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

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.\ud \u

Status of treatment-related severe hypoglycemia in Japanese patients with diabetes

Despite great strides in pharmacotherapy for diabetes, there is increasing concern over the risk of hypoglycemia in patients with diabetes receiving pharmacotherapy as they become increasingly older. This has prompted the Japan Diabetes Society (JDS) to initiate a survey on the current status of severe hypoglycemia in clinical settings. In July 2015, following approval from the JDS Scientific Survey/Research Ethics Committee, the JDS extended an invitation to executive educators, who represented a total of 631 healthcare facilities accredited by the JDS for diabetes education, to participate in the proposed survey. Of these, those who expressed their willingness to participate in the survey were sent an application form required for obtaining ethical approval at these healthcare facilities and were then asked, following approval, to enter relevant clinical data on an unlinked, anonymous basis in a web‐based registry. The current survey was fully funded by the JDS Scientific Survey/Research Committee. A case registry (clinical case database) was launched after facility‐specific information (healthcare facility database) was collected from all participating facilities and after informed consent was obtained from all participating patients. With severe hypoglycemia defined as the “presence of hypoglycemic symptoms requiring assistance from another person to treat and preferably venous plasma glucose levels at onset/diagnosis of disease or at presentation clearly less than 60 mg/dL (capillary whole blood glucose, less than 50 mg/dL)”, the current survey was conducted between April 1, 2014 and March 31, 2015, during which facility‐specific information was collected from a total of 193 facilities with a total of 798 case reports collected from 113 facilities. Of the 193 respondent facilities, 149 reported having an emergency department as well, with the median number of patients who required emergency transportation services to reach these facilities totaling 4,962 annually, of which those with severe hypoglycemia accounted for 0.34% (17). The respondent facilities accommodated a total of 2,237 patients with severe hypoglycemia annually, with the number of patients thus accommodated being 6.5 patients per site. A total of 1,171 patients were admitted for severe hypoglycemia, with the number of patients thus admitted being 4.0 per site, who accounted for 52.3% of all patients visiting annually for severe hypoglycemia. A review of the 798 case reports collected during the survey revealed that 240, 480 and 78 patients had type 1 diabetes, type 2 diabetes, and other types of diabetes, respectively; those with type 2 diabetes were shown to be significantly older (median [interquartile range], 77.0 [68.0–83.0]) than those with type 1 diabetes (54.0 [41.0–67.0]) (P < 0.001); and the BMI was shown to be significantly higher for those with type 2 diabetes (22.0 [19.5–24.8] kg/m2) than for those with type 1 diabetes (21.3 [18.9–24.0] kg/m2) (P = 0.003). It was also found that the median estimated glomerular filtration rate (eGFR) was significantly lower among those with type 2 diabetes (50.6 mL [31.8–71.1]/min/1.73 m2) than among those with type 1 diabetes (73.3 [53.5–91.1] mL/min/1.73 m2) (P < 0.001). Again, the median HbA1c value at onset of severe hypoglycemia was shown to be 7.0 (6.3–8.1)% among all patients examined, 7.5 (6.9–8.6)% among those with type 1 diabetes, and 6.8 (6.1–7.6)% among those with type 2 diabetes, with the HbA1c value at onset of hypoglycemia being significantly lower among those with type 2 diabetes (P < 0.001). Antecedent symptoms of severe hypoglycemia were shown to be present, absent and unknown in 35.5, 35.6, and 28.9% of all patients, respectively, with the incidence of symptomatic hypoglycemia being significantly lower among those with type 1 diabetes (41.0%) than among those with type 2 diabetes (56.9%). The antidiabetic agents used in those with type 2 diabetes were insulin preparations (292 patients including 29 receiving concomitant sulfonylureas [SUs]) (60.8%), SUs (159 insulin‐naïve patients) (33.1%), and no insulin preparations or SUs (29 patients) (6.0%). Of the 798 patients surveyed, 296 patients (37.2%) were shown to have required emergency transportation services for severe hypoglycemia before. Thus, the survey revealed, for the first time, the current status of treatment‐related severe hypoglycemia in Japan and clearly highlights the acute need for implementing preventive measures against hypoglycemia not only through education on hypoglycemia but through optimization of antidiabetic therapy for those at high risk of severe hypoglycemia or those with a history of severe hypoglycemia

Changes in body mass index, leptin and adiponectin in Japanese children during a three-year follow-up period: a population-based cohort study

<p>Abstract</p> <p>Objective</p> <p>The study examined changes in and relationship between body mass index (BMI), leptin and adiponectin levels over a 3-year period in a pediatric population-based cohort.</p> <p>Study design</p> <p>A 3-year prospective cohort study of 268 boys and 251 girls aged 9–10 in Ina, Saitama, Japan.</p> <p>Results</p> <p>Median body mass index (BMI) significantly increased from baseline (age 9–10) to follow up (age 12–13) in boys from 17.1 to 18.3 kg/m²(<it>P </it>< 0.001) and in girls from 16.5 to 18.5 kg/m²(<it>P </it>< 0.001), respectively. Adiponectin values significantly decreased from baseline to follow up in boys (13.5 to 8.9 μg/ml, respectively) (<it>P </it>< 0.001) and in girls (12.4 to 9.5 μg/ml, respectively) (<it>P </it>< 0.001). Leptin values at follow up significantly decreased from baseline in boys (4.9 to 2.3 ng/dl, respectively) (<it>P </it>< 0.001) and also in girls (5.3 to 5.1 ng/dl, respectively) (<it>P </it>= 0.049).</p> <p>A relatively strong correlation was seen in BMI (Spearman's correlation coefficient, <it>r </it>= 0.864, <it>P </it>< 0.001 in boys; <it>r </it>= 0.873, <it>P </it>< 0.001 in girls), adiponectin (<it>r </it>= 0.705, <it>P </it>< 0.001 in boys; <it>r </it>= 0.695, <it>P </it>< 0.001 in girls), and leptin (<it>r </it>= 0.449, <it>P </it>< 0.001 in boys; <it>r </it>= 0.610, <it>P </it>< 0.001 in girls) before and after the three-year period.</p> <p>The ratio of follow up to baseline BMI was negatively correlated with that for adiponectin (<it>r </it>= -0.224, <it>P </it>< 0.001 in boys; <it>r </it>= -0.165, <it>P </it>= 0.001 in girls) and positively correlated with that for leptin (<it>r </it>= 0.518, <it>P </it>< 0.001 in boys; <it>r </it>= 0.609, <it>P </it>< 0.001 in girls).</p> <p>Conclusion</p> <p>This study demonstrated that baseline adiponectin, leptin and BMI values measured at ages 9–10 correlated with those measured three years later. However, adiponectin values decreased and leptin values increased in those subjects whose BMI increased during over this period.</p

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\ud \ud To investigate whether the occurrence of nocturnal asymptomatic hypoglycemia may be predicted based on fasting glucose levels and post-breakfast glucose fluctuations.\ud \ud Patients and Methods\ud \ud 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.\ud \ud Results\ud \ud 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).\ud \ud Conclusions\ud \ud 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