Which is better, high-dose metformin monotherapy or low-dose metformin/linagliptin combination therapy, in improving glycemic variability in type 2 diabetes patients with insufficient glycemic control despite low-dose metformin monotherapy? A randomized, cross-over, continuous glucose monitoring-based pilot study.

AIMS/INTRODUCTION: The present study investigated the effect of high-dose metformin or low-dose metformin/linagliptin combination therapy on glycemic variability (GV) in type 2 diabetes patients with insufficient glycemic control despite low-dose metformin monotherapy in a cross-over study using continuous glucose monitoring. MATERIALS AND METHODS: The present study was carried out with 11 type 2 diabetes outpatients (7% < glycated hemoglobin < 10%) receiving low-dose metformin monotherapy (500-1,000 mg). All patients were assigned to either metformin 1,500 mg monotherapy (HMET) or combination therapy of low-dose (750 mg) metformin and linagliptin 5 mg (LMET + dipeptidyl peptidase-4 [DPP4]). GV was evaluated by continuous glucose monitoring after >4 weeks of the initial treatment and again after cross-over to the other treatment. GV metrics were compared between the treatments using the Wilcoxon signed-rank test. RESULTS: Of the continuous glucose monitoring-derived GV metrics for the HMET versus LMET + DPP4, mean glucose levels, standard deviations and mean amplitude of glucose excursions were not significantly different. Although the pre-breakfast glucose levels were not significantly different among the treatments (P = 0.248), the 3-h postprandial glucose area under the curve (>160 mg/dL) after breakfast was significantly larger with HMET versus LMET + DPP4 (9,550 [2,075-11,395] vs 4,065 [1,950-8,895]; P = 0.041). CONCLUSIONS: A comparison of GV with HMET versus LMET + DPP4 suggested that LMET + DPP4 might reduce post-breakfast GV to a greater degree than HMET in type 2 diabetes patients receiving low-dose metformin monotherapy.

Low sense of coherence is associated with anxiety among adults: Results based on data from all 47 prefectures of Japan.

BACKGROUND: Anxiety disorder is a major societal, economic, and healthcare burden, so it is essential to identify underlying risk factors. Sense of coherence (SOC), defined as an individual's perceived ability to control events and cope with challenges, is strongly associated with healthcare outcomes. METHODS: This study investigated the association between SOC and anxiety among adults in all 47 prefectures of Japan using a cross-sectional online panel survey. SOC was assessed using the University of Tokyo Health Sociology version of the SOC Scale and anxiety was assessed using the Generalized Anxiety Disorder-7 (GAD-7) scale. RESULTS: Among 2100 participants (1051 males and 1049 females), 475 (22.6%) were identified with anxiety (scoring 8 points or higher on the GAD-7 scale). Before adjustment for potential confounders, there was a significant negative association between SOC and presence of anxiety. Even after adjustment, the presence of anxiety was significantly higher among the lower SOC subgroup than the higher SOC subgroup. CONCLUSIONS: These results indicate that approximately one-fifth of adults in Japan suffer from anxiety and that low SOC is a significant risk factor.

The Effect of Novel Glucose Monitoring System (Flash Glucose Monitoring) on Mental Well-being and Treatment Satisfaction in Japanese People with Diabetes.

INTRODUCTION: FreeStyle Libre (Abbot Diabetes Care Ltd) has been launched as a novel glucose monitoring system called flash glucose monitoring (FGM) in Europe. Several reports are becoming available on its usefulness and safety. To date, however, reports from Asian countries have not been made available. In this study, we evaluated its usefulness in Japanese people with diabetes in terms of its mental well-being and patient satisfaction outcomes. METHODS: Individuals with type 1 and 2 diabetes treated with insulin were enrolled, and they performed self-monitoring of blood glucose. All participants were subjected to FGM for 14 days and compared for changes in mental well-being using the WHO-Five Well-Being Index (WHO-5) (1998 version) as well as in patient satisfaction using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) before and after implementation of FGM. RESULTS: The study included a total of 80 subjects (type 1/2 diabetes, 57/23). The WHO-5 scores were significantly improved from 15.5 ± 4.1 at baseline to 17.2 ± 4.5 after implementation of FGM (P < 0.001); the DTSQ scores also were significantly improved from 24.8 ± 6.0 to 26.7 ± 5.2 (P = 0.001). In type 1 diabetes, both the WHO-5 and DTSQ scores were significantly improved from baseline (P = 0.001, P = 0.001), while neither the WHO-5 scores nor the DTSQ scores were improved in type 2 diabetes. CONCLUSIONS: The study results suggest that FGM has the potential to improve mental well-being and treatment satisfaction among individuals with type 1 diabetes.

