[Show abstract][Hide abstract]ABSTRACT: The well-documented latitudinal clines of genes affecting human skin color presumably arise from the need for protection from intense ultraviolet radiation (UVR) versus the need to use UVR for vitamin D synthesis. Sampling 751 subjects from a broad range of latitudes and skin colors, we investigated possible multi-locus correlated adaptation of skin color genes with the vitamin D receptor gene (VDR), using a vector correlation metric and network method called BlocBuster. We discovered two multi-locus networks involving VDR promoter and skin color genes that display strong latitudinal clines as multi-locus networks even though many of their single gene components do not. Considered one by one, the VDR components of these networks show diverse patterns: no cline, a weak declining latitudinal cline outside of Africa, and a strong in-versus-out of Africa frequency pattern. We confirmed these results with independent data from HapMap. Standard linkage disequilibrium analyses did not detect these networks. We applied BlocBuster across the entire genome, showing that our networks are significant outliers for interchromosomal disequilibrium that overlap with environmental variation relevant to the genes' functions. These results suggest that these multi-locus correlations most likely arose from a combination of parallel selective responses to a common environmental variable and coadaptation, given the known Mendelian epistasis among VDR and the skin color genes.
Preview · Article · Feb 2016 · G3-Genes Genomes Genetics
[Show abstract][Hide abstract]ABSTRACT: In patients with TM, uncontrolled iron overload has serious clinical consequences with considerable morbidity and mortality. Complications include liver damage, cardiac disease and endocrine dysfunction. Diabetes is an important complication of TM. The mechanisms of abnormal glucose homeostasis are complex and multifactorial. This review updates the current knowledge about glycemic abnormalities in TM patients and directs the attention to an early diagnosis and proper management.
Full-text · Article · Dec 2015 · Expert Review of Hematology
[Show abstract][Hide abstract]ABSTRACT: In many countries, the current options for transferring an adolescent to adult care services are: an abrupt transfer; staying in the care of children's services longer than is really appropriate or leaving medical supervision altogether, either voluntarily or by default; and in some countries, transferring prematurely at an early age. In recent years, several professional groups and international agencies have attempted to create recommendations and guidelines to improve the transition care of adolescents with CD and/or disabilities. This paper aims to review the available information in the literature on transition programs.
[Show abstract][Hide abstract]ABSTRACT: Both insulin and IGF-1 have been implicated in the control of retinal endothelial cell growth, neovascularization and diabetic retinopathy. Recent findings have established an essential role for IGF-1 in angiogenesis and demonstrated a new target for control of retinopathy that explains why diabetic retinopathy initially increases with the onset of insulin treatment.
This cross-sectional study was designed to give insights into relationship between Insulin-Growth-Factor 1 (IGF-1) levels and diabetic retinopathy (DR) in a sample of thalassemia major (TM) patients with insulin dependent diabetes mellitus (IDDM). This relation was not previously evaluated, despite the fact that both diseases co-exist in the same patient. The study also describes the clinical and biochemical profile of the associated complications in TM patients with and without IDDM.
A population-based cross-sectional study.
The study includes 19 consecutive TM patients with IDDM and 31 age- and sex-matched TM patients without IDDM who visited our out-patient clinics for an endocrine assessment.
An extensive medical history, with data on associated complications and current medications, was obtained. Blood samples were drawn in the morning after an overnight fast to measure the serum concentrations of IGF-1, glucose, fructosamine, free thyroxine (FT4), thyrotropin (TSH) and biochemical analysis. Serologic screening assays for hepatitis C virus seropositivity (HCVab and HCV-RNA) were also evaluated; applying routine laboratory methods. Plasma total IGF-1 was measured by a chemiluminescent immunometric assay (CLIA) method. Ophthalmology evaluation was done by the same researcher using stereoscopic fundus biomicroscopy through dilated pupils. DR was graded using the scale developed by the Global Diabetic Retinopathy Group. Iron stores were assessed by direct and indirect methods.
Eighteen TM patients with IDDM (94.7 %) and ten non-diabetic patients (32.2 %) had IGF-1 levels below the 2.5(th) percentile of the normal values for the Italian population. The mean serum IGF-1 concentrations were significantly lower in the diabetic versus the non-diabetic TM groups (p < 0.001). DR was present in 4 (21 %) of 19 TM patients with IDDM and was associated with the main classical risk factors, namely inefficient glycemic control and duration of the disease but not hypertension. Using the scale developed by the Global Diabetic Retinopathy Group, the DR in our patients was classified as non proliferative diabetic retinopathy (NPDR). Only a few numbers of microaneurysms [1-3] were detected. Our data also confirm the strong association of IDDM in TM patients with other endocrine and non-endocrine complications.
