IntroductionThe primary objective of this study is to report the results of an online questionnaire and the in-person discussion sessions of physicians specializing in diabetes care in which their opinions about current diabetes management was obtained.MethodsThe Diabetes Innovation Summit 2023 drew attendance from a diverse group of specialized physicians from multiple countries. A comprehensive literature review was conducted to examine the technologies and medical needs associated with diabetes management. Using the results of the review, a questionnaire was developed by three experts from the steering committee to solicit feedback from specialized physicians. The online survey was made accessible between 10th December 2022 and 10th January 2023. Following the online survey, six structured in-person discussion sessions were conducted with specialized physicians from the Middle East, Central-Eastern Europe, and North Africa regions.ResultsThe study revealed that about 59% of survey requests were answered, with many participants being pediatric endocrinologists from North Africa. Around 60% of diabetes patients followed Multiple Daily Injections (MDI) according to specialized physicians. Among MDI users, 62% employed Blood Glucose Monitors (BGM), 31% used intermittent-scanning Continuous Glucose Monitors (isCGM), and 23% used CGM. In North Africa, nearly 90% of patients used MDI due to financial constraints. While physicians focused on both Time in Range (TIR) and HbA1c for MDI-treated patients, satisfaction with TIR achieved was expressed by 31%, while 74·1% believed Real-Time CGM (rtCGM) was effective. Concerns arose about potentially misleading HbA1c results and the relatively low patient achievement of target TIR despite CGM usage. The Smart MDI System was seen favorably compared to other applications. The system’s affordability was a significant barrier, particularly in the Middle East and Africa.ConclusionThe present study highlights that physicians are generally supportive of utilizing new technology. The questionnaires and the open discussion revealed the expectation that the Smart MDI technology provides better control, primarily by identifying missed boluses, while expressing concerns on the use of the technology by teenagers and children, who might forget the device and be reluctant to use in public, and by the older population, who might be challenged by the technology.

Hyperinsulinemic hypoglycemia is a rare disease, and only two cases complicated with pregnancy were published previously when our patient became pregnant. We introduce a successful management of a pregnancy in a patient with endogenous hyperinsulinemic hypoglycemia, a condition also known as non-insulinoma pancreatogenous hypoglycemia syndrome or formerly as nesidioblastosis. A 29-year-old female patient was treated with endogenous hyperinsulinemic hypoglycemia since the age of 4 months, taking daily 3 × 75 mg diazoxide, which adds up to 225 mg per day. Adequate glycemic control could be achieved with this therapy. Genetic testing and various imaging examinations were carried out earlier to specify the disease and to exclude focal forms. The patient came to the clinic with a positive pregnancy test and consequential hypoglycemic episodes. Hospital admission was needed to correct the metabolic condition. Although the patient was informed about the potential risks, she decided to carry out the pregnancy. According to the quite limited literature, somatostatin analogs are the only therapy used previously during pregnancy in hyperinsulinemic hypoglycemic patients. One publication reported normal pregnancy outcomes, but in another case, restricted fetal growth was observed. In our case, we stopped diazoxide and parallelly introduced short-acting somatostatin analog octreotide in the therapy, and further dietetic changes were proposed. In addition to daily regular self-blood glucose monitoring, regular gynecological controls were carried out monthly, and healthy fetal development was confirmed. The patient gave birth to her first child, a well-developed female neonate, in the 38th week, by a cesarean section.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

