Introduction: The GEMINI trial compared the effects of treatment with metoprolol versus carvedilol in patients with type 2 diabetes. Carvedilol demonstrated a more favorable effect on factors associated with the metab...Introduction: The GEMINI trial compared the effects of treatment with metoprolol versus carvedilol in patients with type 2 diabetes. Carvedilol demonstrated a more favorable effect on factors associated with the metabolic syndrome than metoprolol. We hypothesize that carvedilol will have additional beneficial effects on markers of inflammation, oxidative stress, and endothelial function than metoprolol. Methods: Twenty subjects were randomized to either carvedilol or metoprolol. Study procedures including assessment of metabolic parameters and endothelial function, while fasting and after a 75 g oral glucose tolerance were conducted at baseline and following 5 months of treatment. Results: Following 5 months of treatment, PAI-1 increased significantly from baseline in the metoprolol group. There were no changes in PAI-1 in the carvedilol group. While not reaching statistical significance, there was a trend toward worsening insulin resistance with metoprolol treatment compared to carvedilol treatment. Flow mediated vasodilation increased in both groups following the 2-hr OGGT during the baseline study. After five months of treatment, there was a non-significant increase in flow-mediated vasodilation under both fasting and post OGTT conditions in the carvedilol group compared to baseline. Conversely, there was no change in fasting flow mediated vasodilation in the metoprolol group. Additionally, metoprolol treatment blunted the increase in flow mediated vasodilation following OGGT compared to baseline (p < 0.05). Conclusion: Treatment with metoprolol was associated with adverse metabolic effects including increases in PAI-1 and trends toward worsening insulin resistance and endothelial function compared to treatment with carvedilol.展开更多
Objective: Evidence supporting the twice-daily administration of insulin glargine as an approach to address its waning effectiveness at the end of a 24 hour period is sparse. We hypothesized that insulin concentration...Objective: Evidence supporting the twice-daily administration of insulin glargine as an approach to address its waning effectiveness at the end of a 24 hour period is sparse. We hypothesized that insulin concentrations determined during the last four hours of a 24 hour period would be greater when identical doses of insulin glargine were administered twice-daily as compared to once-daily among type 1 diabetes patients. Research Methods: Ten subjects with insulin deficient type 1 diabetes were admitted for two 38-hour studies at least one week apart. Patients received full-dose insulin glargine once daily at 0800 and half-dose insulin glargine twice-daily at 0800 and 2000 for at least one week in random order prior to overnight studies. Overnight glucose was stabilized with intravenous insulin on the evening prior to study, and subjects fasted and did not receive short acting insulin during the study period. Insulin concentrations were assessed every 30 minutes with an ultrasensitive assay between study hours 20 and 24. Results: Insulin concentrations for the final four hours of study period did not differ between once-daily and twice-daily insulin glargine administration (p = 0.38). Home glucose testing results and overnight plasma glucose concentrations did not differ between study conditions. Conclusions: These results demonstrate that insulin concentrations are equivalent during the last four hours of a 24-hour period when insulin glargine is administered once- or twice-daily. These findings do not support a role for twice-daily insulin glargine in the management of patients with type 1 diabetes.展开更多
文摘Introduction: The GEMINI trial compared the effects of treatment with metoprolol versus carvedilol in patients with type 2 diabetes. Carvedilol demonstrated a more favorable effect on factors associated with the metabolic syndrome than metoprolol. We hypothesize that carvedilol will have additional beneficial effects on markers of inflammation, oxidative stress, and endothelial function than metoprolol. Methods: Twenty subjects were randomized to either carvedilol or metoprolol. Study procedures including assessment of metabolic parameters and endothelial function, while fasting and after a 75 g oral glucose tolerance were conducted at baseline and following 5 months of treatment. Results: Following 5 months of treatment, PAI-1 increased significantly from baseline in the metoprolol group. There were no changes in PAI-1 in the carvedilol group. While not reaching statistical significance, there was a trend toward worsening insulin resistance with metoprolol treatment compared to carvedilol treatment. Flow mediated vasodilation increased in both groups following the 2-hr OGGT during the baseline study. After five months of treatment, there was a non-significant increase in flow-mediated vasodilation under both fasting and post OGTT conditions in the carvedilol group compared to baseline. Conversely, there was no change in fasting flow mediated vasodilation in the metoprolol group. Additionally, metoprolol treatment blunted the increase in flow mediated vasodilation following OGGT compared to baseline (p < 0.05). Conclusion: Treatment with metoprolol was associated with adverse metabolic effects including increases in PAI-1 and trends toward worsening insulin resistance and endothelial function compared to treatment with carvedilol.
文摘Objective: Evidence supporting the twice-daily administration of insulin glargine as an approach to address its waning effectiveness at the end of a 24 hour period is sparse. We hypothesized that insulin concentrations determined during the last four hours of a 24 hour period would be greater when identical doses of insulin glargine were administered twice-daily as compared to once-daily among type 1 diabetes patients. Research Methods: Ten subjects with insulin deficient type 1 diabetes were admitted for two 38-hour studies at least one week apart. Patients received full-dose insulin glargine once daily at 0800 and half-dose insulin glargine twice-daily at 0800 and 2000 for at least one week in random order prior to overnight studies. Overnight glucose was stabilized with intravenous insulin on the evening prior to study, and subjects fasted and did not receive short acting insulin during the study period. Insulin concentrations were assessed every 30 minutes with an ultrasensitive assay between study hours 20 and 24. Results: Insulin concentrations for the final four hours of study period did not differ between once-daily and twice-daily insulin glargine administration (p = 0.38). Home glucose testing results and overnight plasma glucose concentrations did not differ between study conditions. Conclusions: These results demonstrate that insulin concentrations are equivalent during the last four hours of a 24-hour period when insulin glargine is administered once- or twice-daily. These findings do not support a role for twice-daily insulin glargine in the management of patients with type 1 diabetes.
