VARIATIONS IN MONOGENIC DIABETES AND DIABETES SUSCEPTIBILITY GENES IN PEDIATRIC CASES: SINGLE CENTER EXPERIENCE.

Context: Diabetes is a chronic disorder with a complex pathogenetic background including monogenic, polygenic, and environmental causes. Objective: The aim of the present paper is to share the information related to genetic and clinical data of large pediatric diabetes cohort. Design: The present study retrospectively analyzes genetic and clinical findings of subjects diagnosed with diabetes under the age of 18 year and are in follow-up in a pediatric diabetes referral center. Subjects and Methods: Out of 1205 children with diabetes (902 treated with insulin) 246 underwent genetic tests on the basis of clinical selection criteria since 2007. Results: One hundred and ten variants related to diabetes were found in 89 of them. Age at presentation was 9.5±4.02 years (F/M 44/45). In total 49 pathogenic and likely pathogenic, 11 "hot and warm" of unknown significance variants were found in fourteen MODY and fifteen non-MODY genes according to criteria developed by American College of Medical Genetics. Thirty novel mutations were found. GCK (26.6%) and ABCC8 (10%) were two most frequently affected genes. Antibody testing revealed negative results in 80% of cases. Conclusions: Genetic interpretation in selected cases is important to understand the nature of the disease better. Improvement in testing opportunity and awareness might increase the prevalence of genetically explained diabetes cases. The distribution of subtypes differs between countries and even regions of the same country.

Evaluation of eye health in children with type 1 diabetes mellitus and celiac disease.

Background: Pediatric celiac disease (CeD) and type 1 diabetes mellitus (T1DM) have well established effects on eye health but comorbid effect is not known. Aim: To evaluate the eye health of children with T1DM and CeD to predict microvascular retinal pathologies by diagnosis of probable intraocular pressure increase which is an important glaucoma trigger. Patients and Methods: In this case-controlled study, 28 eyes of 14 children both T1DM and CeD, with a mean age of 12.6 ± 3.9 years, and 28 eyes of gender-matched 14 healthy children as a control group were included. In both groups, detailed ocular examinations and measurement of intraocular pressure (IOP), ocular pulse amplitude (OPA), thicknesses of ganglion cell layer (GCL), inner plexiform layer (IPL), retinal nerve fiber layer (RNFL), and choroid thicknesses (CT) were done. All the patients with T1DM and CeD were newly diagnosed. The evaluations of IOP and OPA were made using a Pascal dynamic tonometer and thicknesses measured by optical coherence tomography. Results: The IOP and OPA values of the patient group were found to be statistically significantly higher than those of the control group (17.1 and 1.86 vs 14.78 and 1.57 mmHg, P <.0001, P <.001, respectively). IOP values of all patients were higher than IOP cut off levels for diagnosis of hypertension. CT was significantly thinner in the patient group than in the control group (385.4 µm vs 331.71 µm, respectively, P < 0.03). No significant difference was found between the groups in respect of GCL, IPL, and RNFL values. Conclusion: The higher IOP and OPA values of the children with T1DM and CeD were considered to be the result of the microvascular pathologies in T1DM and increased inflammation associated with CeD. High IOP and OPA values can lead to damage in the eye as intraocular blood flow and choroidal perfusion are affected. In order to prevent these eye problems, measurement of IOP and OPA should be done in children with diagnosis of T1DM and CeD and also follow up studies needed.

Characteristics of Turkish children with Type 2 diabetes at onset: a multicentre, cross-sectional study.

AIMS: To describe the baseline clinical and laboratory findings and treatment modalities of 367 children and adolescents diagnosed with Type 2 diabetes in various paediatric endocrinology centres in Turkey. METHODS: A standard questionnaire regarding clinical and laboratory characteristics at onset was uploaded to an online national database system. Data for 367 children (aged 6-18 years) newly diagnosed with Type 2 diabetes at 37 different paediatric endocrinology centres were analysed. RESULTS: After exclusion of the children with a BMI Z-score < 1 SD, those with genetic syndromes associated with Type 2 diabetes, and those whose C-peptide and/or insulin levels were not available, 227 cases were included in the study. Mean age was 13.8 ± 2.2 (range 6.5-17.8) years, with female preponderance (68%). Family history of Type 2 diabetes was positive in 86% of the children. The mean BMI was 31.3 ± 6.5 kg/m2 (range 18.7-61) and BMI Z-score was 2.4 ± 0.8 (range 1-5). More than half (57%) of the children were identified by an opportunistic diabetes screening due to existing risk markers without typical symptoms of diabetes. Only 13% (n = 29) were treated solely by lifestyle modification, while 40.5% (n = 92) were treated with metformin, 13% (n = 30) were treated with insulin, and 33.5% (n = 76) were treated with a combination of insulin and metformin initially. Mean HbA1C levels of the insulin and combination of insulin and metformin groups were 98 (11.1%) and 102 mmol/mol (11.5%), respectively, and also were significantly higher than the lifestyle modification only and metformin groups mean HbA1C levels (70(8.6%) and 67 mmol/mol (8.3%), respectively). CONCLUSIONS: An opportunistic screening of children who are at high risk of Type 2 diabetes is essential, as our data showed that > 50% of the children were asymptomatic at diagnosis. The other important result of our study was the high rate of exclusion from the initial registration (38%), suggesting that accurate diagnosis of Type 2 diabetes in youth is still problematic, even for paediatric endocrinologists.