Biphasic insulin aspart-30 reduces glycemic variability to a greater degree than insulin detemir: A randomized controlled trial of once-daily insulin regimens using continuous glucose monitoring.

INTRODUCTION: We compared the efficacy of insulin detemir and biphasic insulin aspart-30 given in the morning as an add-on to oral hypoglycemic agents in type 2 diabetes patients. MATERIALS AND METHODS: The present study enrolled 30 patients with poorly controlled type 2 diabetes (8% ≤ glycated hemoglobin < 11%) being treated with oral hypoglycemic agent mono- or combination therapy with biguanides, sulfonylureas or thiazolidinediones. The patients were randomly assigned to insulin detemir (group D) or insulin aspart-30 (group A) given in the morning as add-on to oral hypoglycemic agents. After adjusting their insulin doses, the patients that underwent continuous glucose monitoring during a 3-day hospitalization and with day 2 continuous glucose monitoring data were subjected to analysis. RESULTS: There was no significant difference in patient background, baseline glycated hemoglobin levels and insulin doses during continuous glucose monitoring between the two groups. The percent coefficient of variation of 24-h glucose levels was significantly lower in group A (20.4 ± 7.6) than in group D (27.1 ± 6.5; P = 0.015). Similarly, mean amplitude of glycemic excursions was significantly smaller in group A (80 ± 32) than in group D (102 ± 14; P = 0.021). Postprandial glucose excursions were significantly smaller after breakfast in group A (65 ± 31 mg/dL) than in group D (106 ± 32 mg/dL; P = 0.002). CONCLUSIONS: As once-daily insulin injection therapy given before breakfast in type 2 diabetes patients, the biphasic insulin analog might represent a better insulin option in significantly lowering the percent coefficient of variation and mean amplitude of glycemic excursions than the long-acting insulin preparation.

Prediction of nocturnal hypoglycemia unawareness by fasting glucose levels or post-breakfast glucose fluctuations in patients with type 1 diabetes receiving insulin degludec: A pilot study.

OBJECTIVE: To evaluate whether nocturnal asymptomatic hypoglycemia (NAH) can be predicted by fasting glucose levels or post-breakfast glucose fluctuations in patients with type 1 diabetes (T1D) receiving insulin degludec. METHODS: Patients with T1D receiving insulin degludec underwent at-home CGM assessments. Indices for glycemic variability before and after breakfast included fasting glucose levels and the range of post-breakfast glucose elevation. For comparison, the patients were classified into those with NAH and those without. The optimal cut-off values for the relevant parameters were determined to predict NAH using ROC analysis. RESULTS: The study included a total of 31 patients (mean HbA1c values, 7.8 ± 0.7%), and 16 patients (52%) had NAH. Those with NAH had significantly lower fasting glucose levels than did those without (82 ± 48 mg/dL vs. 144 ± 69 mg/dL; P = 0.009). The change from pre- to post-breakfast glucose levels was significantly greater among those with NAH (postprandial 1-h, P = 0.028; postprandial 2-h, P = 0.028). The cut-off values for prediction of NAH were as follows: fasting glucose level <84 mg/dL (sensitivity 0.80/specificity 0.75/AUC 0.80; P = 0.004), 1-h postprandial elevation >69 mg/dL (0.75/0.67/0.73; P = 0.033), and 2-h postprandial elevation >99 mg/dL (0.69/0.67/0.71; P = 0.044). CONCLUSIONS: The results suggest that fasting glucose level of < 84 mg/dL had approximately 80% probability of predicting the occurrence of NAH in T1D receiving insulin degludec. It was also shown that the occurrence of hypoglycemia led to greater post-breakfast glucose fluctuations and steeper post-breakfast glucose gradients.

