Glucagon Stimulation Test Research Articles

Comparison of glucagon stimulation test and low dose ACTH test in assessing hypothalamic-pituitary-adrenal (HPA) axis in children.

Children with a pituitary hormone deficiency are at risk for secondary adrenal insufficiency (AI). A stimulation test is usually performed for diagnosing AI, evaluating both the hypothalamic-pituitary-adrenaland growth hormone (GH)-IGF-1 axes. This single test is preferred by clinicians and is considerably more tolerable by patients. The objective of this study was to evaluate the glucagon stimulation test (GST), which is commonly used to assess both axes. Its diagnostic capability for GHdeficiencyis high and well accepted, however its utility for determining secondary AI has not been well established. This retrospective study involved 120 patients under 18 years of age with short stature who had undergone both a GST and low dose ACTH stimulation test (LDACTH test). Twenty-six children who had more than 6months elapsed between the two tests were excluded from the study. The study was conducted on patients of the Pediatric Endocrinology Department at Soroka University Hospital, a tertiary medical centre in Beer Sheva, Israel. Statistical analyses were carried out via IBM SPSS (v. 22), with a significance level determined at p < .05. Different cortisol cut-off values were assessed for GST and it was determined that the highest combined sensitivity and specificity yielded a cut-off point of 320 nmol/L (56% sensitivity and 83% specificity) while the currently accepted cut-off value (500 nmol/L) yielded 100% sensitivity and 6% specificity. The results of this study show that GST is not an optimal tool for diagnosing secondary AI. Therefore, clinicians using this test should interpret its results with caution.

Adrenocortical, somatotropic, and antidiuretic response to nasal glucagon in healthy subjects.

The glucagon stimulation test involves the peptide intramuscular or subcutaneous administration for the diagnosis of hypopituitarism. To date, no data are available regarding its intranasal formulation. Our study intended to investigate the role of intranasal glucagon as a potential stimulus test for the evaluation of the corticotropic, somatotropic, and antidiuretic axes. Non-randomized, single-blinded, cross-over study including 10 healthy subjects (50% women). All participants underwent 2 days of testing, and intranasal glucagon or placebo was administered. At baseline, every 15' up to +90', and then every 30' up to +180', a blood sample was taken for adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH), copeptin, glucose, insulin, sodium, potassium, and plasma osmolarity. At baseline and at the end of the test, urinary osmolarity was evaluated as well. After administration of both glucagon and placebo, ACTH and cortisol values decreased progressively (P < 0.001), but in the drug group, the reduction in cortisol was less accentuated up to +90' (P < 0.05). Growth hormone values decreased after placebo administration (P < 0.001); on the other hand, after glucagon, an increasing, yet non-significant trend was observed (P = 0.096) with the difference between the two groups evident starting from +120' onwards (P < 0.005). The placebo administration led to a reduction of copeptin, while its stability was observed after glucagon administration. Six subjects developed hypokalemia (ie, potassium <3.5 mmol/L) post-glucagon, with the nadir at 45' (3.6 [3.2-3.8] mmol/L) significantly correlated with the immediate post-glycemic rise insulin peak (Spearman's rho -0.719; P = 0.019). No significant differences were observed compared to the other analytes tested. Intranasal glucagon administration is not an effective stimulus for hypophyseal secretion. Hypokalemia secondary to hyperinsulinemic rebound appears to be a frequent complication of its acute administration.

Growth Hormone Cut-Off Post Glucagon Stimulation Test in an Indian Cohort of Overweight/Obese Hypopituitary Patients for the Diagnosis of Adult Growth Hormone Deficiency.

Obesity has been associated with reduced growth hormone (GH) secretion, which might lead to the over diagnosis of adult GH deficiency (GHD) in overweight (OW)/obese hypopituitary patients. Currently, there are no body mass index (BMI)-specific peak GH cut-offs for the glucagon stimulation test (GST) for assessing adult GHD in India, given the BMI cut-offs vary for Asians. The study's main objective was to determine a peak GH cut-off level for the diagnosis of adult GHD in overweight (OW)/obese individuals utilizing the GST. Forty OW/obese subjects were studied in two groups of 20 each. The first group included 20 OW/obese hypopituitary adults and the second group included 20 control subjects. The intervention consisted of a 3 h GST. The main outcome measured was the peak GH level on GST. The mean age of control subjects was lower (33.15 ± 7.67 v/s. 42.10 ± 13.70 years; P = 0.017) in comparison with hypopituitary adults. The mean BMI (27.93 ± 1.63 v/s. 25.81 ± 1.66 kg/m2; P < 0.001), mean IGF1 (272.81 ± 38.57 v/s. 163.75 ± 42.42; P < 0.001, and mean HOMA IR (11.8 ± 9.7 v/s. 6.02 ± 3.14; P = 0.02) was greater in OW/obese controls. The mean GH peak was significantly higher in control subjects (5.41 ± 3.59 ng/mL v/s. 1.49 ± 1.25 ng/mL; P < 0.001) compared to hypopituitary subjects. ROC curve analysis demonstrated a GH cut-off of 3.3 ng/mL with a moderate sensitivity of 70% and high specificity of 95%, with an AUC of 0.838 (P < 0.001; 95% confidence interval [CI] of 0.710-0.965) for the diagnosis of GHD in overweight/obese hypopituitary adults. This study demonstrates that a cut-off of 3.3 ng/mL would diagnose GHD in Indian overweight/obese hypopituitary adults.

