Glucagon Test Research Articles

The Glucagon Test in the Diagnosis of Growth Hormone Deficiency in Children With Short Stature Younger than 6 Years

Few studies have addressed the diagnostic role of the glucagon test in children with suspected GH deficiency (GHD). The objective of the study was to investigate the diagnostic value of the glucagon test as an alternative test to insulin tolerance test (ITT) and arginine in GHD children younger than 6 yr. This study was conducted in two pediatric endocrinology centers. Forty-eight children (median age 4.2 yr, median height -3.0 sd score) with GHD confirmed by a peak GH to ITT and arginine less than 10 microg/liter (median 4.7 and 3.4 microg/liter, respectively) underwent a glucagon stimulation test. Magnetic resonance imaging showed normal hypothalamic-pituitary anatomy in 24 children, isolated anterior pituitary hypoplasia in seven, and structural hypothalamic-pituitary abnormalities in 17. Median GH peak response to glucagon (13.5 microg/liter) was significantly higher than that observed after ITT and arginine (P < 0.0001). GH peak after glucagon was less than 10 microg/liter in 20 subjects (group 1) and greater than 10 microg/liter in 28 subjects (group 2) without significant clinical or biochemical differences between the two groups. Median GH peak after glucagon was similar between patients with multiple pituitary hormone deficiency and those with isolated GHD and between subjects with and without structural hypothalamic-pituitary abnormalities. The magnitude of the GH peak after glucagon was negatively correlated to age at diagnosis (rho = -0.636, P < 0.0001). This study shows that glucagon has an effective GH-releasing activity and can be used to evaluate somatotroph function in young children with short stature. Normative data for this test in young children need to be established before its use in clinical practice.

Hypopituitarism following traumatic brain injury: prevalence is affected by the use of different dynamic tests and different normal values

Traumatic brain injury (TBI) has emerged as an important cause of hypopituitarism. However, considerable variations in the prevalence of hypopituitarism are reported. These can partly be explained by severity of trauma and timing of hormonal evaluation, but may also be dependent on endocrine tests and criteria used for diagnosis of hypopituitarism. Systematic review of studies reporting prevalence of hypopituitarism in adults >or=1 year after TBI focusing on used (dynamic) tests and biochemical criteria. We included data from 14 studies with a total of 931 patients. There was considerable variation in definition of hypopituitarism. Overall, reported prevalences of severe GH deficiency varied between 2 and 39%. Prevalences were 8-20% using the GHRH-arginine test (cutoff <9 microg/l), 11-39% using the glucagon test (cutoff 1-5 microg/l), 2% using the GHRH test (no cutoff), and 15-18% using the insulin tolerance test (ITT; cutoff <3 microg/l). Overall, the reported prevalence of secondary adrenal insufficiency had a broad range from 0 to 60%. This prevalence was 0-60% with basal cortisol (cutoff <220 or <440 nmol/l), 7-19% using the ACTH test, and 5% with the ITT as first test (cutoff <500 or <550 nmol/l). Secondary hypothyroidism was present in 0-19% (free thyroxine) or 5-15% (thyroid-releasing hormone stimulation). Secondary hypogonadism was present in 0-29%. The reported variations in the prevalence rates of hypopituitarism after TBI are in part caused by differences in definitions, endocrine assessments of hypopituitarism, and confounding factors. These methodological issues prohibit simple generalizations of results of original studies on TBI-associated hypopituitarism in the perspective of meta-analyses or reviews.

Addition of n-3 fatty acids to a 4-hour lipid infusion does not affect insulin sensitivity, insulin secretion, or markers of oxidative stress in subjects with type 2 diabetes mellitus

