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Among growth hormone (GH) provocative tests, insulin tolerance test (ITT) is considered a valuable test in children with short stature to diagnose GH deficiency. However, many pediatric endocrinologists are reluctant to perform it. We conducted a nationwide survey among all the pediatric endocrine clinics' heads in Israel regarding their position on this issue. We found that the number of endocrine units performing ITT is almost nil. Sense of fear from severe hypoglycemia was a dominating cause for not performing ITT. We review the pros and cons of performing ITT versus other tests, especially glucagon test. Glucagon tolerance test is not considered the test of choice by some endocrinologists but recommended by others including in Israel. We also note the influence of a widely cited report published in 1992 (many times inaccurately) on endocrinologists' views. Conclusion: A nationwide survey in Israel revealed a high rate of reluctance to perform ITT. The rationale behind this attitude was a sense of fear of performing the test by many endocrinologists. We discuss the preferences for choosing GH stimulation tests and the pros and cons of alternatives to ITT. The fear of not performing ITT was not always justified. What is Known: • ITT test is considered a gold standard in the evaluation of short stature to diagnose GH deficiency by many endocrinologists. What is New: • High reluctance rate found in Israel to perform ITT, prompted us to evaluate the attitudes of pediatric endocrinologists around the world showing conflicting ideas. • The role of a single paper sometimes misquoted also contributed to these conflicting results. [ABSTRACT FROM AUTHOR]

There are many tests for evaluating endogenous insulin secretory capacity. However, there are only a limited number of studies that have examined in detail in clinical practice which method most accurately reflects the ability to secrete endogenous insulin especially in hyperglycemic state. The purpose of this study was to find the endogenous insulin secretory capacity and a possible predictor of insulin withdrawal in subjects with type 2 diabetes requiring hospitalization due to hyperglycemia. In the endogenous insulin secretory test during hospitalization, CPR, CPR index, and DCPR after glucagon loading were all significantly higher in the insulin withdrawal group. On the other hand, there were no difference in fasting CPR index, HOMA-b, SUIT, and 24-hour urinary CPR excretion between the two groups. In the glucagon test of the insulin withdrawal group, the cutoff value of DCPR was 1.0 ng/mL, the withdrawal rate of DCPR of 1.0 ng/mL or more was 69.2%, and the withdrawal rate of less than 1.0 ng/mL was 25.0%. In conclusion, it is likely that glucagon test is the most powerful tool for predicting the possibility of insulin withdrawal as well as for evaluating endogenous insulin secretory capacity in subjects with type 2 diabetes requiring hospitalization due to hyperglycemia. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective 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. Subjects and methods 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. Results 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. Conclusion 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.

Background and Objectives: Insulin treatment may be initially required to stabilize patients presenting with metabolic crisis at type 1 and 2 diabetes mellitus (DM) onset. Some patients with type 2 DM may need persistent insulin treatment. This study aimed to examine the predictive performance of non-stimulated C-peptide level at the time of diagnosis for future insulin use in pediatric diabetic patients. Materials and Methods: We reviewed the medical charts of diabetic patients aged 18 years or younger in a medical center in southern Taiwan from January 2000 to December 2019. Clinical and individual data were collected at the time of DM diagnosis. Outcomes were persistent insulin use at the time of diagnosis, as well as at one and two years after diagnosis. Results: The final analysis included a total of 250 patients. The best cut-off point of non-stimulated C-peptide was 0.95 ng/mL, and the predictive indices for the insulin use were 0.84 for sensitivity and 0.94 for specificity at two years after DM diagnosis. Incorporating age at onset and presence of GAD antibodies can further increase the predictive power of non-stimulated C-peptide. Conclusions: The value of non-stimulated C-peptide at diabetic onset was feasible and effective for predicting future insulin treatment up to the time point of two years after diagnosis. [ABSTRACT FROM AUTHOR]