Full-text · Article · May 2015 · Mediterranean Journal of Hematology and Infectious Diseases
[Show abstract][Hide abstract]ABSTRACT: The VIII ICET-A International Symposium was held in Muscat (Sultanate of Oman) on the 20th of
December, 2014. The symposium included four sessions on a wide range of topics covering growth
disorders and endocrine complications in thalassaemia. Despite the fact that endocrine complications are very common in multi-transfused thalassaemia patients a recent survey conducted by the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) in 2014 in Acitrezza (Catania, Italy) showed that the major difficulties reported by hematologists or pediatricians experienced in thalassaemias or thalassaemia syndromes in following endocrine complications included: Lack of familiarity with medical treatment of endocrine complications, interpretation of endocrine tests, lack of collaboration and on-time consultation between thalassaemic centres supervised by haematologists and endocrinologists. Endocrinal monitoring of growth, pubertal development, reproductive ability and endocrine function in general are essential to achieve a good quality of life as well as controlling the pain which results from the defects of bone structure, all of which increase with the age of patients. Such comprehensive care is best provided by coordinated, multidisciplinary teams working in expert centres. The multidisciplinary team must include an endocrinologist, preferably someone experienced in the management of hormonal deficiencies caused early in life by transfusion-induced iron overload.
Full-text · Article · Mar 2015 · Pediatric endocrinology reviews: PER
[Show abstract][Hide abstract]ABSTRACT: The IX Symposium of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) was held in the glamorous city of Abu Dhabi on the 6th of February, 2015 in the Course of IV Pan Arab Hematology Conference and XIII Saudi Society of Hematol-ogy Congress. Both meetings were merged with the highlights of the European Hematology Association (EHA).The symposium included four sessions on a wide range of topics covering growth disorders and endocrine complications in thalassaemia. The goals of the meeting were to provide an update on current research, to inspire younger investigators in this field, to promote interaction between different countries, and to introduce the ICET-A group, its aims and directions for its progress.
[Show abstract][Hide abstract]ABSTRACT: The American Academy of Pediatrics recommends that young people between the ages of 11 and 21 years should be seen annually by their pediatricians, since annual checkups can be an important opportunity for health evaluation and anticipatory guidance. Parents of infants and young children are accustomed to regularly visiting a pediatrician for their child's checkups. Unfortunately, when children reach the teen years, these annual checkups may decrease in frequency. In routine check-ups and medical office visits, particular attention should be paid to the possibility of a developmental or endocrine disorder. Early diagnosis and treatment may prevent medical complications in adulthood and foster age-appropriate development. Our purpose is to acquaint readers with the concept, based on current scientific understanding, that some endocrine disorders may be associated with a wide range of deleterious health consequences including an increased risk of hypertension and hyperlipidemia, increased risk of coronary artery disease, type 2 diabetes, significant anxiety and lack of self-esteem. Understanding the milestones and developmental stages of adolescence is essential for pediatricians and all other health providers who care for adolescents. Treating adolescents involves knowledge of a variety of medical, social and legal information; in addition, close working relationships must be established within the adolescent's network to create an effective care system. In summary, we underline the importance of a periodic endocrine checkup in adolescents in order to identify endocrine problems early and develop an approach to treatment for those patients who need help during this time. Indications for endocrine referral for professional and other healthcare providers are also included. These lists are clearly not intended to be comprehensive, but will hopefully serve as a guide for specific clinical circumstances.
Full-text · Article · Nov 2014 · Iranian Journal of Endocrinology and Metabolism
[Show abstract][Hide abstract]ABSTRACT: We believe that the role of liver iron overload in IGF-1 deficiency should be further evaluated by MRI assessment of liver iron concentration (LIC) and not with serum ferritin levels. In addition, the role of chronic active hepatitis C and liver function impairment necessitates more extensive studies.
Finally, given the high prevalence of hormonal deficiencies and the non-specificity of clinical signs and symptoms, a systematic annual endocrine referral is recommended in TM patients. It is advisable to define multidisciplinary cost-effective protocols in which first-line specialists order baseline pituitary function tests and endocrinologists do the clinical evaluation, interpret the hormonal results and evaluate the possible related complications.
