Glucagon Test Research Articles

Neonatal Hypo-Ketotic Hypoglycemia Secondary to Transient Hyperinsulinism: Diazoxide Responsiveness and Experience With Fasting Test After Treatment Withdrawal

Introduction:: Transient neonatal hyperinsulinism (TNH) is frequently reported in neonates with stress factors (intrauterine growth restriction (IUGR), large for gestational age (LGA), perinatal asphyxia, infants of diabetic mother, etc.). Early recognition and treatment are prioritary to avoid neurological morbidity. Objective: Clinical, molecular characterization and treatment response in neonates with hypoglycemia due to transient hyperinsulinism admitted to a tertiary hospital Neonatal Unit from January 2015 to August 2020. Materials and Methods: Prospective cohort study. Newborns older than 7 days of age, with diagnostic criteria of hyperinsulinism: non ketotic hypoglycemia with detectable insulin, low free fatty acids, glucose infusion rate > 10mg/kg/min, and positive response to glucagon test, were recruited. Results: Out of 5374 patients admitted, 46 (0.85%) presented hypoglycemia secondary to TNH (57% males and 43% females). 78% were delivered by Cesarean section, 59% were European, 17% Latino-Americans, 11% Asians, 9% Africans, and 4% Arabs. 78% were preterm newborns (median 33 weeks gestational age), 70% had birth weights or heights <-1.6 SDS (medians: -1.8 SDS and -2 SDS, respectively). Median age at diagnosis was 22 days (IQE 10–29 days), and feeding was exclusively enteral. Median blood glucose at diagnosis was 37mg/dl (IQE 31-44mg/dl), median insulin: 3mu/ml, median ketonemia: 0.2mmol/L, GH: 15 ng/ml, Cortisol: 16 ug/dl and AAL: 75mg/dl. 90% received diazoxide (dose ranged between 5-10mg/kg/day), presenting as most prevalent side effects hypertrichosis (80%) and edema (13%). Diazoxide median treatment duration was 83 days (IQE 41–110). Response was positive in 100%, with fasting tests response yielding a glycemia > 60mg / dl after 10 hours of fasting post treatment withdrawal. Molecular analysis was carried out with help of a custom NGS panel (MonDIAB.V3; 385 genes) in 80% of the patients. No mutations were identified in known genes implicated in the etiology of congenital hyperinsulinism (ABCC8, KCNJ11, HNF4A, GLUD1, HADH, SLC16A1, GCK, UCP2, HNF1A, AKT2, INSR, CACNA1D), however, predicted deleterious variants were found in other candidate genes such as G6PC2, TH, PMM2, and APPL1, implicated in insulin secretion or glycemic homeostasis. Conclusions: TNH is a prevalent entity to be considered in neonates with risk factors. In our series, TNH is also present in term newborns (22% of patients) and in newborns with weight and/or height appropriate for gestational age (30%). Treatment with diazoxide at low doses is effective in the resolution of these hypoglycemias. The fasting test could be useful for a safe treatment withdrawal when resolution is suspected. No monogenic cause explaining the TNH was identified. Most of the cases molecularly examined presented with 2 or more predicted deleterious variants, suggesting a multifactorial genetic component.

Abscisic Acid Treatment in Patients with Prediabetes.

Aim: to evaluate the effects of abscisic acid (ABA), contained in dwarf peaches, on the regression of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) conditions. Materials and methods: sixty-five patients with IFG or IGT were randomized to take ABA or placebo for 3 months. We evaluated: fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbA1c), fasting plasma insulin (FPI), homeostatic model assessment of insulin resistance (HOMA-IR), lipid profile and high sensitivity C-reactive protein (Hs-CRP). At baseline, and after 3 months, all patients underwent an oral glucose tolerance test (OGTT), an euglycemic hyperinsulinemic clamp, and a glucagon test. Results: a significant reduction of HbA1c, FPG, PPG, FPI and HOMA-IR was observed in the ABA group. After 3 months, 26.7% of patients returned to a normal glycemic status in the ABA group versus zero patients in placebo group; 20.0% were classified as IFG and 53.3% as IGT in the nutraceutical group versus 33.3% and 63.3% in the placebo group. The M value was higher in the ABA group at the end of the treatment. Finally, Hs-CRP was reduced after 3 months of ABA consumption. Conclusions: abscisic acid can be effective in ameliorating glyco-metabolic compensation and in reducing inflammatory status in patients with IFG or IGT.