To understand the importance of autoimmunity in the development of type 1 diabetes in Taiwanese children, we evaluated the presence of β-cell autoantibodies and their correlation with residual β-cell function. Methods: From 1989 to 2006, 157 Taiwanese children with newly diagnosed type 1 diabetes were enrolled in this study. We determined the presence of β-cell autoantibodies, such as glutamic acid decarboxylase autoantibodies (GADAs), insulinoma antigen 2 autoantibodies (IA-2As), and insulin autoantibodies (IAAs). A 6-minute glucagon test was also performed at diagnosis. Results: At diagnosis, 73% of children tested positive for GADAs, 76% for IA-2As and 21% for IAAs. Ninety-two percent of them had at least one of the β-cell autoantibodies detected. Positivity for IAAs was more frequent in patients younger than 5 years than in those older than 5 years (45% vs. 13%). Using multiple regression analysis, the presence of GADAs or IAAs, or age of onset of these patients was an independent factor for residual β-cell function. Younger patients and those with GADAs had less residual β-cell function at disease onset, whereas those with IAAs had more insulin reserve. Conclusion: Autoimmunity plays an important role in the pathogenesis of type 1 diabetes in Taiwanese children, and the presence of IAAs tends to be more common in younger children.

Laparoscopic Roux-en-Y gastric bypass (RYGB) achieves a higher remission of type 2 diabetes mellitus (T2DM) than laparoscopic sleeve gastrectomy (SG) in non-morbidly obese patients. However, the mechanisms of the higher remission are unknown. To compare glucagon-provoked acute insulin responses, as well as changes of gut and pancreatic hormones and adipokines between patients with T2DM after RYGB and SG at one year post-operatively, a total of 14 RYGB and 13 SG patients were followed-up and evaluated for glucose metabolism, gut and pancreatic hormones, and adipokines. One year after surgery, 1-mg intravenous glucagon tests were performed. The differences in each hormone at different time points and the area under the curve (AUC) were compared between the two groups. Glucagon-stimulated acute insulin responses were not different between the RYGB and SG groups, nor were they different between the remitters and non-remitters at one year after the metabolic surgery. Plasma des-acyl ghrelin and nesfatin-1 levels significantly decreased at 6 min after glucagon stimulation in the RYGB and SG groups, as well as in the remitters and non-remitters. The glucagon test did not affect intestinal hormones. Plasma resistin was suppressed after intravenous glucagon stimulation in both RYGB and SG groups. In conclusion, intravenous glucagon inhibited plasma levels of des-acyl ghrelin, nesfatin-1, and resistin in T2DM patients at one year after both RYGB and SG, whereas post-glucagon suppression of plasma obestatin and resistin was shown in the remitters but not in the non-remitters. [ABSTRACT FROM AUTHOR]