Full-text · Article · Nov 2014 · Mediterranean Journal of Hematology and Infectious Diseases
[Show abstract][Hide abstract]ABSTRACT: Background
Abdominal obesity is a strong determinant of obesity related metabolic complications. Data about pre-pubertal children are scarce.
The aim of this study is to assess the presence of insulin resistance using different insulin sensitivity indices and investigate its relationship with abdominal fat distribution by Dual energy X-ray absorptiometry scan (DXA). Secondary outcome is to determine the frequency of the metabolic syndrome components.
Subjects and methods
Twenty-three pre-pubertal obese children were recruited (14 females, 9 males). Height, weight, body mass index (BMI), waist and hip circumferences, waist to hip ratio, and blood pressure were measured. Fasting blood samples were withdrawn for glucose, insulin, lipid profile, thyroid and liver functions. Patients underwent oral glucose tolerance testing (OGTT) and DXA scan for body composition. Insulin sensitivity was determined using homeostasis model assessment for insulin resistance (HOMA-IR), fasting glucose to insulin ratio, Matsuda, and Cederholm indices.
All patients had BMI, waist circumference, and DXA trunk fat more than 2 SDS. Mean fasting glucose, insulin, fasting glucose to insulin ratio, 120 min glucose and HOMA-IR were within normal limits, but mean Matsuda and Cederholm indices exceeded cut off limits. Dyslipidaemia was detected in 13 patients (56.5%), disturbed glucose homeostasis in 8 patients (34.8%), and systolic hypertension in 1 patient (4.3%). Metabolic syndrome diagnosis was established in three patients (13%). More insulin resistant patients were detected by Matsuda index. Trunk fat SDS correlated with Matsuda and Cederholm indices only.
Dysglycaemia and dyslipidaemia are common among pre-pubertal obese children. Insulin sensitivity indices based on OGTT are superior to fasting indices in identifying at risk children. OGTT should be included in assessing obese children with BMI > 2 SDS. DXA scanning has limited value for this purpose in clinical settings.
Full-text · Article · Jul 2014 · Egyptian Journal of Medical Human Genetics
[Show abstract][Hide abstract]ABSTRACT: Children with thalassemia are living longer due to better care. Physicians dealing with this group of patients now have to contend with new challenges resulting from iron overload. Endocrine complications represent the most common morbidities encountered. To provide a better quality of life, these complications have to be addressed in a consistent way. For this purpose, we have compiled a set of recommendations to help physi-cians provide the best care possible to these patients.
[Show abstract][Hide abstract]ABSTRACT: Abstract Children with thalassemia are living longer due to better care. Physicians dealing with this group of patients now have to contend with new challenges resulting from iron overload. Endocrine complications represent the most common morbidities encountered. To provide a better quality of life, these complications have to be addressed in a consistent way. For this purpose, we have compiled a set of recommendations to help physicians provide the best care possible to these patients.
Full-text · Article · May 2014 · Journal of pediatric endocrinology & metabolism: JPEM
[Show abstract][Hide abstract]ABSTRACT: Rates of overweight and obesity are continually rising worldwide. Recent data show that the highest prevalence
rates are reported from regions in the Middle East, North Africa, and Asia. Excess weight is a major contributor to cardiovascular disease, type 2 diabetes, and premature death. Obese children and adolescents are at increased risk of developing obesity related co-morbidities before reaching adulthood. Six of the top ten countries with the highest prevalence of diabetes are Arab speaking countries located in the Middle East and North Africa. This review summarizes the magnitude of childhood and adolescent obesity and its consequences in the Middle East and North Africa.
Key words: Adolescents, obesity, epidemiology, co-morbidities.
No preview · Article · Apr 2014 · Rivista Italiana di Medicina dell'Adolescenza
[Show abstract][Hide abstract]ABSTRACT: Background/aim:
Growth hormone insensitivity syndrome (GHIS) is a spectrum of disorders. Laron syndrome was the earliest discovered. Insulin-like growth factor 1 (IGF-1) therapy is used to improve growth. IGF-1 has diverse effects on the growth of body organs. We aim to assess the long-term effects of IGF-1 therapy in patients with GHIS particularly on adiposity and acral growth.
