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Objectives International guidelines recommend additional salt supplementation during infancy in classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The influence of corticoid medication and growth has not been assessed. Aim To investigate the current use of salt supplementation, fludrocortisone (FC) and hydrocortisone (HC) dosage as well as weight, height, BMI and blood pressure (BP) in CAH children aged 0–3 years. Methods Retrospective multicentre analysis using data from the I-CAH registry. Salt-treated (ST) and non-salt-treated (NST) children were compared regarding FC and HC dosage, weight, height and BP at 0, 3, 6, 9, 12, 18, 24, 30, and 36 months. Results We analysed 2483 visits of 331 patients born after year 2000 in 13 countries (male, n = 145) with 203 ST patients (61%). NST children had significantly higher FC dosages at 1.5–4.5 months and higher HC dosages until 1.5 months of age. No differences in weight, length and BP between subgroups were observed. Children of the whole cohort showed increased BMI-SDS during the study period and about half of the reported BP readings were >P95. Conclusion In children treated with additional salt supplementation, FC and HC dosages are lower during the first months of life but without differences in weight, length and BP until 3 years of age compared to NST children. All children showed an increase in BMI-SDS and a high rate of BP readings >P95 until 3 years, indicating the start of weight gain and negative effects on blood pressure already in very early life.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive genetic disorder affecting the biosynthesis of dopamine, a precursor of both norepinephrine and epinephrine, and serotonin. Diagnosis is based on the analysis of CSF or plasma metabolites, AADC activity in plasma and genetic testing for variants in the DDC gene. The exact prevalence of AADC deficiency, the number of patients, and the variant and genotype prevalence are not known. Here, we present the DDC variant (n = 143) and genotype (n = 151) prevalence of 348 patients with AADC deficiency, 121 of whom were previously not reported. In addition, we report 26 new DDC variants, classify them according to the ACMG/AMP/ACGS recommendations for pathogenicity and score them based on the predicted structural effect. The splice variant c.714+4A>T, with a founder effect in Taiwan and China, was the most common variant (allele frequency = 32.4%), and c.[714+4A>T];[714+4A>T] was the most common genotype (genotype frequency = 21.3%). Approximately 90% of genotypes had variants classified as pathogenic or likely pathogenic, while 7% had one VUS allele and 3% had two VUS alleles. Only one benign variant was reported. Homozygous and compound heterozygous genotypes were interpreted in terms of AADC protein and categorized as: i) devoid of full-length AADC, ii) bearing one type of AADC homodimeric variant or iii) producing an AADC protein population composed of two homodimeric and one heterodimeric variant. Based on structural features, a score was attributed for all homodimers, and a tentative prediction was advanced for the heterodimer. Almost all AADC protein variants were pathogenic or likely pathogenic.

Introduction Obesity is a component of eating disorders grouped under several eating disturbances due to emotional problems. Eating habits are directly influenced by eating disorders. Eating disorder rates in obese patients are reported to be 15-50% in various populations. This study aimed to evaluate obesity related eating habits (OREH) in obese patients who followed in an obesity center. Methods A total of 752 (F/M: 636/116, 42.6G11.6 yrs ) obese patients (BMIO30) who applied to the Obesity Center of Marmara University Pendik Education and Research Hospital (ERH) were included in this cross-sectional study. Obesity is classified as Stage 1 (BMI 30-34.9), Stage 2 (BMI 35-39.9), and Stage 3 (BMIO 40). We evaluated graze eating, night eating, eating addiction, and binge eating in the context of OREH in accordance with the literature. Self-report tests including The Short Inventory of Grazing (SIG), Modified Yale Food Addiction Scale (mYFAS), Night Eating Questionnaire (NEQ), Emotional Eating Scale (EES), and Binge Eating Scale (BES) were given to the patients. OREH results were determined based on these test’s cut-off points. Results Mean BMI was found to be 42.1G6.6 kg/m2 . There were no statistically significant difference between both genders in respect of age and BMI (PO0.05). Mild grazing habits was observed in 136 (18%) cases, moderate grazing in 309 (41%) cases, and severe grazing in 229 (30%) cases. Modarete stage grazing was more common in women (265, 41.6%) and men (44, 47.6%). Binge eating was recorded in 337 of the total (44.8%) patients, in 287 of women (45.1%) and 50 men (43.1%). Emotional eating was present in 113 of the total patients (15%), in 103 of women (16.1%) and 10 men (8.6%). Food addiction were seen in 402 of all cases (53.4%). High stage food addiction was more common in women (169, 51.1%) and men (30, 42.2%). Night eating was found in 225 patients among all (29.9%) with 185 (29%) to be in women and 40 (34.4%) in men. Emotional eating (PZ0.032) and night eating (PZ0.025) were found to be statistically significant in regard of BMI. Conclusion In this cross-sectional study, many of obese patients had obesity related eating habits whereas 65% of all cases had more than one component of obesity related eating habits. Determining the eating disorders prior to obesity treatment are necessary for planning and treatment compliance. DOI: 10.1530/endoabs.90.EP462

Objective Neurofibromatosis type 1 is an autosomal dominant inherited neurocutaneous condition characterized with multipl cafe-au-lait spots, neurofibromas, predisposition to malignancies, and the incidence of disease is 1:3000. Patients are diagnosed according to diagnostic criteria and 97% of the patents meet the criteria before 8 years of old. Diagnosis and follow-up of patients for manifestations of neurofibromatosis is important for early diagnosis and treatment of malignancies. Case Twenty-one year old female patient admitted to neurosurgery outpatient clinic with complaint of scoliosis. She was consultated to endocrinology clinic for low bone mineral density levels and osteoporotic findings in vertebral x-ray examination. In physical examination she was short statured and she had growth retardation. She had multipl cafe-au-lait spots and scoliosis. On right lower limb, she had a brown lesion and after consultation with dermatology clinic it was considered as plexiform neurofibroma. Her bone mineral density level (BMD) in L1-L4 was 1.006, z score was -0.7, femur neck BMD was 0.669 z score was -2.1. Her osteocalcin level was 21.5 ng/ml (9-42), c-telopeptide was 0.23. Hypophysial hormones were evaluated and her IGF-1 level was found to be low according to age reference range. Insulin tolerance test was performed and her growth hormone was found to be 0.206 when her blood glucose was 36 mg/dl. In family history, her mother and brother were also learnt to have multiple cafe-au-lait spots and in physical examination her mother had cutaneous neurofibromas. Neurofibromatosis diagnosis was confirmed after genetic consultation and genetic test. Hamartomatous lesion in both basal ganglia and thalamus and in right frontal lobe were found in cranial magnetic resonaunce imaging (MRI). In abdominal MRI, neurofibromas in right coxofemoral articulation and right acetabulum were found. Her urine metabolites were examined for pheochromacytoma and found in normal levels. Follow-up visits were planned and she was concultated to relevant departments. Her mother and brother were also diagnosed as neurofibromatosis. Discussion and Conclusion Patients with neurfibromatosis have a high predisposition to develop both benign and malign tumours. Although most of the manifestations effect the nervous system, multiple organs and tissues can be affected. Patients can present with different clinical symptoms to different clinics so being aware of the different clinical manifestations of the disease is important for prompt diagnosis. DOI: 10.1530/endoabs.90.EP201

