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Aims/Introduction Continuous glucose monitoring (CGM) metrics, such as times in range (TIR) and time below range, have been shown to be useful as clinical targets that complement glycated hemoglobin (HbA1c) for patients with type 2 diabetes mellitus. We investigated the relationships between TIR, glycemic variability and patient characteristics in patients with type 2 diabetes mellitus. Materials and Methods We carried out continuous glucose monitoring in 281 outpatients with type 2 diabetes mellitus who participated in a multicenter cohort (Hyogo Diabetes Hypoglycemia Cognition Complications) study. Results The results are shown as the median (interquartile range). The age, disease duration and HbA1c were 68 years (62–71 years), 13 years (7–23 years) and 6.9% (6.5–7.5%), respectively. TIR and standard deviation obtained by continuous glucose monitoring worsened significantly with increasing disease duration. Multiple regression analyses showed that disease duration (standard partial regression coefficient, β = −0.160, P = 0.003), diabetic peripheral neuropathy (β = −0.106, P = 0.033) and urinary albumin excretion (β = −0.100, P = 0.043) were useful explanatory factors for TIR. In contrast, HbA1c (β = −0.398, P < 0.001) and the use of antidiabetic drugs potentially associated with severe hypoglycemia (β = 0.180, P = 0.028), such as sulfonylureas, glinides and insulin, were useful explanatory factors for time below range in the elderly patients with type 2 diabetes mellitus. Conclusions The results of this study suggest that disease duration and diabetic complications are associated with TIR deterioration. In addition, low HbA1c levels and the use of antidiabetic drugs potentially associated with severe hypoglycemia might worsen the time below range in the elderly.

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Aquaporin-3 (AQP3) is a water channel that is predominantly expressed in the colon, where it plays a critical role in the regulation of fecal water content. This study investigated the role of AQP3 in the colon in morphine-induced constipation. AQP3 expression levels in the colon were analyzed after oral morphine administration to rats. The degree of constipation was analyzed after the combined administration of HgCl(2) (AQP3 inhibitor) or fluoxetine (5-HT reuptake transporter [SERT] inhibitor) and morphine. The mechanism by which morphine increased AQP3 expression was examined in HT-29 cells. AQP3 expression levels in rat colon were increased during morphine-induced constipation. The combination of HgCl(2) and morphine improved morphine-induced constipation. Treatment with morphine in HT-29 cells did not change AQP3 expression. However, 5-HT treatment significantly increased the AQP3 expression level and the nuclear translocation of peroxisome proliferator-activated receptor gamma (PPARγ) 1 h after treatment. Pretreatment with fluoxetine significantly suppressed these increases. Fluoxetine pretreatment suppressed the development of morphine-induced constipation and the associated increase in AQP3 expression in the colon. The results suggest that morphine increases the AQP3 expression level in the colon, which promotes water absorption from the luminal side to the vascular side and causes constipation. This study also showed that morphine-induced 5-HT secreted from the colon was taken into cells by SERT and activated PPARγ, which subsequently increased AQP3 expression levels.