Neonatal hyperinsulinemic hypoglycemia: case report of kabuki syndrome due to a novel KMT2D splicing-site mutation

BackgroundPersistent neonatal hypoglycemia, owing to the possibility of severe neurodevelopmental consequences, is a leading cause of neonatal care admission. Hyperinsulinemic hypoglycemia is often resistant to dextrose infusion and needs rapid diagnosis and treatment. Several congenital conditions, from single gene defects to genetic syndromes should be considered in the diagnostic approach. Kabuki syndrome type 1 (MIM# 147920) and Kabuki syndrome type 2 (MIM# 300867), can be associated with neonatal hyperinsulinemic hypoglycemia.Patient presentationWe report a female Italian (Sicilian) child, born preterm at 35 weeks gestation, with persistent hypoglycemia. Peculiar facial dysmorphisms, neonatal hypotonia, and cerebellar vermis hypoplasia raised suspicion of Kabuki syndrome. Hyperinsulinemic hypoglycemia was confirmed with glucagon test and whole-exome sequencing (WES) found a novel heterozygous splicing-site mutation (c.674-1G > A) in KMT2D gene. Hyperinsulinemic hypoglycemia was successfully treated with diazoxide. At 3 months corrected age for prematurity, a mild global neurodevelopmental delay, postnatal weight and occipitofrontal circumference growth failure were reported.ConclusionsKabuki syndrome should be considered when facing neonatal persistent hypoglycemia. Diazoxide may help to improve hyperinsulinemic hypoglycemia. A multidisciplinary and individualized follow-up should be carried out for early diagnosis and treatment of severe pathological associated conditions.

Comparison of a combination test (1 μg ACTH test plus glucagon test) versus 1 μg ACTH test and glucagon test in the evaluation of the hypothalamic-pituitary-adrenal axis in patients with pituitary disorders.

To investigate whether a combination of the low-dose (1 μg) adrenocorticotropin (ACTH) stimulation test and glucagon stimulation test (GST) could overcome the problem of equivocal results with the GST or ACTH test alone in patients with pituitary disorders. The study included 41 adult patients with pituitary disorders and 20 healthy subjects who underwent evaluation of cortisol response to ACTH, GST, and a combination of both tests. Blood samples for cortisol measurement were obtained at baseline and 30, 60, 90, and 120 minutes after intravenous administration of ACTH 1 μg and 90, 120, 150, 180, 210, and 240 minutes after subcutaneous injection of glucagon 1 mg. The combination test was performed by injecting ACTH 1 μg at the 180-minute time point of the GST, with blood samples for cortisol measurement obtained at 210 and 240 minutes. Overall, 28 patients with normal cortisol response to both tests also had a normal cortisol response to the combination test. Ten patients with adrenal insufficiency in both tests also had adrenal insufficiency in the combination test, including a patient who had a peak cortisol value of 12.4 μg/dL (which is the cutoff value for the combination test). Two patients with adrenal insufficiency in the ACTH stimulation test and one patient with adrenal insufficiency in the GST had normal cortisol responses to the combination test. By using an appropriate cutoff value, the combination test may offer additional information in patients with equivocal results in the GST and ACTH stimulation test.

66-LB: Combined Immunotherapy with T Regulatory Cells and Anti-CD20 Antibody Prolongs Survival of Pancreatic Islets in Type 1 Diabetes

Background: Immunotherapy using T regulatory cells (Tregs, Tr) prolongs remission in type 1 diabetes (T1DM) but the effect fades with the time. Here, we report phase II trial in which Tregs therapy was combined with anti-CD20 antibody (TrCD20) to make the effect more sustained. Methods: Thirty-six children with newly diagnosed T1DM were randomized 1:1:1 into the following groups: Tr, TrCD20 and control. The treatment in Tr group consisted of autologous expanded CD3+CD4+CD25highCD127- Tregs in the two doses (30x106 of Tregs/kg b.w. each), three months apart. TrCD20 group received additionally 4 doses of rituximab (375 mg/m2, each) between the first and second dose of Tregs. Control group was left without the treatment and all patients were followed for 2 years. Results: The best results were found in TrCD20 group, who was characterized by stable serum levels of both fasting C-peptide and stimulated C-peptide in glucagon and MMT tests throughout the entire trial (for fasting C-peptide only 20% decrease at +24months when compared to baseline). Tr group was characterized by stable levels of fasting and stimulated C-peptide up to +12months and then it dropped gradually until the end of the trial. As compared to control group, there was a better glycemic control measured as HbA1c and mean fasting glucose in both interventional groups throughout the whole follow up. TrCD20 group was in partial remission defined as insulin dose below 0.5IU/kg up to +21 months. The longest insulin independent follow up lasted 18months. The end of the remission in Tr group was noted at +18month and in controls at +12months. At the +24months daily insulin requirement and HbA1c levels were significantly lower in TrCD20 as compared to control group. Conclusions: The combined immunotherapy with Tregs and anti-CD20 antibody prolonged the most significantly survival of pancreatic islets in T1DM children. Trial registration: EudraCT: 2014-004319-35. Disclosure M. Zielinski: None. M. Zalinska: None. D. Iwaszkiewicz-Grzes: None. M. Gliwinski: None. M. Hennig: None. A. Jazwinska-Curyllo: None. H. Kaminska: None. J. Sakowska: Employee; Self; Poltreg S.A. R. Owczuk: None. W. Mlynarski: None. P. Jarosz-Chobot: None. A. Bossowski: None. A. Szadkowska: None. J. Siebert: None. M. Mysliwiec: Stock/Shareholder; Self; POLTREG SA. N.M. Marek-Trzonkowska: Stock/Shareholder; Self; Poltreg SA. P. Trzonkowski: Board Member; Self; Poltreg S.A. Stock/Shareholder; Self; Poltreg S.A. Funding National Centre for Research and Development in Poland (STRATEGMED1/233368/1/NCBR/2014)