Comparison of glycemic variability in Japanese patients with type 1 diabetes receiving insulin degludec versus insulin detemir using continuous glucose monitoring: a randomized, cross-over, pilot study.

OBJECTIVE: To use continuous glucose monitoring (CGM) to compare glycemic variability in patients with type 1 diabetes (T1D) treated with insulin degludec (IDeg) versus insulin detemir (IDet). METHODS: Ten patients with T1D were randomly assigned to receive once-daily IDeg, followed by twice-daily IDet, or vice versa. Glucose variability was evaluated by CGM after >4 weeks of the first insulin and again after crossover to the second insulin. RESULTS: The total daily insulin dose (U/kg/day) and the total daily basal insulin dose (U/kg/day) were significantly lower during treatment with IDeg than with IDet [median (interquartile range): 0.55 (0.54-0.73) vs. 0.64 (0.54-0.83); P = 0.028, 0.24 (0.19-0.36) vs. 0.30 (0.19-0.39); P = 0.027]. The 24-hour mean glucose levels were not significantly different. However, their standard deviation (SD) was significantly smaller during treatments with IDeg than those with IDet [59.5 (39.5-71.0) vs. 72.8 (61.8-92.8); P = 0.008]. Their mean fasting glucose levels and the mean postprandial peak levels after breakfast and after dinner were significantly lower with IDeg. CONCLUSIONS: A CGM-based comparison demonstrated that once-daily IDeg showed fewer glycemic fluctuations than twice-daily IDet. IDeg appears to stabilize blood glucose levels better during both daytime and nighttime (particularly, before and after breakfast) with a lower insulin dosage.

Population-based cross-sectional study on insulin resistance and insulin-secretory capacity in Japanese school children.

AIMS/INTRODUCTION: Little information is available regarding the status of insulin resistance (IR) and insulin deficiency (ID), as well as their relationship with obesity in children using the homeostasis model assessment (HOMA) in a population-based setting. MATERIALS AND METHODS: The study included a total of 445 ninth-grade children participating in health check-up programs implemented in Tsunan Town, Niigata, Japan (boys/girls, 252/193 [participation rates: 98.1/95.5%]). HOMA of insulin resistance ≥2.5 was defined as IR, and HOMA of ß-cell function <40 defined as ID. RESULTS: The medians (25-75th percentiles) of HOMA of insulin resistance, HOMA of ß-cell function, Disposition Index and body mass index in boys were 1.2 (0.8-1.7), 64 (44-93), 52 (43-64) and 19.2 (18.0-20.7) kg/m2 , respectively, vs 1.5 (1.0-2.0), 86 (63-120), 60 (50-74) and 20.4 (18.9-22.0) kg/m2 , respectively, in girls. The HOMA of insulin resistance, HOMA of ß-cell function and Disposition Index values were significantly higher in the girls (P = 0.002, P < 0.001 and P < 0.001, respectively). Those with IR accounted for a significantly higher proportion of girls than boys (15.5/8.7%; P = 0.027); those with obesity accounted for 9.9/10.7% (boys/girls); and those with IR and obesity accounted for 2.4/4.7%. Those with ID accounted for a significantly higher proportion of boys than girls (20.6/8.8%; P = 0.001), whereas those with ID and obesity accounted for a very small proportion of either group (0.4/0.5%). CONCLUSIONS: The presence of IR was higher among the girls. In contrast, ID was more frequent among the boys. The infrequent presence of ID among children might support the presence of non-obese type 2 diabetes adults in Japan.

Comparison of glycemic variability in Japanese patients with type 1 diabetes receiving insulin degludec versus insulin glargine using continuous glucose monitoring: A randomized, cross-over, pilot study.