Ispitivanje beta ćelijske funkcije pacijenata sa novootkrivenim dijabetes melitusom tip 2 u kliničkoj praksi

Dysfunctions underlining type 2 diabetes mellitus (DM2) evolution are insulin resistance and beta-cell secretory insufficiency. Practical but reliable beta-cell function (BCF) testing is still elusive. Methods of BCF measurement include the homeostasis model assessment (HOMA), glucagon stimulation test (GST), oral glucose tolerance tests (OGTT), intravenous glucose tolerance tests (IVGTT), meal tolerance tests (MTT) and the hyperglycemic clamp procedure. Oral tests have the advantage of simpler use and superior approximation of real-life stimulation inclusive for incretin activation effects. The advantage of the test meal over the OGTT incudes a more adequate simulation of nutrients effect on incretin secretion. Therefore, a standardized test meal (STO) would best reflect the spike in insulin secretion after a meal in real life. Conclusion: Standardized test meal, as potent stimulus of C-peptide secretion, is a promising simple and naturalistic alternative to in vivo assess beta-cell function in an affordable outpatient setting, through analysis of C-peptide response in newly diagnosed diabetic patients, as potent stimulus of C-peptide secretion.

Prediabetes and mild hepatosteatosis are associated with blunted cortisol response to glucagon but not to growth hormone

BackgroundAlthough there is a close relationship between cortisol and growth hormone (GH) levels, glucose intolerance and hepatosteatosis, changes in GH and the hypothalamo-pituitary-adrenal (HPA) axis were not previously studied in prediabetes. The main purpose of the present study was to assess changes in GH and HPA axis and their relationship with hepatosteatosis in prediabetic patients. MethodsForty prediabetic patients, with body-mass index (BMI) 25–35kg/m2, and 23 healthy individuals, with normal glucose tolerance and similar age and BMI, were included. The 75g oral glucose tolerance test and glucagon stimulation test (GST) were used. ResultsNo significant differences were detected between prediabetic patients and healthy individuals in terms of insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein-3 (IGFBP-3), IGF-1/IGFBP3 ratio or adrenocorticotropic hormone (ACTH). GH responses to GST did not differ between groups. On the other hand, peak cortisol and area under the curve (AUC) (cortisol) response on GST were significantly lower in prediabetic patients. Both peak GH and AUC (GH) response on GST correlated negatively with waist circumference and body weight. The degree of hepatosteatosis correlated negatively with peak cortisol, GH, AUC (cortisol) and AUC (GH) response on GST. ConclusionCortisol response to GST is decreased in prediabetic patients, with relatively well conserved GH response. This suggests altered HPA axis responsiveness in prediabetes, as is known in diabetes. Thus, HPA axis changes in patients with diabetes probably start before the development of diabetes as such.

