Concise syntheses of (-)-habiterpenol and (+)-2,3-epi-habiterpenol via redox radical cyclization of alkenylsilane.

The concise syntheses of (-)-habiterpenol and (+)-2,3-epi-habiterpenol from (3aR)-(+)-sclareolide and 6-methoxyindanone in 11 and 12 steps, respectively, were enabled by the regioselective addition of the TMS-indenyl anion and the facile stereoselective metal hydride hydrogen atom transfer (MHAT)-initiated redox radical cyclization of alkenylsilane.

A Study of the Vascular Endothelial Function in Patients with Type 2 Diabetes Mellitus and Rheumatoid Arthritis.

Objective Type 2 diabetes mellitus (T2DM) and rheumatoid arthritis (RA) are both complicated by arteriosclerosis, resulting in increased rates of cardiovascular events. No previous studies have compared the index between RA and T2DM. We assessed the vascular endothelial function in early-stage arteriosclerosis for each disease to determine the influential factors and compared the extent to which these two diseases cause vascular endothelial dysfunction. Methods This study is a retrospective study based on medical records. Differences in the reactive hyperemia index (RHI) among the groups and factors affecting the RHI in each group was analyzed. The vascular endothelial function was assessed by measuring the RHI using peripheral arterial tonometry. Patients The study subjects were 114 patients with non-functional thyroid tumors (healthy n=14), T2DM (T2DM n=64), and RA (RA n=36). Results The RHI was 2.29 in the control, 1.85 in the T2DM, and 1.83 in the RA group, with values lower in the T2DM and RA groups than in the control group (p=0.033) but not markedly different between the two disease groups. The RHI distribution (<1.68/1.68 to <2.10/≥2.1) was as follows: control group: 14.3%/28.6%/57.1%; T2DM group: 42.2%/39.1%/18.8%; and RA group: 36.1%/44.4%/19.4% (p=0.031), respectively. A multivariate analysis identified the triglyceride level and dyslipidemia in the control group and the Disease Activity Score in 28 joints with the erythrocyte sedimentation rate and fasting plasma glucose level in the RA group to influence the RHI. Conclusion The vascular endothelial function was impaired in approximately 80% of patients with T2DM and RA, with comparable degrees of impairment between the two diseases. No factors affecting the function were identified in the T2DM group, while the function was more impaired in patients with a higher disease activity in the RA group.

Glycemic Profiling in Patients with Drug-Naïve Type 2 Diabetes by Continuous Glucose Monitoring.

The purpose of this study was to determine the glycemic profiles of drug-naïve type 2 diabetes patients according to hemoglobin A1c (HbA1c) level using continuous glucose monitoring. We aimed to clarify factors associated with HbA1c and average blood glucose level. Patients were divided into three groups according to their HbA1c level (< 7.0% n=23, 7.0% ≤ HbA1c < 8.0% n=17 and ≥ 8.0% n=31), and the factors associated with HbA1c and average glucose of each group were evaluated. Pre-meal glucose levels were the highest before lunch, and the 2 hour postprandial blood glucose level was the lowest after lunch. The pre-meal and postprandial blood glucose levels increased after each meal with increases in HbA1c. Average glucose level was the most significant determinant of HbA1c, whereas pre-meal glucose level at dinner was the most significant determinant of average glucose level, and the range of increase in glucose from pre-meal at dinner was the most significant determinant of standard deviation (SD) of 24 hour glucose levels. HbA1c subgroup analysis indicated that pre-meal glucose level at lunch significantly correlated with average glucose level in the HbA1c < 8.0% group, while pre-meal glucose level at dinner significantly correlated with average glucose level in the HbA1c ≥ 8.0% group. The range of increase in glucose from pre-meal in the morning significantly correlated with SD of 24 hour glucose levels in the HbA1c < 8.0% group, and the postprandial peak glucose level at lunch significantly correlated with SD of 24 hour glucose levels in the HbA1c ≥ 8.0% group. The results suggest that improvement of the average glucose level is necessary to improve the HbA1c levels. For patients with HbA1c < 7.0%, it is important to improve blood glucose level after breakfast and before lunch to decrease the average glucose level. For patients with 7.0% ≤ HbA1c < 8.0%, it is important to improve blood glucose level before lunch and after dinner to decrease the average glucose level. For patients with HbA1c ≥ 8.0%, it is important to improve blood glucose levels after lunch and before dinner to decrease the average glucose level.

Twenty-four-hour variations in blood glucose level in Japanese type 2 diabetes patients based on continuous glucose monitoring.

