Aims/IntroductionTo assess the effects of sodium glucose co-transporter 2 inhibitor therapy on the pathophysiology of type 2 diabetes.Materials and MethodsWe administered ipragliflozin to 21 inpatients with type 2 diabetes for 7 days, and analyzed the diurnal profiles of plasma glucose and 3-hydroxybutyrate. A total of 21 age-, sex- and body mass index-matched diabetic patients served as controls.ResultsContinuous glucose monitoring showed that the 24-h glucose curve was shifted downward without hypoglycemia by the administration of ipragliflozin. The average glucose level was reduced from 182 ± 54 mg/dL to 141 ± 33 mg/dL (P < 0.0001). The magnitude of the reduction was highly correlated with the baseline average glucose level. Homeostasis model assessment of insulin resistance was decreased, and homeostasis model assessment of β-cell function was increased during the treatment. Urinary glucose excretion was correlated with the average glucose level both on day 0 and on day 7, although the regression line was steeper and shifted leftward on day 7. The ipragliflozin-treated patients lost more weight than the control patients (1.4 ± 0.5 vs 0.5 ± 0.6 kg, P < 0.0001). Plasma levels of 3-hydroxybutyrate were significantly increased with peaks before breakfast and before dinner. Patient age and bodyweight loss were negatively and positively correlated with the peak levels of 3-hydroxybutyrate on day 7, respectively.ConclusionsThe ipragliflozin treatment improved the 24-h glucose curve without causing hypoglycemia. The close correlation between the magnitude of glucose reduction and the baseline plasma glucose concentration suggests that the risk of hypoglycemia is likely low. It might be prudent to monitor ketone body levels in younger patients and in patients with rapid weight loss.
Intravenous methylprednisolone (IVMP) pulse therapy is the first-line treatment for the active phase of moderate to severe Graves' orbitopathy (GO). However, acute and severe liver damage has been reported during and after IVMP therapy. In this retrospective study, we investigated risk factors for liver dysfunction during and after IVMP therapy based on 175 Japanese patients with moderate to severe GO and treated at our center between 2003 and 2011. The results showed that seven patients developed severe liver dysfunction with elevated serum alanine aminotransferase (ALT > 300 U/L). Mild (40–100 U/L) and moderate (100–300 U/L) increases of ALT occurred in 62 patients (35%) and 10 patients (6%), respectively. Liver dysfunction was more frequently observed in males, in patients receiving high-dose methylprednisolone, and patients aged over 50 years. Preexistent viral hepatitis was significantly associated with liver dysfunction (65% in patients positive for hepatitis B core antibody and patients positive for hepatitis C virus antibodies). Our study confirmed the association of liver dysfunction with IVMP during and after treatment. It suggests that, in patients with GO, evaluation of preexisting risk factors—including viral hepatitis—and careful weekly monitoring of liver function during IVMP therapy and monthly thereafter for 12 months are warranted.
Aims. Efficacy and safety of DPP-4 inhibitor, sitagliptin, add-on therapy to insulin were investigated in Japanese patients with type 2 diabetes. Subjects and Methods. Two hundred and sixteen patients (126 men, 65 ± 12 years old, BMI 24.9 ± 4.5, means ± S.D.) who had been treated by insulin alone or insulin combined with other oral hypoglycemic agents (OHAs) were recruited, and sitagliptin was added for 3 months. Results. HbA1c was significantly decreased after 3 months of add-on therapy as a whole (8.56 ± 1.50% to 7.88 ± 1.25%, P < 0.0001). Body weight did not change and insulin dosage was significantly (P < 0.0001) decreased for 3 months. Furthermore, day-to-day glucose variability was significantly reduced (18.3 ± 9.1 to 16.1 ± 8.1%, P < 0.05). In stepwise multiple regression analysis on ΔHbA1c as an outcome variable, the higher baseline HbA1c value and a preserved CPR were selected as significant predictive variables. Fifteen patients complained of mild hypoglycemia without any assistance during 3 months of sitagliptin add-on, while no severe hypoglycemic episode was reported. Conclusions. Add-on of sitagliptin to ongoing insulin therapy effectively reduced either HbA1c level or glucose fluctuation and could be a practical and well-tolerated alternative to treat Japanese patients with type 2 diabetes who had been inadequately controlled by insulin with or without other OHAs.
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