PurposeMultiple endocrine neoplasia type 1 is a rare tumor syndrome caused by germline mutations of MEN1 gene. Phenotype varies widely, and no definitive correlation with the genotype has been observed. Mutation-negative patients with MEN1-associated tumors represent phenocopies. By comparing mutation-positive and mutation-negative patients, we aimed to identify phenotype features predictive for a positive genetic test and to evaluate the role of MEN1 mutations in phenotype modulation.MethodsMutation screeening of MEN1 gene by Sanger sequencing and assessment of clinical data of 189 consecutively enrolled probands and relatives were performed at our national and European Reference Center. Multiple ligation probe amplification analysis of MEN1 gene and Sanger sequencing of CDKN1B were carried out in clinically suspicious but MEN1-negative cases.ResultsTwenty-seven probands and twenty family members carried MEN1 mutations. Five mutations have not been described earlier. Pronouncedly high number of phenocopies (>70%) was observed. Clinical suspicion of MEN1 syndrome emerged at significantly earlier age in MEN1-positive compared to MEN1-negative probands. Gastroenteropancreatic neuroendocrine tumors developed significantly earlier and more frequently in carriers compared to non-carriers. Probands with high-impact (frameshift, nonsense, large deletions) mutations, predicted to affect menin function significantly, developed GEP-NETs more frequently compared to low-impact (inframe and missense) mutation carriers.ConclusionsMEN1 phenocopy is common and represents a significant confounder for the genetic testing. GEP-NET under 30 years best predicted a MEN1 mutation. The present study thus confirmed a previous proposal and suggested that GEP-NET under 30 years should be considered as a part of the indication criteria for MEN1 mutational analysis.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Glucocorticoid resistance is a rare, sporadic or familial condition caused by mutation of the gene encoding the glucocorticoid receptor (GR). Clinically it is characterized by symptoms developed due to local, tissue-specific, or generalized partial insensitivity to glucocorticoids.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Inherited, germline mutations of menin-coding MEN1 gene cause multiple endocrine neoplasia type 1 (MEN1), while somatic MEN1 mutations are the sole main driver mutations in sporadic primary hyperparathyroidism (PHPT), suggesting that menin deficiency has a central role in the pathogenesis of PHPT. MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene expression. Our aim was to investigate both the role of MEN1 mutations and potentially MEN1-targeting miRNAs as the underlying cause of menin deficiency in MEN1-associated and sporadic PHPT tissues. Fifty six PHPT tissues, including 16 MEN1-associated tissues, were evaluated. Diagnosis of MEN1 syndrome was based on identification of germline MEN1 mutations. In silico target prediction was used to identify miRNAs potentially targeting MEN1. Menin expression was determined by immunohistochemistry while expression of miRNAs was analyzed by quantitative real-time PCR. Sporadic PHPT tissues were subjected to somatic MEN1 mutation analysis as well. Lack of nuclear menin was identified in all MEN1-associated and in 28% of sporadic PHPT tissues. Somatic MEN1 mutations were found in 25% of sporadic PHPTs. The sensitivity and specificity of menin immunohistochemistry to detect a MEN1 mutation were 86 and 87%, respectively. Expression levels of hsa-miR-24 and hsa-miR-28 were higher in sporadic compared to MEN1-associated PHPT tissues; however, no difference in miRNA levels occurred between menin-positive and menin-negative PHPT tissues. Menin deficiency is the consequence of a MEN1 mutation in most menin-negative PHPT tissues. Elevated expression of hsa-miR-24 and hsa-miR-28 mark the first epigenetic changes observed between sporadic and MEN1-associated PHPT.

BACKGROUND:Tissue-specific dipeptidyl-peptidase 4 (DPP4) dysregulation has been described in adults with diabetes mellitus. The DPP4 -incretin system has not been studied in foetal life. In this study, DPP4 activity and glucagon-like peptide-1 (GLP-1) levels were assessed in cord blood of neonates born to women with gestational diabetes mellitus (GDM) and nondiabetic controls.MATERIAL AND METHODS:This study has been conducted in two Hungarian and one Austrian centres.PATIENTS:A total of 568 pregnant women were enrolled in the study after their OGTT between the 24th and 28th gestational week. Cord blood samplings with DPP4 activity and GLP-1 level measurements were possible in 270 (DPP4: 159 control, 111 GDM) and 112 (GLP-1: 72 control, 40 GDM) cases. OGTT (24-28th gestational week) and cord blood sampling at delivery were performed. Cord serum DPP4 activity was determined in a continuous monitoring microplate-based kinetic assay, and cord plasma GLP-1 was measured using a fluorescence ELISA method.RESULTS:Cord serum DPP4 activity was lower in GDM [mean (95% CI): 28.07 U/L (26.32-29.82 U/L)] than in controls [31.61 U/L (29.93-33.29 U/L), MWU P = 0.0015]. Cord plasma active GLP-1 levels were close to the lower detection limit and were not altered in GDM (control: mean = 3.43 pM, 95% CI: 3.04-3.82 pM, GDM: mean = 3.61 pM, 95% CI: 2.96-4.28 pM - MWU test P = 0.6).CONCLUSIONS:Decreased cord serum DPP4 activity in gestational diabetes mellitus might be the result of an adaptive foetal response or an early dysregulation in the entero-insular axis with consequences beyond the incretin system. Cord plasma GLP-1 levels may reflect the missing oral intake with a limited glucose sensing of L cells via the circulation in foetal life.