Aims: In this study, we evaluated the diagnostic usefulness of oral L-dopa as a stimulatory agent for cortisol. Methods: In27 short children that were evaluated for possible growth hormone deficiency (GHD), the levels of serum GH and cortisol were determined after oral L-dopa administration and after i.m. glucagon administration. We defined cortisol concentrations >18 μg/dl (496 nmol/l) as adequate response. Peak GH concentration <10 ng/ml in both tests defined GHD. Results: Twenty-five out of the 27 children (93%) studied showed a normal cortisol response, i.e. a peak serum cortisol >18 μg/dl in the L-dopa test, whereas 19 children (70%) had a normal cortisol response after stimulation with glucagon. In the children with normal cortisol response in both tests, the mean peak serum cortisol concentration was 28.7 (SD 1.59) after L-dopa and 26.65 (SD 1.26) μg/dl after glucagon administration. There was no statistically significant difference in peak serum cortisol response to L-dopa between GH-deficient and GH-sufficient children [25.90 (SD 4.9) vs. 29.87 (SD 9.9) μg/dl, respectively]. Conclusions: These results clearly suggest that L-dopa administration is a potent stimulus for cortisol secretion at least in short children. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Overall adiposity is associated with insulin resistance. Decline in insulin sensitivity induces a compensatory increase in insulin secretion from beta cells. The impact of adipose tissue distribution, i.e., visceral versus subcutaneous fat, on beta cell function remains to be elucidated. The aim of this study was to retrospectively investigate the relation between the areas of subcutaneous and visceral fat and the increment in C-peptide levels (CPR) during glucagon load (ΔCPR) in Japanese patients with type 2 diabetes. In 195 Japanese patients with type 2 diabetes, beta cell function was evaluated by ΔCPR, CPR index (100 × fasting CPR divided by fasting glucose), and 24-h urinary C-peptide excretion (U-CPR) during the 1-week hospitalization for diabetes education. Then, we investigated the relationships between markers of beta cell function and the areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) determined by abdominal computed tomography. Stepwise multiple regression analyses identified SAT, but not VAT, as an independent variable of both ΔCPR and U-CPR [standard regression coefficient (Std β) = 0.332, P < 0.01 for ΔCPR, and Std β = 0.181, P < 0.05 for U-CPR], and both SAT and VAT were identified as independent variables for CPR index (Std β = 0.253, P < 0.01 for SAT, and Std β = 0.193, P < 0.01 for VAT). Our results indicated that SAT is independently correlated with beta cell function by glucagon test in Japanese patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Cystinosis is an autosomal recessive disorder characterized by intralysosomal cystine accumulation. Growth retardation is more pronounced in cystinosis than in other chronic kidney diseases and is mostly not corrected by cysteamine. Methods: Growth was evaluated in nine cystinosis patients, all treated with cysteamine, both after cysteamine and recombinant human growth hormone (rhGH) therapy initiation. Growth hormone (GH) secretion was studied by nocturnal GH measurements in four of nine patients and by glucagon test in four of nine patients. Results: RhGH was administered to seven of nine patients. At rhGH initiation, height was below −2 SDS in five of seven patients, final height was above −2 SDS in six of seven. In two patients not treated with rhGH, final height remained below −4 SDS despite cysteamine treatment being started at the age of 6.1 and 8.1 years, respectively. Nocturnal GH secretion was normal in all patients. Glucagon tests revealed GH deficiency in one patient; two of four patients had abnormal GH peak timing. Conclusions: We present the first reported case of GH deficiency in cystinosis. Although no overt GH deficiency was detected in other patients, abnormal GH peak timing can indicate a subclinical GH secretion problem. RhGH significantly improved growth in cystinosis patients and should be initiated early in life. [ABSTRACT FROM AUTHOR]

A 52-year-old lean woman was admitted to hospital for a medical examination in July 2010. A 75 g oral glucose test (75 g OGTT) revealed postprandial hyperglycemia (above 200 mg/dl at 120 min) and she was diagnosed with diabetes mellitus. She was negative for diabetes-related autoantibodies. The 75 g OGTT also revealed a very low insulinogenic index (I.I.) of 0.024 μU/ml/mg/dl; however, her plasma C-peptide immunoreactivity (CPR) response to glucagon was preserved (0.94 and 5.56 at 0 and 6 min, respectively). At the same time, she also suffered from Fe-deficiency anemia due to endometriosis, for which treatment with leuprorelin was initiated after hospitalization in August 2010. Meanwhile, her postprandial plasma glucose level continued to increase. Subsequently, on November 30, 2010, alogliptin therapy at a dose of 6.25 mg was initiated, which was increased to 25 mg on December 28, 2010. Leuprorelin therapy was discontinued on January 14, 2011; however, her plasma glucose level remained high despite the alogliptin therapy. Administration of 0.3 mg liraglutide was initiated on March 15, 2011, and the dose was increased to 0.6 mg on June 7, 2011. The plasma glucose level, glycosylated hemoglobin (HbA1c) level, and 1.5 anhydroglucitol level gradually improved, as did her I.I. Moreover, fasting plasma glucagon levels were suppressed by liraglutide. Her fasting serum CPR to plasma glucose ratio and homeostasis model assessment (HOMA-R) were low both before and after liraglutide administration. These results suggest that the fasting CPR to glucose ratio may underestimate residual islet function in lean patients with high insulin sensitivity. Thus, a glucagon test may be useful to estimate residual islet function when administering liraglutide treatment in lean diabetes patients. [ABSTRACT FROM AUTHOR]