Fatty acids (FA) can impair glucose metabolism to a varying degree depending on time of exposure and also of type of FA. Here we tested for acute effects of marine n-3 FA on insulin sensitivity, insulin secretion, energy metabolism, and oxidative stress. This was a randomized, double-blind, crossover study in 11 subjects with type 2 diabetes mellitus. A 4-hour lipid infusion (Intralipid [Fresenius Kabi, Halden, Norway], total of 384 mL) was compared with a similar lipid infusion partly replaced by Omegaven (Fresenius Kabi) that contributed a median of 0.1 g fish oil per kilogram body weight, amounting to 0.04 g/kg of marine n-3 FA. Insulin sensitivity was assessed by isoglycemic hyperinsulinemic clamps; insulin secretion (measured after the clamps), by C-peptide glucagon tests; and energy metabolism, by indirect calorimetry. Infusion of Omegaven increased the proportion of n-3 FA in plasma nonesterified fatty acids (NEFA) compared with Intralipid alone (20:5 n-3: median, 1.5% [interquartile range, 0.6%] vs −0.2% [0.2%], P = .001; 22:6 n-3: 0.8% [0.4%] vs −0.7% [0.2%], P = .001). However, glucose utilization was not affected; neither was insulin secretion or total energy production ( P = .966, .210, and .423, respectively, for the differences between the lipid clamps). Omegaven tended to lower oxidation of fat ( P = .062) compared with Intralipid only, correlating with the rise in individual n-3 NEFA ( r = 0.627, P = .039). The effects of clamping on phospholipid FA composition, leptin, adiponectin, or F 2-isoprostane concentrations were not affected by Omegaven. Enrichment of NEFA with n-3 FA during a 4-hour infusion of Intralipid failed to affect insulin sensitivity, insulin secretion, or markers of oxidative stress in subjects with type 2 diabetes mellitus.

Is Lack of Recombinant Growth Hormone (GH)-Releasing Hormone in the United States a Setback or Time to Consider Glucagon Testing for Adult GH Deficiency?

The use of the combined GHRH and arginine (GHRH-ARG) test has gained increasing acceptance in the United States as a reliable alternative test to the insulin tolerance test (ITT) for diagnosing adult GH deficiency (GHD). In July 2008, the only manufacturer of recombinant GHRH in the United States, EMD Serono, Inc., announced the discontinuation of Geref, thus raising the question of which reliable alternative GH stimulation test should practicing endocrinologists be considering in place of the GHRH-ARG test. In this article, we review the existing published data and consensus guidelines and provide recommendations for alternative stimulation tests to the GHRH-ARG test. The major source of data acquisition included PubMed search strategies and personal experience of the authors from clinical experience. Previous consensus guidelines and previous data assessing the reliability and discriminatory value of the GHRH-ARG, glucagon, ARG, and GH secretagogues on assessing GH reserve are discussed. Our recommendations for performing the glucagon stimulation test, potential drawbacks in conducting this test, and caveats in interpreting this test are also discussed. The ITT should remain the test of choice in diagnosing adult GHD. However, when the ITT is not desirable and recombinant GHRH remains unavailable in the United States, we recommend the alternative to the GHRH-ARG test to be the glucagon stimulation test, based on its reliability and availability. Nevertheless, further studies into alternative GH stimulation tests that are available in the United States, comparable, and simpler to perform than the ITT in diagnosing adult GHD are still needed.

The polymorphism Arg585Gln in the gene of the sterol regulatory element binding protein-1 (SREBP-1) is not a determinant of ketosis prone type 2 diabetes (KPD) in Africans

Aim Ketosis prone type 2 diabetes (KPD) is an atypical form of diabetes described mainly in people of sub-Saharan African origin. Its pathogenesis is unknown, although we have previously described a high prevalence of glucose-6-phosphate-dehydrogenase (G6PD) deficiency in patients with KPD. However, 50% of these deficient patients lacked the G6PD gene mutation. The isoforms of the transcription factor sterol regulatory element binding protein 1 (SREBP-1) are known to stimulate G6PD gene expression, and some polymorphisms in the SREBP-1 gene ( SREBF-1) have been described only in Africans. We investigated one of these, the Arg585Gln polymorphism, in a candidate gene approach for KPD. Methods We examined the presence of the Arg585Gln polymorphism in SREBF-1 in 217 consecutive unrelated Africans [73 patients with KPD, 80 with classical type 2 diabetes (T2D) and 64 nondiabetic subjects]. Patients underwent clinical and biochemical evaluations, and were assessed for G6PD activity and insulin secretion (glucagon test). Results There were no differences in frequency of the Arg585Gln polymorphism and the 585Gln allele among the three groups (allele frequency: KPD: 0.089, T2D: 0.031, nondiabetic group: 0.070; P = 0.1). When the 585Gln allele frequency was compared separately between patients with KPD and those with T2D, it was significantly higher in the former ( P = 0.032). There was no difference between carriers and noncarriers of the 585Gln allele regarding G6PD activity and insulin secretion. Conclusion The results of this exploratory study show that the polymorphism Arg585Gln in SREBF-1 is not associated with the KPD phenotype. Further studies in larger populations are needed to confirm our findings.

