Comparison of the efficacy and safety of once-daily insulin degludec/insulin aspart (IDegAsp) and long-acting second-generation basal insulin (insulin degludec and insulin glargine 300 units/mL) in insulin-naïve Japanese adults with type 2 diabetes: a pilot, randomized, controlled study.

To examine the efficacy and safety of once-daily insulin degludec/insulin aspart (IDegAsp) or once-daily second-generation basal insulin analogs (insulin degludec and insulin glargine 300 units/mL) in insulin-naïve Japanese adults with type 2 diabetes in routine clinical practice. A 12-week multicenter, open-label, randomized, pilot study was performed in 52 subjects with type 2 diabetes treated with oral antidiabetic drugs (OADs). Subjects were randomized to once-daily IDegAsp (n = 26) or basal insulin (n = 26). The primary endpoint was percent change in HbA1c from baseline to week 12. Furthermore, it was analyzed post hoc in subgroups stratified by baseline HbA1c. During a follow-up period, percent change in HbA1c was not significantly different between the two groups (p = 0.161). Daily insulin doses and frequency of overall hypoglycemia were also similar in the two groups. In post hoc analyses, once-daily basal insulin was more effective than IDegAsp in subjects with HbA1c more than or equal to 8.5% (p < 0.05); however, in subjects with HbA1c less than 8.5%, once-daily IDegAsp showed a significant improvement in percent change in HbA1c at week 12, compared with basal insulin (p < 0.01). Although there was no apparent difference in the HbA1c-lowering effects between two groups, when compared in subjects with HbA1c less than 8.5%, once-daily IDegAsp showed a significant effect in comparison with once-daily basal insulin. These findings suggest that the baseline HbA1c level might provide the important information for choosing IDegAsp or basal insulin in patients insufficiently controlled with OADs. This trial was registered with UMIN (no. UMIN000035431).

Comparison of the conventional Macintosh laryngoscope, the Pentax Airwayscope, and the McGrath MAC video laryngoscope under restricted cervical motion: a manikin study.

Aim: We compared the utility of the conventional Macintosh laryngoscope, the Pentax Airway Scope, and the McGrath MAC video laryngoscope under restricted cervical motion using a manikin. Methods: We recruited 36 participants into the simulation study. The manikin's cervical motion was restricted with a cervical collar and a head immobilizer, as occurs in trauma cases. We recorded the time to intubation and the success rate of the intubations. Results: Data are medians and ranges. The time to intubation under normal and restricted cervical motion were 22.5 (10-78) and 23 (9-119) s with the Macintosh laryngoscope, 13.5 (5-50) and 14 (7-119) s with the Airway Scope, and 13 (6-32) and 18 (7-80) s with the McGrath MAC video laryngoscope. The differences in the time to intubation between normal and restricted cervical motion were significant only with the McGrath MAC (P = 0.0008). With restricted cervical motion, the times to intubation in the Airway Scope attempts were significantly shorter than those in the Macintosh laryngoscope (P = 0.0005) and McGrath MAC (P = 0.0282) attempts. The success rates under normal and restricted cervical motion were 100% and 80.6% with the Macintosh laryngoscope (P = 0.0054), 100% and 100% with the Airway Scope, and 100% and 97.2% with the McGrath MAC, respectively. Conclusion: In the present study, the Airway Scope was the best among the three devices. However, the differences between the Airway Scope and the McGrath MAC video laryngoscope may not be serious in a clinical situation. Data were gathered using a manikin, and further studies will be necessary.

An analysis of the relationship between Glasgow Coma Scale score and plasma glucose level according to the severity of hypoglycemia.