Abstract 87

Introduction: Severe short stature is defined as a height standard deviation score (SDS) of less than −3 below the mean for chronological age and sex. Growth hormone deficiency (GHD) is one of the most important causes of short stature. The diagnosis of GHD is classically established after two provocative tests in patients with short stature. Only three growth hormone (GH) provocative agents like insulin, clonidine, and glucagon are available in India. The insulin tolerance test (ITT), although considered agold standard test, is infrequently used nowadays as it poses several risks. Clonidine stimulation test (CST) is the most performed stimulation test due to being easily available and less cumbersome. The glucagon stimulation test (GST), offers several advantages over other tests, in view ofmultiple sample requirements, it has been poorly studied to date in India. In this study, weanalyzedthe diagnostic efficacy of GST andCST in suspected GHD cohorts and compared the peak GH level between these tests. Materials and Methods: The study was conducted in 3000 bedded multi-specialty tertiary care center, in South Tamil Nadu between 2020 and 2022. Based on the auxological criteria, 33 patients of severe short stature with suspected GHD were included in this cross-sectional study after IEC approval. They were subjected to CST and GST on two different weeks according to standard protocols. Blood samples were collected for GH at 0, 30, 60, 90 and 120 minutesfollowing clonidine stimulation and 0, 30, 60, 90, 120, 150 and 180 minutesafter Glucagon stimulation. GH assay was performed by using electrochemiluminescence (ECLIA - Roche Diagnostics - Cobas e411 analyzer). A Peak GH level of less than 8 ng/ml is considered diagnostic of GHD. All procedures were carried out inthe early morning after an overnight fast. Patients of peripubertal age were primed with Estradiol valerate for 3 days before performing the tests. Results: Among 33 patients,18 were males and 15 were females. The mean chronological age was 11.5 ± 4.1 years. The mean height SDS, weight SDS and target height SDSwere-4.22 ± 1.2, -3.55 ± 1.14, and -1.45 ± 0.95 respectively. Among 33 patients, 27 patients were diagnosed withGHD, and 6 patients with Idiopathic short stature (ISS). The mean peak GH level during CST and GST in diagnosing GHD were 2.0015 ± 0.718 (Range 0.17 – 6.4 ng/ml) and 1.244 ± 0.442 (Range 0.16 – 5.3 ng/ml) respectively. Whereas mean peak GH levels with CST and GST in patients with ISS were 16.3233 ± 7.579 (Range 11.3 – 23.9 ng/ml) and 12.7717 ± 2.812 (Range 11.0 – 14.7 ng/ml) respectively. The sensitivity and specificity of CST was 100.00% (87.23% to 100.00%), 90% (52.1 to 92.2%) respectively. Whereas sensitivity and specificity of GST were 100.00%(80.49% to 100.00%), and 100%(54.07% to 100.00%). Results of both CST and GST were concordant in 30 (91%) patients whereas discordant in 3 (9%) patients. The number and percentage of peak GH levelsnoted with CST at 0 min, 60 min, and 90 minwere 3 (9.1%), 10 (30.3%), and 20 (60.6%) respectively. No peak GH level was noted at 30 min, and 120 min during CST. The number and percentageof peak GH levels with GST at0 min, 120 min, and 180 min were 3 (9.1%), 14 (42.4%), and 16 (48.5%) respectively. No peak GH level occurredat 30, 60, 90 and 150 min during GST. MRI showed normal pituitary, hypoplastic pituitary, and pituitary stalk interruption syndrome in 10 (30%), 13 (40%), and 10 (30%) of patients respectively. Conclusions: The utility of both CST and GST was comparable in diagnosing short stature with severe GHD. However, CST performs better than GST inassessing the severity of GH deficiency in these patients. Our study concluded that the number and timing of blood sampling can be minimized into three following both CST (0, 60, 90 minutes) as well as GST (0, 120, 180 min) without sacrificing accuracy.

Limited Role of Endogenous Vasopressin/Copeptin in Stimulation of ACTH-Cortisol Secretion during Glucagon Stimulation Test in Humans.

Copeptin is a stable part of a vasopressin precursor that closely mirrors arginine vasopressin (AVP) secretion. It is known that AVP/copeptin is also released in response to nonosmotic stimuli, such as stress evoked during anterior pituitary dynamic testing. In order to examine the role of AVP in challenging the hypothalamo-pituitary-adrenal axis, we assessed adrenocorticotropic hormone (ACTH), cortisol, copeptin and growth hormone (GH) during a glucagon stimulation test (GST) in 10 patients with satisfactory initial cortisol concentrations (mean ± SD: 20.34 ± 5.10 µg/dL) and failure to show any further cortisol increment on stimulation. For comparison, we measured copeptin in two subjects during an insulin tolerance test (ITT). During GST, there was an increase in copeptin (p = 0.02, average individual increase of 98%, range 10% to 321%). There was a robust increase in GH (p = 0.002, average increase 3300%), a decline in cortisol (p = 0.02, average decline 21.8%) and a fall in ACTH (p = 0.06). The relative increase in copeptin during ITT (176% and 52.2%) overlapped with increments observed during GST; however, here there was an increase in cortisol (20.45→24.26 µg/dL and 4.23→29.29 µg/dL, respectively). There was a moderate correlation between copeptin and GH concentrations (r = 0.4235, p = 0.0007). These results confirm that AVP is not crucial for ACTH-cortisol stimulation, though it might be an important factor in GH secretion.

