Toshiyuki Hayashi

Relationship between daily and day-to-day glycemic variability and increased oxidative stress in type 2 diabetes

AIMS To determine the association of daily and day-to-day glucose variability with oxidative stress. METHODS This was a cross-sectional analysis of 68 patients with type 2 diabetes mellitus (T2DM) over 72h of continuous glucose monitoring. Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) were measured before breakfast on day 1. Glucose variability, mean glucose level (MGL), mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD) in glucose levels and area under the postprandial plasma glucose curve (AUCPP) were measured on days 2 and 3. Plasma oxidant capacity against N,N-diethylparaphenylenediamine was measured with the diacron-reactive oxygen metabolites (d-ROMs) test on day 1. RESULTS Overall, 66.2% males with the mean age of 63.2±12.6years, diabetes duration of 12.9±10.4years, and HbA1c level of 8.1±1.6% (65±17mmol/mol) were included. MGL (r=0.330), HbA1c (r=0.326), MAGE (r=0.565), MODD (r=0.488), and AUCPP (r=0.254) exhibited significant correlations with d-ROMs and not FPG; these correlations remained significant after adjustment for clinical factors (sex, age, duration of diabetes, smoking habit, insulin use, statin use, angiotensin II receptor blocker use, BMI, LDL-C, HDL-C, TG, eGFR, and systolic blood pressure) (R2=0.268, R2=0.268, R2=0.417, R2=0.314, and R2=0.347, respectively). MAGE was significantly correlated with MODD (r=0.708) and MAGE and MODD were independently correlated with d-ROMs by multivariate analysis. CONCLUSIONS Therefore, oxidative stress is associated with daily and day-to-day glucose variability in patients with T2DM.

Comparison of liraglutide plus basal insulin and basal-bolus insulin therapy (BBIT) for glycemic control, body weight stability, and treatment satisfaction in patients treated using BBIT for type 2 diabetes without severe insulin deficiency: A randomized prospective pilot study

AIMS We examined whether 0.9 mg/day liraglutide plus basal insulin (Lira-basal) is superior to basal-bolus insulin therapy (BBIT) for type 2 diabetes (T2DM) without severe insulin deficiency as determined by glucagon stimulation. METHODS Fifty patients receiving BBIT were enrolled in this 24-week, prospective, randomized, open-labeled study. After excluding subjects with fasting C-peptide immunoreactivity (CPR) < 1.0 ng/mL and CPR increase < 1.0 ng/mL at 6 min post glucagon injection, 25 were randomly allocated to receive Lira-basal (n = 12) or continued BBIT (n = 13). Primary endpoint was change in HbA1c. Secondary endpoints were changes in body weight (BW), 7-point self-monitored blood glucose (SMBG), and Diabetes Treatment Satisfaction Questionnaire status (DTSQs) scores. RESULT The Lira-basal group demonstrated reduced HbA1c, whereas the BBIT group showed no change. BW was reduced in the Lira-basal group but increased in the BBIT group. The Lira-basal group also exhibited significantly reduced pre-breakfast and pre-lunch SMBG. DTSQs scores improved in the Lira-basal group but not the BBIT group. Plasma lipids, liver function, and kidney function were not significantly changed in either group. CONCLUSIONS Lira-basal therapy is superior to BBIT for T2DM without severe insulin deficiency. This study was registered with UMIN Clinical Trials Registry (UMIN000028313).

Improvements of ambient hyperglycemia and glycemic variability are associated with reduction in oxidative stress for patients with type 2 diabetes

AIMS We aimed to evaluate which parameters of improvement in glucose metabolism reduce oxidative stress for patients with Type 2 diabetes mellitus (T2DM). METHODS Sixty-seven outpatients with T2DM underwent 72 h of continuous glucose monitoring (CGM) and were measured for oxidative stress before and after a 24-week intervention with the following targets: fasting plasma glucose (FPG), <130 mg/dl; postprandial plasma glucose (PPG), <180 mg/dl; and glycated hemoglobin (HbA1c), <7% (53 mmol/mol). The mean glucose level (MGL), mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), percentage coefficient of variation for glucose (%CV) and area under the postprandial plasma glucose curve (AUCPP) were calculated from the CGM data. Oxidative stress was estimated using the diacron-reactive oxygen metabolites (d-ROMs) test. Finally, the association between the improvements in glucose metabolism and oxidative stress was evaluated. RESULTS FPG, MGL, HbA1c, MAGE, MODD, %CV, AUCPP, and d-ROMs significantly improved after 24 weeks of intervention. The change in d-ROMs was significantly correlated with that in FPG (r = 0.414), MGL (r = 0.402), HbA1c (r = 0.271), MAGE (r = 0.457), MODD (r = 0.371), and AUCPP (r = 0.352). The correlation of the change in d-ROMs with that in FPG, MAGE, and MODD and the use of glucose-like peptide 1 receptor agonists and statins remained significant after adjustment for other markers of diabetes control (multiple R2 = 0.406). CONCLUSIONS Improvements in glucose metabolism, including FPG and daily and day-to-day glucose variability, were all correlated with reduced oxidative stress for patients with T2DM.

Analysis of pancreatic volume in acute-onset, slowly-progressive and fulminant type 1 diabetes in a Japanese population

A decrease in the size of the pancreas is observed in islet autoantibody‐positive non‐diabetic donors and acute‐onset type 1 diabetes irrespective of the diabetes duration. Little is known, however, about the relationship between the size of the pancreas and type 1 diabetes subtypes, including fulminant type 1 diabetes.