MON-077 A Case of Growth Hormone Deficiency in Sturge-Weber Syndrome

Introduction: Sturge-Weber syndrome (SWS) is a congenital neurocutaneous disorder characterized by a port wine stain on the skin in the distribution of the ophthalmic branch of the trigeminal nerve (vascular malformation of skin), glaucoma, and leptomeningeal angiomas. Central nervous system abnormalities may increase the risk of hypothalamic-pituitary dysfunction. One previous study showed that SWS patients had higher prevalence of growth hormone deficiency than the general population although the etiology is unclear. This case report describes a patient who was initially diagnosed with SWS and later confirmed with complete growth hormone deficiency.Case: A 7-year-and-11-month-old boy who had been diagnosed with SWS visited a tertiary center for the evaluation of short stature [111.1cm (<3 percentile)]. He was born at 37 weeks of gestational age with birth weight of 3230g by cesarean section and had a port wine nevus on the right side of the face since birth. He had a history of epilepsy first occurring at 6 months of age when he was diagnosed with SWS. There were two more attacks of seizure till 32 months of age. Brain magnetic resonance imaging revealed leptomeningeal angioma, choroidal hemangioma, and diffuse brain atrophy. He was diagnosed with glaucoma and had been managed with surgery and medication. There was no family history of SWS or any other brain anomaly. His mid-parental height was 167.7cm. All blood tests were normal including complete blood count, chemistry, and thyroid function test. Hand x-ray showed delayed bone age. Cocktail test was performed for the evaluation of short stature. As a result, he was diagnosed with complete growth hormone deficiency (peak GH on L-dopa test: 2.46 ng/mL, peak GH on glucagon test: 3.71 ng/mL). The recombinant growth hormone therapy was started at the age of 8 years and 1 month. He showed good response to GH treatment. His height became 125.8cm at the age of 9 years and 5 months (height velocity 9.2 cm/year), and 134.3cm at the age of 10 years and 6 months.Conclusion: We experienced a case with Sturge-Weber syndrome and complete growth hormone deficiency which was successfully managed by recombinant growth hormone therapy. It may be better to consider the possibility of GH deficiency even if there are certain conditions that affect the growth itself.

Changes in glucose tolerance after pancreatectomy in patients with pancreatic ductal adenocarcinoma.

668 Background: Diabetes mellitus (DM) is reported to be related to pancreatic ductal adenocarcinoma (PDAC). Long-standing DM is a risk factor for PDAC, meanwhile, quite a few patients with PDAC develop DM as a paraneoplastic disorder and some papers reported that DM affected prognosis for PDAC. In this study, we investigated pre- and post-operative glucose tolerance in patients with pancreatectomy for PDAC or other disease. Methods: This single-center prospective study included 69 patients with pancreatectomy (40 pancreaticoduodenectomy (PD) and 29 distal pancreatectomy (DP) ) who received 75-g oral glucose tolerance test (OGTT) and glucagon test pre- and one month postoperatively. Plasma glucose, insulin, and C-peptide (CPR) at 0-, 30-, 60-, and 120-min during OGTT; and 0- and 6-min during glucagon test were obtained. These data and survival outcomes were analyzed. Results: There were 20 (29%) PDAC patients: 12 (30%) in PD group and eight (28%) in DP group. Nine patients with PDAC (45%) and seven patients (18%) without PDAC demonstrated DM type in preoperative OGTT. After pancreatectomy, 11 patients (55%) with PDAC and seven patients (15%) without PDAC experienced improvement in OGTT (P=0.0005). Greater improvement in homeostasis model assessment insulin resistance that were obtained by OGTT and used to measure insulin resistance, was noted after surgery in PDAC patients compared with non-PDAC patients (-1.4 vs -0.5 in PD group, P=0.07; -0.8 vs +0.06 P=0.05 in DP group). Delta CPRs obtained by glucagon test were significantly decreased postoperatively (3.0 to 1.1 ng/mL, P&lt;0.0001 in PD group; 3.3 to 1.8 ng/mL, P&lt;0.0001 in DP group). In survival analysis, fasting plasma glucose &gt;110 mg/dL (HR 3.9, 95%CI 1.5-10, P=0.005) and the average of plasma insulin &gt; 25 µIU/mL during OGTT (HR 0.36, 95%CI 0.14-0.93, P=0.035) were significant prognostic factor for PDAC. Conclusions: Pancreatectomy impaired insulin secretion and improve insulin resistance especially in PDAC patients. About half of PDAC patients demonstrated the improvement of glucose tolerance after surgery. Of note, glucose tolerance differed between PDAC and other disease, and affect the survival outcome for PDAC patients.