INTRODUCTIONLaboratory diagnosis of pheochromocytoma-paraganglioma syndrome has been markedly improved during the past two decades.AIMRetrospective assessment of diagnostic utility of urinary catecholamines and their metabolites as well as serum chromogranin A in 155 patients diagnosed at the 2nd Department of Medicine, Semmelweis University.METHODUrinary catecholamines and metabolites were measured using high-performance liquid chromatography with electrochemical detection in 155 patients with pheochromocytoma-paraganglioma (of whom 28.4% had hereditary background) and in 170 non-pheochromocytoma patients used as controls. Serum chromogranin A was measured by immunoradiometry.RESULTSSensitivity (93.2%) and specificity (87.0%) of urinary fractionated metanephrines were higher than those of urinary catecholamines (90.9% vs. 85.7%, respectively) and serum chromogranin A (88.7% and 77.5%, respectively). Urinary normetanephrine and serum chromogranin A correlated positively with tumor size (r = 0.552, p<0.0001 and r = 0.618, p<0.0001, respectively).CONCLUSIONSThese data confirm the diagnostic utility of urinary catecholamines and their metabolites. Urinary normetanephrine and serum chromogranin A may help to estimate tumour mass and probably tumour progression.

The authors present a case of a 42-year-old male patient, who was referred for evaluation for tachycardia. Detailed studies revealed Brugada syndrome and hypokalaemia due to primary aldosteronism. With this case report the authors draw attention to the risk of malignant ventricular tachycardia in a patient with low potassium level, especially in case of coexisting Brugada syndrome.

AbstractIdentification of ghrelin started with the discovery of growth hormone secretagogues, continued with the description of ghrelin receptors and ended with the elucidation of the chemical structure of ghrelin. However, several issues concerning the role of ghrelin in physiological and pathophysiological processes are still under investigation. Most of the ghrelin produced in the body is secreted in the stomach, but it is also expressed in the hypothalamus, pituitary, pancreas, intestine, kidney, heart and gonads. Ghrelin stimulates growth hormone secretion via growth hormone secretagogue receptors. Ghrelin secretion in the stomach depends on both acute and chronic changes in nutritional status and energy balance. Current data support the hypothesis that the stomach, in addition to its important role in digestion, not only influences pituitary hormone secretion but, via ghrelin production, it also sends orexigenic (appetite increasing) signals to hypothalamic nuclei involved in the regulation of energy homeostasis. In addition to these main effects, ghrelin influences insulin secretion and glucose metabolism and it may exert potentially important effects on cardiovascular and gastrointestinal functions. Because of its effects on a large number of physiological functions, ghrelin may be involved in the pathomechanism of several human disorders, including disturbances of appetite, energy homeostasis and glucose metabolism. Further research might lead to a better understanding of the pathophysiology of ghrelin and might provide more effective therapy for the above disorders. Copyright © 2008 John Wiley & Sons, Ltd.

