Vascular Endothelium as a Target of Beraprost Sodium and Fenofibrate for Antiatherosclerotic Therapy in Type 2 Diabetes Mellitus

Diabetes mellitus is an important risk factor for cardiovascular morbidity and mortality. The metabolic abnormalities caused by diabetes mellitus induce vascular endothelial dysfunction that predisposes patients with diabetes mellitus to atherosclerosis. Two mega clinical trials showed that intensive glycemic control does not have favorable effects on reducing macrovascular events although it demonstrated significant reductions in microvascular complications. It is becoming worthwhile to clarify the beneficial effects of tight controls on blood pressure, serum lipids, and postprandial hyperglycemia to prevent atherosclerosis in patients with type 2 diabetes mellitus. Here, we focus on vascular endothelium as a target of the prostaglandin I2 analog beraprost sodium and the peroxisome proliferators-activated receptor α activator fenofibrate for the prevention and treatment of atherosclerosis in patients with type 2 diabetes mellitus. Beraprost sodium lowered circulating vascular cell adhesion molecule-1 (VCAM-1) concentration and prevented the progression of carotid atherosclerosis in type 2 diabetic patients, probably through inhibiting VCAM-1 expression in vascular endothelium. Fenofibrate up-regulated endothelial nitric oxide synthase expression, which may explain its effects to improve endothelium-dependent vasodilatation and to prevent the progression of coronary atherosclerosis. The approaches to target the molecules expressed in vascular endothelium will become important for preventing the atherosclerosis in type 2 diabetes mellitus

Effectiveness of metformin and lifestyle interventions as an initial treatment in Japanese patients with newly diagnosed type 2 diabetes : a prospective observational study

Although global guidelines recommend metformin and lifestyle interventions as an initial treatment in patients with newly diagnosed type 2 diabetes (T2DM), few reports exist about its effectiveness in Japanese patients. To examine its effectiveness, we performed a prospective observational study within a routine clinical setting. We provided metformin (≥1,500 mg/day) and lifestyle interventions to 23 patients with newly diagnosed T2DM (20 men and 3 women, mean age 53 years, mean body mass index [BMI] 25.7 kg/m2). After 16 weeks, HbA1c levels significantly decreased from 9.1±2.1% (mean±SD) to 6.6±0.8% (p<0.001). Thirteen patients (56.5%) achieved a target HbA1c<6.5%. We did not find a significant correlation between baseline BMI and the changes in HbA1c (ΔHbA1c) (r=-0.165, p=0.451). In contrast, we found a significant correlation between baseline fasting plasma glucose and ΔHbA1c (r=-0.755, p<0.001). Body weight decreased from 73.3±13.3 kg to 69.8±11.6 kg (p<0.001). Total cholesterol, low density lipoprotein-cholesterol, non-high density lipoprotein-cholesterol, and serum vitamin B-12 concentrations also significantly decreased. Adverse events included diarrhea (26.1%) and mild elevation of liver enzymes (8.7%). These results suggest that metformin and lifestyle interventions is effective and safe as an initial treatment in Japanese patients with newly diagnosed T2DM

The glycated albumin to HbA1c ratio is elevated in patients with fulminant type 1 diabetes mellitus with onset during pregnancy

Fulminant type 1 diabetes mellitus (FT1DM) develops as a result of very rapid and almost complete destruction of pancreatic β cell. The most common form of type 1 diabetes mellitus with onset during pregnancy has been shown to be FT1DM at least in Japan. We previously reported that the ratio of glycated albumin (GA) to HbA1c (GA/HbA1c ratio) is elevated in FT1DM patients at the diagnosis. In the present study, we investigated whether the GA/HbA1c ratio is also elevated in FT1DM with onset during pregnancy (P-FT1DM). The study subjects consisted of 7 patients with P-FT1DM. Ten patients with untreated type 2 diabetes mellitus (T2DM) discovered during pregnancy (P-T2DM) and 9 non-pregnant women with untreated T2DM (NP-T2DM) were used as controls. All study patients satisfied HbA1c<8.7%, the diagnostic criteria for FT1DM. The GA/HbA1c ratio in the P-FT1DM patients at the diagnosis was significantly higher than that in the P-T2DM patients and the NP-T2DM patients. The GA/HbA1c ratio was ≥3.0 in all P-FT1DM patients, whereas it was <3.0 in 8 of 10 P-T2DM patients and all NP-T2DM patients. The GA/HbA1c ratio was also elevated in P-FT1DM patients at the diagnosis compared with T2DM with or without pregnancy

Improvement of Reduced Bone Mineral Density by Intermittent Cyclical Etidronate in Postmenopausal Asthmatic Patients Receiving Inhaled Corticosteroids

Background: We have recently shown that early postmenopausal but not premenopausal asthmatic women treated with inhaled corticosteroids demonstrate reduced bone mineral density(BMD)and decreased serum intact osteocalcin levels. Thus, the development of therapeutic approaches would be desirable for the prevention and intervention of BMD reduction in postmenopausal asthmatic women receiving inhaled corticosteroids. Methods: This study was aimed at examining the effects of etidronate disodium on BMD in 20 postmenopausal asthmatic women with reduced BMD of the lumbar spine(T score ; −1.5 or less). These patients had been managed by inhaled beclomethasone dipropionate or inhaled fluticasone propionate, without regular use of oral or parentheral corticosteroids. They were given a 200 mg/day oral dose of etidronate disodium for 14 days every three months. BMD of the lumbar spine was determined at baseline and at 1 or 3 years after the treatment. Results: The baseline BMD was 0.692±0.018(SE)g/cm2(T score, −3.0±0.8). The BMD significantly increased by 5.2±2.0% at 1 year(P=0.022)and by 7.3±2.9% at 3 years(P=0.037)after the treatment. Conclusions: : Intermittent cyclical treatment with ethidronate improves reduced BMD in postmenopausal asthmatic women on inhaled corticosteroid therapy

INTRODUCTION Effectiveness of metformin and lifestyle interventions as an initial treatment in Japanese patients with newly diagnosed type 2 diabetes : a prospective observational study

Optimal control of hyperglycemia and associated risk factors reduces the risk of diabetes-related complications. Metformin is the most widely prescribed biguanide, which lowers blood glucose level primarily through the inhibition of hepatic glucose production. The UK Prospective Diabetes study (UKPDS) showed that metformin reduces the risk of diabetesrelated endpoints, myocardial infarction, diabetesrelated death and all-cause mortality in overweight patients with newly diagnosed type 2 diabetes (1, 2). Moreover, recent observational studies reveal that body mass index (BMI) of patients is unlikely to influence the antihyperglycemic effect of metformi