AIMS: To compare glucose variability in patients with type 1 diabetes (T1D) treated with insulin glargine (IGla) versus insulin degludec (IDeg) using continuous glucose monitoring (CGM). METHODS: Thirteen patients with T1D were randomly assigned to receive IDeg once-daily followed by IGla twice-daily or vice versa. They were evaluated for glucose variability by CGM after >4weeks of treatment with either insulin, and then were crossed over to the other, and evaluated by CGM after >4weeks. RESULTS: The total daily insulin dose (TDD) (U/kg/day) and the total daily basal insulin dose (U/kg/day) in the patients were significantly lower while taking IDeg than while taking IGla (mean [95% confidence interval] 0.72 [0.61-0.83] vs. 0.76 [0.64-0.88]; P=0.001, 0.29 [0.22-0.36] vs. 0.33 [0.26-0.40]; P=0.001), although no significant difference was noted in the patients while on IDeg versus while on IGla in 24-h mean glucose and SDs of 24-h glucose. Again, the range of postprandial glucose increase was not significantly different between the meals in the patients while taking IDeg (P=0.288) but significantly different in the patients while taking IGla (P=0.033). CONCLUSIONS: The use of once-daily IDeg leads not only to similar glycemic control to that seen with twice-daily IGla even in those who received IGla prior to the study, but also to significant decreases in TDD and long-acting basal insulin dose.

The relationship between HbA1c values and the occurrence of hypoglycemia as assessed by continuous glucose monitoring in patients with type 1 diabetes.

BACKGROUND: We aimed to examine the relationship between the occurrence of hypo-/hyperglycemia and HbA1c values, as assessed by continuous glucose monitoring (CGM) in patients with type 1 diabetes. METHODS: The study subjects comprised 101 type 1 diabetic patients on basal-bolus insulin therapy, who were put on masked CGM immediately after admission. The subjects were divided into four groups equally by HbA1c values and the 24-h CGM data were compared among the groups. RESULTS: Groups A to D comprised 24 patients with HbA1c ≤7.2 %, 26 patients with 7.2 % 9.2 %, respectively. The higher the HbA1c values, the significantly higher the 24-h mean glucose levels [median (25-75 percentiles)], with the HbA1c in groups A to D being 133 (114-155), 158 (132-188), 182 (152-206), and 186 (143-215) mg/dL, respectively (P < 0.001). Conversely, the higher the HbA1c values, the significantly shorter the time in hypoglycemia (<70 mg/dL), with the time in groups A to D being 170 (58-341), 78 (0-210), 45 (0-105), and 20 (0-105) min, respectively (P = 0.014); and the higher the HbA1c values, the significantly shorter the time in nocturnal hypoglycemia, with the time in groups A to D being 120 (5-269), 25 (0-120), 0 (0-60), and 0 (0-89) min, respectively (P = 0.019). No significant difference was seen between groups A to D in the standard deviations (SDs) of 24-h glucose values at 53 (40-65), 54 (45-70), 64 (55-76), and 58 (48-80), respectively. CONCLUSION: In type 1 diabetic patients, lower HbA1c was not associated with lower SD of 24-h glucose values, but may result in increased hypoglycemia. Trial Registration Current controlled trials UMIN000019190.

Can Fasting Glucose Levels or Post-Breakfast Glucose Fluctuations Predict the Occurrence of Nocturnal Asymptomatic Hypoglycemia in Type 1 Diabetic Patients Receiving Basal-Bolus Insulin Therapy with Long-Acting Insulin?

OBJECTIVE: To investigate whether the occurrence of nocturnal asymptomatic hypoglycemia may be predicted based on fasting glucose levels and post-breakfast glucose fluctuations. PATIENTS AND METHODS: The study subjects comprised type 1 diabetic patients who underwent CGM assessments and received basal-bolus insulin therapy with long-acting insulin. The subjects were evaluated for I) fasting glucose levels and II) the range of post-breakfast glucose elevation (from fasting glucose levels to postprandial 1- and 2-hour glucose levels). The patients were divided into those with asymptomatic hypoglycemia during nighttime and those without for comparison. Optimal cut-off values were also determined for relevant parameters that could predict nighttime hypoglycemia by using ROC analysis. RESULTS: 64 patients (mean HbA1c 8.7 ± 1.8%) were available for analysis. Nocturnal asymptomatic hypoglycemia occurred in 23 patients (35.9%). Fasting glucose levels (I) were significantly lower in those with hypoglycemia than those without (118 ± 35 mg/dL vs. 179 ± 65 mg/dL; P < 0.001). The range of post-breakfast glucose elevation (II) was significantly greater in those with hypoglycemia than in those without (postprandial 1-h, P = 0.003; postprandial 2-h, P = 0.005). The cut-off values determined for relevant factors were as follows: (I) fasting glucose level < 135 mg/dL (sensitivity 0.73/specificity 0.83/AUC 0.79, P < 0.001); and (II) 1-h postprandial elevation > 54 mg/dL (0.65/0.61/0.71, P = 0.006), 2-h postprandial elevation > 78 mg/dL (0.65/0.73/0.71, P = 0.005). CONCLUSIONS: Nocturnal asymptomatic hypoglycemia was associated with increases in post-breakfast glucose levels in type 1 diabetes. Study findings also suggest that fasting glucose levels and the range of post-breakfast glucose elevation could help predict the occurrence of nocturnal asymptomatic hypoglycemia.