BACKGROUND: The Glasgow Coma Scale (GCS) score of an individual with hypoglycemia is expected to be low due to an insufficient glucose supply to the brain. However, we sometimes encounter hypoglycemic patients with high GCS scores. This study was undertaken to analyze the relationship between the GCS score and the plasma glucose level. METHODS: Among the patients with neurological impairments admitted to our institution between October 1, 2010 and March 31, 2013, the cases of 41 hypoglycemic patients were examined in this retrospective cohort study. The defined plasma glucose level for mild hypoglycemia was 41-60 mg/dL, that for moderate hypoglycemia was 21-40 mg/dL, and that for extreme hypoglycemia was below 20 mg/dL. We divided the patients into two groups: those with mild hypoglycemia (n = 14) and those with moderate/extreme hypoglycemia (n = 27). We compared the two groups' physiological data and assessed the relationship between the GCS score and the plasma glucose level by Spearman rank correlation (ρ), the significance of which was determined by Spearman's rank sum test. We used the Mann-Whitney U-test and the chi-square (χ (2)) test to test for differences between the two groups when appropriate. RESULTS: Three hundred twenty-six patients with neurological impairments were admitted during the study period, and 41were eligible hypoglycemic patients. The GCS scores of the 14 patients with mild hypoglycemia were significantly higher than those of the 27 patients with moderate or extreme hypoglycemia (median score 12, range 7-15 vs. 10, 3-15, p = 0.0367). There were no significant differences in physiological data (including autonomic symptoms) between the two groups. Spearman's rank sum test was 0.491 in the total group of 41 hypoglycemic patients, 0.053 in the mild hypoglycemic patients, and 0.493 in the moderately or extremely hypoglycemic patients. CONCLUSIONS: The relationship between the GCS score and the plasma glucose level differed according to the severity of hypoglycemia. Even when a patient has a high GCS score, careful assessment of differential diagnosis should be conducted and the possibility of hypoglycemia should be considered in light of his or her neurogenous symptoms.

Comparison of the McGrath MAC video laryngoscope and the Pentax Airwayscope during chest compression: a manikin study.

We tested the utility of the McGrath MAC(®) (McG) video laryngoscope during chest compression compared with the Pentax Airwayscope(®) (AWS). We recruited 59 participants into the simulation study. The difference in the time to intubation (TTI [sec]) between without and with chest compression was significant for the AWS attempts (median 13, range 6-28 vs. median 15, range 6-72, p = 0.0247) but not significant for the McG attempts (median 16, range 6-75 vs. median 16, range 6-71); however, the difference of the TTIs is not serious clinically. The utility of the two devices during chest compressions is almost similar although their characteristics are different.

Comparison of the efficacy of sitagliptin and glimepiride dose-up in Japanese patients with type 2 diabetes poorly controlled by sitagliptin and glimepiride in combination.

AIMS/INTRODUCTION: The goal of the study was to examine the effects of sitagliptin dose-up or glimepiride dose-up in Japanese patients with type 2 diabetes who were controlled inadequately by sitagliptin and glimepiride in combination. MATERIALS AND METHODS: A multicenter, prospective, randomized, open-label study was carried out in 50 patients with type 2 diabetes treated with sitagliptin and low-dose glimepiride. The patients were randomly assigned to receive the addition of 50 mg/day sitagliptin or 0.5 mg/day glimepiride. The primary end-point was the percentage change in glycated hemoglobin (HbA1c). RESULTS: During a follow-up period, the difference in the percentage changes in HbA1c between the two groups was not significant (P = 0.13). However, HbA1c was significantly decreased by glimepiride dose-up (P < 0.01 vs baseline), but not by sitagliptin dose-up (P = 0.74). Univariate linear regression analyses showed that the percentage change in HbA1c was significantly associated with the serum level of arachidonic acid (AA) in both groups. CONCLUSIONS: There was no significant difference in the HbA1c-lowering effects between the two groups. However, a significant HbA1c-lowering effect from baseline of glimepiride dose-up was found, and the AA level showed a negative correlation with the decrease in HbA1c in the sitagliptin dose-up group, but a positive correlation in the glimepiride dose-up group. These findings suggest that the AA level is associated with HbA1c reduction in response to dose-up with these drugs in patients with type 2 diabetes in a combination therapy with sitagliptin and glimepiride. This trial was registered with UMIN (no. 000009544).