Introduction Various rates were reported regarding diabetes remission and improvement in hyperglycemia in many studies from different populations. Determinants of diabetes remission have not been definitively established so far. In this study, we aimed to evaluate the long-term glycemic status after bariatric surgery in diabetic obese patients followed by Marmara University Endocrinology Outpatient Clinic. Method The retrospective study included 233 type 2 diabetic obese patients who underwent either sleeve gastrectomy or gastric bypass between 2011-2021. Preoperative, postoperative sixth month, first year, and second year data were collected from the patient files. In the analysis of the dependent variables, patients who fulfilled whole visits were included. The glycemic status of diabetic patients at postoperative first and second year visits was classified as complete remission, partial remission, recovery, no change, and recurrence in accordance with the criteria of the American Society of Bariatric and Metabolic Surgery, 2022. Remission ratios were calculated for each visit, seperately. Logistic regression was used to analyse the factors affecting diabetes remission for the whole diabetic group. Results Postoperative BMI values were significantly lower than the preoperative level (P!0,001), additionally remained similar between the first and the second years. BMI change was found to be similar between gastric bypass and sleeve gastrectomy. Fasting blood glucose and HbA1c levels were significantly lower than the preoperative levels as well (P!0,001). 24.9% (nZ58) of the patients were on insulin preoperatively. This ratio was found to be 3.5% (nZ6) in the first year and 3.3% (nZ4) in the second year. Complete remission rate was 68.0% (nZ132) in the first year. In the second year, complete remission and recurrence rates were 59.5% (nZ72) and 8.3% (nZ10), respectively. Remission rates were similar among the two surgical procedures. To determine the factors affecting remission across the whole sample, a regression model was conducted. Duration of diabetes, preoperative insulin usage, preoperative BMI, and the type of the surgery were included in the model. Preoperative insulin use of patients was associated to diabetes remission outcomes. Patients who were not taking insulin before the surgery were more likely to experience postoperative diabetes remission (ORZ7.523, P!0.001, 95%CI 3,075-18.404 for the 1st year; ORZ 5.096, PZ0.002, 95%CI 1.781-14.577 for the 2nd year). Conclusion At the postoperative first and second year checkpoints, complete remisson rates were 68.0% and 59.5%, and recurrence rate was 8.3% in the second year. Not using insulin preoperatively made the probability of diabetes remission 5.1 times higher. DOI: 10.1530/endoabs.90.P56

Biallelic RNPC3 variants have been reported in a few patients with growth hormone deficiency, either in isolation or in association with central hypothyroidism, congenital cataract, neuropathy, developmental delay/intellectual disability, hypogonadism, and pituitary hypoplasia. To describe a new patient with syndromic congenital hypopituitarism and diffuse brain atrophy due to RNPC3 mutations and to compare her clinical and molecular characteristics and pituitary functions with previously published patients. A 20-year-old female presented with severe growth, neuromotor, and developmental delay. Her weight, height, and head circumference were 5135 gr (-25.81 SDS), 68 cm (-16.17 SDS), and 34 cm (-17.03 SDS), respectively. She was prepubertal, and had dysmorphic facies, contractures, and spasticity in the extremities, and severe truncal hypotonia. There were no radiological signs of a skeletal dysplasia. The bone age was extremely delayed at 2 years. Investigation of pituitary function revealed growth hormone, prolactin, and thyroid-stimulating hormone deficiencies. Whole-exome sequencing revealed a novel homozygous missense (c.1328A > G; Y443C) variant in RNPC3. Cranial MRI revealed a hypoplastic anterior pituitary with diffuse cerebral and cerebellar atrophy. The Y443C variant in RNPC3 associated with syndromic congenital hypopituitarism and abnormal brain development. This report extends the RNPC3-related hypopituitarism phenotype with a severe neurodegenerative presentation.

© Author(s).Objective: Vitamin D deficiency is a common health problem around the world. This study aimed to evaluate the nationwide prevalence of vitamin D status in tertiary care hospitals in Turkey. Methods: Retrospectively, the data on vitamin D levels from 33 tertiary care hospitals’ clinical biochemistry laboratories around Turkey between January and December were collected. Results: In total, 706 434 serum samples from adult subjects (female/male: 469 028/237 406; 66.4%/33.6%) were included. While vitamin D levels were sufficient in 20.3% (n = 14 222), they were insufficient in 21.9% (n = 154 360) and deficient in 57.8% (n = 408 882). We observed the highest rates of deficiency in those aged between 18 and 29 years (62.9%, n = 70 235) and lowest rates between 60 and 69 years (52.3%, n = 61 121) and between 70 and 79 years (52.3%, n = 32 397). Hypervitaminosis D was detected in 5.5% of adult subjects; highest rates of hypervitaminosis D were observed in those who were over 80 years (6.6%) and 70-79 years (6.5%) and the lowest in 18-29 years (2.8%). Discussion: In this cohort, over half of the subjects admitted to the tertiary care hospitals in Turkey had vitamin D deficiency and required vitamin D supplementation. The elderly population had the lowest prevalence of vitamin D insufficiency and the highest prevalence of hypervitaminosis D.