ODP372 A Rare Case Of Cornelia de Lange Syndrome With Hyperinsulinism And Hypopituitarism

Abstract Background Cornelia de Lange syndrome (CdLS) is characterized by slow growth with short stature, intellectual disability with developmental delays, distinctive facial features, and limb defects. Various genetic mutations have been associated with CdLS, with approximately 60% of cases having a mutation in the NIPBL gene. There are few published reports of endocrine disorders in individuals affected by CdLS. Clinical Case A four month old female was admitted for hypoglycemic seizures. She had previously undergone workup for CHARGE syndrome. Physical exam was remarkable for acrocephaly, malar hypoplasia, hypertelorism with downslanting eyes, hirsutism, and bradydactyly. During her hospitalization, she remained persistently hypoglycemic despite repeated dextrose boluses, prompting a scheduled fasting test. Results indicated severe hypoglycemia (37 mg/dL) with inappropriate suppression of beta-hydroxybutyrate (0. 08 mmol/L) and negative urine ketones. Her glucagon stimulation test result showed an exaggerated increase of the glucose greater than 30 mg/dL after glucagon administration (glucose was 31 mg/dL at the start of the test; peak glucose was 77 mg/dL after receiving 0. 03 mg/kg of glucagon), indicating excessive glycogen stores. These findings were consistent with hyperinsulinism. Furthermore, she was found to have an undetectable cortisol (&amp;lt;1. 0 ug/dL) with hypoglycemia, prompting a low dose ACTH stimulation test with results consistent with central adrenal insufficiency (baseline ACTH: &amp;lt;5 pg/mL, baseline cortisol: &amp;lt;1. 0 ug/dL, peak cortisol after receiving 10 micrograms of cosyntropin was 1.1 ug/dL). Additional evaluation revealed a low free T4 (0.5 ng/dL). Interestingly, the initial TSH was 6.46 uIU/mL, which later became undetectable (&amp;lt;0. 05 uIU/mL), consistent with central hypothyroidism. Ultimately, a brain MRI showed sella turcica hypoplasia with absence of the dorsum sella as well as corpus callosum hypoplasia and a thin pituitary infundibulum. The child was treated with diazoxide, hydrocortisone, and levothyroxine with improvement in clinical course. Genetic testing eventually confirmed CdLS, showing a heterozygous variant mutation (c.8077_8079dupGAC: p. D2693dup) in exon 47 of NIPBL gene, classified as autosomal dominant. Conclusion There are very few clinical reports that mention either hyperinsulinism or hypopituitarism in an individual affected by CdLS. This patient is a rare documented case of CdLS presenting with both hyperinsulinism and hypopituitarism. Further understanding of the different genetic mutations seen with CdLS could help identify atypical forms of CdLS associated with endocrinopathies and more clearly direct unifying treatment. Presentation: No date and time listed

Three-Year Observation of Glucose Metabolism After Pancreaticoduodenectomy: A Single-Center Prospective Study in Japan.

The glucose tolerance of patients changes considerably from before to after pancreaticoduodenectomy wherein approximately half of the pancreas is resected. The aim of this prospective study was to investigate the incidence of and risk factors for diabetes after pancreaticoduodenectomy. This study is a part of an ongoing prospective study, the Kindai Prospective Study on Metabolism and Endocrinology after Pancreatectomy (KIP-MEP) study. Of the 457 patients enrolled to date, 96 patients without diabetes who underwent pancreaticoduodenectomy were investigated in this study. Preoperatively, 1 month post-pancreaticoduodenectomy, and every 6 months thereafter, the glucose metabolism and endocrine function were evaluated using the 75 g oral glucose tolerance test. Various other metabolic, endocrine, and exocrine indices were also examined over a period of up to 36 months. Of the 96 patients analyzed in this study, 33 were newly diagnosed with diabetes. The cumulative diabetes incidence at 36 months following pancreaticoduodenectomy was 53.8%. The preoperative insulinogenic index and ΔC-peptide in the glucagon stimulation test were significantly lower in the progressors to diabetes than in the nonprogressors. Multivariate Cox regression analysis demonstrated that the insulinogenic index was the only significant risk factor for new-onset diabetes. The majority of patients developed new-onset diabetes after pancreaticoduodenectomy, and a low value of the insulinogenic index was suggested to be a risk factor for diabetes. Preoperative assessment for the prediction of the onset of diabetes serves as useful information for patients and is important for postoperative glycemic control and diabetes management in patients who require pancreaticoduodenectomy.

Performance of glucagon stimulation test in diagnosing central adrenal insufficiency in children when utilising the Roche Elecsys® cortisol II assay: a pilot study.