BACKGROUND: Little is known about the pathophysiology of ghrelin secretion in growth hormone-deficient adults treated with growth hormone, and the relationship between plasma ghrelin and hyperinsulinemia induced by an oral glucose load has not been investigated in these patients. OBJECTIVE: In the present study we examined the relationship between plasma ghrelin, insulin, C-peptide and leptin after an oral glucose load in growth hormone-deficient adults receiving treatment with growth hormone. METHODS: Plasma ghrelin, leptin, insulin, C-peptide and blood glucose were measured before and then at 30, 60, 90 and 120 min after the ingestion of glucose (75 g orally) in 20 growth hormone-deficient adults (12 women and 8 men), who had been treated with growth hormone for 7.2 ± 1.3 years (mean ± SE). Plasma ghrelin was also determined before and after the glucose load in 10 age-and weight-matched healthy persons (5 women and 5 men). RESULTS: The oral glucose load induced a similar percent suppression of plasma ghrelin in the growth hormone-deficient patients and in the healthy persons. In both groups plasma ghrelin decreased significantly 30 min after the glucose load and remained suppressed throughout the test period. In the patients plasma insulin (baseline, 15.9 ± 3.9 µIU/ml) and C-peptide (baseline, 2.5 ± 0.3 ng/ml) showed opposite changes with peak responses at 30 min (insulin, 109.5 ± 15.6 µIU/ml) or 60 min (C-peptide, 10.3 ± 1.1 ng/ml). In these patients, post-glucose, but not baseline plasma ghrelin levels correlated negatively with plasma insulin, C-peptide and blood glucose levels, whereas baseline plasma ghrelin correlated inversely with baseline plasma leptin. CONCLUSIONS: The similar suppression of plasma ghrelin in growth hormone-deficient patients treated with growth hormone and in healthy persons after an oral glucose load argues against disturbed regulation of ghrelin secretion in these patients. The correlations between post-glucose plasma ghrelin, insulin and blood glucose support the existence of a previously proposed link between hyperinsulinemia (or increased blood glucose) and suppression of ghrelin levels.

Objective The transcription factor nuclear factor-kappaB (NF-kappa B) has been implicated in cardiomyocyte hypertrophy in vitro as well as in vivo; however, it is unknown if activation of NF-kappa B plays a mandatory role in the hypertrophic process. Here we characterize the importance of NF-kappa B signaling in moderate and severe left ventricular (LV) hypertrophy in rats with chronic pressure overload induced by angiotensin II (Ang II) infusion.Methods and results Electrophoretic mobility shift assay analysis revealed that Ang 11 infusion (2.5 mu g/kg per min) for 6 days increased LV NF-kappa B/DNA-binding activity in a biphasic manner in Sprague-Dawley rats. Pyrrolidine dithiocarbamate (PDTC) (1100 mg/kg per day), an NF-kappa B inhibitor, abolished Ang U-induced NF-kappa B activation and concomitant increase in tumor necrosis factor-alpha gene expression, while activator protein-1/DNA binding was not affected. Inhibition of NF-kappa B signaling for 6 days significantly attenuated Ang II-induced increases in LV/body weight ratio, LV mean wall thickness and cardiomyocyte cross-sectional area, without compromising LV systolic function. Moreover, PDTC abolished Ang II-induced cardiomyocyte apoptosis and interstitial fibrosis, and attenuated the gene expression of type I collagen. In contrast, a moderate LV hypertrophy induced by Ang II at a lower dose (0.5 mu g/kg per min) was not associated with a significant activation of NF-kappa B, and PDTC treatment had no effect on the hypertrophic indices.Conclusion Our in-vivo data indicate a critical role of NF-kappa B signaling in the advanced stage of the remodeling process, whereas development of moderate LV hypertrophy is not dependent on NF-kappa B activation.

Chronic pancreatitis is an inflammatory, usually painful disease characterized by progressive fibrosis and the loss of exocrine and endocrine functions. Pain influences the quality of life of patients and may lead to inability to work and frequent hospitalisation. The pathogenesis of pain in chronic pancreatitis is still unclear. Several different mechanisms of pain have been proposed, but pain in chronic pancreatitis is most probably multifactorial. Pain management in chronic pancreatitis is difficult. This is due to the multifactorial origin, there are no standardized methods to quantify pain and patients are often addicted to alcohol in chronic pancreatitis. This review summarises the different hypotheses of pain and the possibilities of pain management in chronic pancreatitis.