Objective: The aim of this study was to investigate the role of vitamin D replacement therapy on advanced glycation end-products in prediabetes and type 2 diabetes mellitus patients with vitamin D deficiency. Methods: One hundred twenty subjects with serum 25-hydroxyl vitamin D levels less than 20 ng/mL were included in the study. Forty type 2 diabetes mellitus patients (type 2 diabetes mellitus group), 40 prediabetes patients (prediabetes group), and 40 non-diabetes controls (non-diabetes group) were given oral vitamin D3 50 000 units/week for 8 weeks as loading and followed by 1500 U/day as a maintenance dose. We measured serum 25-hydroxyl vitamin D, glycated hemoglobin, carboxymethyl lysine levels, and skin autofluorescence before and on the fourth month of the therapy. Results: Basal serum carboxymethyl lysine and skin autofluorescence measurement in type 2 diabe-tes mellitus and prediabetes groups were significantly higher than the non-diabetes group. While no difference was found between glycated hemoglobin and skin autofluorescence, serum carboxy-methyl lysine levels were significantly elevated for each group following vitamin D replacement. Conclusions: Vitamin D loading did not affect skin advanced glycation end-product levels and gly-cated hemoglobin but was associated with increased serum carboxymethyl lysine levels in all groups.

Introduction: Endogenous Cushing’s syndrome (CS) is a rare, severe disease that can cause multiple systemic involvement and behavioral problems due to excessive cortisol production. Structural changes can be noted in the brain magnetic resonance imaging (MRI) scans of these cases. Cases: A 9-year-old girl and a 13-year-old boy were admitted with hypercortisolism. In the female patient, altered consciousness was prominent along with cerebral and cerebellar brain atrophy, and findings indicating posterior reversible encephalopathy syndrome were detected in the brain MRI. Although the male patient's neurological examination was normal, significant cerebral atrophy was seen in the brain MRI. Case 1 was diagnosed as having ectopic ACTH syndrome (EAS) due to a thymic carcinoid tumor. Case 2 underwent a pulmonary lobectomy upon detection of a bronchial lesion in the Ga-68 DOTATATE PET/CT scan while being examined for EAS due to a lack of suppression in the high-dose dexamethasone suppression test. However, hypercortisolism persisted despite the removal of the bronchial lesion, and subsequently, a diagnosis of Cushing’s disease was established following bilateral inferior petrosal sinus sampling. Discussion: Endogenous hypercortisolism may cause brain atrophy of varying severity. Central nervous system findings can be overlooked in children with CS. More comprehensive studies are needed to better understand the behavioral changes caused by the effects on the brain and to evaluate whether these changes are reversible. In addition, identifying the source of hypercortisolism can be difficult due to a lack of experience related to the rarity of the disease in children.

Context Stress triggers a cascade of reactions that alter the organism's dynamic steady state. There is a scarcity of interventional studies that show cortisol variability upon stress over time in groups of patients with chronic noncommunicable diseases and comorbidities. Objective We aimed to examine salivary cortisol changes in the cognitive stress response of patients with hypertension and diabetes mellitus (HT&DM) and patients with hypertension (HT) and to determine differences between them. Methods The study was conducted using a stress test of solving an arithmetic task in 62 patients with HT&DM and HT who were being treated in the outpatient clinic of the Medical Pharmacology and Clinical Pharmacology Department in Istanbul University, Istanbul Medical Faculty Hospital. Results There was no statistically significant difference between the HT&DM and HT groups for systolic blood pressure (SBP) and diastolic blood pressure (DBP) values (P = .331 and P = .058). When measured by repeated ANOVA, salivary cortisol level [F (1.842, 60) = 8.771, P < .0001], SBP [F (2.185, 60) = 12.080, P < .0001], DBP [F (2.793, 60) = 6.043, P = .001], and heart rate [F (2.073, 60) = 13.259, P < .0001] were statistically significant for the main effect (time), while the effect of the group × time interaction factor was statistically not significant (P = .773; P = .751; P = .713 and P = .506, respectively). Conclusion The arithmetic problem-solving task used with the HT&DM and HT patients was useful as an acute stress test in the laboratory environment. There was no statistically significant difference for group × time interaction factor between the HT&DM and HT groups; however, the salivary cortisol and BP values increased significantly after acute stress within each group.

Objectives: Central precocious puberty (CPP) develops as a result of early stimulation of the hypothalamic-pituitary-gonadal (HPG) axis. The loss-of-function mutations in the Makorin-ring-finger3 (MKRN3) gene appear to be the most common molecular cause of familial CPP. We aimed to identify MKRN3 gene mutations in our CPP cohort and to investigate the frequency of MKRN3 mutations.Methods: 102 patients with CPP included. 53 of them had family history of CPP in the first and/or second-degree relatives. MKRN3 gene was analyzed by next-generation sequencing.Results: Possible pathogenic variants were found in 2/53 patients with family history of CPP (3.8%) and 1/49 patient without family history (2%). A novel heterozygous c.1A > G (p.Met1Val) mutation, a novel heterozygous c.683_684delCA (p.Ser228*) and a previously reported c.482dupC (Ala162Glyfs*) frameshift variations were detected. The two novel variants are predicted to be pathogenic in silico analyses.Conclusions: In our cohort, possible pathogenic variants in MKRN3 gene were detected in 2.9% of the total cohort, 3.8% of the familial and 2% of the nonfamilial cases, slightly lower than that reported in the literature. Two novel variants detected contribute to the molecular repertoire of MKRN3 defects in CPP. Classical pattern of paternal inheritance has been demonstrated in all three cases. However, the father of the patient 3 did not have history of CPP suggesting that the father inherited this variant from his mother and had phenotype skipping. Therefore, we emphasize that the absence of history of CPP in the father does not exclude the possibility of a MKRN3 mutation.

Denosumab is a human-derived monoclonal immunoglobulin G2 antibody against the receptor activator of nuclear factor kappa B ligand, inhibiting the differentiation and function of osteoclast precursor cells by its antiosteoclastic action. Denosumab is approved for postmenopausal, glucocorti coid-induced, and male osteoporozis with high risk of fracture. The use of denosumab has increased in recent years. While new medications continue to be developed, the number of agents causing drug-induced vasculitis is expected to increase. It may be a good strategy to identify risk factors for vasculitis development and look for these factors before drug administration. Here, we present a rare complication of denosumab, urticarial vasculitis, after the first denosumab injection in an osteoporotic woman diagnosed with Cushing\"s syndrome.

