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.

Age at Transition from Pediatric to Adult Care Has No Relationship with Mortality for Childhood-Onset Type 1 Diabetes in Japan: Diabetes Epidemiology Research International (DERI) Mortality Study.

OBJECTIVE: To follow up Japanese patients with type 1 diabetes for a maximum of 40 years to examine when they transitioned from pediatric care to adult care and to explore whether the attending physician, i.e., pediatrician or internist, was associated with prognosis. METHODS: Participants consisted of 1,299 patients who had been diagnosed as having type 1 diabetes at less than 15 years old between 1965 and 1979 identified through two nationwide surveys. Patients were classified as having received either pediatric care or adult care at the age of 15 and 30, and were compared for differences in mortality associated with the attending physician. RESULTS: The attending physicians were confirmed for a total of 1,093 patients at the age of 15. Of these patients, 43.8% and 40.3% received pediatric care and adult care, respectively. Of the 569 patients receiving pediatric care, 74.2%, 56.6%, 53.4%, and 51.3% continued with pediatric care at 20, 30, 40, and 50 years old, respectively. The attending physicians (pediatrician or internist) at the age of 15 and 30 had no significant impact on their survival (P = 0. 892, 0.411, respectively). CONCLUSIONS: More than half of the patients who had received pediatric care at the age of 15 continued to receive pediatric care even after the age of 30, suggesting that their transition was far from smooth, while the attending physician at the age of both 15 and 30 was not a prognostic factor for mortality. Thus, the timing for transition to adult care in these patients has no relationship with mortality in Japan.

Causes of death in patients with childhood-onset type 1 diabetes receiving dialysis in Japan: Diabetes Epidemiology Research International (DERI) Mortality Study.

AIMS: To investigate the causes of death and how they changed over time in patients with childhood-onset type 1 diabetes who were receiving dialysis. METHODS: Of the 1384 patients who were diagnosed with type 1 diabetes at<18 years of age between 1965 and 1979, 113 who were subsequently confirmed as having received dialysis and having died as of January 1, 2008 were found eligible for the study. The cause of death trends were expressed according to the duration of dialysis. RESULTS: The leading causes of death were end-stage renal disease (ESRD) (36.3%), cardiovascular disease (CVD) (31.9%), and infections (20.3%). Among CVD, cerebral hemorrhage was the most frequent (38.9%) and showed a significant trend for an increase in the duration of dialysis (P=0.01, the Cochran-Armitage trend test). The mortality from ESRD concentrated within 5 years of dialysis and that from CVD increased after 10 years of dialysis, while the mortality from infections peaked during 5 to 10 years from initiation of dialysis. CONCLUSIONS: The leading causes of death in dialysis patients with type 1 diabetes were ESRD, CVD, and infections. As the duration of dialysis increased, however, CVD contributed more to mortality. Special attention should be paid to CVD, particularly cerebral hemorrhage, to improve the long-term prognosis of patients.

Cause-specific mortality trends in a nationwide population-based cohort of childhood-onset type 1 diabetes in Japan during 35 years of follow-up: the DERI Mortality Study.

AIMS/HYPOTHESIS: The aim of this study was to investigate long-term, cause-specific mortality trends among patients with childhood-onset type 1 diabetes in Japan. METHODS: Individuals included in the study had received a diagnosis of type 1 diabetes at age <18 years between 1965 and 1979. All individuals were followed up for their survival status until 1 January 2005. The causes of death were divided into end-stage renal disease (ESRD), acute diabetic complications (ADC), accident/suicide, cardiovascular disease (CVD), infections, cancers, others (non-diabetic/diabetic) and unknown. The cause-specific mortality trends were expressed according to the follow-up period and year of diagnosis. RESULTS: A total of 1,385 patients were enrolled in the study, and the survival status of 1,324 was confirmed. Mortality rate at the 35 year follow-up (per 100,000 person-years) was 659.3, and the standardised mortality ratio (SMR) was 10.7. The SMR at the 25 year follow-up markedly declined from 19.3 in the 1965-1969 diagnosis group to 6.6 in the 1975-1979 diagnosis group. Approximately 40% died of ADC among those with <10 years of follow-up. A similar proportion of individuals died of ESRD among those with 10-19 years of follow-up. The longer the duration of follow-up, the lower the mortality from ADC and the greater the mortality from CVD. CONCLUSIONS/INTERPRETATION: In Japanese people with childhood-onset type 1 diabetes of more than 20 years of duration, CVD was the leading cause of death, as is the case among similar white people. The longer the duration of diabetes, the more attention should be paid to preventing CVD.