BackgroundHaemoglobinopathies constitute the commonest recessive monogenic disorders worldwide, and the treatment of affected individuals presents a substantial global disease burden. β-thalassaemia is characterised by the reduced synthesis (β+) or absence (βo) of the β-globin chains in the HbA molecule, resulting in accumulation of excess unbound α-globin chains that precipitate in erythroid precursors in the bone marrow and in the mature erythrocytes, leading to ineffective erythropoiesis and peripheral haemolysis. Approximately 1.5% of the global population are heterozygotes (carriers) of the β-thalassemias; there is a high incidence in populations from the Mediterranean basin, throughout the Middle East, the Indian subcontinent, Southeast Asia, and Melanesia to the Pacific Islands.AimThe principal aim of this paper is to review, from a historical standpoint, our knowledge about an ancient disease, the β-thalassemias, and in particular, when, how and in what way β-thalassemia spread worldwide to reach such high incidences in certain populations.ResultsMutations involving the β-globin gene are the most common cause of genetic disorders in humans. To date, more than 350 β-thalassaemia mutations have been reported. Considering the current distribution of β- thalassemia, the wide diversity of mutations and the small number of specific mutations in individual populations, it seems unlikely that β-thalassemia originated in a single place and time.ConclusionsVarious processes are known to determine the frequency of genetic disease in human populations. However, it is almost impossible to decide to what extent each process is responsible for the presence of a particular genetic disease. The wide spectrum of β-thalassemia mutations could well be explained by looking at their geographical distribution, the history of malaria, wars, invasions, mass migrations, consanguinity, and settlements. An analysis of the distribution of the molecular spectrum of haemoglobinopathies allows for the development and improvement of diagnostic tests and management of these disorders.

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Aim:Chronic iron overload resulting from frequent transfusions, poor compliance to efficient chelation therapy and chronic liver disease is basically responsible for the most severe complications of thalassemia major (TM). Before conventional treatment, TM was entirely childhood disease with a very short survival. Today, survival improved to 40–50 years and becomes a prevalent disease of adulthood and in the near future it will be one of senility. Furthermore, clinical phenotype of TM is changing with age and appearance of severe complications from the heart and endocrine glands that require special health care from well-informed specialists.Objectives:The aims of our study were to: (1) Imprint the clinical profile of long-lived TM patients; (2) evaluate retrospectively the cumulative incidence of endocrine diseases; (3) identify potential risk factors; and (4) orient the physicians in the modified clinical phenotype and the relative patients' health needs.Design:A retrospective cross-sectional study followed from childhood to adulthood by the same physician in a tertiary thalassemia clinic.Participants:Forty-three long-lived TM patients (mean age: 50.3 ± 10.8 years; range: 45.8–59.5 years; 23 females) were studied.Patients and Methods:An extensive medical history, with detailed clinical and laboratory data, endocrine complications, and current treatments, was obtained.Results:The data indicate that 88.4% of adult TM patients suffered from at least one endocrine complication. The majority of patients developed endocrine complications in the second decade of life when serum ferritin level was very high (12/23 TM female and 8/20 TM male patients, the serum ferritin levels at the diagnosis were above 5.000 ng/ml).Conclusions:These data underline that endocrine and bone complications in adult TM patients are highly prevalent and necessitate close monitoring, treatment, and follow-up. Physicians' strategies to optimize chelation therapy include identifying patients who are at risk for developing organ damage, developing chelation plans, promoting compliance, and educating patients. Several clinical aspects remain to be elucidated such as growth and impairment of glucose tolerance in relation to hepatitis C virus infection. Furthermore, affordable worldwide-established long-term treatment protocols for hypogonadism and osteoporosis are needed.

Hypogonadism is the most frequently reported endocrine complication, affecting 40%-80% of thalassemia major (TM) patients. The prevalence and severity of hypogonadism in TM varies among studies, depending on patients' age, genotype, transfusion frequency and starting age and efficiency of iron chelation. Areas covered: The diagnosis requires careful clinical assessment and appropriate laboratory testing. Its management is more complex compared to other 'classical' causes of hypogonadism because of multiple associated disorders (cardiac, hepatic and endocrine) and other contributing factors basically iron overload and iron toxicity. Expert commentary: Early recognition and treatment of hypogonadism in TM patients is most important to prevent late complications and to enhance the chances of parenthood. The goal of management is to restore deficient glandular function. If fertility is the issue and the testis is under-stimulated because of gonadotropin deficiency, it is possible to induce or restore spermatogenesis with exogenous gonadotropins in some patients. Assisted reproductive techniques may supplementary help to overcome previously untreatable causes of male infertility. These positive achievements should encourage health care providers to pay closer attention to the reproductive health of TM patients. This would involve the collaboration of clinicians caring for thalassemia with endocrinologists and specialists in assisted reproductive technologies.

RationaleBoth 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 treatmentObjectiveThis 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.DesignA population-based cross-sectional study.ParticipantsThe 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 assessmentMethodsAn 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.ResultsEighteen TM patients with IDDM (94.7 %) and ten non-diabetic patients (32.2 %) had IGF-1 levels below the 2.5th 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.