Hipoparatiroidi (hipoPT) hipokalsemi ve eşlik eden düşük/ölçülemeyecek kadar düşük paratiro id hormon (PTH) düzeyleri ile karakterize ender bir hastalıktır (1). Hipoparatiroidi tanısı biyokimyasal olarak dü zeltilmiş kalsiyum veya iyonize kalsiyum düzeyi nin normalin altında olması ve eşlik eden uygun suz serum PTH düşüklüğü/ölçülemeyecek kadar düşük olması ile konur (1,2). Hipoparatiroidi prevalansı Kuzey Amerika’da 100,000 de 37, Avrupa’da 100,000 de 22 olarak rapor edilmiştir. Ülkemizdeki prevalansı bilinme mektedir. Hipoparatiroidi, renal yetmezlik, böbrek taşı, posterior subkapsüler katarakt, intraserebral kal sifikasyon riskini arttırmaktadır. Kardiyovasküler hastalık, kemik kırığı ve malinite riskini de art tırabileceği rapor edilmektedir. Kronik hipokal semi, hiperkalsiüri ve diğer komorbid sorunların mortaliteye etkisi açık değildir. Uzun dönemde hipoPT tedavisinde yetersizlik, akut ve kronik komplikasyonlar hastalığın morbiditesini etkile yen unsurlardır (1,2

Objectives In this study, we examined executive function (EF) abilities, behavioral and emotional (BE) issues, and overall quality of life (QoL) of adolescents with obesity and compared them with a control group and also aimed to investigate whether the presence of insulin resistance (IR) is associated with these problems. Methods This cross-sectional study included a sample of 50 adolescents aged 11–18 years with obesity and age- and gender-matched 50 normal weight adolescents who had attended and were treated at the pediatric outpatient clinic. Sociodemographic data were collected through personal interviews with the adolescents and their parents. Measurements of the height and weight, fasting blood glucose, and insulin levels of all adolescents were assessed. In addition, the participants and their parents completed the Kiddo-KINDL, the Strengths and Difficulties Questionnaire, and the Behavior Rating Inventory Scale from Executive Function. Results Of the 50 adolescents with obesity, 27 (54.0 %) were girls, and 23 (46.0 %) were boys, with a mean age of 14.06 ± 1.83 years. Adolescents with obesity have more EF deficiencies, BE difficulties, more problems in peer relationships and lower QoL scores than those without obesity. The QoL was worse in girls, adolescents with obesity, and those with IR. Adolescents with obesity and those with and without IR did not differ about EF deficiencies and BE problems. Conclusions Addressing these EF deficits and BE problems in interventions for adolescents who have difficulty adapting to lifestyle changes, an essential part of obesity treatment in clinical practice, may contribute to treatment success.

Thyroid-stimulating hormone (TSH) suppression treatment can induce signs and symptoms of hyperthyroidism and hypothyroidism due to inappropriate treatment or poor compliance to the treatment. The current study aimed to investigate TSH levels, frequency of being on target TSH, adherence to levothyroxine (LT4) suppression treatment in differentiated thyroid cancer (DTC) patients after surgery in a multicentric setting.This multicentric cross-sectional study was conducted at 21 medical centres from 12 cities in Turkey. DTC patients followed at least one year in the same center included in the study. Clinical data, serum TSH, free thyroxine (FT4), thyroglobulin (Tg) and anti-Tg levels were recorded during the most recent visit. Body mass index, systolic and diastolic blood pressures, pulse rate were measured. LT4 doses were recorded and doses per kilogram of bodyweight were calculated. Pill ingestion habits recorded and adherence to the therapy were evaluated using the Morisky Medication Adherence Scale and categorized as good, moderate or poor compliant based on their scores. Risk stratification forpredicting the disease persistance and/or reccurence was assessed using the American Joint Committee on Cancer-7th edition thyroid cancer staging calculator. TSH serum concentrations were classified as severe suppression (TSH lt; 0.01 mU/L), moderate suppression (TSH: 0.01-0.1 mU/L), mild suppression (TSHL 0.1-0.5 mU/L), euthyroid (TSH: 0.5-4 mU/L) and hypothyroid (TSH gt; 4 mU/L). TSH levels can also be classified as on being on target, under the target, or beyond over the target, according to the American Thyroid Association recommendations.A group of 1125 patients (F/M: 941/184, 50.7 ± 11.7 years) were included in the study. The mean LT4 daily dosage was 132.4 ± 39.6 mcg/day. TSH levels showed severe suppression in 99 (%8.8) patients, moderate suppression in 277 (%24.6) patients and mild suppression in 315 (%28) patients and euthyroid range in 332 (%29.5) patients and hypothyroid range in 97 (8.6%). TSH levels were in target in 29.2% of the patients 20.4% of the patients were undertreated, 50.4% overtreated. The daily LT4 dose and LT4 dose/kg were significantly higher in the severe suppression group (p lt; .001, p lt; .001). According to the Morisky scale, 564 patients (50.1%) were good compliant, 368 patients (32.7%) were moderate compliant, and 193 patients (17.1%) were noncompliant. Patients with poor compliance need a higher dose of LT4 compared to the good compliance group (p lt; .001). TSH levels of patients with good compliance were 0.67 ± 1.96 mU/L and TSH with poor compliance was 2.74 ± 7.47 mU/L (p lt; .001). TSH levels were similar in patients on fixed and alternating dosages.In 29.2% of the DTC patients, serum TSH levels were at target levels. Remaining of the study group have TSH levels under or over treatment range, exposing the patient to medication side effects. Majorty of the study group 82.8% have good or moderate adherence to LT4 therapy. Reaching TSH targets requires simplified and applicable guidelines and following the guideline recommendations.

Non-alcoholic fatty liver disease (NAFLD), based on the elevating obesity incidence, is one of the major health issue worldwide. Transition from NAFLD to non-alcoholic steatohepatitis (NASH) is driven by increased apoptosis and is relevant to higher morbidity rates. In regard to limited understanding on cholesterol mediated hepatocyte alterations in NALFD/NASH transition, we investigated endoplasmic reticulum (ER) stress and related apoptosis. Our findings suggest that cholesterol upregulates ER stress and enhances C/EBP homologous protein (CHOP) either in hypercholesterolemic rabbits or in hepatocytes treated with liposome-cholesterol complex. Mechanistically, cholesterol accumulation in hepatocytes activates IRE1/p38 branch of ER stress, stimulating CHOP levels. In liver tissues of cholesterol fed rabbits, α-tocopherol supplementation decreased IRE1/p38/CHOP activation and prevented NASH development. Thus, our study provides a critical role of hepatocyte cholesterol in inducing IRE1/p38/CHOP pathway and suggests novel candidates for therapeutic targets against NASH.