Retesting the childhood-onset GH-deficient patient

GH deficiency (GHD) in adults has to be shown by a single provocative test, provided that it is validated. Insulin tolerance test (ITT) has been indicated as the test of choice; now also glucagon test is validated and represents an alternative. The GHRH plus arginine (ARG) test and testing with GHRH plus a GH secretagogue are equally reliable diagnostic tools, and are now considered as 'golden' standards as ITT. Childhood-onset (CO) GHD needs retesting in late adolescence or young adulthood; this is a major clinical challenge and raises questions about the most appropriate method and cut-off value. Appropriate re-evaluation of GH status is represented by simple measurement of IGF1 concentration off rhGH treatment. Clearly, low IGF1 levels are evidence of persistent severe GHD in subjects with genetic GHD or panhypopituitarism. However, normal IGF1 levels never rule out severe GHD and CO-GHD with normal IGF1 levels must undergo a provocative test. The appropriate GH cut-off limit is specific for each provocative test. As shown by the ROC curve analysis, in late adolescents and young adults, the lowest normal GH peak response to ITT is 6.1 microg/l while that to GHRH+ARG test is 19.0 microg/l. These cut-off limits, however, are just indicative as being variable as a function of the assay used. No other test is validated for retesting. As GHRH+ARG test mostly explores the GH-releasable pool, normal GH response would be verified by a second ITT in order to rule out subtle hypothalamic defect.

Independent measures of insulin secretion and insulin sensitivity during the same test: the glucagon–insulin tolerance test

To validate a test for independent assessment of insulin secretion and insulin sensitivity during the same occasion for metabolic studies in clinical practice, i.e. combined glucagon-stimulated C-peptide test and insulin tolerance test (GITT). We measured C-peptide response to 0.5 mg of intravenous glucagon followed 30 min later by administration of 0.05 U kg(-1) insulin (insulin tolerance test, ITT). Ten subjects with normal glucose tolerance participated on different days in an ITT, glucagon-C-peptide test, ITT followed by glucagon-C-peptide test and glucagon-C-peptide test followed by ITT to establish whether and how the tests could be combined. The test was then repeated in nine patients with type 2 diabetes to investigate its reproducibility. In 20 subjects with varying degrees of glucose tolerance, the test was compared with the Botnia clamp (an intravenous glucose tolerance test combined with a euglycaemic hyperinsulinemic clamp). When ITT preceded the glucagon test, C-peptide response was blunted. Therefore, we first administered glucagon and then insulin (GITT). The K(ITT) from the GITT was reproducible (CV = 13 %) and correlated strongly with the glucose disposal rate from the Botnia clamp (r = 0.87, r(2) = 0.75, P < 0.001). The C-peptide response to glucagon was reproducible (CV = 13 %). The disposition index, providing a measure of beta-cell function adjusted for insulin sensitivity, calculated from the GITT showed good discrimination between individuals with varying degrees of glucose tolerance. The GITT provides simple, reproducible and independent estimates of insulin sensitivity and secretion on the same occasion for metabolic studies in individuals with normal and abnormal glucose tolerance.

Effects of Glucagon on Islet β Cell Function in Patients With Diabetes Mellitus

To evaluate islet beta cell response to intravenous glucagon (a non-glucose secretagogue) stimulation in diabetes mellitus. Nineteen patients with type 1 diabetes (T1D) and 131 patients with type 2 diabetes (T2D) were recruited in this study. T2D patients were divided into two groups according to therapy: 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intravenous injection of 1 mg of glucagon. Both fasting and 6-minute post-glucagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients (0.76 +/- 0.36 ng/mL vs. 1.81 +/- 0.78 ng/mL, P < 0.05; 0.88 +/- 0.42 ng/mL vs. 3.68 +/- 0.98 ng/mL, P < 0.05). In T1D patients, the C-peptide level after injection of glucagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy (2.45 +/- 0.93 ng/mL vs. 1.61 +/- 0.68 ng/mL, P < 0.05; 5.26 +/- 1.24 ng/mL vs. 2.15 +/- 0.76 ng/mL, P < 0.05). The serum C-peptide level after glucagon stimulation was positively correlated with C-peptide levels at fasting in all three groups (r = 0.76, P < 0.05). The 6-minute glucagon test is valuable in assessing the function of islet beta cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.

