The goal of diabetes treatment is to maintain good glycemic control, prevent the development and progression of diabetic complications, and ensure the same quality of life and life expectancy as healthy people. Hemoglobin A1c (HbA1c) is used as an index of glycemic control, but strict glycemic control using HbA1c as an index may lead to severe hypoglycemia and cardiovascular death. Glycemic variability (GV), such as excessive hyperglycemia and hypoglycemia, is associated with diabetic vascular complications and has been recognized as an important index of glycemic control. Here, we reviewed the definition and evaluated the clinical usefulness of GV, and its relationship with diabetic complications and therapeutic strategies to reduce GV.

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.

Introduction Insulin degludec is a new, ultra-long-acting basal insulin. The aim of this study was to analyze the changes of basal insulin dose and blood glucose profile in basal–bolus therapy of type 1 diabetes mellitus (T1DM) at the switching of basal insulin from insulin glargine or detemir to insulin degludec. Methods Sixteen patients with T1DM were enrolled. The patients underwent continuous glucose monitoring before and after the switching of insulin glargine or detemir to degludec. Ten patients treated with insulin glargine or detemir twice daily, were switched to insulin degludec with 80–90% of the prior insulin dose. The remaining six patients treated with insulin glargine once daily, were switched to insulin degludec without down titration. The changes of daily insulin dose and glycated hemoglobin (HbA1c) were also examined for 12 weeks after switching to insulin degludec. Results In the patients switched from twice-daily basal insulin, no significant difference was found between before and after switching in the blood glucose profile. In the once-daily group, blood glucose levels showed a tendency to decrease after switching to the degludec treatment. During the study period, total daily insulin dose (TDD) and total daily basal insulin dose (TBD) decreased significantly in the twice-daily group, and TDD and TBD showed a tendency to decrease after switching to degludec in the once-daily group. In both groups, the changes of HbA1c were not significantly different. Conclusion It is possible to achieve similar glycemic control with once-daily injection and lower doses of insulin degludec in patients with T1DM who have been treated with insulin glargine or detemir.

Aims/Introduction: Hemoglobin A1c (HbA1c), glycated albumin (GA) and 1,5‐anhydro‐d‐glucitol (1,5‐AG) are used as indicators of glycemic control, whereas continuous glucose monitoring (CGM) is used to assess daily glucose profiles. The aim of this study was to investigate the relationships between CGM metrics, such as time in range (TIR), and glycemic control indicators.Materials and Methods: We carried out retrospective CGM and blood tests on 189 outpatients with impaired glucose tolerance (n = 22), type 1 diabetes mellitus (n = 67) or type 2 diabetes mellitus (n = 100).Results: In type 1 diabetes mellitus and type 2 diabetes mellitus patients, HbA1c and GA were negatively correlated with TIR, whereas 1,5‐AG was positively correlated with TIR. In type 1 diabetes mellitus patients, a TIR of 70% corresponded to HbA1c, GA and 1,5‐AG of 6.9% (95% confidence interval [CI] 6.5–7.2%), 20.3% (95% CI 19.0–21.7%) and 6.0 µg/mL (95% CI 5.1–6.9 µg/mL), respectively. In type 2 diabetes mellitus patients, a TIR of 70% corresponded to HbA1c, GA and 1,5‐AG of 7.1% (95% CI 7.0–7.3%), 19.3% (95% CI 18.7–19.9%) and 10.0 µg/mL (95% CI 9.0–11.0 µg/mL), respectively. TIR values corresponding to HbA1c levels of 7.0% were 56.1% (95% CI 52.3–59.8%) and 74.2% (95% CI 71.3–77.2%) in type 1 diabetes mellitus and type 2 diabetes mellitus patients, respectively.Conclusions: The results of this study showed that the estimated HbA1c corresponding to a TIR of 70% was approximately 7.0% for both type 1 diabetes mellitus and type 2 diabetes mellitus patients, and that the estimated 1,5‐AG calculated from the TIR of 70% might be different between type 1 diabetes mellitus and type 2 diabetes mellitus patients.

The enzyme xanthine oxidoreductase (XOR) catalyzes the synthesis of uric acid (UA) from hypoxanthine and xanthine, which are products of purine metabolism starting from ribose-5-phosphate. Several studies suggested a relationship between hyperuricemia and hepatic steatosis; however, few previous studies have directly examined the relationship between XOR activity and hepatic steatosis. A total of 223 subjects with one or more cardiovascular risk factors were enrolled. The liver-to-spleen (L/S) ratio on computed tomography and the hepatic steatosis index (HSI) were used to assess hepatic steatosis. We used a newly developed highly sensitive assay based on [¹³C₂,¹⁵N₂] xanthine and liquid chromatography/triple quadrupole mass spectrometry to measure plasma XOR activity. Subjects with the L/S ratio of < 1.1 and the HSI of < 36 had increased XOR activity and serum UA levels. Independent of insulin resistance and serum UA levels, multivariate logistic regression analysis revealed that plasma XOR activity was associated with the risk of hepatic steatosis as assessed by the L/S ratio and HSI. According to the findings of this study, plasma XOR activity is associated with hepatic steatosis independent of insulin resistance and serum UA levels.