© 2022 Wiley-VCH GmbH.Testicular ischaemia reperfusion (I/R) injury results with serious dysfunctions in testis. This study aims to explore effects of soluble guanylate cyclase (sGC) stimulator Riociguat on experimental testicular I/R injury in rats. Twenty-one male rats were divided into three groups (Control, IR and IRR). The control group was not exposed to any application. Bilateral testis from IR and IRR animals were rotated 720° in opposite directions for 3 h to induce experimental testicular ischaemia. Animals in IR and IRR groups were subjected to 3 h of reperfusion. Isotonic and Riociguat were administered to the animals 30 min prior reperfusion by oral gavage. At the end of experiment, animals were sacrificed and tissue samples were used for analyses. Riociguat treatment significantly decreased tissue malondialdehyde and Luminol levels compared to the IR group (p < 0.05). The pathological changes, pro-apoptotic proteins (Bax, Caspase 3, and Caspase 9) and apoptotic index in the IR group were down regulated in Riociguat treated animals (p < 0.05). Riociguat treatment was also significantly increased anti-apoptotic Bcl-2 expression, but alleviated tissue injury via modulating pro-inflammatory cytokine IL-1β levels and significantly (p < 0.05) down-regulating NF-κB activity. Moreover, mTOR and ERK phosphorylation increased in IR group (p < 0.05), but Riociguat treatment reduced protein phosphorylation. Our experiment indicated that targeting sGC might support surgical interventions in testicular I/R injury by modulating oxidative stress, inflammation, and apoptotic protein expression levels, but more detailed studies are required to explore the protective activity of Riociguat and underlying mechanisms in testicular I/R injury.

Primary adrenal insufficiency; Primary hypothyroidism; Sphingosine-1-phosphate lyase Insuficiencia suprarrenal primaria; Hipotiroidismo primario; Esfingosina-1-fosfato liasa Insuficiència suprarenal primària; Hipotiroïdisme primari; Esfingosina-1-fosfat liasa Sphingosine-1-phosphate lyase (SGPL1) insufficiency syndrome (SPLIS) is an autosomal recessive multi-system disorder, which mainly incorporates steroid-resistant nephrotic syndrome and primary adrenal insufficiency. Other variable endocrine manifestations are described. In this study, we aimed to comprehensively annotate the endocrinopathies associated with pathogenic SGPL1 variants and assess for genotype–phenotype correlations by retrospectively reviewing the reports of endocrine disease within our patient cohort and all published cases in the wider literature up to February 2022. Glucocorticoid insufficiency in early childhood is the most common endocrine manifestation affecting 64% of the 50 patients reported with SPLIS, and a third of these individuals have additional mineralocorticoid deficiency. While most individuals also have nephrotic syndrome, SGPL1 variants also account for isolated adrenal insufficiency at presentation. Primary gonadal insufficiency, manifesting with microphallus and cryptorchidism, is reported in less than one-third of affected boys, all with concomitant adrenal disease. Mild primary hypothyroidism affects approximately a third of patients. There is paucity of data on the impact of SGPL1 deficiency on growth, and pubertal development, limited by the early and high mortality rate (approximately 50%). There is no clear genotype–phenotype correlation overall in the syndrome, with variable disease penetrance within individual kindreds. However, with regards to endocrine phenotype, the most prevalent disease variant p.R222Q (affecting 22%) is most consistently associated with isolated glucocorticoid deficiency.To conclude, SPLIS is associated with significant multiple endocrine disorders. While endocrinopathy in the syndrome generally presents in infancy, late-onset disease also occurs. Screening for these is therefore warranted both at diagnosis and through follow-up. This work was supported by the Medical Research Council (MRC) UK Clinical Academic Research Partner Grant (MR/T02402X/1, 2019 to R P), Barts and the London Charity (MGU0361, 2017 to L A M), Barts and the London Charity Research Fellow Grant (MGU0528 to R K), Medical Research Council (MRC) UK Clinical Research Training Fellowship Grant (MR/W015935/1 to RK), Government of Trinidad and Tobago Research Fellowship (to A M) and Wellcome Trust (209328/Z/17/Z to J C A).

In this systematic review, we highlight the differences between the male and female zebrafish brains to understand their differentiation and their use in studying sex-specific neurological diseases. Male and female brains display subtle differences at the cellular level which may be important in driving sex-specific signaling. Sex differences in the brain have been observed in humans as well as in non-human species. However, the molecular mechanisms of brain sex differentiation remain unclear. The classical model of brain sex differentiation suggests that the steroid hormones derived from the gonads are the primary determinants in establishing male and female neural networks. Recent studies indicate that the developing brain shows sex-specific differences in gene expression prior to gonadal hormone action. Hence, genetic differences may also be responsible for differentiating the brain into male and female types. Understanding the signaling mechanisms involved in brain sex differentiation could help further elucidate the sex-specific incidences of certain neurological diseases. The zebrafish model could be appropriate for enhancing our understanding of brain sex differentiation and the signaling involved in neurological diseases. Zebrafish brains show sex-specific differences at the hormonal level, and recent advances in RNA sequencing have highlighted critical sex-specific differences at the transcript level. The differences are also evident at the cellular and metabolite levels, which could be important in organizing sex-specific neuronal signaling. Furthermore, in addition to having one ortholog for 70% of the human gene, zebrafish also shares brain structural similarities with other higher eukaryotes, including mammals. Hence, deciphering brain sex differentiation in zebrafish will help further enhance the diagnostic and pharmacological intervention of neurological diseases.

