scholarly journals Cotreatment with Pegvisomant and a Somatostatin Analog (SA) in SA-Responsive Acromegalic Patients

2011 ◽  
Vol 96 (8) ◽  
pp. 2405-2413 ◽  
Author(s):  
Michael Madsen ◽  
Per L. Poulsen ◽  
Hans Ørskov ◽  
Niels Møller ◽  
Jens O. L. Jørgensen
Keyword(s):  
Glucose Tolerance ◽  
Low Dose ◽  
Tolerance Test ◽  
Somatostatin Analog ◽  
Oral Glucose ◽  
Tertiary Referral Center ◽  
Elevated Liver Enzymes ◽  
Igf I ◽  
Insufficient Response

Abstract Context: Cotreatment of acromegaly with pegvisomant and a somatostatin analog (SA) has proven feasible. Previous studies in the field have focused on patients with an insufficient response to SA monotherapy in whom pegvisomant was added without changing the SA dose. Objective: The objective of the study was to study whether patients sufficiently controlled on SA monotherapy can be transferred to combination therapy with low-dose pegvisomant and a reduced SA dose. Design: Eighteen acromegalic patients well controlled on SA monotherapy, mean ± se aged 54 ± 3 yr, were randomized in a parallel study over 24 wk to unchanged SA monotherapy or cotreatment with pegvisomant (15–30 mg twice a week) and SA (half the usual dosage). Setting: This was an investigator-initiated study in a single tertiary referral center. Main Outcome Measures: Glucose tolerance, substrate metabolism, insulin sensitivity, body composition, and quality of life were measured. Results: Median pegvisomant dose was 52.5 mg/wk (range 30–60). IGF-I (micrograms per liter) was comparable both at baseline (P = 0.88) and after 24 wk of treatment (P = 0.48). The change in IGF-I between baseline and wk 24 also did not differ between groups (P = 0.15). Apart from increased peak insulin levels during the oral glucose tolerance test in the cotreatment group, no substantial differences between the two groups were detected. Moderately elevated liver enzymes were found in 17% of the patients on pegvisomant therapy. Conclusion: Acromegalic patients well controlled on SA monotherapy can maintain safe IGF-I levels during 24 wk of cotreatment with low-dose pegvisomant and a 50% reduced SA dose. This treatment modality, however, does not seem to provide significant benefits for the patients.

scholarly journals The Role of Insulin-Like Growth Factor (IGF) Binding Protein-2 in the Insulin-Mediated Decrease in IGF-I Bioactivity

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 5192-5192
Author(s):  
Ayman M. Arafat ◽  
Martin O. Weickert ◽  
Jan Frystyk ◽  
Joachim Spranger ◽  
Christof Schöfl ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Igf System ◽  
Igf I ◽  
Igf Binding

ABSTRACT Context: Insulin interacts with the GH-IGF system by a reciprocal regulation of IGF-binding proteins (IGFBP) and GH, which in turn regulate insulin sensitivity via bioactive IGF-I. This network is linked to metabolic syndrome and cardiovascular diseases. Objective: We evaluated the effect of glucose and insulin on IGFBP-1-4, particularly IGFBP-2, in the regulation of bioactive IGF-I and its relation to insulin resistance. Setting: The study was conducted at an endocrinology center. Research Design and Methods: Twenty-four healthy subjects (12 men; aged 21–72 yr; body mass index 25.9 ± 0.9 kg/m2) and 19 subjects with impaired glucose tolerance (IGT; eight men; aged 26–71 yr; body mass index 28.9 ± 1.2 kg/m2 ) were prospectively studied using oral glucose tolerance test and hyperinsulinemic euglycemic clamp. Results: During the clamp, insulin decreased IGF-I bioactivity in both IGT subjects and controls (−16.2 ± 2.8 and −13.9 ± 3.3%, respectively; P < 0.01). In addition, insulin increased IGFBP-2 and GH and decreased IGFBP-1 and -4 but did not alter total IGF-I, IGF-II, or IGFBP-3 levels. During the oral glucose tolerance test, GH and IGFBP-1 were markedly suppressed. Subjects with IGT showed more pronounced insulin resistance and lower GH, IGFBP-1, and IGFBP-2 levels (P < 0.05). In multiple regression analysis, IGFBP-2 was an independent predictor of insulin sensitivity (β = 0.36, P < 0.05) and IGF-I bioactivity (β = −0.5, P < 0.05). Conclusions: Our data indicate that insulin acutely decreases IGF-I bioactivity through differential modulation of IGFBPs. Furthermore, IGFBP-2 plays a central role in the insulin-IGF system cross talk and is closely linked to insulin resistance, thereby providing a further explanation for its association with the metabolic syndrome.

