with normal morphology (r = 0.60, 0.69, 0.66, and 0.86, respectively, P < 0.001). CONCLUSION: Our study suggests that in males with SCD blood transfusion is associated with significant acute enhancement of sperm parameters and with increased concentrations of serum T, LH, and FSH. Improvement of sperm parameters were significantly better in the ETx group verses the TTx group. These "acute" effects on spermiogenesis are reached with an unknown mechanism/s and suggest a number of pathways that need further human and/or experimental studies.

Acute effects of blood transfusion on pituitary gonadal axis and sperm parameters in adolescents and young men with thalassemia major: a pilot study.

OBJECTIVE: To evaluate semen parameters and measure serum FSH, LH, T, and insulin-like growth factor (IGF) 1 concentrations before and 7 days after packed red cell transfusion (PCTx) in young adults with thalassemia major (TM). DESIGN: Prospective study. SETTING: Tertiary care hospital. PATIENT(S): This study investigated 10 young adults with TM, aged 17-32 years, with full pubertal development (Tanner stage 5, eugonadal) and capacity to ejaculate. They had been regularly transfused since early childhood and underwent chelation therapy with the use of desferrioxamine replaced by deferasirox for the past 4-5 years. At the time of the study their serum ferritin levels ranged from 500 to 5,922 ng/mL (mean 2,686 ng/mL). Basal serum concentrations of FSH, LH, T, and IGF-1 were evaluated before and 7 days after PCTx. INTERVENTION(S): We studied the effect of PCTx on semen parameters and the endocrine functions in these 10 patients with TM. MAIN OUTCOME MEASURE(S): After PCTx, a significant increase of hemoglobin from 8.7 ± 0.86 g/dL to 11.1 ± 0.82 g/dL was associated with increased T (from 16.5 ± 8 nmol/L to 20 ± 8.8 nmol/L), IGF-1 (from 173 ± 46 ng/mL to 214 ± 61 ng/mL), and gonadotropin concentrations. RESULT(S): Total sperm count increased significantly from 57.8 ± 38.3 million/mL to 166 ± 132 million/mL, and rapid progressive sperm motility progressive motility increased from 20.6 ± 16.6% to 79.7 ± 67.4%. After PCTx, LH concentrations were correlated significantly with T concentrations and sperm volume and count. The increase of IGF-1 concentration was correlated significantly with hemoglobin level after PCTx and negatively with ferritin concentration. Significant correlations were found before and after PCTx between serum T concentrations and semen parameters, including sperm count, rapid progressive motility, and the number of sperm with normal morphology, and between IGF-1 levels and seminal parameters. No correlations were found between serum FSH and IGF-1 concentrations and seminal parameters. CONCLUSION(S): This study suggests that in thalassemic men, blood transfusion is associated with significant acute enhancement of sperm parameters and increased concentrations of serum T, LH, FSH, and IGF-1. These "acute" effects on spermiogenesis are reached by an unknown mechanism and suggest a number of pathways that need further human and/or experimental studies.