Summary Denosumab leads to improvements in BMD levels and is a well-tolerated agent according to results of randomized controlled studies but results in real-life setting are important to evaluate drug adherence and real-life efciency. In this study, we present the results of 305 patients that were treated with denosumab in our clinic. Introduction The long-term efcacy of anti-osteoclastic drugs in treatment of osteoporosis is well known. Denosumab, a novel human monoclonal antibody, is an anti-osteoclastic agent that has been shown to lead to reductions in vertebral, nonvertebral, and hip fracture risk in randomized and observational studies. Real-life data of this agent is increasing. In this study, we presented our real-life data about the 2-year follow-up of patients under denosumab treatment. Methods Osteoporotic patients who were treated with at least one denosumab injection between 2014 and 2020 years were included. Clinical and demographic data, bone turnover markers, and radiological reports (bone mineral densitometry (BMD), vertebral x-ray) were obtained from patient fles retrospectively. Results A total of 305 patients (f/m: 275/30, 68.1±11.05 years) were included. The median injection number was 4 (1–10). Two hundred seventy-three patients (89.8%) were persistent on treatment at the 12th month; 175 patients (57.3%) were persistent at 24th month. Sixty-eight patients (22%) were not using denosumab anymore, 55 of the patients were not continuing by doctor desicion and 13 were not continuing due to patient-related causes. Median BMD levels signifcantly increased from 0.809 (0.2–1.601, IQR: 0.136) to 0.861 (0.517–1.607, IQR: 0.14) in L1–L4 and from 0.702 (0.349–0.997, IQR: 0.125) to 0.745 (0.508–1.008, IQR: 0.137) in femur area at the 24th month of treatment. An improvement of 8.04% in L1–L4 BMD and 4.5% in femur neck BMD levels at the 24th month of treatment was observed. There was a signifcant decrease in bone turnover markers at the 24th month of treatment. Conclusion In our group of patients under denosumab treatment, 53% of persistence was found at 24 months and associated with improvement in BMD levels without any signifcant side efects except one case with urticarial reaction. Denosumab leads to improvements in BMD levels and is a well-tolerated agent in a real-life setting comparable to results of randomized controlled studies in patients with diferent comorbidities.

Vitamin A is the first defined vitamin and is also known as an anti-inflammatory micronutrient. Although the primary biological function is preservation of epithelial tissue integrity, vision and growth, vitamin A also plays a role in immune system regulation. It is known that susceptibility to infections increases in developing countries due to vitamin A deficiency. Therefore, the purpose of this review is to evaluate the role of vitamin A on the immune system in line with current studies. In this review, we focused on the immunobiological effects of vitamin A and its precursors. Vitamin A refers to retinoids and carotenoids, but both function in the body through the most active form, all trans retinoic acid. All trans retinoic acid has the highest affinity of nuclear retinoic acid receptor. Reports from in-vivo and in-vitro studies shown that the formation of retinoic acid/retinoic acid receptor complex is important in the generation of innate and adaptive immune cell response. In addition to immune cell response, vitamin A also plays an important role in mucus secretion, morphological formation and functional maturation of epithelial cells. In this way, vitamin A appears to contribute to immune development by regulating immune cell response and providing mechanistic defense. Vitamin A has received particular attention in recent years as the vitamin have been shown to have a crucial effect on the immune response. Although more randomized controlled studies are needed, data from observational human studies have shown that vitamin A is associated with infectious, inflammatory, allergic diseases and cancers. ?? 2021 Published by Elsevier Masson SAS on behalf of Soci??t?? francophone nutrition clinique et m??tabolisme (SFNCM).

© 2022, Acta Endocrinologica Foundation. All rights reserved.Objectives. We aimed to determine lipodystrophy frequency according to insulin treatment regimen and insulin injection frequency in type 2 diabetic patients. Methods. A total of 345 type 2 diabetic patients under insulin treatment for at least one year were included in this cross-sectional study. Patients were examined for presence of lipodystrophy, insulin injection frequency and dosage. Lipodystrophy was evaluated with visual inspection and palpation of all injection sites. Patients were evaluated into three categories according to daily insulin dose requirement: Group 1= Standard-dose insulin users 0.6 U/ kg/day; Group 2= Medium-dose insulin users 0.61-1.9 U/kg/ day, Group 3= High-dose insulin users ≥2 U/kg/day. Results. Lipodystrophy was seen in 28% of the patients. Lipodystrophy was significantly higher in group 3. There was no significant difference between the groups in terms of lipodystrophy size. Duration of insulin treatment, daily total insulin dose, daily insulin dose per weight and number of daily insulin injections were significantly higher in the group with lipodystrophy. Daily injection number of long-acting, rapidly-acting analog and total insulin injections were significantly higher in group 3 than group 1 and 2. Number of daily insulin injections and lipodystrophy frequency were significantly higher in basal-bolus insulin user group. Multivariate analysis showed that insulin injection frequency is the independent risk factor for lipodystrophy. Conclusion. Lipodystrophy is still a clinical problem in patients with high-dose insulin requirement and frequent insulin injections. Reducing daily insulin requirement and daily number of injections should be given priority in the management of patients to prevent the development of lipodystrophy.

Introduction: the coronavirus disease 2019 (COVID-19) pandemic led to a lockdown period. Confinement periods have been related to unhealthy lifestyle behaviors. Our study aimed to determine weight change, changes in eating and exercise habits, the presence of depression and anxiety, and diabetes mellitus (DM) status in a cohort of patients with obesity. Methods: the study was undertaken in nine centers of Collaborative Obesity Management (COM) of the European Association for the Study of Obesity (EASO) in Turkey. An e-survey about weight change, eating habits, physical activity status, DM status, depression, and anxiety was completed by patients. The International Physical Activity Questionnaire (IPAQ) score was used to determine physical activity in terms of metabolic equivalents (METs). A healthy nutrition coefficient was calculated from the different categories of food consumption. The Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7) Questionnaire were used for determining depression and anxiety, respectively. Results: four hundred twenty-two patients (age 45 +/- 12.7 years, W/M = 350/72) were included. The healthy nutrition coefficient before the pandemic was 38.9 +/- 6.2 and decreased to 38.1 +/- 6.4 during the pandemic (p < 0.001). Two hundred twenty-nine (54.8%) patients gained weight, 54 (12.9%) were weight neutral, and 135 (32.3%) lost weight. Patients in the weight loss group had higher MET scores and higher healthy nutrition coefficients compared with the weight gain and weight-neutral groups (p < 0.001). The PHQ and GAD scores were not different between the groups. Percent weight loss was related to healthy nutrition coefficient (CI: 0.884 [0.821-0.951], p = 0.001) and MET categories (CI: 0.408 [0.222-0.748], p = 0.004). One hundred seventy patients had DM. Considering glycemic control, only 12 (8.4%) had fasting blood glucose, NA