scholarly journals The Oral Glucose Tolerance Test—An Assessment of the Quality of its Performance

1987 ◽  
Vol 24 (5) ◽  
pp. 440-446 ◽  
Author(s):  
K Wiener
Keyword(s):  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Glucose Tolerance Test ◽  
Clinical Chemistry ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
External Quality Assessment Scheme ◽  
The Uk

By means of a questionnaire, an attempt was made to assess the quality of performance and interpretation of the oral glucose tolerance test by laboratories participating in the UK External Quality Assessment Scheme for Clinical Chemistry. The results showed a general awareness of current recommendations in terms of both protocol for the test and criteria for interpretation of results, but some deficiencies were observed in both these areas and in some case deviations in protocol may have been sufficient to invalidate comparison of results with currently recommended criteria for interpretation of the test.

scholarly journals GH Replacement Improves Quality of Life and Metabolic Parameters in Cured Acromegalic Patients with Growth Hormone Deficiency

2012 ◽  
Vol 97 (11) ◽  
pp. 3983-3988 ◽  
Author(s):  
Claudia Giavoli ◽  
Eriselda Profka ◽  
Elisa Verrua ◽  
Cristina L. Ronchi ◽  
Emanuele Ferrante ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Body Composition ◽  
Glucose Tolerance ◽  
Lipid Profile ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Glucose Levels ◽  
Gh Replacement ◽  
Group A

Objective: Effects of GH replacement in patients with GH deficiency (GHD) after a cure for acromegaly so far have been poorly studied, although its prevalence among acromegalic patients may reach the 60%. The aim of the study was to evaluate whether metabolic parameters and quality of life are improved by GH replacement in patients with prior acromegaly and severe GHD. Design and Methods: This was a prospective study on 42 GHD subjects [22 men, mean age (sd): 48 ± 10]: 10 acromegalics treated with recombinant human GH (group A), 12 acromegalics who refused treatment (group B), and 20 subjects operated for nonfunctioning pituitary adenoma on recombinant human GH (group C). Serum IGF-I levels, lipid profile, glucose levels (fasting and after an oral glucose tolerance test), glycosylated hemoglobin, insulin resistance (homeostasis model assessment insulin resistance index), anthropometric parameters (body mass index, waist circumference, body composition), and quality of life (Questions on Life Satisfaction-Hypopituitarism Z-scores) were evaluated at baseline and after 12 and 36 months. Results: At baseline, group B showed higher IGF sd score than group A and C, as well as better quality of life and higher post-oral glucose tolerance test glucose levels than group A. After 12-months, similarly in group A and C, the IGF-I sd score significantly increased, and body composition and lipid profile improved, without deterioration of glucose tolerance. Quality of life significantly improved too, and the baseline difference between group A and B disappeared. Results were confirmed after 36 months. Conclusions: In GHD acromegalic patients, GH therapy improved body composition, lipid profile, and quality of life as in patients with GHD due to nonfunctioning pituitary adenoma, without negative effects on glucose metabolism. GH replacement therapy should be considered in these patients, as in patients with GHD from other causes.

scholarly journals The Utility of Oral Glucose Tolerance Testing for Diagnosis and Assessment of Treatment Outcomes in 166 Patients with Acromegaly

2009 ◽  
Vol 94 (2) ◽  
pp. 523-527 ◽  
Author(s):  
John D. Carmichael ◽  
Vivien S. Bonert ◽  
James M. Mirocha ◽  
Shlomo Melmed
Keyword(s):  
Glucose Tolerance ◽  
Medical Therapy ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Biochemical Control ◽  
Oral Glucose Tolerance Testing ◽  
Postoperative Assessment ◽  
Igf I ◽  
Tolerance Testing

Abstract Context: GH suppression after oral glucose load [oral glucose tolerance test (OGTT)] and normal age- and gender-matched IGF-I levels reflect biochemical control of acromegaly. The OGTT is the gold standard for determining control of GH secretion at diagnosis and after surgical treatment, but the usefulness of performing an OGTT in patients treated with medical therapy has not been determined. Objective: Our objective was to assess relationships between basal GH levels (basal GH), GH responses to OGTT [GH nadir (GHn)], and IGF-I levels. Design: This was a retrospective electronic database review. Setting: This study was performed at a tertiary outpatient pituitary center. Patients: A total of 166 patients with acromegaly (79 females, 87 males) were included in the study. Four categories of testing were performed: diagnosis, postoperative assessment without medication, testing during somatostatin analog (SA) therapy, and testing during dopamine agonist (DA) therapy. Main Outcome Measures: Basal serum GH and IGF-I levels and GH levels 2 h after 75 g OGTT were measured. Results: A total of 482 simultaneous OGTT and IGF-I measurements were observed from 1985–2008. Discordant results of oral glucose tolerance testing (GHn and IGF-I) were observed 33, 48, and 18% in postoperative assessment without medication, SA, and DA categories, respectively. In the SA category, 42% of tests were discordant with normal IGF-I and nonsuppressed GHn. In contrast, 4% of tests were discordant with normal IGF-I and nonsuppressed GH in those treated with DA. No significant differences in discordance were observed when basal GH was used. Conclusions: Both basal and GHn levels are highly discordant with IGF-I levels during medical therapy with SAs. The OGTT is not useful in assessing biochemical control in these subjects.