The glucagon test in diagnosis of secondary adrenal insufficiency after craniospinal irradiation: the feasibility of application, the features of performing the test, and its diagnostic informativity

The glucagon test (GT) is a promising alternative to the insulin hypoglycemia test (IHT) in diagnosis of secondary adrenal insufficiency (SAI). To study the feasibility of using the GT in patients after craniospinal irradiation and to determine the cut-off value to rule out SAI. A total of 28 patients (14 males and 14 females) with the median age of 19 years (17; 23) who had undergone combination treatment (surgery, craniospinal irradiation (35 Gy) with boost to the tumor bed, and polychemotherapy) of extrapituitary brain tumors no later than 2 years before study initiation and 10 healthy volunteers of matching sex and age were examined. All the subjects underwent the GT and IHT with an interval of at least 57 days. The cortisol, ACTH, and glucose levels were measured. Twelve out of 28 patients were diagnosed with SAI according to the IHT results. ROC analysis revealed that cortisol release during the GT 499 nmol/L ruled out SAI [100% sensitivity (Se); 62% specificity (Sp)], while the absence of a rise 340 nmol/l verified SAI (Sp 100%; 55% Se). For GT, the area under a curve (AUC) was 93.6%, which corresponds to a very good diagnostic informativity. In 19 patients, the IHT and GT results were concordant (in ten patients, the release of cortisol occurred above the cut-off value in both tests; no release was detected in nine patients). In nine cases, the results were discordant: the maximum cortisol level detected in the GT was 500 nmol/l, but the IHT results ruled out SAI (the GT yielded a false positive outcome). Contrariwise, in three (10.7%) patients the release of cortisol detected in the GT was adequate, while being insufficient in the IHT test. Adverse events (nausea) were reported during the GT test in 9 (25%) subjects; one patient had hypoglycemia (1.8 mmol/l). GT is highly informative and can be used as a first-level stimulation test for ruling out SAI in patients exposed to craniospinal irradiation performed to manage brain tumors. The cortisol level of 500 nmol/L is the best cut-off value for ruling out SAI according to the GT results. The insulin hypoglycemia test is used as the second-level supporting test in patients with positive GT results.

Cortisol Levels in Glucagon Stimulation Test in Children Assessed for Short Stature: Clinical and Laboratorial Correlations.

To assess total cortisol levels in children being evaluating for short stature with normal cortisol reserve and to correlate this response to clinical and laboratory data. Children assessed with glucagon test in our department were recruited in this study retrospectively. Inclusion criteria were: i) age>1 year, ii) absence of chronic illness or medication interfering with ACTH-cortisol axis, iii) GH stimulation levels>3ng/mL at least in one provocation test (glucagon or clonidine), iv) absence of multiple pituitary growth hormone deficiencies, v) normal short Synacthen test in cases of low cortisol response in glucagon test.Two hundred and thirty-seven subjects (160 males, 67.5%) with a mean age of 9.02±3.19 years, were finally included in the analysis. Cortisol peak levels but not cortisol AUC were significantly increased in females compared to males (26.83±7.31 μg/dl vs. 24.04±7.20 μg/dl). When linear correlations were studied, both cortisol peak levels and cortisol AUC were linearly but inversely correlated to age (r=-0.234, p<0.001 and r=-0.315, p<0.001, respectively). Finally, cortisol AUC was inversely correlated to weight Z-scores (r=-0.160, p=0.014). When our analysis was limited only to subjects with intact GH response (GH peak> 7 ng/mL), age was still inversely correlated to cortisol AUC (r=-0.312, p<0.001), and cortisol AUC was linearly correlated to GH AUC assessed with clonidine test (r=0.223, p=0.013). Girls, younger and thinner children exhibit higher cortisol response to glucagon test.