Obez bireylerde aterosklerozdaki en önemli erken değişiklik endotel disfonksiyonudur. Sistemik inflamatuvar belirteçlerin yükselmiş serum seviyeleri endotel disfonksiyonu ile ilişkili bulunmuştur. Endocan (Endotel hücre spesifik molekülü-1, ESM-1)'ın inflamatuar bir belirteç olduğu ve endotel disfonksiyonu patofizyolojisinde rol oynadığı bildirilmiştir. Bu çalışmada, serum endocan düzeylerinin obez bireylerdeki endotel disfonksiyonunun varlığı ve şiddeti ile ilişkisinin olup olmadığını ve sICAM-1, adiponektin, inflamasyon markerı olan hsCRP (yüksek duyarlıklı c-reaktif protein) düzeyleri ve karotis intima media kalınlığı (CIMT) ile olan ilişkisini araştırmayı amaçladık. Vücut Kitle Endeksi (VKİ) ≥30kg/m² olan 76 obez kadınla, VKİ˂25kg / m² olan 53 kontrol grubu kadında, serum endocan, sICAM-1, adiponektin, hsCRP düzeyleri ve CIMT'ı değerlendirdik. Obez kadınlarda kontrol grubuna göre sICAM-1 (p=0,01), hsCRP (p˂0,001), CIMT (p˂0,001) düzeyleri anlamlı olarak daha yüksek bulunurken, adiponektin (p=0,006) düzeyleri kontrol grubuna göre obez kadınlarda anlamlı olarak daha düşüktü. Serum endocan düzeyleri obez (470.5± 171.3 pg/ml) ve kontrol (471.9± 146.3 pg/ml) gruplarında benzer saptandı (p=0,732). Serum endocan düzeyleri ile endotel disfonksiyon belirteçlerinden olan hsCRP (r=-0,021), ICAM-1 (r=-0,054), adiponektin (r=0,113) ve CIMT (r=-0,060) arasında korelasyon saptanmadı. Sonuç olarak bu çalışmada, endocanın obezite ile ilişkili endotel disfonksiyonu için iyi bir belirteç olmadığı bulunmuştur. Obezitedeki inflamatuar süreçlerin düzenlenmesinde endocanın rolünü araştıran başka çalışmalara ihtiyaç vardır. Endothelial dysfunction is one of the most important early change of atherosclerosis in obese individuals. High levels of systemic inflammatory markers are associated with endothelial dysfunction. Endocan (Endothelial cell spesific molecule-1, ESM-1), is a potential inflamatuary marker and has been reported to play a role in the pathophysiology of endotelial dysfunction. We aimed to assess whether serum endocan levels are correlated with the presence and severity of endothelial dysfunction and relationships with sICAM-1, adiponectin, marker of inflamation: high sensitivity c-reaktif protein (hsCRP) levels and CIMT in obese subjects. We evaluated serum endocan, sICAM-1, adiponektin, hsCRP levels and CIMT in 76 obese women (BMI˃30kg/m²) and 53 controls (BMI˂25kg/m²). sICAM-1 (p=0,01), hsCRP (p˂0,001), CIMT (p˂0,001) were significantly higher and adiponectin (p=0,006) was significanly lower in obese women than in controls. Serum endocan levels were similarly in obese (470.5± 171.3 pg/ml) and control (471.9± 146.3 pg/ml) groups (p=0,732). Serum endocan levels were not correlated with markers of endothelial dysfunction hsCRP (r=-0,021), ICAM-1 (r=-0,054), adiponectin (r=0,113) and CIMT (r=-0,060) in obesity. In conclusia we found that endocan is not a good marker of endothelial dysfunction related with obesity. Other studies are necessary in order to evaluate the role of endocan in the regulation of inflammatory processess in obesity. 112

