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

AIM AND METHOD: 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.

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Effect of telmisartan on selected adipokines, insulin sensitivity, and substrate utilization during insulin-stimulated conditions in patients with metabolic syndrome and impaired fasting glucose

Acta Endocrinologica ◽

10.1530/eje-10-0436 ◽

2010 ◽

Vol 163 (4) ◽

pp. 573-583 ◽

Cited By ~ 11

Author(s):

Petr Wohl ◽

Eva Krušinová ◽

Martin Hill ◽

Simona Kratochvílová ◽

Kateřina Zídková ◽

...

Keyword(s):

Metabolic Syndrome ◽

Insulin Sensitivity ◽

Impaired Fasting Glucose ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Fasting Glucose ◽

Substrate Utilization ◽

Metabolic Effects ◽

Plasma Adiponectin ◽

Fasting Plasma

ObjectiveTelmisartan improves glucose and lipid metabolism in rodents. This study evaluated the effect of telmisartan on insulin sensitivity, substrate utilization, selected plasma adipokines and their expressions in subcutaneous adipose tissue (SAT) in metabolic syndrome.Design and methodsTwelve patients with impaired fasting glucose completed the double-blind, randomized, crossover trial. Patients received telmisartan (160 mg/day) or placebo for 3 weeks and vice versa with a 2-week washout period. At the end of each period, a hyperinsulinemic euglycemic clamp (HEC) combined with indirect calorimetry was performed. During HEC (0, 30, and 120 min), plasma levels of adipokines were measured and a needle biopsy (0 and 30 min) of SAT was performed.ResultsFasting plasma glucose was lower after telmisartan compared with placebo (P<0.05). There were no differences in insulin sensitivity and substrate utilization. We found no differences in basal plasma adiponectin, resistin and tumour necrosis factor α (TNFα), but an increase was found in basal leptin, after telmisartan treatment. Insulin-stimulated plasma adiponectin (P<0.05), leptin and resistin (P<0.001) were increased, whereas TNFα was decreased (P<0.05) after telmisartan treatment. Expression of resistin, but not adiponectin, TNFα and leptin was increased after telmisartan treatment.ConclusionsDespite the decrease in fasting plasma glucose, telmisartan does not improve insulin sensitivity and substrate utilization. Telmisartan increases plasma leptin as well as insulin-stimulated plasma adiponectin, leptin and resistin, and decreases plasma TNFα during HEC. Changes in plasma adipokines cannot be explained by their expressions in SAT. The changes in plasma adipokines might be involved in the metabolic effects of telmisartan in metabolic syndrome.

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Distribution of fasting plasma glucose and prevalence of impaired fasting glucose, impaired glucose tolerance and type 2 diabetes in the Mexican paediatric population

Paediatric and Perinatal Epidemiology ◽

10.1111/j.1365-3016.2009.01035.x ◽

2009 ◽

Vol 23 (4) ◽

pp. 363-369 ◽

Cited By ~ 15

Author(s):

Fernando Guerrero-Romero ◽

Rafael Violante ◽

Martha Rodríguez-Morán

Keyword(s):

Type 2 Diabetes ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Impaired Fasting Glucose ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Fasting Glucose ◽

Paediatric Population ◽

Fasting Plasma

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The Effects on Insulin Action in Adult Hypopituitarism of Recombinant Human GH Therapy Individually Titrated for Six Months

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.11.8044 ◽

2001 ◽

Vol 86 (11) ◽

pp. 5342-5347 ◽

Cited By ~ 4

Author(s):

E. M. McConnell ◽

A. B. Atkinson ◽

C. Ennis ◽

D. R. Hadden ◽

D. R. McCance ◽

...