AIMS/INTRODUCTION: High fluctuations in blood glucose are associated with various complications. The correlation between glycated hemoglobin (HbA1c) level and fluctuations in blood glucose level has not been studied in Japanese patients with type 2 diabetes. In the present study, blood glucose profile stratified by HbA1c level was evaluated by continuous glucose monitoring (CGM) in Japanese type 2 diabetes patients. MATERIALS AND METHODS: Our retrospective study included 294 patients with type 2 diabetes who were divided by HbA1c level into five groups (≥6.0 to <7.0%, ≥7.0 to <8.0%, ≥8.0 to <9.0%, ≥9.0 to <10.0% and ≥10%). The correlation between HbA1c level and CGM data was analyzed. The primary end-point was the difference in blood glucose fluctuations among the HbA1c groups. RESULTS: The mean blood glucose level increased significantly with increasing HbA1c (Ptrend  < 0.01). The standard deviation increased with increases in HbA1c (Ptrend  < 0.01). The mean amplitude of glycemic excursions did not vary significantly with HbA1c. The levels of maximum blood glucose, minimum blood glucose, each preprandial blood glucose, each postprandial maximum blood glucose, range of increase in postprandial glucose from pre-meal to after breakfast, the area under the blood concentration-time curve >180 mg/dL and percentage of the area under the blood concentration-time curve >180 mg/dL were higher with higher HbA1c. Mean glucose level and pre-breakfast blood glucose level were significant and independent determinants of HbA1c. CONCLUSIONS: In Japanese patients treated for type 2 diabetes, the mean amplitude of glycemic excursions did not correlate with HbA1c, making it difficult to assess blood glucose fluctuations using HbA1c. Parameters other than HbA1c are required to evaluate fluctuations in blood glucose level in patients receiving treatment for type 2 diabetes.

Hyperparathyroidism-jaw Tumor Syndrome Confirmed by Preoperative Genetic Testing.

We herein report the case of a young woman who was diagnosed with primary hyperparathyroidism and in whom genetic testing confirmed a diagnosis of hyperparathyroidism-jaw tumor syndrome. Familial hyperparathyroidism was suspected based on the patient's young age at the onset of the disease. Thus, genetic testing was performed. It showed a germline mutation in the HRPT2/CDC73 gene and confirmed the diagnosis of hyperparathyroidism-jaw tumor syndrome. Total parathyroidectomy was performed to prevent recurrence. In patients with early-onset hyperparathyroidism, genetic testing should be considered to facilitate the selection of a proper surgical procedure based on the consideration of future life expectancy.

A Case of Type 2 Diabetes with a Change from a Non-Dipper to a Dipper Blood Pressure Pattern by Dapagliflozin.

Dapagliflozin, a selective inhibitor of sodium glucose co-transporter 2 (SGLT2), is a novel glucose-lowering agent that has pleiotropic actions on blood pressure and lipids. Its glucose-lowering effect is not mediated by insulin. We report a type 2 diabetic patient whose blood pressure pattern improved from non-dipper to dipper after treatment with dapagliflozin. The 60-year-old man was treated with 5 mg/day dapagliflozin, and the effect of treatment on his blood pressure (BP) was evaluated by ambulatory blood pressure monitoring (ABPM) before and at 8 and 14 days after the start of treatment. The 24-h systolic blood pressure/diastolic blood pressure decreased from 131/87 to 127/83 mmHg at day 14, with a particular decrease in nocturnal blood pressure from 123/84 to 116/75 mmHg (nocturnal blood pressure dip increased from 9.6% to 12.8%), changing from a non-dipper to a dipper blood pressure pattern. Dapagliflozin might potentially improve not only the average blood pressure, but also nighttime blood pressure from non-dipper to dipper in type 2 diabetic patients.

Effects of exenatide on postprandial vascular endothelial dysfunction in type 2 diabetes mellitus.

BACKGROUND: Basic studies have shown that glucagon-like peptide-1 (GLP-1) analogs exert a direct protective effect on the vascular endothelium in addition to their indirect effects on postprandial glucose and lipid metabolism. GLP-1 analogs are also reported to inhibit postprandial vascular endothelial dysfunction. This study examined whether the GLP-1 analog exenatide inhibits postprandial vascular endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM). METHODS: Seventeen patients with T2DM underwent a meal tolerance test to examine changes in postprandial vascular endothelial function and in glucose and lipid metabolism, both without exenatide (baseline) and after a single subcutaneous injection of 10 µg exenatide. Vascular endothelial function was determined using reactive hyperemia index (RHI) measured by peripheral arterial tonometry before and 120 min after the meal loading test. The primary endpoint was the difference in changes in postprandial vascular endothelial function between the baseline and exenatide tests. RESULTS: The natural logarithmically-scaled RHI (L_RHI) was significantly lower after the baseline meal test but not in the exenatide test. The use of exenatide resulted in a significant decrease in triglycerides (TG) area under the curve and coefficient of variation (CV). The change in L_RHI correlated with changes in CV of triglycerides and HDL-cholesterol. Multivariate analysis identified changes in triglyceride CV as the only determinant of changes in L_RHI, contributing to 41% of the observed change. CONCLUSIONS: Exenatide inhibited postprandial vascular endothelial dysfunction after the meal loading test, suggesting that exenatide has a multiphasic anti-atherogenic action involving not only glucose but also lipid metabolism. TRIAL REGISTRATION: ClinicalTrials.gov: UMIN000015699.