The glucagon stimulation test (GST) is used for the simultaneous assessment of central adrenal insufficiency (CAI) and growth hormone deficiency. The new Roche cortisol II (C II) assay was recently introduced, confounding interpretation of the GST. The performance of the GST in diagnosing central adrenal insufficiency (CAI), utilising the C II assay, was therefore compared with that of the overnight metyrapone test (ONMTPT). A diagnostic accuracy study was performed by retrospectively analysing folders and laboratory records of 25 children and adolescents investigated for hypopituitarism with the GST and the ONMTPT between September 2016 and December 2019. The peak serum cortisol (C)of the GST, the post-metyrapone serum 11-deoxycortisol and adrenocorticotropin levels of the ONMTPT were recorded. Diagnostic performance of the GST at a previously suggested cut-off of 374nmol/L was evaluated. Seventeen boys and 8 girls, aged 1.7-16.3years (median 7.3years) were identified. The sensitivity of the post-GST C-level at 374nmol/L was 0.40 (95% confidence interval [CI] 0.17-0.69), specificity 0.64 (95% CI 0.39-0.84), positive predictive value 0.44 (95% CI 0.19-0.73), negative predictive value 0.60 (95% CI 0.36-0.80), accuracy 0.54 (95% CI 0.35-0.72), positive likelihood ratio (+LR) 0.93 (95% CI 0.49-1.77) and negative LR 1.12 (95% CI 0.40-3.15). The area under the receiver of operating characteristics(ROC) curve was 0.379 (95% CI 0.142-0.615). This study suggests that the GST at any C II cut-off cannot replace the ONMTPT as a diagnostic test for CAI in children. Findings should be confirmed in a larger study.

An Examination of Donor Factors That Impact the Results of the Glucagon Stimulation Test as an Assessment of the Pancreatic Graft Endocrine Function.

Delta C-peptide derived by the glucagon stimulation test is a reliable value for the evaluation of the pancreatic endocrine function after pancreas transplantation. We examined the associations between delta C-peptide as pancreatic graft endocrine function and donor background factors. Sixty-five cases of pancreatic transplantation from brain-dead donors, which were performed in our facility, were enrolled in this study. Enrolled recipients underwent a glucagon stimulation test within 1 to 3 months after transplantation to evaluate the pancreatic graft endocrine function with delta C-peptide to compare donor background factors. The following factors were associated with significant deterioration of the delta C-peptide: age of 50 years or greater, death from cerebrovascular accident, hemoglobin A1c level of 5.6% or greater, creatinine level of 1.0 mg/dL or greater, C-reactive protein level of 25 mg/dL or greater, and sodium level of 150 mmol/L or greater. In addition, increased numbers of these donor factors indicated significantly greater deterioration of the posttransplant pancreatic endocrine function ( P &lt; 0.001). To secure insulin independence after pancreas transplantation, which means maintaining a delta C-peptide level of 1.0 ng/mL or greater on a glucagon stimulation test, the utilization of donors, who possesses more than equal to 3 of the donor factors identified in this study, should be carefully considered.

The effect of glucose dynamics on plasma copeptin levels upon glucagon, arginine, and macimorelin stimulation in healthy adults

PurposeNon-osmotic stimulation tests using glucagon, arginine, or macimorelin were recently evaluated for their ability to assess posterior pituitary function. Glucagon and arginine, but not macimorelin, stimulated copeptin secretion (a surrogate marker of vasopressin) and, therefore, provide novel tests to assess the posterior pituitary. The exact underlying mechanism behind their stimulatory effect remains elusive.MethodsThis analysis combined data from three diagnostic studies conducted at the University Hospital Basel, Switzerland. In total, 80 healthy adults underwent the glucagon (n = 22), arginine (n = 30), or macimorelin (n = 28) stimulation tests. The primary objective was to investigate glucose course upon glucagon, arginine, and macimorelin stimulation tests and its effect on plasma copeptin release.ResultsUpon glucagon stimulation, the median [IQR] glucose level at baseline was 5.0 [4.6, 5.2] mmol/l, peaked at 8.1 [7.2, 9.4] mmol/l after 30 min and decreased to a minimum of 3.8 [3.5, 4.5] mmol/l after 120 min. The median copeptin increase upon glucagon stimulation was 7.7 [2.6, 28.0] pmol/l. Upon arginine, the glucose level at baseline was 4.9 [4.8, 5.5] mmol/l, peaked at 6.0 [5.2, 6.4] mmol/l after 30 min and decreased to a minimum of 4.3 [3.8, 4.8] mmol/l after 60 min. The median copeptin increase upon arginine stimulation was 4.5 [2.9, 7.5] pmol/l. Upon macimorelin, glucose levels showed no notable dynamics over the 120 min, and no major change in copeptin was observed.In the pooled dataset, a decrease in glucose levels was significantly correlated with copeptin increase (ρ = 0.53, p < 0.01).ConclusionA similar course in plasma glucose was observed in the copeptin-stimulating test, i.e., after glucagon and arginine, while macimorelin had no effect on glucose and copeptin levels. We hypothesize that a drop in glucose levels observed upon glucagon and arginine might stimulate copeptin.