A Case of Fulminant Type 1 Diabetes Associated With Significant Elevation of Mumps Titers

Type 1 diabetes mellitus is classified as either autoimmune or idiopathic. Fulminant type 1 diabetes was originally reported as a subtype of idiopathic type 1 diabetes. Though involvement of viral infections has been suggested as a triggering mechanism, its pathogenesis remains unknown. Here, we present a case of fulminant type 1 diabetes associated with significant elevation of mumps titers. A 56-year-old Japanese man had suffered from nausea and generalized fatigue for two days before being transferred to our hospital in a confused state. Findings on admission revealed a high blood glucose level, near-normal HbA1c level, metabolic acidosis, and increased urinary ketone levels. Serum tests for islet-associated autoantibodies were negative. The serum, urinary C-peptide levels and the result of glucagon test indicated severe impairment of insulin secretion. These results were compatible with the diagnosis of fulminant type 1 diabetes. Also, he was suspected as having mumps infection on the basis of serological testing. These findings suggest that fulminant type 1 diabetes developed after mumps virus infection in our case. To the best of our knowledge, no other report has indicated an association between a recent mumps infection and the onset of fulminant type 1 diabetes. This case suggests an association between fulminant type 1 diabetes and mumps virus infection.

The Neuroendocrine Effects of Traumatic Brain Injury

The Neuroendocrine Effects of Traumatic Brain Injury

The Glucagon Provocative Test for the Diagnosis and Treatment of Zollinger–Ellison Syndrome

ObjectiveOur aim was to determine whether the glucagon provocative test could be used in place of secretin test in patients with gastrinoma. MethodsThree patients with gastrinoma underwent the following examinations: (1) preoperative intravenous glucagon test to enable a definitive diagnosis, (2) intra-arterial glucagon injection test to localize the tumor, and (3) intraoperative and postoperative intravenous glucagon test to confirm the completeness of the resection. ResultsSerum gastrin levels increased in response to intravenous glucagon in all three patients preoperatively. Computed tomography scans revealed a tumor in the lesser omentum, pancreatic head, and the pancreatic uncinate in cases 1, 2, and 3, respectively. Intra-arterial glucagon test revealed that the feeding artery for the tumor was the left gastric artery in case 1 and the superior mesenteric artery in case 3. Resection of the remnant stomach with tumor, pancreaticoduodenectomy with portal vein resection, and enucleation of the tumor were performed in cases 1, 2, and 3, respectively. Serum gastrin levels did not increase in response to intravenous glucagon intraoperatively and postoperatively in cases 1 and 3. Although intravenous glucagon caused a slight increase in serum gastrin in case 2, no recurrent tumors were evident. ConclusionThese results indicate that the glucagon provocative test is a suitable alternative to testing with secretin, which is not commercially available in Japan.

The Neuroendocrine Effects of Traumatic Brain Injury

Neuroendocrine dysfunction after traumatic brain injury (TBI) is under-diagnosed, under-treated, and may adversely affect the rate of recovery. Single or multiple pituitary-target hormone disruption occurs in up to two-thirds of persons with TBI, most commonly affecting the gonadal and growth hormone axes. The time course of decline in and recovery of pituitary function in relation to cognitive dysfunction and rehabilitation progress are not well described. This article reviews the clinical spectrum of neuroendocrine deficits after TBI and their underlying mechanisms. Future studies of the effects of hormonal replacement on recovery are recommended.

Evaluation of β-cell function in diabetic Taiwanese children using a 6-min glucagon test

This study evaluates the effects of glucagon 30 mug/kg (maximal 1 mg) on beta-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 beta-cell function in children and can help pediatricians in the differential diagnoses of diabetes mellitus in children.

