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Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant. 2003

W M Drake, and S V Rowles, and M E Roberts, and F K Fode, and G M Besser, and J P Monson, and P J Trainer
Department of Endocrinology, St Bartholomew's Hospital, London, UK. w.m.drake@qmul.ac.uk

OBJECTIVE Insulin resistance leading, in some cases, to glucose intolerance is an important contributory factor to the cardiovascular morbidity and mortality associated with acromegaly. The aim of this study was to document changes in insulin sensitivity (IS) in a group of seven patients with acromegaly (three male, four female, mean+/-s.d. age 59+/-13 Years) treated initially with a stable dose of depot octreotide (OT; median dose 30 mg four times weekly, range 10-30 mg) for a median of 18 Months (range 16-19 Months) and who were then transferred to treatment with pegvisomant (median dose 15 mg daily, range 10-20 mg) for a median of 8 Months (range 7-9 Months). IS was assessed by homeostatic model assessment (HOMA) using fasting glucose and insulin concentrations and by a short insulin tolerance test (sITT). Body composition was assessed by dual energy X-ray absorptiometry. RESULTS Mean+/-s.d. serum IGF-I concentrations during therapy with OT and with pegvisomant were not statistically different (283+/-119 ng/ml on OT vs 191+/-39 ng/ml on pegvisomant (P=0.4)). However, mean+/-s.d. fasting plasma glucose fell from 6.2+/-1.0 mmol/l on OT to 5.2+/-0.6 mmol/l on pegvisomant (P=0.017) and was lower on pegvisomant in all seven patients. In four patients, fasting plasma glucose fell from values diagnostic of diabetes mellitus or impaired fasting glucose on OT to within the normal range on pegvisomant. Mean+/-s.d. peripheral IS (by sITT) increased from 139+/-39 micromol/l per min on OT to 169+/-59 micromol/l per min on pegvisomant (P=0.037). Mean+/-s.d. IS (by HOMA %S) was unchanged over the course of the study (149.1+/-43.7% on OT vs 139.9+/-76.6% on pegvisomant, P=0.28). Mean+/-s.d. pancreatic beta-cell secretory function (HOMA %B) improved significantly on pegvisomant compared with OT (49.4+/-19.2% vs 82.4+/-43.5%, P=0.01). No statistically significant change in total fat (P=0.3), % fat (P=0.28) or circulating non-esterified fatty acids (P=0.35) was observed. CONCLUSIONS IS and glucose tolerance improved in patients converted from OT therapy to pegvisomant, without a change in body composition and even when serum IGF-I concentrations remained equally well controlled. This may be an important factor in the choice of medical therapy for patients with acromegaly.

UI MeSH Term Description Entries
D007333 Insulin Resistance Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS. Insulin Sensitivity,Resistance, Insulin,Sensitivity, Insulin
D007334 Insulin-Like Growth Factor I A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor. IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011986 Receptors, Somatotropin Cell surface proteins that bind GROWTH HORMONE with high affinity and trigger intracellular changes influencing the behavior of cells. Activation of growth hormone receptors regulates amino acid transport through cell membranes, RNA translation to protein, DNA transcription, and protein and amino acid catabolism in many cell types. Many of these effects are mediated indirectly through stimulation of the release of somatomedins. Growth Hormone Receptors,Receptors, Growth Hormone,Somatomammotropin Receptors,Somatotropin Receptors,Growth Hormone Receptor,Receptor, Growth Hormone,Receptors, Somatomammotropin,Somatomammotropin Receptor,Somatotropin Receptor,Hormone Receptor, Growth,Hormone Receptors, Growth
D005260 Female Females
D005951 Glucose Tolerance Test A test to determine the ability of an individual to maintain HOMEOSTASIS of BLOOD GLUCOSE. It includes measuring blood glucose levels in a fasting state, and at prescribed intervals before and after oral glucose intake (75 or 100 g) or intravenous infusion (0.5 g/kg). Intravenous Glucose Tolerance,Intravenous Glucose Tolerance Test,OGTT,Oral Glucose Tolerance,Oral Glucose Tolerance Test,Glucose Tolerance Tests,Glucose Tolerance, Oral
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000172 Acromegaly A condition caused by prolonged exposure to excessive HUMAN GROWTH HORMONE in adults. It is characterized by bony enlargement of the FACE; lower jaw (PROGNATHISM); hands; FEET; HEAD; and THORAX. The most common etiology is a GROWTH HORMONE-SECRETING PITUITARY ADENOMA. (From Joynt, Clinical Neurology, 1992, Ch36, pp79-80) Inappropriate Growth Hormone Secretion Syndrome (Acromegaly),Somatotropin Hypersecretion Syndrome (Acromegaly),Inappropriate GH Secretion Syndrome (Acromegaly),Hypersecretion Syndrome, Somatotropin (Acromegaly),Hypersecretion Syndromes, Somatotropin (Acromegaly),Somatotropin Hypersecretion Syndromes (Acromegaly),Syndrome, Somatotropin Hypersecretion (Acromegaly),Syndromes, Somatotropin Hypersecretion (Acromegaly)
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

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