Timing of GH Peak in Both Glucagon and Clonidine Tests is of Major Clinical Importance

Objective: To detect a possible correlation between timing of the peak value of growth hormone (GH) during stimulatory tests (STs) and the effectiveness of treatment with recombinant human growth hormone (rhGH) in children with idiopathic GH deficiency (iGHD). Methods: We retrospectively studied 92 patients with iGHD (57 boys; mean age at diagnosis: 9.93 years). Diagnosis was confirmed by 2 different STs, glucagon stimulation test (GST), and clonidine stimulation test (CST). Auxologic parameters were recorded, while observed and predicted (according to KIGS Prediction Model) height velocity during the first year of treatment and the index of responsiveness (IoR) were calculated for the prepubertal children (n = 65). Results: Atypical GST was defined as that with peak GH value at time 0 minutes, 30 minutes, 60 minutes, or 180 minutes, whereas atypical CST was defined as that with peak timing at 0 minutes, 30 minutes, or 120 minutes. Atypical GST was detected in 18 patients (19.57%). IoR was lower in the prepubertal children with atypical GST (-1.81 ± 0.67 versus -1.34 ± 0.85; P = .051). In the CST, the 18 children who had atypical timing, had significantly lower IoR (-1.86 ± 0.66 versus -1.35 ± 0.84; P = .047). When the patients were categorized according to the number of atypical tests, significant differences in the IoR were detected (-2.09 ± 0.68 with 2 atypical STs [n = 6], -1.64 ± 0.61 with 1 atypical ST [n = 16], and -1.29 ± 0.87 with no atypical ST [n = 43], P = .045). Conclusion: The presence of atypical peak GH timing during ST may be a factor that predicts lower growth hormone velocity during the first year of rhGH treatment in prepubertal children with iGHD. Abbreviations: CST = clonidine stimulation test; GH = growth hormone; GHD = growth hormone deficiency; GST = glucagon stimulation test; iGHD = idiopathic growth hormone deficiency; IoR = index of responsiveness; rhGH = recombinant human growth hormone; SDS = standard deviation scores; ST = stimulatory test.

A brief interactive training with medical students improves their diabetes knowledge about hypoglycemia

BackgroundHypoglycemia is a severe clinical problem with physical and psychosocial implications for people with type 1 and type 2 diabetes. Medical students would benefit from formal education on how to treat hypoglycemia as well as how to administer glucagon in case of a severe hypoglycemic emergency. The purpose of this study was to assess the effectiveness of a brief training to improve medical students’ knowledge and attitudes about diabetes, hypoglycemia, and glucagon administration.MethodsWe conducted a feasibility study to assess the effectiveness of an interactive training session on diabetes education with an emphasis on hypoglycemia. We measured medical students’ knowledge and attitudes toward diabetes, hypoglycemia, and glucagon before and after the training. We performed Chi-Square tests, paired t-tests, determined effect sizes using Cohen’s d, and analyzed short answer responses via content and thematic analyses.ResultsTwo hundred and seventeen participants (age = 25.1 ± 2.3 years, 45.2% female, 78.3% white, 36.4% planned to pursue primary care, response rate of 94.3%) completed surveys. Following the training, participants’ total knowledge scores improved by five percentage points to 82.6 ± 11.0% (t-value = 7.119, p < 0.001). We also observed positive improvements in the General Test scores to 82.3 ± 12.6% (t-value = 5.844, p < 0.001) and Insulin Use Test scores to 82.4 ± 17.4% (t-value = 4.103, p < 0.001). For the hypoglycemia test, participants averaged 55.7 ± 24.8% pre-training and 83.0 ± 22.4% post-training (t-value = 14.258, p < 0.001). Lastly, participants scored 87.6 ± 18.5% on the glucagon test after the training session. In addition, we observed positive improvements in all five diabetes attitudes subscales after the training, with the largest magnitude of change in the “Psychosocial impact of diabetes” subscale (t-value = 9.249, p < 0.001, Cohen’s d = 0.60). Qualitatively, more participants recognized the severity of hypoglycemia after the training. They also learned how to approach diabetes from the patient’s perspective and valued the clinically relevant and practical information provided during the training session, such as the “15–15 Rule.”ConclusionsMedical students need to learn about patients’ everyday experiences of diabetes in order to have an understanding of and confidence to assess and treat hypoglycemia. These findings underscore the importance of training medical students on how to actively assess and manage the risk of hypoglycemia in people with diabetes.

Paraneoplastična hipoglikemija kod pacijenta sa recidivom fibroznog tumora pleure

BACKGROUND: Solitary fibrous tumor of pleura represents a prototypical mesenchymal neoplasm that induces non-islet cell tumor hypoglycemia due to overproduction of insulin-like growth factor 2, named Doege Potter syndrome. CASE PRESENTATION: An 86-year-old man, non-diabetic, was admitted to hospital with a few months history of repetitive hypoglycemic symptoms and documented low blood glucose of 1.9 and 1.2 mmol/L on two occasions when he lost consciousness. His medical history was notable for primary pleural fibroma which was resected twenty years previously and for tumorous mass of right pulmonal lobe 103mm described on CT chest scan for respiratory infection six months prior to hospitalization. During hospitalization hypocorticism and hypoptuitarism were ruled out. He spontaneously developed mild neuroglycopenic episodes, when we confirmed hypoinsulinemic hypoglycemia accompanied with suppressed levels of growth hormone and IGF1, and IGF2 : IGF1 ratio of 7, which was all suggestive of paraneoplastic etiology. The response of glucose in Glucagon test was adequate. Beta-hydroxybutyrate was not done due to technical limitations. Abdominal MRI showed a few well-circumscribed cysts in the liver and hemangioma. Octreoscan revealed zone of diffuse increased uptake in right hemithorax. Subsequently, he was started on prednisolon for COPD exacerbation with which his hypoglycemic episodes subsided. Patient declined surgery and he was released with corticosteroid therapy. CONCLUSIONS: We report a case of hypoinsulinemic hypoglycemia in a patient with suppressed levels of hGH and IGF1 and higher-than-normal IGF2 : IGF1 ratio, along with recurrent pleural tumor which is somatostatine-receptor positive.