Background/purpose: To understand the importance of autoimmunity in the development of type 1 diabetes in Taiwanese children, we evaluated the presence of beta-cell autoantibodies and their correlation with residual beta-cell function.Methods: From 1989 to 2006, 157 Taiwanese children with newly diagnosed type 1 diabetes were enrolled in this study. We determined the presence of beta-cell autoantibodies, such as glutamic acid decarboxylase autoantibodies (GADAs), insulinoma antigen 2 autoantibodies (IA-2As), and insulin autoantibodies (IAAs). A 6-minute glucagon test was also performed at diagnosis.Results: At diagnosis, 73% of children tested positive for GADAs, 76% for IA-2As and 21% for IAAs. Ninety-two percent of them had at least one of the beta-cell autoantibodies detected. Positivity for IAAs was more frequent in patients younger than 5 years than in those older than 5 years (45% vs. 13%). Using multiple regression analysis, the presence of GADAs or IAAs, or age of onset of these patients was an independent factor for residual beta-cell function. Younger patients and those with GADAs had less residual beta-cell function at disease onset, whereas those with IAAs had more insulin reserve.Conclusion: Autoimmunity plays an important role in the pathogenesis of type 1 diabetes in Taiwanese children, and the presence of IAAs tends to be more common in younger children. [ABSTRACT FROM AUTHOR]

This study evaluates the effects of glucagon 30 μg/kg (maximal 1 mg) on β-cell function in children by C-peptide determined before and 6 min after intravenous administration. From 1990 to 2005, 118 Taiwanese children with newly diagnosed diabetes mellitus (98 children with type 1 and 20 children with type 2) and 29 normal Taiwanese children were enrolled in this study. Fasting and 6-min post-glucagon C-peptide levels were analyzed. In the pre-pubertal group, the median fasting serum C-peptide levels were 0.2 and 0.8 nmol/l in type 1 diabetes and normal children, respectively. These levels rose to 0.3 and 1.9 nmol/l after glucagon stimulation. In the pubertal group, the median fasting serum C-peptide levels were 0.3, 1.0 and 0.9 nmol/l in type 1 diabetes, type 2 diabetes and normal children, respectively. They rose to 0.4, 2.5 and 2.7 nmol/l after glucagon stimulation. Both fasting and post-glucagon C-peptide levels in type 1 diabetes patients were significantly lower than those of normal children and children with type 2 diabetes. The optimal cut-off values to distinguish type 1 diabetes patients from those with type 2 as determined by the receiving operating characteristic curve were 0.7 and 1.1 nmol/l, respectively. The sensitivities of both C-peptide values were 93%. The post-glucagon C-peptide level was more powerful in distinguishing type 1 diabetes from type 2 diabetes with higher specificity (95% vs. 85%). The 6-min glucagon test is valuable in assessing β-cell function in children and can help pediatricians in the differential diagnoses of diabetes mellitus in children. [ABSTRACT FROM AUTHOR]

The hypothalamo-pituitary-adrenal (HPA) axis plays a major role in the regulation of responses to stress. Human stress-related disorders such as chronic fatigue syndrome (CFS), fibromyalgia syndrome (FMS), chronic pelvic pain and post-traumatic stress disorder are characterized by alterations in HPA axis activity. However, the role of the HPA axis alterations in these stress-related disorders is not clear. Most studies have shown that the HPA axis is underactive in the stress-related disorders, but contradictory results have also been reported, which may be due to the patients selected for the study, the methods used for the investigation of the HPA axis, the stage of the syndrome when the tests have been done and the interpretation of the results. There is no structural abnormality in the endocrine organs which comprise the HPA axis, thus it seems that hypocortisolemia found in the patients with stress-related disorder is functional. It may be also an adaptive response of the body to chronic stress. In this review, tests used in the assessment of HPA axis function and the HPA axis alterations found in CFS and FMS are discussed in detail. [ABSTRACT FROM AUTHOR]