Effect of hemodialysis on plasma glucose profile and plasma level of liraglutide in patients with type 2 diabetes mellitus and end-stage renal disease: a pilot study.

The effect of hemodialysis on the plasma glucose profile and liraglutide level after liraglutide injection was investigated in patients with diabetes and end-stage renal disease (ESRD). Either 0.6 mg or 0.9 mg liraglutide was subcutaneously administered daily to 10 Japanese type 2 diabetic patients with ESRD. Hemodialysis was conducted on days 1 and 3. Plasma liraglutide and glucose concentrations were measured by enzyme-linked immunosorbent assay and a continuous glucose monitoring system, respectively. The safety profile of liraglutide was also assessed. Hemodialysis had no effect on the pharmacokinetic parameters of liraglutide in patients with diabetes and ESRD; the maximum plasma concentration (Cmax), tmax, area under the concentration-time curve (AUC), and CL/f were unaltered. Similarly, hemodialysis did not affect the mean or minimum glucose levels, AUC, or duration of hyperglycemia (>180 mg/dL) and hypoglycemia (<70 mg/dL) following liraglutide administration. However, significant increases in mean amplitude of glycemic excursions (MAGE) and standard deviation (SD) as markers of glucose fluctuation, and the maximum glucose level were observed during hemodialysis. No adverse events, including hypoglycemia, were observed after liraglutide injection, either off-hemodialysis (day 2) or on-hemodialysis (day 3). Liraglutide was well tolerated in patients with type 2 diabetes and ESRD undergoing hemodialysis. The present results suggested that hemodialysis did not affect the pharmacokinetic profile of liraglutide or most glycemic indices, with the exception of MAGE, SD, and the maximum glucose level. These results suggested that it may be possible to use liraglutide during hemodialysis for diabetes with ESRD, without dose adjustment. Trial Registration UMIN Clinical Trials Registry (UMIN-CTR) UMIN000010159.

Comparing postprandial efficacy in type 2 diabetic patients receiving mitiglinide and sitagliptin by using continuous glucose monitoring: a pilot study.

OBJECTIVE: To compare postprandial efficacy in type 2 diabetic patients given mitiglinide and sitagliptin, both of which are known to improve postprandial hyperglycemia, by using continuous glucose monitoring (CGM). METHODS: Eleven patients with type 2 diabetes were given mitiglinide 10 mg three times a daily or sitagliptin 50 mg once a day for 1 month and were hospitalized for 4 days and evaluated by CGM. On discharge, they were crossed over to the other regimen for 1 month of treatment/4 days of evaluation. The CGM data were used to compare each parameter for glycemic variability. RESULTS: The patients were 60 ± 10 (mean ± SD) years old, and had HbA1c value 7.3 ± 0.9%. The pre-meal glucose levels before lunch were significantly lower with mitiglinide than with sitagliptin (116 ± 26/131 ± 34 mg/dl, p = 0.022). The AUC measuring over 140 mg/dl 3 h after breakfast (mitiglinide 4812 ± 4219/sitagliptin 7807 ± 6391 mg/dl·min, p = 0.042) and lunch (mitiglinide 5658 ± 5856/sitagliptin 8492 ± 7161, p = 0.050) was significantly lower with mitiglinide than with sitagliptin. CONCLUSIONS: A CGM-based comparison showed that mitiglinide and sitagliptin were different in their glucose-lowering effects, where mitiglinide significantly improved hyperglycemia after breakfast and lunch, and significantly lowered pre-meal glucose levels before lunch, compared to sitagliptin.