Keyword(s):

Glucose Tolerance ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Insulin Action ◽

Serum Insulin ◽

Gh Therapy ◽

Gh Replacement ◽

Fasting Plasma ◽

Glucose Clamp Technique ◽

Igf I

There is controversy about the effect of replacement GH on insulin action in adult hypopituitary patients. GH replacement calculated from weight leads to unacceptable side effects in some patients. Recent studies suggest it should be individually titrated in adults using serum IGF-I levels. We have assessed the effect of titrated GH replacement on peripheral and hepatic insulin action in 13 adult-onset hypopituitary patients (8 males and 5 females; ages 47 ± 10 yr, mean duration of hypopituitarism 6 yr) with confirmed GH deficiency (GHD; maximum GH <5 mU/liter during insulin induced hypoglycemia), ACTH deficiency, and normal glucose tolerance. All patients were on stable hydrocortisone replacement (15 mg with breakfast, 5 mg with evening meal) for at least 2 months before the trial. Insulin action was assessed by the euglycemic hyperinsulinemic glucose clamp technique (1 mU/kg·min) before and after 6 months of GH therapy. GH was started at 0.8 IU sc daily and titrated monthly until the serum IGF-I increased to within 1–2 sd of the mean of normal age-matched controls. Body mass index did not change significantly during the 6 months of GH therapy. Fasting plasma glucose and HbA1c increased significantly after 6 months (5.2 ± 0.0 vs. 5.5 ± 0.0 mmol/liter, P < 0.0001, and 4.5 ± 0.1 vs. 4.7 ± 0.1%, P < 0.0005, respectively). There was no increase in fasting serum insulin (51.6 ± 10.2 vs. 60.0 ± 10.2 pmol/liter, P= 0.12). Exogenous glucose infusion rates required to maintain euglycemia were similar after GH (23.0 ± 0.4 vs. 21.1 ± 0.3 μmol/kg·min, P = 0.6). Endogenous glucose production in the fasting state was also unchanged following GH (11.8 ± 0.7 vs.12.3 ± 0.9μ mol/kg·min, P = 0.5) and suppressed to a similar extent following insulin (4.4 ± 0.8 vs. 5.5 ± 0.8 μmol/kg·min, P = 0.3). In summary, GH therapy for 6 months, with serum IGF-I maintained in the upper physiological range, increased fasting plasma glucose and HbA1c. There was no effect on peripheral or hepatic insulin sensitivity. Patients receiving GH therapy require long-term monitoring of glucose tolerance.

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Effect of a 4 week physical training program on plasma concentrations of inflammatory markers in patients with abnormal glucose tolerance

Acta Endocrinologica ◽

10.1530/eje.1.02127 ◽

2006 ◽

Vol 154 (4) ◽

pp. 577-585 ◽

Cited By ~ 105

Author(s):

Andreas Oberbach ◽

Anke Tönjes ◽

Nora Klöting ◽

Mathias Fasshauer ◽

Jürgen Kratzsch ◽

...

Keyword(s):

Regression Analysis ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Body Fat ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Physical Training ◽

Plasma Concentrations ◽

Percentage Body Fat ◽

Fasting Plasma

Objective: Subclinical chronic inflammation could be a unifying factor linking type 2 diabetes (T2D) and atherosclerosis. The beneficial effects of physical activity on a reduced risk of coronary heart disease could at least in part be mediated by improved markers of inflammation. Research design and methods: The aim of this study was to determine the effect of 4 weeks of physical training on plasma concentrations of interleukin (IL)-6, C-reactive protein (CRP), adiponectin and IL-10 in 60 individuals with normal glucose tolerance, impaired glucose tolerance (IGT) or T2D. Results: In patients with IGT and T2D, significant improvement in body fat, fitness level, glucose metabolism and insulin sensitivity after 4 weeks of physical training was associated with significantly improved plasma concentrations of adiponectin and CRP, but not IL-6. Regression analysis demonstrated only for the anti-inflammatory parameters adiponectin and IL-10 a significant relationship with the decrease in fasting plasma glucose, whereas changes in IL-6 and CRP were not significantly related to changes in fasting plasma glucose, body fat, maximal oxygen uptake, or insulin sensitivity. In a multivariate linear regression analysis, only changes in circulating adiponectin, fasting plasma glucose and percentage body fat were determinants of changes in insulin sensitivity. Conclusions: Physical training was associated with a near normalization of adiponectin and CRP plasma concentrations in subjects with IGT and T2D. Increased insulin sensitivity after training was most strongly related to changes in adiponectin plasma concentrations, in fasting plasma glucose and percentage body fat, whereas changes in IL-6, IL-10 and CRP plasma concentrations did not significantly contribute to improved insulin sensitivity.

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