Consistent evidence associates IGF-1 deficiency and metabolic syndrome. In this review, we will focus on the metabolic effects of IGF-1, the concept of metabolic syndrome and its clinical manifestations (impaired lipid profile, insulin resistance, increased glucose levels, obesity, and cardiovascular disease), discussing whether IGF-1 replacement therapy could be a beneficial strategy for these patients. The search plan was made in Medline for Pubmed with the following mesh terms: IGF-1 and “metabolism, carbohydrate, lipids, proteins, amino acids, metabolic syndrome, cardiovascular disease, diabetes” between the years 1963–2015. The search includes animal and human protocols. In this review we discuss the relevant actions of IGF-1 on metabolism and the implication of IGF-1 deficiency in the establishment of metabolic syndrome. Multiple studies (in vitro and in vivo) demonstrate the association between IGF-1 deficit and deregulated lipid metabolism, cardiovascular disease, diabetes, and an altered metabolic profile of diabetic patients. Based on the available data we propose IGF-1 as a key hormone in the pathophysiology of metabolic syndrome; due to its implications in the metabolism of carbohydrates and lipids. Previous data demonstrates how IGF-1 can be an effective option in the treatment of this worldwide increasing condition. It has to distinguished that the replacement therapy should be only undertaken to restore the physiological levels, never to exceed physiological ranges.

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Insulin-like growth factor-1 deficiency and metabolic syndrome

Objective To provide outcome data concerning pregnancies exposed to the Interleukin-1 (IL-1) inhibitors prior to conception in both men and women, during pregnancy and breast feeding. Methods Retrospective data were collected from members of the International Society for Systemic Autoinflammatory diseases and collated in a single centre. A uniform data collection sheet was used to obtain standardized data including maternal age and diagnosis, type, duration of and response to IL-1 blockade, pregnancy duration, delivery, mode of feeding and neonatal development. Results There were 31 maternal-exposed pregnancies from seven countries and we report the first data on paternal exposure: six to anakinra and five to canakinumab, with no negative outcomes. We also report the first data on canakinumab-exposed pregnancies: eight pregnancies that resulted in the delivery of seven healthy infants of normal gestational age and birthweight. There were 23 anakinra-exposed pregnancies resulting in the birth of 21 healthy infants, and one baby with unilateral renal agenesis and ectopic neurohypophysis. There were two first trimester miscarriages affecting a mother with active disease. There were no serious neonatal infections. Fourteen infants were breast fed with no complications. There were no reports of developmental delay, with follow-up of up to 10 years (median 18 months). Conclusion This series substantially increases the published experience of IL-1 blockade and reproduction including the first data on canakinumab and on paternal exposure to these agents. Data are generally reassuring, although the case of renal agenesis is the second reported in an anakinra-exposed pregnancy.

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International multi-centre study of pregnancy outcomes with interleukin-1 inhibitors

:The clinical and pathological features of 63 steroid cell tumors, not otherwise specified, were reviewed. The patients ranged in age from 2'A to 80 years. The most common initial manifestation was virilization (41%); four patients had estrogenic manifestations, and four had hypercortisolemi

Ovarian Steroid Cell Tumors (Not Otherwise Specified): A Clinicopathological Analysis of 63 Cases

Autoimmune forms of hypoglycemia are a rare cause of low blood sugar levels among Caucasians, and often go misdiagnosed, exposing patients to lengthy series of pointless, potentially harmful and expensive tests. There are two types of autoimmune hypoglycemia. One is insulin autoimmune syndrome (IAS), which is characterized by hyperinsulinemic hypoglycemia, elevated insulin autoantibody (IAA) titers, no prior exposure to exogenous insulin, and no of pathological abnormalities of the pancreatic islets. This condition is also known as “Hirata’s disease”. The other is type B insulin resistance syndrome (TBIRS), a rare autoimmune disorder resulting in a broad array of abnormalities in glucose homeostasis—from hypoglycemia to extremely insulin-resistant hyperglycemia—caused by the presence of insulin receptor autoantibodies (IRAbs). This review focuses on these two syndromes, describing their epidemiology, possible genetic background, clinical presentation, pathophysiology, diagnosis and treatment.

/pdf/insulin-autoimmune-syndrome-from-diagnosis-to-clinical-23jq7biacz.pdf

Insulin autoimmune syndrome: from diagnosis to clinical management.

Lessons from 50 years of study of laron syndrome

Objective: Training teachers and education professionals on diabetes is crucial for full-time monitoring of diabetic children in schools. The objective of this study was to assess the knowledge on diabetes in a group of school teachers in Turkey.

Methods: Between November 2010 and November 2011, 1054 teachers from three regions of Ankara were given a questionnaire to assess their knowledge on diabetes. The mean age of the group (27% males, 73% females) was 38.8±8 years. 61.7% of the participants were class teachers, 23.3% were school counselors, and the rest were physical education teachers and administrators.

Results: A fair percentage (47.6%) of the participants had a moderate knowledge level on diabetes and 32.4% expressed a lower level of knowledge. A large proportion (94%) gave an accurate definition of diabetes. Of the total group of 1054 teachers, 625 were aware that blood glucose level might decrease in diabetic children during follow-up. Also, 75% believed that diabetic children were eligible for physical education classes. 52.8% of these teachers had no diabetic child in their classes and teachers with a diabetic patient in their family had better knowledge of diabetes compared to their counterparts.

Conclusions: Our study results indicate that school teachers have limited knowledge on diabetes. We believe that their knowledge levels can be improved by widespread training programs.

Conflict of interest:None declared.

Assessment of the knowledge of diabetes mellitus among school teachers within the scope of the managing diabetes at school program.