Evaluation of copeptin levels during glucagon stimulation test in children with suspected growth hormone deficiency

Evaluation of copeptin levels during glucagon stimulation test in children with suspected growth hormone deficiency

Evaluation of the Efficacy and Effects of Common Hepatic Artery Reconstruction in Pancreas Transplantation: A Randomized Controlled Trial.

Maintenance of postoperative graft flow is important in pancreas transplantation. In Japan, reconstruction of the common hepatic artery is performed primarily to increase perfusion in the pancreatic head. We investigated the effects of common hepatic artery reconstruction on patient and graft survival and endocrine functions. Twenty-nine cases of pancreas transplantation were registered in the clinical trial. Of the 29 cases, four were excluded because of the risk of ischemia without reconstruction or complicated reconstruction due to a narrow artery. A total of 25 cases were randomized into two groups: 13 in the non-reconstructed group and 12 in the reconstructed group. The 1-year patient survival and graft survival rates of the non-reconstructed and reconstructed groups were 92.3% and 83.3%, and 91.7% and 82.5%, respectively. The incidence of complications in the two groups was comparable, with 38.5% (5/13 cases) in the non-reconstructed group and 33.3% (4/12 cases) in the reconstructed group. The results of the glucagon stimulation test and oral glucose tolerance test at 1 month and 1 year post-transplantation were comparable. Common hepatic artery reconstruction is not essential unless there is risk of ischemia. This study was registered at the University Hospital Medical Information Network Clinical Trials Registry under UMIN000027213.

Improved Insulin Resistance and Glucose Variability by Super-Low Carbohydrate Diet

Background Diabetes mellitus (DM) has been more prevalent. American Diabetes Association (ADA) proposed the Standards of Medical Care in Diabetes-2022. For nutritional therapy, low carbohydrate diet (LCD) has been recognized for its benefits. Authors have continued diabetic research concerning LCD and meal tolerance test (MTT). Case Presentation The case is 61-year-old male with type 2 diabetes mellitus (T2DM) for years. His hemoglobin A1c (HbA1c) increased to 7.8% in autumn 2021, and further evaluation and treatment was conducted including LCD, daily check of meal and carbohydrate amount, 75 g OGTT, glucagon stimulation test (GST) and others. Results He was on super-LCD method including 12% of carbohydrate. His carbohydrate intake amount and 45-minutes post-prandial blood glucose showed significant correlation. The results of 75 g OGTT twice in May 2020 and December 2021 showed that similar pattern of glucose and insulin responses and insulinogenic index (IGI). In contrast, they showed decreased fasting immuno-reactive insulin (IRI) and Homeostasis model assessment insulin resistance (HOMA-R). For GST, C-peptide showed normal response. Discussion and Conclusion Judging from the results of MTT, OGTT, GST and IGI, he seems to show rather decreased insulin resistance by LCD associated with preserved insulin secretion ability to some degree. Further investigation would be required from pathophysiological point of view.

Gender-specific soluble α-klotho levels as marker of GH deficiency in children: a case–control study

PurposeTo evaluate circulating soluble α-klotho (sαKL) levels in GHD children before and after 12 months of GH treatment (GHT).MethodsAuxological and basal metabolic parameters, oral glucose tolerance test for glucose and insulin levels, insulin sensitivity indices and klotho levels were evaluated before and after 12 months of follow-up in 58 GHD children and 56 healthy controls.ResultsAt baseline, GHD children showed significantly lower growth velocity standard deviation score (SDS) (p < 0.001), bone/chronological age ratio (p < 0.001), GH peak and area under the curve (AUC) after arginine test (ARG) (both p < 0.001) and glucagon stimulation test (GST) (p < 0.001 and 0.048, respectively), IGF-1 (p < 0.001), with higher BMI (SDS) (p < 0.001), WC (SDS) (p = 0.003) and sαKL (p < 0.001) than controls. After 12 months of GHT, GHD children showed a significant increase in height (SDS) (p < 0.001), growth velocity (SDS) (p < 0.001), bone/chronological age ratio (p < 0.001) IGF-1 (p < 0.001), fasting insulin (p < 0.001), Homa-IR (p < 0.001) and sαKL (p < 0.001) with a concomitant decrease in BMI (SDS) (p = 0.002) and WC (SDS) (p = 0.038) than baseline. At ROC curve analysis, we identified a sαKL cut-off to discriminate controls and GHD children of 1764.4 pg/mL in females and 1339.4 pg/mL in males.At multivariate analysis, the independent variables significantly associated with sαKL levels after 12 months of GHT were the oral disposition index (p = 0.004, β = 0.327) and IGF-1 (p = 0.019, β = 0.313).ConclusionsGender-related sαKL may be used as a marker of GHD combined to GH and IGF-1. Insulin and IGF-1 are independently associated with sαKL values after 12 months of GHT.