The Common C49620T Polymorphism in the Sulfonylurea Receptor Gene (ABCC8), Pancreatic Beta Cell Function and Long-Term Diabetic Complications in Obese Patients with Long-Lasting Type 2 Diabetes Mellitus

A gene polymorphism associated with accelerated beta-cell failure may lead to a more rapid development of long-term complications of type 2 diabetes (T2DM) due to a worse metabolic control of the disease. Evaluation of an association between the intronic C49620T (exon 16 -3c-->t) polymorphism in the ABCC8 (SUR1) gene and beta-cell function, as well as the prevalence of long-term diabetic complications in obese patients with long-lasting type 2 diabetes. Two hundred and fifteen obese patients with at least a 10-year history of T2DM were thoroughly characterized clinically. In all the patients the intravenous glucagon test was performed and the C49620T ABCC8 polymorphism was assessed. Subgroups of patients, classified either according to genotype or to allele carriage, were compared. No difference was found between the groups in variables describing beta-cell function and the prevalence of chronic diabetic complications, with the exception of a significantly lower incidence of brain stroke in CC homozygotes than in patients carrying T allele (CT+TT). Body mass index was higher in patients carrying C allele than in TT homozygotes. HDL-cholesterol was higher in CT heterozygous than in homozygous CC or TT patients. There is no association between the ABCC8 polymorphism gene and the beta-cell function or the prevalence of chronic diabetic complications in obese patients with long-term T2DM, except for brain stroke. The results might suggest that the homozygous CC subjects are at lower risk of the complication, but additional studies are warranted to test this finding.

Multi-organ failure after a glucagon test

In November, 2005, a glucagon test (1 mg intravenously) was done in a lean 43-year-old man to measure his insulin reserve as part of the assessment of recently diagnosed type 2 diabetes mellitus. He was taking glimepiride 2 mg daily and metoprolol 50 mg daily for mild hypertension. 12 h after the test he presented to the emergency department with dyspnoea and haemoptysis. On examination, he was pale, tachypnoeic, and hypoxic (oxygen saturation 86% on room air). Blood pressure was 140/100 mm Hg, heart rate was 160 beats per min, and temperature was 35∙4°C. General examination showed no abnormalities. Chest radiography suggested consolidation in the right lower lobe. Blood tests showed a raised white-cell count of 24∙4×10/L with neutrophilia (86·3%), lactic acidosis (pH 7·22, pCO2 3·4 kPa, pO2 10·6 kPa, bicarbonate 11 mmol/L, and lactate 9·1 mmol/L), and high creatinine concentration (268 μmol/L). He was admitted to the intensive care unit with a presumed diagnosis of respiratory failure due to pneumonia. Benzylpenicillin and ciprofl oxacin were initiated. His condition deteriorated, and he developed hypotension, anuric renal failure, shock liver, rhabdomyolysis, and widespread bilateral lung infi ltrates. Dobutamine and norepinephrine were started, and activated protein C was administered. He was ventilated in the prone position and continuous venovenous ultrafi ltration was initiated. 2 days after admission, inotropes and vasopressors were withdrawn. He then developed hypertension (with blood pressure up to 250/140 mm Hg) and microangiopathic haemolytic anaemia (platelets 52×10/L); blood test results showed fragmented red cells (8%) and high lactate dehydrogenase (5190 IU/L). The hypertension in combination with negative blood and sputum cultures raised our suspicion of a phaeochromocytoma. Abdom inal ultrasonography showed a mass measuring 9·4×7·9×8·3 cm above the right kidney—this was confi rmed by CT (fi gure). We deduced that the phaeochromocytoma crisis was triggered by the glucagon test. Plasma catecholamine concentrations measured in samples obtained during the glucagon test were very high, confi rming the diagnosis (norepinephrine and epinephrine each >100 000 nmol/L). Our patient’s condition improved after administration of intravenous labetalol (up to 2400 mg daily), doxazosin 16 mg daily, and phentolamine (up to 1440 mg daily). 31 days after admission an uncomplicated adrenal extirpation was done, after which he remained normotensive and normoglycaemic. Histological examin ation of the tumour confi rmed the diagnosis of phaeochromocytoma. He was discharged from the hospital 3 months after admission. When seen in September, 2006, our patient remained well—no urinary catecholamine excess was found and MRI of the abdomen showed no remaining tumour. Multi-organ failure is a rare initial presentation of a phaeochromocytoma, but in most cases is fulminant. In this case, the phaeochromocytoma crisis was precipitated by a glucagon test, which stimulates the phaeochromocytoma to secrete catecholamines—lactic acidosis ensued as a result of the metabolic and vascular eff ects of catecholamine excess. Haemolytic anaemia was probably the result of extreme hypertension and resulting endothelial injury. The increase in catecholamines in such patients is the basis on which the glucagon test was used as a provocative test in the diagnosis of a phaeochromocytoma—because of the unpredictable response and the danger of a hypertensive crisis, its use for this purpose is almost obsolete. In our patient, the glucagon test was used to measure the C-peptide response to fi nd out whether his diabetes was caused by a secretory defect of insulin and to assess the effi cacy of treatment with oral antidiabetic drugs. Hyperglycaemia is a common fi nding in patients with phaeochromocytoma owing to insulin defi ciency and resistance. The glucagon test is often used in patients with diabetes mellitus; however, it rarely leads to a hypertensive crisis due to an undiscovered phaeochromocytoma. Although the incidence of phaeochromocytoma is low, we suggest that it is prudent to be aware of the signs leading to a phaeochromocytoma crisis in lean diabetic and hypertensive patients undergoing a glucagon test.