Effects of SGLT2 Inhibitors on Insulin Secretion and Insulin Resistance—Results from a Cross-Sectional Study

SGLT2 inhibitors lower blood glucose levels by inhibiting renal glucose reabsorption independently of insulin action. In addition, SGLT2 inhibitors are known to enhance endogenous glucose production by increasing glucagon level, despite lowering fasting glucose. However, the effect of SGLT2 inhibitors on glucose metabolism have not been fully elucidated yet. Therefore, we investigated the effect of SGLT2 inhibitors on insulin secretion and resistance. In this cross-sectional study, we recruited the subjects with type 2 diabetes mellitus who admitted to our hospital for diabetes education from January 2015 to September 2017. A total of 197 patients were enrolled in this study and divided into 26 subjects taken with SGLT2 inhibitor (S) and 171 subjects without SGLT2 inhibitor (NS). β-Cell function were assessed by 24-hour urinary C-peptide immune reactivity (CPR), fasting CPR, HOMA2-%β, δ CPR by glucagon test, and fasting and 2 hours after breakfast CPR index (CPI). Insulin resistance was assessed by HOMA2-IR which was calculated using HOMA2 Computer Model. The visceral and subcutaneous fat areas (VFA and SFA) were measured at the umbilical level using CT scans. Age, BMI, GA, HbA1c were comparable between the two groups. Regarding the β-Cell function, 24-hour urinary CPR, fasting CPI, 2 hours after breakfast CPI, HOMA2-%β showed no significant difference between the two groups, however, 6 minutes CPR and δ CPR in the glucagon test were significantly lowered by 27% (P = 0.0002) and 38% (P = 0.00001) in the S group compared to the NS group, respectively. Regarding the insulin resistance, HOMA2-IR was significantly lowered by 21% (P = 0.0077) in the S group compared to the NS group, although BMI, VFA, and VFA/VSA were not significantly different between the two groups. In conclusion, this cross-sectional study indicates the possibility that SGLT2 inhibitors blunt the glucagon induced insulin secretion in β-Cell and improve insulin resistance independently of visceral fat mass. Disclosure N. Waseda: None. H. Satoh: None. C. Yoshida: None. F. Ikeda: None. A. Kanazawa: Speaker's Bureau; Self; Sanofi K.K., Kissei Pharmaceutical Co., Ltd. H. Watada: Advisory Panel; Self; AstraZeneca. Consultant; Self; Astellas Pharma US, Inc., AstraZeneca, Boehringer Ingelheim GmbH, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Novartis AG, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Takeda Development Center Asia, Pte. Ltd.. Research Support; Self; Abbott, Astellas Pharma US, Inc., AstraZeneca, Bayer AG, Benefit One Health Care Co., Ltd., Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Johnson &amp; Johnson Diabetes Institute, LLC., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nitto Boseki Co., Ltd., Novartis AG, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Pfizer Inc., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Terumo Medical Corporation.

Limited Availability of Glucagon by Emergency Personnel

Hypoglycemia causes more than 100,000 emergency department visits per year costing over $120 million. Glucagon can reduce the number and severity of hypoglycemic episodes requiring emergency medical attention and hospital admission. However, EMS personnel are often unable to administer glucagon. U.S. EMS offices were queried for glucagon administration and blood glucose testing protocols. Only paramedics are able to administer glucagon in most states, whereas the 198,200 EMT-Basics personnel nationally cannot. The average response time to calls was 15.34 minutes. Dispatchers correctly coded 44.67% of these calls as a “diabetic problem,” increasing the likelihood of dispatching providers who cannot administer glucagon. The National Emergency Management Information System (NEMIS) (2013- 2015) indicates 89, 263 cases in which glucagon was administered with only 3,944 events with side effects. Despite its’ favorable safety profile, glucagon cannot be administered by EMT-basics in most states, even though family members can often with minimal training. 3 out of 4 emergency personnel are unable to use glucagon. The likelihood of the correct personnel being dispatched based on dispatcher information alone is poor. Increasing the availability of glucagon in the prehospital setting will likely result in reduced cost burden and adverse consequences of severe hypoglycemia. EMS Policies Regarding Use of Glucagon and Blood Glucose Testing. Disclosure P. Kahn: None. N. Wagner: None. R.A. Gabbay: Consultant; Self; Merck Sharp &amp; Dohme Corp.. Advisory Panel; Self; Onduo, health reveal.

