Measurement

Medical history, concomitant drugs, bodyweight and height were investigated. After 12‐h overnight fasting, venous blood was collected, and the following were measured: hemoglobin (Hb), hemoglobin A_1c (HbA_1c; Sysmex XN‐9000 with Bio‐Rad Variant II Turbo; Bio‐Rad Laboratories, Hercules, CA, USA), glucose, C‐peptide, total cholesterol, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatinine levels (Toshiba‐200FR auto‐analyzer; Toshiba Medical Systems Corporation, Tokyo, Japan). Total serum bilirubin (Toshiba‐200FR, HITACHI 7170 Auto Analyzer; Hitachi, Ltd., Tokyo, Japan) was measured using the azobilirubin method (Daiichi Pure Chemical Co. Ltd., Tokyo, Japan). Intra‐assay coefficients of variance (CV) for bilirubin measurement was 1.9% and inter‐assay CV was 0.6%. Spot urine albumin and creatinine (Toshiba‐120FR auto‐analyzer; Toshiba Medical Systems Corporation) were also measured. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease Study equation method¹².

To assess GV, CGMS was applied for 3 days¹⁰, and the first 48 h were used for the calculation of mean blood glucose (MBG) and the GV indices⁴, such as standard deviation (SD), mean amplitude of glucose excursion (MAGE), continuous overall net glycemic action calculated with 6‐h time intervals (CONGA‐6), M100 (a measure of the stability of the glucose excursions in comparison with glucose value of 5.55 mmol/L [100 mg/dL]), J‐index, mean post‐meal maximum glucose (MPMG) and area under the curve for glucose above 9.99 mmol/L (180 mg/dL; area under the curve for glucose above 180 mg/dL). MAGE is the mean of the absolute difference of peak‐to‐nadir or nadir‐to‐peak direction, in the glycemic excursions more than one SD during the 48 h. CONGA‐6 is the standard deviation of the differences between each glucose level and the corresponding glucose level measured 6 h earlier. M100 is a measure of the stability of the glucose excursions in comparison with glucose value of 5.55 mmol/L (100 mg/dL). J‐index takes account of both the mean glucose level and variability of glycemia.