[Continuous glucose monitoring (CGM)].

Self-monitoring of blood glucose (SMBG) is now commonly used as a tool to measure blood glucose levels of diabetic patients, as health insurance started to cover its cost for patients receiving insulin. However, SMBG is used to evaluate blood glucose levels at different time points, making it impossible to speculate on changes in blood glucose levels occurring before and after measurement. Currently, continuous glucose monitoring (CGM), which determines diurnal blood glucose patterns on a continuous basis, is being introduced into routine clinical diabetic care. CGM results sometimes show abnormal blood glucose variations or hypoglycemia after meals or during sleep, even if SMBG results show normal levels in the same patient. The identification of blood glucose variations is the main advantage of CGM. This study reviewed the characteristic of and methods for preventing hypo and hyperglycemia based on the pattern of blood glucose variations in type 1 and type 2 diabetes that was identified by the introduction of CGM.

24-hour glycemic variations in drug-naïve patients with type 2 diabetes: a continuous glucose monitoring (CGM)-based study.

OBJECTIVE: To investigate a 24-hour glycemic variation in drug-naïve, type 2 diabetic patients by using CGM. METHODS: A total of 30 inpatients with type 2 diabetes were included in the study to analyze the 24-hour CGM data. RESULTS: The patients' median age was 58 years old (interquartile range: 42-66 years), and their median HbA1c value was 7.6 (6.7-8.8)%. The median time to postprandial peak glucose levels(Peak Time) for each meal was 70-85 minutes, with the range of postprandial glucose increases(Increase Range) for each meal being 83-109 mg/dL. There was a significant positive correlation between the HbA1c values and Increases Range, Peak Time observed after breakfast and dinner, respectively. When the patients were stratified by a median HbA1c value of 7.6% into 2 groups, Increases Range and Peak Time, after breakfast, were shown to be significantly higher in the high-HbA1c group (H) than in the low-HbA1c (L) group. When the subjects were divided into four groups according to HbA1c levels:1 (<7.0%, n = 8), 2 (7.0-7.9%, n = 8), 3 (8.0-8.9%, n = 8), and 4 (≥9%, n = 6), the average glucose level, pre-meal glucose level and postprandial peak glucose level increased steadily from group 1 to 4 in a stepwise manner. CONCLUSIONS: In drug-naïve, Japanese type 2 diabetic patients, the Peak Time and the Increase Range were maximal after dinner. It was shown that the greater the HbA1c values, the longer Peak time and the higher Increase Range after breakfast and dinner. The average glucose level, pre meal glucose level and postprandial peak glucose level increased steadily as HbA1c level increased.

Comparison of glycemic variability in patients with type 2 diabetes given sitagliptin or voglibose: a continuous glucose monitoring-based pilot study.

OBJECTIVE: This study compared glycemic variability in patients with type 2 diabetes given sitagliptin or voglibose. PATIENTS AND METHODS: Seventeen type 2 diabetes patients were given sitagliptin 50 mg/day or voglibose 0.9 mg/day for 2 months and were hospitalized for a 4-day evaluation by continuous glucose monitoring (CGM). On discharge, they were crossed over to the other regimen for 2 months of treatment/4 days of evaluation. The CGM data were used to compare each parameter for glycemic variability. RESULTS: The average glucose levels with sitagliptin and voglibose were significantly different at 138.6 and 152.6 mg/dL for 24 h (P=0.014) and 147.2 and 160.9 mg/dL for during daytime (P=0.050), respectively. The patients' glucose levels with sitagliptin and voglibose were significantly different at 125.3 and 139.7 mg/dL before breakfast (P=0.015) and 112.7 and 131.4 mg/dL before lunch (P=0.049), respectively. The time from before meal to postprandial peak glucose levels was significantly longer after dinner with voglibose than with sitagliptin (91.5 and 122.3 min, respectively; P=0.012). All of the slopes of glucose elevation were significantly lower with voglibose after each meal, with that after breakfast, lunch, and dinner being 1.16 and 0.86 mg/dL/min (P=0.031), 0.70 and 0.45 mg/dL/min (P=0.048), and 1.06 and 0.73 mg/dL/min (P=0.028), respectively. CONCLUSIONS: This CGM-based pilot study revealed that sitagliptin significantly lowered 24-h and daytime mean glucose levels and glucose levels before breakfast and lunch compared with voglibose, whereas the time from before dinner to peak postprandial glucose levels was significantly longer, and the slope of postprandial elevation of glucose level was significantly lower after each meal, with voglibose compared with sitagliptin.

Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM): crossover pilot study (J-VICTORIA study).

BACKGROUND: No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters. METHODS: Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1) mean (± standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood glucose level and time, 5) increase in blood glucose level after each meal, 6) area under the curve (AUC) for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7) area over the curve (AOC) for daily blood glucose level <70 mg/dL. Plasma glycosylated hemoglobin (HbA1c), glycoalbumin (GA), 1,5-anhydroglucitol (1,5AG), immunoreactive insulin (IRI), C-peptide immunoreactivity (CPR), brain natriuretic peptide (BNP), and plasminogen activator inhibitor-1 (PAI-1) levels, and urinary CPR levels, were measured. RESULTS: The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012). In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015), the AUC (≥180 mg/dL) within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 µg/day; p = 0.008) than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin. CONCLUSIONS: CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and sitagliptin. TRIAL REGISTRATION: UMIN000007687.

A crossover comparison of glycemic variations in Japanese patients with type 1 diabetes receiving insulin glargine versus insulin detemir twice daily using continuous glucose monitoring (CGM): J COLLECTION (Jikei COmparison of Lantus and LEvemir with Cgm for Thinking Insulin OptimizatioN).

BACKGROUND: This study aimed to compare glycemic variations seen among Japanese patients with type 1 diabetes treated with insulin glargine versus insulin detemir using continuous glucose monitoring (CGM) in a crossover design. SUBJECTS AND METHODS: Twenty-three patients with type 1 diabetes were enrolled in this study. The subjects were on either insulin glargine followed by insulin detemir twice daily, or vice versa, with no change in the timing of injections. The glycemic variations during 4-day hospitalizations were monitored by CGM while the patients were on either regimen, with a second hospitalization scheduled more than 1 month after the change of the long-acting insulin analogs. CGM data obtained on Day 3 of both hospitalizations were compared. RESULTS: The subjects had a median age of 44.0 years, a median body mass index of 22.2 kg/m(2), and a median glycosylated hemoglobin of 7.3%. There was no significant difference between the two treatments with a mean glucose level of 156 mg/dL with the insulin glargine treatment versus 150 mg/dL with the insulin detemir treatment; their SD values were 60 versus 51 mg/dL, their mean amplitude of glycemic excursions values were 121 versus 105 mg/dL, and their mean of daily differences values were 45.7 versus 41.4 mg/dL, respectively. In addition, the insulin detemir treatment was associated with a narrower range of postprandial glucose increases after lunch (80 vs. 59 mg/dL; P=0.007). CONCLUSIONS: A comparison of the long-acting insulin analogs administered twice daily in type 1 diabetes demonstrated that insulin detemir may potentially offer better glycemic control after lunch than insulin glargine.

Relationship among A1C, hypoglycemia, and hyperglycemia in Japanese with type 2 diabetes--results from continuous glucose monitoring data.

BACKGROUND: The intensive treatment aimed at achieving optimal A1C may increase a risk of hypoglycemia. Therefore, we examined the rate and duration of hypoglycemia (<70 mg/dL) and the duration of hyperglycemia (≥200 mg/dL) according to their A1C status, using continuous glucose monitoring (CGM) in Japanese patients with type 2 diabetes who were treated with hypoglycemic agents. METHODS: Forty subjects were equally divided into three groups according to their A1C levels (low, intermediate, and high A1C groups). The 24-h CGM data were collected immediately upon admission to hospital with the patients continuing to take the same medications they had prior to hospitalization. RESULTS: There was a significant difference in the total duration of hyperglycemia among the groups, with the low A1C group having a median duration of hyperglycemia of 50 min (25-75(th) percentile, 0-550 min) compared with 302.5 min (220-500 min) in the intermediate A1C group and 660 min (185-830 min) in the high A1C group. However, the incidence rate and total duration of hypoglycemia were similar for all A1C groups. CONCLUSION: The A1C level did not predict the presence or the duration of hypoglycemia.