Comparison of the utility of the Pentax Airway Scope (AWS) with that of the conventional Macintosh laryngoscope during chest compression: is the AWS an easy-to-use device for a novice?

AIM: The Pentax Airway Scope occasionally contacts the arm of the chest compressor at insertion because of its large body. Here, we test the Airway Scope's ease of use compared to that of the conventional Macintosh laryngoscope during chest compression, when operated by a novice. METHODS: We recruited 73 participants into this simulation study. Each participant carried out tracheal intubation using the two devices without and with chest compression. We recorded the time to intubation and the success rate. All of the participants completed a brief questionnaire after finishing the attempts. RESULTS: Data are medians and ranges. The time to intubation (seconds) without and with chest compression were 11 (7-57) and 13 (7-90) by the Macintosh laryngoscope, respectively, and 14 (6-46) and 15 (6-69) by the Airway Scope, respectively. The difference in the time to intubation between the groups without and with chest compression was significant for the Macintosh laryngoscope (P = 0.0434) but not significant for the Airway Scope. The time to intubation in the Airway Scope attempts were slightly longer than those in the Macintosh laryngoscope attempts (not significant). The success rate using the Macintosh laryngoscope with chest compression was significantly lower than that without chest compression (92% versus 100%, P = 0.0124). The success rate using the Airway Scope was 100%, but an accident occurred in four attempts. The questionnaire revealed that 54 participants preferred the Airway Scope and 19 preferred the Macintosh laryngoscope. CONCLUSION: The Pentax Airway Scope appears to be better than the Macintosh laryngoscope during chest compression if the operator is a novice. However, using the Airway Scope does not always reduce the time to intubation.

Electrocardiogram findings of patients with serum potassium levels of nearly 10.0 mmol/L: a report of two cases.

CASES: In Case 1, a 63-year-old woman was admitted with muscular weakness. She had hypertension, diabetes mellitus, and chronic renal failure on hemodialysis. She was taking a beta-blocker. Her pulse rate was 42 b.p.m. (irregular rhythm); serum potassium level was 9.8 mmol/L; electrocardiogram revealed widening of the QRS complex (0.256 s). In Case 2, a 59-year-old man was admitted with muscular weakness. He had hypertension and chronic renal failure, and was taking a renin-angiotensin-aldosterone system inhibitor. His pulse rate was 42 b.p.m. (irregular rhythm); serum potassium level was 10.1 mmol/L; electrocardiogram revealed widening of the QRS complex (0.180 s). OUTCOME: Life-threatening arrhythmia did not occur, and patients survived under appropriate treatment. CONCLUSION: Chronic renal failure, diabetes mellitus, or medications affecting extrarenal potassium homeostasis can produce a tolerance to hyperkalemia. This tolerance may help prevent life-threatening arrhythmia despite fatal levels of serum potassium.

Efficacy and safety of sitagliptin as add-on therapy on glycemic control and blood glucose fluctuation in Japanese type 2 diabetes subjects ongoing with multiple daily insulin injections therapy.