Assessing adrenal function in primary care settings with a single sample subcutaneous glucagon test

To test the efficacy of the low-dose glucagon test in assessing adrenal gland function. Subcutaneous glucagon was used to assess the hypothalamo-pituitary-adrenal gland (HPA) axis in 215 healthy children. Concordance of this test with the low-dose intravenous ACTH test was established for 42 children. Glucagon testing was conducted for 150 minutes after subcutaneous glucagon administration and for 30 minutes after 1 microg intravenous ACTH. Mean peak serum cortisol concentrations were 22.4 +/- 0.6 microg/dL (SEM) after subcutaneous glucagon and 20.0 +/- 0.6 microg/dL after intravenous ACTH. Specificity of 95% was found at peak cortisol concentrations of 9.5 and 12.5 microg/dL for the glucagon and ACTH tests, respectively. Concordance between the glucagon and ACTH tests was 90.5%. The glucagon test was found to be as good a test of the HPA axis as the ACTH test and had a 90.5% concordance with it. The ease of performing the glucagon test, namely, obtaining a single sample of blood 150 minutes after the subcutaneous administration of glucagon, makes it a useful method of assessing the HPA axis in primary care settings.

Using the glucagon test to predict hypoglycemia in anorexia nervosa

Hypoglycemia is an important but uncommon complication of anorexia nervosa (AN) that usually occurs when refeeding begins. The response to an iv bolus of glucagon has been used to investigate hypoglycemia, but not in AN. There are no published standards in AN to screen for hypoglycemia, to treat hypoglycemia, or for the response of the fasting blood sugar to an intravenous bolus of glucagon. We report the change in blood glucose that resulted from bolus iv injection of glucagon in a case series of 9 patients with AN who were suspected of having experienced hypoglycemia. Our standard protocol for the glucagon test in AN is measurement of blood sugar at baseline, 10 minutes, and 20 minutes following a 1.0 mg iv bolus of glucagon in the fasting state. We take as normal any blood glucose measurement of 7.0 mmol/l or greater. Five of nine patients had abnormal tests. The body mass index (BMI) was not different in those who had normal compared to those who had abnormal tests. The glucagon test may be of use to predict the likelihood of developing hypoglycemia in AN. However, a larger study is required to define the normal response to the glucagon test in AN.