Adrenal İnsidentalomalı Hastaların Demografik Özellikleri ve İnsülin Direncinin DeğerlendirilmesiGiriş ve amaç: Adrenal insidentalomalar; adrenal bezde herhangi bir hastalık kuşkusu yokken görüntüleme yöntemleri veya abdominal laparotomide tesadüfen saptanan kitlelerdir. Abdominal ultrasonografinin ve BT?nin kullanımının artması ile adrenal insidentalomaların tespit edilme sıklığıda artmıştır. Bu çalışmamızda Dicle Üniversitesi Endokrinoloji Kliniği?nde takip edilen hastaları retrospektif olarak inceleyip, bu hastalarda diyabet sıklığı ve insülin direncini araştırmayı amaçladık.Materyal-metod: Bu çalışmaya 2007-2013 yılları arasında Dicle Üniversitesi Tıp Fakültesi Endokrinoloji Anabilim Dalı?na başvuran 78 hasta ( 53 kadın; 25 erkek) dahil edildi. Hasta dosyalarından hastalara ait fizik muayene, USG, BT sonuçları kaydedildi. Serum kortizolü, idrar metanefrini, idrar normetanefrini, idrar VMA, serum aldosteronu ve serum renin değerleri kaydedildi. Açlık kan şekeri ve insülin değerleri mevcut olan hastaların HOMA-IR formülüne göre insülin direnci hesaplandı, yaş ve BMI farklı olmayan kontrol grubundaki sağlıklı bireylerle karşılaştırıldı. Bulgular: Hastaların yaş ortalaması 48,6±14,9 idi. Tespit edilen kitlelerin lokalizasyonu açısından anlamlı farklılık saptanmadı. Hastaların vücut kitle indeksi 28,545±5,827 idi. HOMA-IR ortalaması 6,555±11,232 olarak saptandı. 45 hastada (%57,7) non-fonksiyonel adenom, 10 hastada (%12,8) subklinik cushing, 11 hastada (%14,1) feokromasitoma, 3 hastada (%3,8) adrenal karsinom, 2 hastada (%2,6) hiperaldosteronizm, 2 hastada (%2,6) ganglionörom, 1 hastada (%1,3) myelolipom, 1 hastada adrenal adenom, 1 hastada adrenal kist, 1 hastada schwannom ve 1 hastada da küçük yuvarlak hücreli tümör tespit edildi. Adrenal insidentalomalı hastalarda kontrol grubuna göre insülin direnci daha fazla tespit edildi (p=0,004). Adrenal insidentalomalı hastaların 21?inde (%26,9) kontrol grubunda ise 4 hastada (%5,1) diyabet saptanmıştı. Bu karşılaştırmada önceden bilinen diyabeti olan hastalar çalışma dışında bırakıldığında da insülin direnci adrenal insidentalomalı hastalarda daha yüksek bulundu (p=0,000). Non-fonksiyonel adrenal insidentalomalarda da kontrol grubuna göre daha yüksek insülin direnci tespit edildi (p=0,001).Sonuçlar: Adrenal insidentalomalar arasında non-fonksiyonel adrenal kitleler daha fazla görülmektedir. Adrenal insidentalomalı hastalarda diyabet sıklığı artmıştır. Diyabetli olan hastaların dahil edildiği ve hariç tutulduğu her iki durumda da insülin direnci varlığını sürdürmüştür. Demographical Characteristics of Patients With Adrenal Incidentaloma and Evaluate İnsulin ResistanceIntroduction and Purpose: Adrenal incidentaloma are bulks which are stated incidentally by imagining methods or in abdominal laparotomy when there is no suspicion of any disease in adrenal gland. With increase in using abdominal ultrasonography and BT, the frequency of determining adrenal incidentaloma also increases. In this study, we aim to examine patients that are followed in Dicle University Clinic of Endocrinology retrospectively and search the diabetes frequency and insulin resistance in those patients. Material-method: 78 patients, who applied to Dicle University Medical Faculty Department of Endocrinology between years of 2007-2011 (53 female ? 25 male) were included in this study. Results of physical examination, USG and BT were recorded from patients? files. Values of serum cortisol, urine metanephrine, urine normetanephrine, urine VMA, serum aldosterone and serum renin were recorded. Insulin resistance of patients, of which preprandial blood glucose and insulin values were available, were calculated in accordance with HOMA-IR Formula, and were compared with healthy individuals in control group of which ages and BMI are not different. Findings: The average of age of patients were 48,6±14,9. There is no significant difference was stated in terms of localizations of stated bulks. Body Mass Index of patients were 28,545±5,827. Their average of HOMA-IR were stated as 6,555±11,232. There are non-functional adenoma were stated in 45 patients (57,7%), subclinical cushing was stated in 10 patients (12,8%), pheochromocytoma was stated in 11 patients ( 14,1%), adrenal carcinoma was stated in 3 patients (3,8%), hyperaldosteronism was stated in 2 patients (2,6%), ganglioneuroma was stated in 2 patients (2,6%), myelolipoma was stated in 1 patient (1,3%), adrenal adenoma was stated in 1 patient, adrenal cyst was stated in 1 patient schwannoma was stated in 1 patient and neoplasia with small circular cells was stated in 1 patients. Insulin resistance was stated as more in patients with adrenal incidentaloma as to control group (p=0,004). Diabetes Mellitus was stated in 21 (26,9%) patients with adrenal incidentaloma and in 4 patients (5,1%) in control group. In this comparison, when patients who have diabetes mellitus and that is known before, were left out of the study, insulin resistance was stated in patients with adrenal incidentaloma more than control group (p=0,000). Higher insulin resistance was stated in patients with non-functional adrenal incidentaloma as to control group (p=0,001). Results: Non-functional adrenal bulks are seen more in adrenal incidentalomas. Frequency of diabetes mellitus increases in patients with adrenal incidentaloma. Insulin resistance subsists in both conditions whether patients with diabetes mellitus are included or not. 67

Background. Fine needle aspiration biopsy (FNAB) is an important tool in the diagnosis of thyroid nodules. Aim. Our aim was to investigate the malignancy criteria in thyroid nodules by gray-scale ultrasonography (US) and duplex Doppler ultrasonography (DDUS), and their usefulness in reducing the number of unnecessary FNAB’s. Study design. This was a prospective observational study. Subjects and methods. 181 benign and 18 malignant thyroid nodules were evaluated by US and DDUS before FNAB or thyroidectomy. US was used to note size, shape, internal structure, nodule echogenicity, marginal properties, peripheral hypoechogenic halo, and microcalcifications. DDUS studies were used to evaluate the maximum and minimum flow velocity (V max and V min ), systolic/diastolic flow velocity ratio (S/D), pulsatility index (PI), resistive index (RI), acceleration time (AT) and acceleration value. Results. Contour irregularity, size and presence of microcalcifications (p

Bu çalışmada hipotalamik obezite gelişiminde leptin, solubl leptin reseptörü (sOb-R), rezistin ve insülin sekresyon dinamikleri değerlendirilmiştir.Çalışmaya hipotalamohipofizer tümörü olan hastalar alınmıştır. İlk grupta obez-overweight (Hipotalamik obez; HOB, n=23) , ikinci grupta ise obez olmayan çocuk hastalar (Hipotalamik non-obez; HNOB, n=16) bulunmaktaydı. Ekzojen (basit) obez-overweight hastalar kontrol grubu olarak alınmıştır (Obez-overweight; OB, n=22). OGTT'de 0 ve 120. dakikadaki kan şekeri ve insülin değerleri, bazal leptin, solubl leptin reseptörü, rezistin düzeyleri ve homeostasis model assessment (HOMA) indeksleri için gruplar arası karşılaştırmalar yapılmıştır.Gruplar arasında yaş, cinsiyet, pubertal durum açısından fark bulunmamaktaydı. HOB ve OB gruplarında BMI z-skoru medyan ve 25-75 persentil çeyreklerarası arası değerleri birbirine benzerdi (sırasıyla 2.0 (1.5?2.1) ve 2.1 (1.8?2.3)). BMI `e göre düzeltilmiş leptin düzeyleri ve total leptin/sOb-R (FLI) oranları HOB grubunda HNOB ve OB grubuna göre anlamlı olarak yüksekti. Bu bulgular HOB grubunda leptin direncinin diğer gruplara göre daha belirgin olduğunu göstermekteydi (sırasıyla HOB, HNOB ve OB gruplarında leptin/BMI, 4.0 (1.6?5.2), 1.5 (0.8?3.1), ve 2.5 (1.8?3.5); FLI, 2.0 (0.8?3.5), 0.6 (0.3?1.2), ve 1.5 (1?2.3)).Her 3 grubun serum rezistin düzeyleri birbirine benzerdi (HOB, HNOB, ve OB gruplarında sırasıyla (2.6 (1.9?3.1), 2.8(1.7?3.4), ve 3.0 (2.2?3.5) ng/ml)OB grubunda bazal kan şekeri, bazal ve ikinci saat insülin değerleri ve HOMA indeksi HOB ve HNOB grubuna göre daha yüksekti. Bu durum OB grubunda insülin direncinin daha belirgin olduğunu göstermektedir. Ancak OGTT'de 0 ve 120 dakika insülinlerindeki en belirgin artış HOB grubunda saptandı (p