scholarly journals Short-term low-dose growth hormone administration in subjects with impaired glucose tolerance and the metabolic syndrome: effects on beta-cell function and post-load glucose tolerance

2004 ◽  
pp. 39-45 ◽  
Author(s):  
K Yuen ◽  
N Wareham ◽  
J Frystyk ◽  
S Hennings ◽  
J Mitchell ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Low Dose ◽  
Cell Function ◽  
Oral Glucose ◽  
Fasting Insulin ◽  
Short Term ◽  
The Metabolic Syndrome ◽  
Igf I

OBJECTIVE: Modest elevations in circulating IGF-I levels have been suggested to protect against the development of glucose intolerance in insulin-resistant subjects. To further understand the interactions of GH and IGF-I on beta-cell function and post-load glucose tolerance in glucose-intolerant subjects predisposed to diabetes, we performed a pilot study in 12 subjects with impaired glucose tolerance and the metabolic syndrome using a low GH dose (1.7 microg/kg per day) known to increase endogenous IGF-I production. DESIGN: Fourteen daily GH or placebo injections in a double-blind cross-over study. METHODS: Baseline and post-treatment oral glucose tolerance tests were performed. The homeostasis model assessment and the insulinogenic index was used to estimate fasting insulin sensitivity (S(I)) and beta-cell function respectively, whereas changes in the incremental area under the curve were used to estimate post-load glucose tolerance (DeltaAUC(glu)) and post-load insulin levels (DeltaAUC(ins)). RESULTS: GH increased total IGF-I (P<0.02), free IGF-I (P<0.04) and fasting insulin (P<0.04) levels, but did not modify plasma IGF-binding proteins (IGFBPs)-1 and -3, fasting glucose, non-esterified fatty acid and C-peptide levels, and fasting S(I). After oral glucose intake, glucose tolerance improved (P<0.03), but post-load insulin levels and beta-cell function remained unchanged. CONCLUSION: Short-term low-dose GH administration induced fasting hyperinsulinaemia possibly by reducing insulin clearance but improved post-load glucose tolerance, suggesting that increased bioavailable IGF-I enhanced post-load S(I) without altering beta-cell function. Longer-term studies are required to ascertain whether these positive effects on post-load glucose tolerance and the preservation of beta-cell function can be sustained by this GH dose in these high-risk subjects.

THE COMPARISON OF THE SECOND PHASE INSULIN SECRETION DERIVED FROM ORAL GLUCOSE TOLERANCE TEST AND LOW DOSE GRADED GLUCOSE INFUSION TEST

2021 ◽  
pp. 243-246
Author(s):  
Tsung-Ju Chuang ◽  
Te-Lin Hsia
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Gold Standard ◽  
Low Dose ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Second Phase ◽  
Oral Glucose Tolerance ◽  
Glucose Infusion Test

Background: the pathogeneses of type 2 diabetes (T2DM) are impaired insulin action and secretion, including the second phase insulin secretion (SPIS). However, SPIS is difcult to be measured. The study aimed to validate the SPIS derived from the simpler oral glucose tolerance test (OGTT) against the SPIS derived from the more complicated gold standard test, i.e. low dose graded glucose infusion test (LDGGI). Methods: Fourteen participants (3 with normal glucose tolerance, 8 with pre-diabetes and 3 with T2DM) were enrolled. They received both a standard LDGGI and an OGTT. The mathematical method which is called deconvolution was applied in both tests. The slope of the insulin secretion rate (ISR) against glucose levels during the LDGGI was obtained and regarded as the gold standard (SPIS-L). At the same time, the SPIS calculated from OGTT with minimal model was also obtained (SPIS-O). Results: Pearson correlation was used to assess the correlation between SPIS-L and SPIS-O. There was a signicant correlation between SPIS-L and SPIS-O (r = 0.843, p = 0.000). At the same time, a good agreement between the SPIS-L and SPIS-O was also found from the Bland-Altman plot. Conclusion: SPIS-O is highly correlated with the gold standard, i.e., the SPIS-L. Since it is easier to be performed, future researches focusing on SPIS by using OGTT might be expedited.

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