Proinflammatory Cytokines, Insulin Resistance, and Insulin Secretion in Chronic Hepatitis C patients

OBJECTIVE—The purpose of this study was to explore the initial pathogenic mechanisms of diabetes associated with hepatitis C virus (HCV) infection. RESEARCH DESIGN AND METHODS—Insulin resistance, proinflammatory cytokines, and β-cell function were evaluated in a case-control study. A total of 28 consecutive nondiabetic patients with chronic hepatitis C were included in the study (anti-HCV+). Fourteen patients with chronic hepatitis other than HCV infection served as the control group (anti-HCV−). Both groups were closely matched by the main clinical variables associated with insulin resistance and the degree of liver fibrosis. In addition, there were no differences between groups regarding hepatic insulin extraction measured by calculating the ratio between C-peptide and insulin. Serum levels of proinflammatory cytokines (tumor necrosis factor [TNF]-α, soluble TNF receptor [sTNFR] 1, soluble TNFR2, and interleukin-6) were measured by enzyme-linked immunosorbent assay. Insulin resistance (homeostasis model assessment [HOMA] of insulin resistance [HOMA-IR]) and insulin secretion at baseline (HOMA-β) and after various stimulus (oral glucose tolerance test, standard food intake, and intravenous glucagon) were determined by previously validated mathematic indexes. RESULTS—HOMA-IR was higher in anti-HCV+ than in anti-HCV− patients (4.35 ± 2.27 vs. 2.58 ± 1.74; P = 0.01). All the proinflammatory cytokines analyzed were significantly higher in anti-HCV+ patients than in anti-HCV− patients. In addition, sTNFR1 and sTNFR2 were directly correlated to HOMA-IR. HOMA-β as well as insulin and C-peptide responses after the intravenous glucagon test were significantly higher in anti-HCV+ patients than in anti-HC− patients. CONCLUSIONS—Insulin resistance mediated by proinflammatory cytokines, but not a deficit in insulin secretion, could be the primary pathogenic mechanism involved in the development of diabetes associated with HCV infection.

Proinflammatory Cytokines, Insulin Resistance, and Insulin Secretion in Chronic Hepatitis C patients: A case-control study

The purpose of this study was to explore the initial pathogenic mechanisms of diabetes associated with hepatitis C virus (HCV) infection. Insulin resistance, proinflammatory cytokines, and beta-cell function were evaluated in a case-control study. A total of 28 consecutive nondiabetic patients with chronic hepatitis C were included in the study (anti-HCV+). Fourteen patients with chronic hepatitis other than HCV infection served as the control group (anti-HCV-). Both groups were closely matched by the main clinical variables associated with insulin resistance and the degree of liver fibrosis. In addition, there were no differences between groups regarding hepatic insulin extraction measured by calculating the ratio between C-peptide and insulin. Serum levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha, soluble TNF receptor [sTNFR] 1, soluble TNFR2, and interleukin-6) were measured by enzyme-linked immunosorbent assay. Insulin resistance (homeostasis model assessment [HOMA] of insulin resistance [HOMA-IR]) and insulin secretion at baseline (HOMA-beta) and after various stimulus (oral glucose tolerance test, standard food intake, and intravenous glucagon) were determined by previously validated mathematic indexes. HOMA-IR was higher in anti-HCV+ than in anti-HCV- patients (4.35 +/- 2.27 vs. 2.58 +/- 1.74; P = 0.01). All the proinflammatory cytokines analyzed were significantly higher in anti-HCV+ patients than in anti-HCV- patients. In addition, sTNFR1 and sTNFR2 were directly correlated to HOMA-IR. HOMA-beta as well as insulin and C-peptide responses after the intravenous glucagon test were significantly higher in anti-HCV+ patients than in anti-HC- patients. Insulin resistance mediated by proinflammatory cytokines, but not a deficit in insulin secretion, could be the primary pathogenic mechanism involved in the development of diabetes associated with HCV infection.

Diagnosis of adult growth hormone deficiency: Still a matter of debate

The diagnosis of GH deficiency (GHD) in adults is established by laboratory testing in patients with an appropriate clinical history of hypothalamic pituitary disease. As the measurement of IGF-I and IGFBP-3 levels as well as the spontaneous GH secretion are not considered reliable parameters, the diagnosis of GHD in adults may be established by GH provocative tests, provided that a reproducible test with clear normative limits is available. The insulin tolerance test (ITT) is a reliable diagnostic test in adults, but is contraindicated in several clinical conditions which are often observed in adult patients with suspected GHD. The other classic GH provocative tests, except the glucagon test, have a poor diagnostic utility and should be abandoned. GHRH combined with arginine or GH secretagogues represent a potent, safe, reproducible and reliable test which should be preferable to the ITT as a first-choice diagnostic test for GHD.