The comparison of combination test either with 1 μg acth test and glucagon test for the evaluation of hypothalamo-pituitary-adrenal axis in patients with pituitary disorders

The comparison of combination test either with 1 μg acth test and glucagon test for the evaluation of hypothalamo-pituitary-adrenal axis in patients with pituitary disorders

Metabolic Characteristics of Recently Diagnosed Adult-Onset Autoimmune Diabetes Mellitus.

Among patients diagnosed with type 2 diabetes, autoimmune diabetes often remains undetected. Metabolic features of these patients are insufficiently characterized at present. This study compared age- and sex-matched adult (aged 41 to 62 years) humans with recent-onset diabetes: patients positive for antibodies against glutamic acid decarboxylase (GAD) and/or cytoplasmic islet-cell antigen with an insulin-free period of >6 months [antibody positive/insulin negative (ab+/ins-); previously termed latent autoimmune diabetes of adults], type 1 diabetes [antibody positive/insulin positive (ab+/ins+)], and type 2 diabetes [antibody negative/insulin negative (ab-/ins-)], as well as glucose-tolerant humans (controls) of the German Diabetes Study (n = 41/group). β-Cell function was assessed from glucagon tests and intravenous glucose tolerance tests (IVGTTs), and insulin sensitivity was determined from hyperinsulinemic-euglycemic clamps. Of the ab+/ins- patients, 33 (81%) were initially diagnosed as having type 2 diabetes. In ab+/ins-, body mass index (BMI) was higher than in ab+/ins+ (27.8 ± 5.3 kg/m2 vs 25.0 ± 3.5 kg/m2, P < 0.05), lower than in ab-/ins- (31.9 ± 5.8 kg/m2, P < 0.05), and similar to controls (29.4 ± 6.6 kg/m2). In ab+/ins-, GAD antibody titers correlated negatively with BMI (r = -0.40, P < 0.05) and with C-peptide secretion in glucagon stimulation tests (r = -0.33, P < 0.05). β-Cell function from IVGTT was 228% higher in ab+/ins- than in ab+/ins+ but 35% lower than in ab-/ins- and 61% lower than in controls (all P < 0.05). Insulin sensitivity in ab+/ins- was comparable to ab+/ins+ and controls but 41% higher than in ab-/ins- (P < 0.05) after adjustment for BMI and fasting blood glucose or hemoglobin A1c. Even shortly after diagnosis, ab+/ins- patients feature partly preserved β-cell function and chronic hyperglycemia, which possibly contributes to the observed impairment of whole-body insulin sensitivity.

Somatotrope Pituitary Function in Professional Soccer Players.

Soccer is associated with repetitive head trauma, which, as it is known from sports like football and boxing, can result in hypopituitarism. Gonadotropins and GH are the most common pituitary hormones to become deficient. GH deficiency is associated with an increased risk of cardiovascular mortality and has negative influence on body mass index, visceral fat mass, insulin resistance and sensitivity, bone mineral density and inflammatory markers. Therefore the aim of this study was to evaluate the somatotrope pituitary function in professional soccer players. This clinical study included 15 male, professional soccer players with at least 10 years of professional training. Basal hormonal parameters of the pituitary axis were obtained from the participants. To assess GH-IGF-I axis, glucagon stimulation tests were used. Rise in growth hormone during glucagon test was analyzed and the prevalence of newly diagnosed hormone deficiencies was evaluated. Mean age of all participants was 31±10 years. None of the 15 soccer players had GH deficiency. Mean rising factor of GH after stimulation with glucagon was 100 in all participants. We did not find signs of ACTH, TSH or LH/FSH deficiency in any player. In this small collective of soccer players we did not find playing soccer to be a risk factor for the development of GH-deficiency. According to our data screening for somatotrope deficiency is not necessary. Further investigations in larger cohorts are needed.