The role of visfatin in the pathogenesis of gestational diabetes mellitus.

AIM: The objective of the present study was to evaluate the role of visfatin in gestational diabetes mellitus. MATERIALS AND METHODS: Forty-five pregnant women at 24 to 28 weeks' gestation were assigned to consume an initial screening test using a 1-h 50-g glucose load, and then a 3-h 100-g glucose load. The study group consisted of 23 patients who were diagnosed with gestational diabetes mellitus and the control group consisted of 22 healthy pregnant women. We studied the levels of visfatin and the other parameters of inflammation, glucose and lipid metabolism between the 24th and 28th week of gestation and also between the 6th and 10th week after delivery. RESULTS: Plasma visfatin and glucose levels at 60 min after a 50-g and a 100-g glucose load between the 24th and 28th week of gestation were significantly higher in the gestational diabetes group than in the control group. There were no statistical differences in visfatin levels between the groups at 6-10 weeks post-partum. CONCLUSION: Visfatin levels were significantly elevated in women with gestational diabetes mellitus and during the course of pregnancy and increased visfatin concentrations were reduced within 6 to 10 weeks after delivery.

The vitamin D receptor fokI start codon polymorphism and bone mineral density in male hypogonadotrophic hypogonadism.

The genetic factors determining bone mineral density (BMD) are not well characterized. Many studies have investigated the relationship between the fokI polymorphism of vitamin D receptor (VDR) gene in diverse populations and gender, resulting in conflicting outcomes. Because peak bone mass in men is closely related to sufficient androgen release, the contribution of VDR gene on BMD might have been masked by hormonal status of adulthood. We therefore investigated the relationship between the fokI polymorphism of VDR and BMD in male patients with idiopathic hypogonadotrophic hypogonadism (IHH). Sixty-five untreated male patients with IHH and 39 healthy matched controls were evaluated. fokI polymorphism ("f" allele) was detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism using restriction endonuclease fokI, and BMD was measured by dual Energy X-ray absorpsiometry in lumbar spine, femur and radius. The distribution of FF, Ff, and ff alleles in patients with IHH and controls were not different (patients; 46%, 51%, 3% and controls; 51.3%, 46.1%, 2.6%, respectively). BMD levels in patients with IHH were significantly lower than controls. We categorized patients and control subjects in subgroups according to whether they had homozygous FF and heterozygous Ff genotype. No differences in BMD were seen between control subgroups, but total femur and femoral neck BMD were significantly lower in patients bearing heterozygous Ff genotype with IHH than homozygous FF ones (p=0.017 and p=0.009, respectively). Ff genotype might run down the BMD in cortical bone of femur, which needs to be proved in further studies.

Increased abnormal pituitary findings on magnetic resonance in patients with male idiopathic hypogonadotrophic hypogonadism.

Idiopathic hypogonadotropic hypogonadism (IHH) is a well-known disorder apart from its pathogenesis, which is still mostly unclear, even though a diverse subgroup of patients with hypogonadotropic hypogonadism and hyposmia/anosmia--the Kallman syndrome--have been partly linked to a mutated gene, known as kal-1 gene. In this study, we aimed to evaluate the sellar region of patients with IHH on magnetic resonance (MR). Pituitary MR of 120 male patients with IHH, diagnosed by a thorough endocrinologic assessment, were compared with pituitary MR of 49 healthy cases selected randomly who underwent detailed endocrinologic and neurologic evaluation and were assessed as healthy. Patients with IHH were diagnosed with microadenomas and irregularly contrasting pituitary (ICP), 18.2 and 10.7%, respectively. Although some anatomic variations were seen in healthy controls, microadenomas and ICP had solely been observed in patients with IHH and none in controls. Intact appearence of hypophysis in patients with IHH was significantly lower than in randomly selected healthy male subjects (p = 0.021). Mean infundibulum width of hypophysis and transverse diameter of posterior hypophysis were significantly broader in patients with IHH than in controls (both having p < 0.001), while mean hypophysis height and volume did not differ between groups. Results showed unusual incidence of pituitary abnormalities on pituitary MR in male patients with IHH. In conclusion, MR imaging is particularly useful in defining the morphological aspects of the hypothalamo - pituitary region in some endocrine disorders and other researchers might want to bear our findings in mind when performing MR evaluation of similar patient subgroups.