Introduction: During gestation, IGF1 secretion and availability in the maternal blood and at the maternal-fetal interface is mainly regulated by IGF-binding proteins (IGFBP) such as IGFBP-1 synthesized by the decidua. Data about the interaction between maternal, placental, and fetal IGF1/IGFBP in relation to fetal growth and newborn size during diabetic pregnancy (gestational Diabetes (GDM) and Type 1 DM (T1DM) is not clear. Aim of the study and Methods: We reviewed the research papers published in Pubmed, Google scholar, Research gate, and Scopus in the past 20 years on the relationship between maternal, placental, and fetal/infantile/ IGF1/IGFBP-1 in relation to birth size in pregnancies associated with maternal diabetes. Results: Twenty-eight research papers were selected and reviewed (patients’ number = 1902). In GDM pregnancies, higher maternal IGF1 levels and/or its availability due to lower IGFBP1 levels can increase the size (weight) and functions of the placenta. These include the upregulation of specific placental amino acid transporter isoforms and GLUT-1, stimulation of mTOR signaling which stimulates protein synthesis, increasing mitochondrial functions, and accelerating nutrient transport which significantly contributes to fetal growth and newborn birth size. On the other hand, in pregnant women with T1DM, lower maternal IGF1 is associated with subsequent underweight placenta and lower birthweight.

Introduction: Early childhood is a critical time for obesity prevention. Children are developing taste preferences, learning to walk and play. They eagerly mimick both the healthy and unhealthy behavior of their parents, siblings and caregivers. Obesity during early childhood is a major health concern of the developed world and is steadily affecting many low- and middle-income countries, particularly in urban settings. Unfortunately, overweight, and obese children often stay obese into adulthood and more likely to develop many non-communicable diseases at a younger age. Important environmental and socioeconomic factors play a significant role in the initiation and progression of early childhood obesity. In this minireview, we try to shed light on the published data exploring various relevant issues, including possible etiologic factors in this target population at risk (children below 5 years) that may enable the initiation of early and effective policy and tactics for the prevention and management of this problem, particularly in high-risk communities.  Methods: We examined the English language literature (Pubmed, Google scholar, and Cochrane library ) on the environmental and socioeconomic factors that appeared to be important in the pathogenesis of early obesity in children for the past 20 years. Inclusion criteria were obesity and overweight in young children below 5 years of age.  Results: Education, income, and urbanization, food environments and increased energy intake through consumption of fatty foods and a high sugar diet as well as parental effects through conveying their behaviors, attitudes, and feeding styles to their children appear to be among the most important factors that contribute to the initiation and progression of obesity in young children. Overfeeding preterms and small for gestational age infants, using artificial milk formula, and early addition of solid foods play a considerable share in inducing early obesity. In addition, lack of health education to parents and children, poor health care, and scarcity of access to physical activity are important risk factors in poor populations.  Conclusions: Many important social and environmental factors can actively contribute to the production and progression of early childhood obesity. These factors differ considerably among different populations. Understanding these factors is essential for appropriate and early prevention as well as management of early childhood obesity, especially in high risk communities.

Introduction: The placenta expresses significant amounts of insulin and IGF1 receptors at distinct locations on both fetal and maternal surfaces. This makes the IGF1 and the insulin receptor accessible to fetal and/or maternal insulin, IGF1 and IGF2. IGFs are involved in the receptor-mediated regulation of placental growth and transport, and placental angiogenesis. Maternal obesity during gestation mediates significant changes in the metabolism of mothers, placentas as well as fetal growth. Objectives: In obese women. the role of the insulin like growth factor system IGFs, IGF receptors, IGF-binding proteins (IGFBPs) and IGFBP proteases during gestation, and their effect on placental growth and fetal anthropometric changes need further clarification. In this update we reviewed the literature on the detected changes in the maternal and fetal IGFs in relation to placental growth and function and to fetal growth and newborn size in pregnant obese mothers. Eighteen research articles fitted the criteria of this update. Results: Twenty-three research papers were including 2817 pregnant obese and non-obese women (controls) and their babies were selected and reviewed. Results showed that obesity and excessive nutrient intake during gestation increase maternal IGF1and decreases IGBP1. Increased maternal IGF1 and/or its availability due to decreased IGFBP1 can increase the size (weight) and development of the placenta, stimulate mTOR signaling which stimulates protein synthesis, mitochondrial function, and upregulate specific placental amino acid transporter isoforms (amino acids transport), GLUT-1, (glucose transport) and possibly lipid transport to the fetus which can induce fetal IGF1 secretion and lead to overgrowth. Conclusions: In obese women during pregnancy, increased level of IGF1 and/or its availability due to decreased IGFBP1 can increase the size (weight) and development of the placenta, stimulate mTOR signaling which stimulates protein synthesis, mitochondrial function, and upregulate placental transport of amino acids, glucose and possibly fatty acids.