BACKGROUND Maturity-onset diabetes of the youth (MODY), is a genetically and clinically heterogeneous group of diseasesand is often misdiagnosed as type 1 or type 2 diabetes. The aim of this study is to investigate both novel and proven mutations of 11 MODY genes in Turkish children by using targeted next generation sequencing. METHODS A panel of 11 MODY genes were screened in 43 children with MODY diagnosed by clinical criterias. Studies of index cases was done with MISEQ-ILLUMINA, and family screenings and confirmation studies of mutations was done by Sanger sequencing. RESULTS We identified 28 (65%) point mutations among 43 patients. Eighteen patients have GCK mutations, four have HNF1A, one has HNF4A, one has HNF1B, two have NEUROD1, one has PDX1 gene variations and one patient has both HNF1A and HNF4A heterozygote mutations. CONCLUSIONS This is the first study including molecular studies of 11 MODY genes in Turkish children. GCK is the most frequent type of MODY in our study population. Very high frequency of novel mutations (42%) in our study population, supports that in heterogenous disorders like MODY sequence analysis provides rapid, cost effective and accurate genetic diagnosis.

Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing.

Background: Insulin autoimmune syndrome (IAS) is a condition characterized by hypoglycemia associated with the presence of autoantibodies to insulin in patients who have not been injected with insulin. Case Report: A female patient (aged 16 years and 3 months) presented with the complaint of being overweight. Physical examination revealed a body weight of 78.2 kg (+2.6 SD) and a height of 167 cm (+0.73 SD). While the patient's fasting blood glucose level was found to be 40 mg/dl, blood ketone was negative and the serum insulin level was determined as 379 mIU/ml. The patient was diagnosed with hyperinsulinemic hypoglycemia. Abdominal ultrasound, pancreas MRI and endoscopic ultrasound were normal. The daily blood glucose profile revealed postprandial hyperglycemia and reactive hypoglycemia in addition to fasting hypoglycemia. The results of anti-insulin antibody measurements were as high as 41.8% (normal range 0-7%). A 1,600-calorie diet containing 40% carbohydrate and divided into 6 meals a day was given to the patient. Simple sugars were excluded from the diet. Hypoglycemic episodes were not observed, but during 2 years of observation, serum levels of insulin and anti-insulin antibodies remained elevated. Conclusion: In all hyperinsulinemic hypoglycemia cases, IAS should be considered in the differential diagnosis and insulin antibody measurements should be carried out.

An uncommon cause of hypoglycemia: insulin autoimmune syndrome.

BACKGROUND Factors such as vascular/neurological mechanisms, poor glycemic control, abnormalities in vitamin D/calcium, secondary hyperparathyroidism, and hypercalciuria have been blamed for the unfavorable effects of type 1 diabetes mellitus (type 1 DM) on bone health. In this present study, we aimed to evaluate the frequency of low bone mineral density (BMD) in children with type 1 DM. METHOD Among 100 type 1 DM patients, a 25-hydroxy vitamin D level of <10 ng/mL was accepted as vitamin D deficiency and the level of 10-20 ng/dL was accepted as vitamin D insufficiency. BMD was measured, and Z-scores were evaluated according to adjusted Turkish standards. Participants with a Z-score of ≤-2 were defined as having low BMD; BMD between -2 and -1 were defined as being in the low range of normality; and values ≥-1 were accepted as normal. RESULTS The vitamin D deficiency and insufficiency ratios were 28% and 43%, respectively. Low BMD and BMD in the low range of normality were diagnosed in 10% and 25% of patients, respectively. There was no difference in vitamin D, parathormone, and metabolic control levels between three groups: with normal BMD, low BMD, and BMD in the low range of normality. BMD Z-scores were not different between the pubertal and prepubertal groups. CONCLUSION Detailed evaluation should be performed for BMD in the follow-up of DM to prevent complications by decreasing related risks.

Evaluation of bone mineral density in children with type 1 diabetes mellitus.

Ovarian steroid cell tumors are rarely encountered in prepubertal girls. The majority of these tumors produce hormones, testosterone being the leading one. These tumors may either coexist with or imitate congenital adrenal hyperplasia (CAH). We present a 13-year-old female patient who was diagnosed with non-classical CAH at six years of age while being investigated for premature pubarche. She was diagnosed with steroid cell ovarian tumor after a delay of six years. The diagnosis was based on radiologic imaging, which was performed to investigate causes of unsuccessful metabolic control while under high-dose steroid therapy. The right ovarian hypoechoic mass of 23x22 mm was excised laparoscopically, preserving the ovary. Immunohistochemical staining showed that tumor cells were strongly positive with inhibin and focally positive with vimentin. Based on these findings, the patient was diagnosed with ovarian steroid cell tumor not otherwise specified. In the postoperative second week, total testosterone level was <10 ng/ml, and 17 hydroxyprogesterone (17-OHP) level was 1.1 ng/ml. Peak 17-OHP level was 4.2 ng/ml on repeated ACTH stimulations, and the diagnosis of CAH was excluded. Steroid therapy was tapered down and then discontinued. It should be kept in mind that there may be a misdiagnosis in cases of CAH, which may present itself with unsuccessful metabolic control even while under the appropriate treatment dose. Early diagnosis and treatment would prevent the development of irreversible signs.

Aşan Önder

Papers

Assessment of the knowledge of diabetes mellitus among school teachers within the scope of the managing diabetes at school program.

Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing.

An uncommon cause of hypoglycemia: insulin autoimmune syndrome.

Evaluation of bone mineral density in children with type 1 diabetes mellitus.

A girl with steroid cell ovarian tumor misdiagnosed as non-classical congenital adrenal hyperplasia.