Six patients (5 with Laron syndrome and 1 with type 1A growth hormone deficiency) were followed for a mean (±SD) of 8.2 ± 1.8 years. Mean age at start of therapy was 7.6 ± 4.1 years. Anthropometric evaluation including growth of hand, foot, ear, and skin folds, and assessment of internal organ growth were done.
Hand and foot sizes improved significantly, especially when treatment was initiated early. Prominent effects on adiposity were observed, reflected by increment in body mass index standard deviation score (SDS) and skin fold SDS. Mean height, height velocity, sitting height, and head circumference SDS improved with therapy. A significant increase in spleen and right kidney was appreciated.
IGF-1 therapy improves growth in GHIS. The hand and foot sizes increase significantly with therapy, and can even normalize with early initiation of treatment. Ear length further improves with therapy. Other effects include increase in adiposity and internal organ growth.
No preview · Article · Mar 2014 · Hormone Research in Paediatrics
[Show abstract][Hide abstract]ABSTRACT: Abstract: Introduction: Constitutional delay of growth and puberty (CDGP) is a common cause of psychosocial upset among adolescents and their families. Concerns about reduced final height often urge patients to ask for urgent treatment rather than to wait for observation.
Aim: The main objective is to evaluate the concerns, knowledge, understanding, and expectations of a group of children with CDGP and their families. Secondary objective is to study the auxological and socioeconomic characteristics of the patients.
Patients and Methods: Forty nine patients with CDGP were included. Fifteen were followed for two years, and seven until final height. Patients and parents completed a designed question sheet to identify their concerns, knowledge, expectations from treatment, and willingness to follow up for observation. Socioeconomic standard scoring and anthropometric evaluation were performed.
Results: 59.2% presented because of the concern of the whole family. There was a delay of 1.8 years between the time when patients were concerned about short stature and/or delayed puberty and presentation to clinic The delay was greatest in patients who stopped following up. Twenty seven patients (55.1%) were of low socioeconomic background, 17 (34.7%) were medium low, and 5 (10.2%) were medium high. 69.4% of patients were concerned about their height, not puberty. Two thirds were not convinced that shortness was not due to growth hormone deficiency and that treatment if needed would be sex hormones. 69.4% were not convinced to follow up without treatment.
Conclusion: Short stature rather than late puberty is usually the reason for consultation in CDGP. Incomplete
understanding of the condition among families and dissatisfaction with the treatment options available remains a problem even after detailed explanation. Extra effort is needed to raise the awareness and avoid the adverse psychosocial sequels in patients with CDGP.
Keywords: Constitutional delay of growth and puberty, psychosocial satisfaction
[Show abstract][Hide abstract]ABSTRACT: It is a common knowledge that GH exhibits a large number of metabolic effects, involving lipid and glucose homeostasis. The aim of the study was to investigate the effect of one year GH therapy on metabolic parameters and adipokines in GH deficient (GHD) children. Sixteen prepubertal children (11 M and 5 F) with complete GHD (age range: 3.4-14.7 years) and 20 (13 M and 7 F) age and sex-matched healthy children (age range: 4.6-12.3 years) were studied. Blood was collected from patients before starting GH therapy (0.025 mg/kg/day) and one year later, and from healthy children to measure adiponectin, leptin, osteoprotegerin, resistin, interleukin (IL)-6, tumor necrosis factor (TNF)-α levels, and other glucose and lipid metabolism parameters. Adiponectin and resistin levels were significantly higher (49 980 ng/ml vs. 14 790 ng/ml and 11.0 pg/ml vs. 6.3, respectively) in GHD children before GH therapy than in controls. Serum IGF-I levels (p=0.0001) and height SDS (p<0.0001) significantly increased after 12 months' of GH therapy. There was a loss of body fat reflected by a significant decline in tricep (p=0.0003) and subscapular skinfold thickness SDS (p=0.0023). After 12 months, there was a significant rise in insulin (p=0.0052) and leptin levels (p=0.0048) and a significant decrease in resistin (p=0.0312) and TNF-α (p=0.0137). We observed that lipid and glucose metabolisms are only slightly affected in GHD children. Growth hormone replacement therapy affects some factors, such as leptin, resistin and fat mass, suggesting that also in children, GH treatment has a role in the regulation of factors secreted by adipose tissue.
Full-text · Article · Dec 2013 · Hormone and Metabolic Research