Objective: To clarify whether random C-peptide is a valuable test in the classification of diabetes.Research Design and Methods: All C-peptide measurements conducted in the diabetic population of Skaraborg (280,539 inhabitants and 3.2% diabetes) between 1995 and 1998 (3,115 samples) were considered, but only patients with well-defined diabetes type (1,449 samples from 1,093 patients) were analyzed for the correlation between diabetes type and C-peptide concentration. Serum C-peptide was measured after fasting over night (fCP), after glucagon stimulation (gCP), and randomly (rCP) without considering previous meals at an ordinary visit to the diabetic clinic (rCP). Receiver Operating Characteristic (ROC) curves were constructed to illustrate the power of the different C-peptide protocols and to determine the optimal cut-off values.Results: Although all three tests had high discriminative power, the ROC curves demonstrated that rCP was superior to fCP and gCP in discriminating type 1 from type 2 diabetes. The optimal cut-off value for rCP was 0.50 nmol/L, for fCP 0.42 nmol/L, and for gCP 0.60 nmol/L.Conclusions: rCP is more powerful than fCP and gCP in distinguishing type 1 from type 2 diabetes and can therefore be recommended as a classification tool, particularly in outpatients. [ABSTRACT FROM AUTHOR]

There are many tests for evaluating endogenous insulin secretory capacity. However, there are only a limited number of studies that have examined in detail in clinical practice which method most accurately reflects the ability to secrete endogenous insulin especially in hyperglycemic state. The purpose of this study was to find the endogenous insulin secretory capacity and a possible predictor of insulin withdrawal in subjects with type 2 diabetes requiring hospitalization due to hyperglycemia. In the endogenous insulin secretory test during hospitalization, CPR, CPR index, and ΔCPR after glucagon loading were all significantly higher in the insulin withdrawal group. On the other hand, there were no difference in fasting CPR index, HOMA-β, SUIT, and 24-hour urinary CPR excretion between the two groups. In the glucagon test of the insulin withdrawal group, the cutoff value of ΔCPR was 1.0 ng/mL, the withdrawal rate of ΔCPR of 1.0 ng/mL or more was 69.2%, and the withdrawal rate of less than 1.0 ng/mL was 25.0%. In conclusion, it is likely that glucagon test is the most powerful tool for predicting the possibility of insulin withdrawal as well as for evaluating endogenous insulin secretory capacity in subjects with type 2 diabetes requiring hospitalization due to hyperglycemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Iwamoto, Kimura, Tatsumi, Sugisaki, Kubo, Nakao, Dan, Wamata, Iwamoto, Takahashi, Sanada, Fushimi, Katakura, Shimoda, Nakanishi, Mune, Kaku and Kaneto.)

Copyright of Acta Diabetologica Latina is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Diabetologica Latina is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Objectives : Insulin treatment may be initially required to stabilize patients presenting with metabolic crisis at type 1 and 2 diabetes mellitus (DM) onset. Some patients with type 2 DM may need persistent insulin treatment. This study aimed to examine the predictive performance of non-stimulated C-peptide level at the time of diagnosis for future insulin use in pediatric diabetic patients. Materials and Methods : We reviewed the medical charts of diabetic patients aged 18 years or younger in a medical center in southern Taiwan from January 2000 to December 2019. Clinical and individual data were collected at the time of DM diagnosis. Outcomes were persistent insulin use at the time of diagnosis, as well as at one and two years after diagnosis. Results : The final analysis included a total of 250 patients. The best cut-off point of non-stimulated C-peptide was 0.95 ng/mL, and the predictive indices for the insulin use were 0.84 for sensitivity and 0.94 for specificity at two years after DM diagnosis. Incorporating age at onset and presence of GAD antibodies can further increase the predictive power of non-stimulated C-peptide. Conclusions : The value of non-stimulated C-peptide at diabetic onset was feasible and effective for predicting future insulin treatment up to the time point of two years after diagnosis.

Objective: 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., Methods: 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., Results: 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., Conclusion: 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.