Safety Assessment and Potential Risks of the Glucagon Stimulation Test in the Diagnosis of Secondary Adrenal Insufficiency.

Although it takes more time, the Glucagon Stimulation Test (GST) is a reliable measure for assessing growth hormone (GH) and Adrenocorticotropic Hormone (ACTH) secretion. The GST is considered to be a safe test; however, it still has mild side effects and potential risks. The objective of this study was to analyze the side effects of the GST while testing adrenal-insufficient patients. This was a prospective study in which GST was performed in eighty-one patients (44 men, 37 women, mean age: 35.83A9.62 years) with the pituitary disorder. The GST consisted of an intramuscular injection of 1 mg of glucagon. Blood samples were collected at baseline, and 30, 60, 90, 120, 150, 180, and 210 min after glucagon injection for cortisol measurements. All patients were asked to report side effects associated with this test. The mean peak blood glucose level under GST was 9.01A.03 mmol/L, and the mean glycemic nadir was 4.34A.75 mmol/L most frequently found during the 30th minute (p <10-3). During the test, 35 subjects (43.2%) had side effects with a mean age of 42.89 A19.75 years. Frequent side effects included: nausea (29.62%), vomiting (27.16%), abdominal cramps (18.51%) and hunger (13.58%). All patients tolerated the test until the end. Adverse effects were significantly more prevalent in patients older than 50 years (p=0.012). The GST is a reliable alternative to assess the hypothalamic pituitary adrenal axis but should be cautiously used especially in the elderly, despite minor side effects.

Investigation of pituitary functions after acute coronavirus disease 2019.

Although coronavirus disease 2019 (COVID-19) mainly involves the lungs, it also affects many systems. The hypothalamic/pituitary axis is vulnerable to hypoxia, hypercoagulation, endothelial dysfunction and autoimmune changes induced by COVID-19 infection. Given that there is no extensive investigation on this issue, we investigated the pituitary functions three to seven months after acute COVID-19 infection. Forty-three patients after diagnosis of COVID-19 infection and 11 healthy volunteers were included in the study. In addition to the basal pituitary hormone levels, growth hormone (GH) and hypothalamo-pituitary adrenal (HPA) axes were evaluated by glucagon stimulation test (GST) and low-dose adrenocorticotropic hormone (ACTH) stimulation test, respectively. The peak cortisol responses to low-dose ACTH test were insufficient in seven (16.2%) patients. Twenty (46.5%) and four (9.3%) patients had inadequate GH and cortisol responses to GST, respectively. Serum insulin-like growth factor-1 (IGF-1) values were also lower than age and sex-matched references in four (9.3%) patients. The peak GH responses to GST were lower in the patient group when compared to the control group. Other abnormalities were mild thyroid-stimulating hormone elevation in four (9.3%) patients, mild prolactin elevation in two (4.6%) patients and central hypogonadism in four (9.3%) patients. Mean total testosterone values were lower in male patients when compared to male controls; however, the difference was not significant. These findings suggest that COVID-19 infection may affect pituitary functions, particularly the HPA and GH axes. These insufficiencies should be kept in mind in post-COVID follow-up. Long-term data are needed to determine whether these deficiencies are permanent or not.

207.3: Predictive Value of C-peptide Measures for Clinical Outcomes of Islet Transplantation in Type 1 Diabetes: A Report From the Collaborative Islet Transplant Registry (CITR)