The impact of pancreaticoduodenectomy on endocrine and exocrine pancreatic function: A prospective cohort study based on pre- and postoperative function tests

Background/ObjectivesStudies reporting on function after pancreatic surgery are frequently based on diabetes history, fasting glycemia or random glycemia. The aim of this study was to investigate prospectively the evolution of pancreatic function in patients undergoing pancreaticoduodenectomy based on proper pre- and postoperative function tests. It was hypothesised that pancreatic function deteriorates after pancreaticoduodenectomy. MethodsBetween 2013 and 2016, 78 patients undergoing pancreaticoduodenectomy for oncologic indications had a prospective evaluation of their endocrine and exocrine pancreatic function. Endocrine function was evaluated with the 75 g oral glucose tolerance test (OGTT) and the 1 mg intravenous glucagon test. Exocrine function was evaluated with a 13C-labelled mixed-triglyceride breath test. Tests were performed pre- and postoperatively. ResultsIn 90.5% (19/21) of patients with preoperatively known diabetes, no change in endocrine function was observed. In contrast, endocrine function improved in 68.1% (15/22) of patients with newly diagnosed diabetes. 40% (14/35) of patients with a preoperative normal OGTT or prediabetes experienced deterioration in function. In multivariate analysis, improvement of newly diagnosed diabetes was correlated with preoperative bilirubin levels (p = 0.045), while progression towards diabetes was correlated with preoperative C-peptidogenic index T30 (p = 0.037).A total of 20.5% (16/78) of patients had pancreatic exocrine insufficiency preoperatively. Another 51.3% (40/78) of patients deteriorated on exocrine level. In total, 64.1% (50/78) of patients required pancreatic enzyme-replacement therapy postoperatively. ConclusionsAlthough deterioration of endocrine function was expected after pancreatic resection, improvement is frequently observed in patients with newly diagnosed diabetes. Exocrine function deteriorates after pancreaticoduodenectomy.

Autologous bone marrow-derived mononuclear cells transplantation in type 2 diabetes mellitus: effect on \u03b2-cell function and insulin sensitivity

BackgroundInsulin resistance and insulin deficiency are the cardinal defects in the pathogenesis of type 2 diabetes mellitus (T2DM). Despite the plethora of anti-diabetic medications, drugs specifically targeting the β-cells are still desired. Stem cell therapy has emerged as a novel therapeutics strategy to target β-cells; however, their mechanism of action has not been well defined. This study aims to examine the efficacy and safety of autologous bone marrow-derived mononuclear cells (ABM-MNCs) transplantation in T2DM, and explores the mechanistic insights into stem cells action through metabolic studies.MethodsSeven T2DM patients with the duration of disease ≥5 years, receiving triple oral anti-diabetic drugs along with insulin (≥0.4 IU per kg per day) and HbA1c ≤ 7.5% (≤58.0 mmol/mol) were enrolled for ABM-MNCs administration through a targeted approach. The primary end-point was a reduction in insulin requirement by ≥50% from baseline, while maintaining HbA1c < 7.0% (<53.0 mmol/mol) with improvement in insulin secretion, and/or insulin sensitivity after ABM-MNCs transplantation.ResultsSix out of 7 (90%) patients achieved the primary end-point. At 6 months, there was a significant reduction in insulin requirement by 51% as compared to baseline (p < 0.003). This was accompanied by a significant increase in the 2nd phase C-peptide response during hyperglycemic clamp (p = 0.018), whereas there were no significant alterations in insulin sensitivity and glucose disposal rate during hyperinsulinemic–euglycemic clamp relative to the baseline. Other measures of β-cell indices like HOMA-β, and stimulated C-peptide response to glucagon and mixed meal tolerance test were non-contributory.ConclusionABM-MNCs transplantation results in significant reduction in insulin doses and improvement in C-peptide response in patients with T2DM. Metabolic studies may be more useful than conventional indices to predict β-cell function in patients with advanced duration of T2DM.Trial registration-Clinicaltrials.gov NCT01759823

Effect of GLP-1 and GIP on C-peptide secretion after glucagon or mixed meal tests: Significance in assessing B-cell function in diabetes.

The aim of the study was to investigate the different B-cell responses after a glucagon stimulation test (GST) versus mixed meal tolerance test (MMTT). We conducted GST and MMTT in 10 healthy people (aged 25-40years) and measured C-peptide, gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) at different time points after the administration of 1mg i.v. glucagon for GST or a liquid mixed meal for MMTT. The GST stimulated C-peptide showed a mean increase of 147.1%, whereas the mean increase of MMTT stimulated C-peptide was 99.82% (Δincrease=47.2%). Maximum C-peptide level reached with the MMTT was greater than that obtained with the GST (C-pept max MMTT=2.35nmol/L vs C-pep max GST=1.9nmol/L). A positive and linear correlation was found between the GST incremental area under the curve C-peptide and the MMTT incremental area under the curve C-peptide (r=0.618, P=.05). After GST, there was no increment of GIP and glucagon like peptide-1 levels compared to baseline levels. A positive and linear correlation between GIP and C-peptide levels was observed only for the MMTT (r=0.922, P=.008) indicating that in the GST, the C-peptide response is independent of the incretin axis response. Although the 2 stimulation tests may elicit a similar response in C-peptide secretion, B-cell response to MMTT depends on a functionally normal incretin axis. These results may have implications when investigating the B-cell response in people with diabetes and for studies in which stimulated C-peptide secretion is used as primary or secondary outcome for response to therapy.