To assess the efficacy and safety of adding sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, in subjects with type 2 diabetes inadequately controlled with multiple daily insulin injections therapy (MDI). HbA1c, 1,5-anhydroglucitol (1,5-AG), body mass index (BMI), insulin doses, six-point self-measured plasma glucose (SMPG) profiles were assessed before, after 12 weeks, and after 24 weeks of MDI with 50 mg/day of sitagliptin in 40 subjects with type 2 diabetes. Safety endpoints included hypoglycemia and any adverse events. HbA1c significantly decreased during the first 12 weeks ( -0.64±0.60%), and was sustained over 24 weeks ( -0.69±0.85%). 1,5-AG increased significantly from 7.5±4.5 µg/mL at baseline to 9.6±5.5 µg/mL after 24 weeks. The bolus insulin dose at 12 weeks was decreased, and the mean plasma glucose, the SD of daily glucose, M-value, and the mean amplitude of glycemic excursions (MAGE) also decreased significantly as compared with baseline values. BMI and frequency of hypoglycemia were not changed significantly. Univariate linear regression analyses revealed that % change in HbA1c was significantly associated with BMI, and % changes in the indexes of glycemic instability (SD of daily glucose and MAGE) were significantly associated with age. In conclusion, adding sitagliptin to MDI significantly improved glycemic control and decreased the daily glucose fluctuation in subjects with type 2 diabetes inadequately controlled with MDI, without weight gain or an increase in the incidence of hypoglycemia. This trial was registered with UMIN (no. UMIN000010157).

Effects of olmesartan, an angiotensin II receptor blocker, on peripheral insulin sensitivity in Japanese subjects with type 2 diabetes and hypertension.

OBJECTIVE: Several studies have assessed the efficacy of angiotensin receptor blockers (ARBs) on peripheral insulin sensitivity using the euglycemic hyperinsulinemic clamp technique in hypertensive subjects. However, these subjects were mostly non-diabetic, and some studies showed that ARB treatment did not improve insulin sensitivity. Thus, it is still uncertain whether ARBs could improve insulin sensitivity in subjects with hypertension and diabetes. Therefore, we evaluated the effect of olmesartan on peripheral insulin sensitivity in subjects with type 2 diabetes and hypertension using M/I value during the euglycemic-hyperinsulinemic clamp technique. METHODS: We enrolled 10 Japanese subjects with type 2 diabetes and hypertension who had never taken antihypertensive agents. Their blood pressure, fasting plasma glucose level, HbA1c and glucose utilization rate during euglycemic-hyperinsulinemic clamp (M/I value) were examined before and after 6 months of treatment with 10-20 mg/day olmesartan (mean: 13.0 mg/day). RESULTS: Blood pressure decreased significantly from 156/88 mmHg before starting olmesartan to 135/76 mmHg after 6 months of olmesartan treatment. The mean M/I value increased significantly from 6.33 ± 3.19 (mg/kg/min/mU/L) × 100 to 8.11 ± 4.20 (mg/kg/min/mU/L) × 100. Peripheral insulin sensitivity improved in eight out of ten subjects. Fasting glucose levels and HbA1c levels also decreased significantly. CONCLUSION: These results indicate that olmesartan improves glucose metabolism by improving the peripheral insulin sensitivity in subjects with type 2 diabetes.

Inherited adrenocorticotropin-independent macronodular adrenal hyperplasia with abnormal cortisol secretion by vasopressin and catecholamines: detection of the aberrant hormone receptors on adrenal gland.

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare disorder and an unusual cause of Cushing s syndrome, of which familial transmission has rarely been reported. In this study, a mother and her son, the former affected with definite AIMAH and the latter with possible AIMAH, are described. Although the mother manifested overt Cushing s syndrome, her son remained with no stigmata of Cushing s syndrome except for bilateral adrenal tumor and mild hypertension, and a full suppression of plasma cortisol by lowdose dexamethasone was observed in him. Recently, aberrant expression of adrenal receptors for various ligands has been noted in AIMAH patients. In our cases, provocation tests in vivo suggested that AVP and catecholamines promoted cortisol production through V1a and/or V1b receptors and via beta-adrenergic receptor, respectively. Reverse transcriptional-PCR analysis of the operated adrenal tissues of mother revealed the abnormal expression of mRNA of receptors for V1b, V2, and LH/hCG, none of which was observed in a normal control. Inherited AIMAH is very rare, and the son might be at the earliest developmental stage of AIMAH among the cases reported so far. An intervention could be tried to prevent the development of overt Cushing s syndrome by suppression of the possible endogenous ligands or by blockade of the receptors that may be aberrantly expressed in his adrenal glands.