CITR Investigators Introduction: Long-standing type 1 diabetes (T1D) can lead to impaired awareness of hypoglycemia and high-risk for severe hypoglycemic episodes (SHE). Islet transplantation (ITx) can restore endogenous insulin production, ameliorate glucose control, and abolish SHE. In the DCCT, a stimulated C-peptide >0.2 nmol/L was associated with lower HbA1c, reduced insulin requirements, and decreased prevalence of SHE. We set forth to determine what measures of C-peptide and levels are associated with achievement of ITx positive outcomes in T1D. Methods: Collaborative Islet Transplant Registry (CITR) Islet-Alone recipients with pre-transplant C-peptide <0.1 nmol/L and mean follow up of 4.6±1.1 years were included in the analyses (n=677). Post-transplant metabolic measures obtained from arginine stimulation test, IVGTT, OGTT, glucagon stimulation test and mixed meal stimulation test (MMTT) were evaluated. Predictive value of these measures for 7 primary outcomes of clinical ITx (i.e., absence of SHEs (ASHE); HbA1c<7.0%; HbA1c <7.0% & ASHE; HbA1c≤6.5; HbA1c≤6.5% & ASHE; insulin independence; and ASHE, HbA1c≤6.5%, and insulin independence) was assessed by area under the curve of receiver-operator characteristics curves (ROC-AUC). Measures with the highest ROC-AUC were then selected for determination of optimal cut points by ITx outcome. Results: Fasting C-peptide, MMTT stimulated C-peptide, fasting C-peptide to Glucose (Cpep/Glu) ratio, and MMTT stimulated Cpep/Glu ratio showed the highest ROC-AUCs among all measures evaluated (Table 1). Fasting C-peptide was highly predictive for ASHE (ROC-AUC = 0.9228; optimal cut point = 0.07 nmol/L), and the composite outcome of ASHE, HbA1c≤6.5%, and insulin independence (ROC-AUC = 0.8456; optimal cut point = 0.33 nmol/L) (Table 2). However, MMTT stimulated Cpep/Glu ratio outperformed both fasting and stimulated C-peptide for all outcomes except ASHE alone. Optimal cut point for the ideal composite outcome of ASHE, HbA1c≤6.5%, and insulin independence was 0.12 nmol/mmol for the MMTT stimulated Cpep/Glu ratio, and 0.97 nmol/L for MMTT stimulated C-peptide (Table 2). Discussion/Conclusion: Fasting C-peptide reliably predicts rates of ITx primary endpoints and is similar to other C-peptide measures at predicting ASHE. Although marginal endogenous fasting C-peptide is sufficient to eliminate SHEs, higher levels are required to achieve optimal ITx outcomes. The MMTT stimulated Cpep/Glu ratio provides better predictiveness for composite ITX outcomes, including insulin independence. In the absence of a MMTT, a fasting C-peptide ≥0.33 nmol/L is a reassuring measure of optimal metabolic control in ITx T1D recipients.The CITR has been funded continuously by grants from the National Institute of Diabetes and Digestive and Kidney Diseases since 2001 (Grants 1UCHDK098086-01, 1UC4DK114839-01) to collect data on the efficacy and safety of clinical islet transplantation from US and collaborating international institutions. The Juvenile Diabetes Research Foundation provided supplemental funding for reimbursement of efforts to report data from the European and Australian sites from 2006–2015. No other sponsors have provided support to the CITR. MRR is supported in part by Public Health Service Research Grant R01 DK 091331-8. We thank all the study participants and staff.

The stimulatory effects of glucagon on cortisol and GH secretion occur independently from FGF-21.

Glucagon stimulation test (GST) is used to assess the hypothalamo-pituitary-adrenal (HPA) and growth hormone (GH) axes with an incompletely defined mechanism. We aimed to assess if glucagon acted through fibroblast growth factor-21 (FGF-21) to stimulate cortisol and GH secretion. The secondary outcome was to determine the relationship of FGF-21 with variable GH responses to GST in obesity. A total of 26 healthy participants; 11 obese (body mass index (BMI) > 30 kg/m2) and 15 leans (BMI < 25 kg/m2) were included. Basal pituitary and target hormone levels were measured and GST was performed. During GST, glucose, insulin, cortisol, GH, and FGF-21 responses were measured. The mean age of the participants was 26.3±3.6 years. Glucagon resulted in significant increases in FGF-21, glucose, insulin, cortisol, and GH levels. The levels of basal cortisol, GH, FGF-21, and IGF-1 were similar in the two groups. The peak GH and area under the curve (AUC)(GH) responses to GST in the obese group were lower than those of the normal-weight group with a different pattern of response. There were no differences between the groups in terms of peak cortisol, AUC(cortisol), peak insulin, AUC(insulin), peak FGF-21, and AUC(FGF21). Obesity was associated with significantly increased glucose and insulin responses and slightly decreased FGF-21 response to glucagon. Obesity was associated with blunted and delayed GH, but preserved cortisol responses to GST. This is the first study showing that glucagon stimulates the HPA and GH axis independently from FGF-21. The delayed GH response to GST in obesity does not seem to be related to FGF-21.