Comparing the efficacy of α-glucosidase inhibitors in suppressing postprandial hyperglycemia using continuous glucose monitoring: a pilot study-the MAJOR study.

BACKGROUND: This study aimed to compare glucose variability in patients given the α-glucosidase inhibitors miglitol and acarbose using continuous glucose monitoring (CGM). METHODS: Ten type 2 diabetes patients were hospitalized for 4 days, and their glucose levels were measured using CGM. Patients were given miglitol (50 mg) or acarbose (100 mg) before each meal on Day 2, and vice versa on Day 3, in a randomized crossover design. The patients had three identical test meals on Days 2 and 3. The CGM data were used to compare each parameter for glycemic variability after each of the three meals. RESULTS: No significant differences were observed between miglitol treatment or acarbose treatment in regard to the range of increase in glucose levels from baseline to peak, time to peak postprandial glucose levels from the preprandial period, and area under the curve for glycemic variability from the preprandial period to 3 h after each meal. However, the range of increase in glucose levels at 30 min (0.4 vs. 30.7 mg/dL, P < 0.0001) and 60 min (32.8 vs. 67.5 mg/dL, P <0.0001) after lunch and 30, 60, and 90 min after dinner (3.3 vs. 22.2 mg/dL, P = 0.0249; 36.6 vs. 67.5 mg/dL, P < 0.0001; and 60.5 vs. 81.6 mg/dL, P = 0.0073, respectively) was significantly smaller in miglitol treatment compared with acarbose treatment. CONCLUSIONS: In a pilot study with a crossover design in 10 type 2 diabetes patients, it was shown that although there was no significant difference in glucose variability with miglitol or acarbose after a fat-rich diet, glucose increases was significantly reduced with miglitol after a meal comprising typical Japanese diet 60-90 min postprandially.

Analysis of 24-hour glycemic excursions in patients with type 1 diabetes by using continuous glucose monitoring.

BACKGROUND: Little information is available regarding postprandial glycemic excursions and hypoglycemia in Japanese patients with type 1 diabetes (T1D). METHODS: Four male and eight female patients who were on intensive therapy with rapid-acting insulin plus basal insulin underwent retrospective continuous glucose monitoring (CGM). Clinical characteristics (median) of the patients were as follows: age, 40.5 years; body mass index, 22.2 kg/m(2); urinary C-peptide, 0.75 microg/day; hemoglobin A1c (HbA1c) after 2 months of CGM, 6.5%; and total insulin dose, 40.0 units. RESULTS: The largest glycemic excursions were observed after breakfast. The time intervals from the start of each meal to the highest postprandial glucose levels peaked at 65-100 min. Hypoglycemia (blood glucose <70 mg/dL) was observed for more than 100 min per 24-h period. HbA1c and 24-h mean glucose levels were significantly correlated (r = 0.727, P = 0.007). The 12 participants were divided into two groups by HbA1c level after 2 months: those whose HbA1c exceeded the median of HbA1c (HbA1c > 6.5%) (n = 6) and those whose HbA1c fell below the median (HbA1c <6.5%) (n = 6). The premeal glucose levels/the highest postprandial glucose levels after breakfast were insignificantly higher in the HbA1c >6.5% group (183/247 mg/dL, respectively) than in the HbA1c <6.5% group (117/221 mg/dL, respectively). The duration of hypoglycemia lasted longer in the HbA1c <6.5% group, with these episodes often occurring during the nighttime. CONCLUSIONS: These findings suggest that preventing nighttime hypoglycemia and correcting glucose spikes after breakfast are required in patients with T1D receiving intensive therapy to stabilize and improve glycemic control.