2 - TI Pharma
2 - TI Pharma 2 - TI Pharma
Chapter 5 Glucocorticoids, islet-cell function & ANS 92 ABSTRACT objectives: To assess the effects of low- and high-dose glucocorticoid (GC) treatment on pancreatic islet-cell function in healthy males and to study the potential influence of altered autonomous nervous system (ANS) balance and meal-related incretin responses. Research design and methods: In a randomized, placebo-controlled, double-blind, dose-response intervention study, 32 males (age: 21±2 years; BMI: 21.9±1.7 kg/m2 ) were allocated to prednisolone 7.5 mg once daily (n=12), prednisolone 30 mg once daily (n=12), or placebo (n=8) for two weeks using block randomization. Main outcome measures were: 1) C-peptide secretion during a hyperglycemic clamp with additional arginine stimulation 2) fasting and postprandial glucagon levels 3) parasympathetic activity and sympathovagal balance and 4) postprandial incretin responses. Results: Prednisolone treatment did not significantly affect first- and second-phase glucose-stimulated C-peptide secretion, however, C-peptide secretion following arginine stimulation on top of hyperglycemia (ASI-iAUC ) was dose-dependently reduced: -2.8 CP (-5.2;0.2) and -3.1 (-8.8; -1.0) nmol/L.min for prednisolone 7.5 mg and prednisolone 30 mg, respectively (P=0.035 vs. placebo). Fasting glucagon levels and postprandial glucagon levels were only increased by prednisolone 30 mg. Measures of the ANS and incretin responses were not significantly altered by treatment. However, changes in parasympathic activity associated with fasting plasma glucose levels (r=-0.407; P=0.03) and tended to associate with fasting glucagon concentrations (r=-0.337; P=0.07). The change in sympathovagal balance was inversely related to ASI-iAUC (r=-0.365; P=0.05). No side CP effects of prednisolone treatment were reported. Conclusions: Impairments in islet-cell function contribute to prednisolone-induced glucose intolerance in healthy men. Altered sympathovagal balance may contribute to these effects. Clinical Trial Registration Number: ISRCTN78149983
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Chapter 5 Glucocorticoids, islet-cell function & ANS<br />
92<br />
ABSTRACT<br />
objectives: To assess the effects of low- and high-dose glucocorticoid (GC) treatment on<br />
pancreatic islet-cell function in healthy males and to study the potential influence of altered<br />
autonomous nervous system (ANS) balance and meal-related incretin responses.<br />
Research design and methods: In a randomized, placebo-controlled, double-blind,<br />
dose-response intervention study, 32 males (age: 21±2 years; BMI: 21.9±1.7 kg/m2 ) were<br />
allocated to prednisolone 7.5 mg once daily (n=12), prednisolone 30 mg once daily (n=12),<br />
or placebo (n=8) for two weeks using block randomization. Main outcome measures were:<br />
1) C-peptide secretion during a hyperglycemic clamp with additional arginine stimulation<br />
2) fasting and postprandial glucagon levels 3) parasympathetic activity and sympathovagal<br />
balance and 4) postprandial incretin responses.<br />
Results: Prednisolone treatment did not significantly affect first- and second-phase<br />
glucose-stimulated C-peptide secretion, however, C-peptide secretion following arginine<br />
stimulation on top of hyperglycemia (ASI-iAUC ) was dose-dependently reduced: -2.8<br />
CP<br />
(-5.2;0.2) and -3.1 (-8.8; -1.0) nmol/L.min for prednisolone 7.5 mg and prednisolone 30<br />
mg, respectively (P=0.035 vs. placebo). Fasting glucagon levels and postprandial glucagon<br />
levels were only increased by prednisolone 30 mg. Measures of the ANS and incretin<br />
responses were not significantly altered by treatment. However, changes in parasympathic<br />
activity associated with fasting plasma glucose levels (r=-0.407; P=0.03) and tended<br />
to associate with fasting glucagon concentrations (r=-0.337; P=0.07). The change in<br />
sympathovagal balance was inversely related to ASI-iAUC (r=-0.365; P=0.05). No side<br />
CP<br />
effects of prednisolone treatment were reported.<br />
Conclusions: Impairments in islet-cell function contribute to prednisolone-induced<br />
glucose intolerance in healthy men. Altered sympathovagal balance may contribute to these<br />
effects.<br />
Clinical Trial Registration Number: ISRCTN78149983
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