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An open randomized prospective study was performed to elucidate the effect of an alpha-glucosidase inhibitor, voglibose, on the progression of atherosclerosis in subjects with type 2 diabetes.Voglibose at a dose of 0.4-0.6 mg/day was added on 51 subjects out of 101 type 2 diabetic patients being treated with diet, sulphonylurea (SU) or insulin injections, and the average (AveIMT) and maximum intima-media thickness (MaxIMT) of their carotid arteries were examined for 3 years.Irrespective of the differences in treatments, addition of voglibose reduced the progression of AveIMT and MaxIMT to -0.024 +/- 0.047 (+/-S.D.) and -0.021 +/- 0.144 mm/year, respectively. Without voglibose, diabetic patients showed significant (P0.0001) progression of AveIMT and MaxIMT (0.056 +/- 0.046 and 0.098 +/- 0.122 mm/year, respectively). The administration of voglibose resulted in a significant reduction of hemoglobin A1c (HbA1c), total cholesterol and triglyceride concentrations, as well as an increase in HDL cholesterol concentration. Multivariate regression analysis showed that administration of voglibose independently reduced the progression of AveIMT by 0.069 mm/year (P0.0001).These results suggest that voglibose reduces the progression of IMT and may be a candidate for an anti-atherosclerotic drug for type 2 diabetic patients.

Objective: This study was conducted to examine whether tissue characterization of the carotid artery wall by determining integrated backscatter (IBS) can identify subjects with a recent history of acute coronary syndrome (ACS) or atherothrombotic infarction (ATI). Research design and methods: The maximum thickness (Max-IMT) and IBS value (corrected-IBS) of the carotid artery intima–media complex were measured ultrasonographically for 132 type 2 diabetic subjects (62.9±8.5 (±S.D.) years old, 87 men and 45 women) with or without cardiovascular diseases. Results: The diabetic patients with recent ACS or ATI had a significantly lower corrected-IBS and higher Max-IMT than those with Max-IMT ≧ 1.1mm but without cardiovascular diseases. The product of Max-IMT and corrected-IBS (IMT-IBS product) of the patients with recent ACS was significantly lower than that of the patients with chronic stable angina. The multiple logistic model showed that only the IMT-IBS product was associated with a recent history of ACS (odds ratio 0.94, P P Conclusions: Diabetic patients who had a recent history of ACS or ATI showed a lower IBS value and higher IMT for their carotid artery. Both the size and tissue characteristics of the carotid plaque may identify subjects with a high risk of cardiovascular disease.

Oxidative stress is induced under diabetic conditions and causes various forms of tissue damage in patients with diabetes. Recently, pancreatic beta-cells have emerged as a putative target of oxidative stress-induced tissue damage and this seems to explain in part the progressive deterioration of beta-cell function in type 2 diabetes. As a step toward clinical trial of antioxidant for type 2 diabetes, we investigated the possible anti-diabetic effects of probucol, an antioxidant widely used as an anti-hyperlipidemic agent, on preservation of beta-cell function in diabetic C57BL/KsJ-db/db mice. Probucol-containing diet was given to mice from 6 to 16 weeks of age. Immunostaining for oxidative stress markers such as 4-hydroxy-2-nonenal (HNE)-modified proteins and heme oxygenase-1 revealed that probucol treatment decreased reactive oxygen species (ROS) in pancreatic islets of diabetic animals. Oxidative stress is known to enhance apoptosis of beta-cells and to suppress insulin biosynthesis, but probucol treatment led to preservation of beta-cell mass and the insulin content. According to intraperitoneal glucose tolerance tests, the probucol treatment preserved glucose-stimulated insulin secretion and improved glucose tolerance at 10 and 16 weeks: insulin, 280+/-82 vs. 914+/-238 pmol/l (120 min, at 16 weeks; P

To investigate the role of heart rate (HR) and blood pressure (BP) for diabetic retinopathy, 24-h ambulatory HR and BP were monitored for 162 in patients with type 2 diabetes and normoalbuminuria. The fundus was assessed as no retinopathy, simple diabetic retinopathy (SDR) and proliferative retinopathy (PDR). Comparing the highest with the lowest quartile of diabetic duration, the relative risk for retinopathy was 9.3 and for nocturnal HR, it was 3.6. Comparison among three retinopathy groups (no retinopathy, group 1, n=122; SDR, group 2, n=24; Pre-PDR or PDR, group 3, n=16) showed that 24-h and nocturnal HR were significantly higher in group 3 (80+/-9 and 71+/-9 beats per min) than in group 2 (73+/-8 and 64+/-8) and group 1 (72+/-7 and 60+/-7). In multiple logistic analysis, the odds ratio of diabetic duration and nocturnal HR to the existence of retinopathy was 1.17 (95% CI, 1.10-1.25, P=0.00001) and 1.11 (95% CI, 1.05-1.17, P=0.0002). We concluded that diabetic retinopathy is related to diabetic duration and high heart rate in type 2 diabetes mellitus with normoalbuminuria. Heart rate elevation may be a predictor of advanced retinopathy.

To elucidate the mechanism of impaired pancreatic A cell function in hypoglycemia in diabetics, the effect of long-term strict glycemic regulations on hypoglycemia-induced glucagon secretion was studied. Firstly, the effect of plasma insulin concentrations on suppressing A cell was studied in healthy volunteers by injecting insulin at doses of 0.1 U/kg and 0.3 U/kg. With 0.3 U/kg of insulin, the rate of fall in glycemia and the nadir of blood glucose were made similar to those with 0.1 U/kg of insulin by glucose infusion with artificial endocrine pancreas. Plasma glucagon response after 0.3 U/kg of insulin was significantly suppressed as compared to that after 0.1 U/kg of insulin, demonstrating that not only hypoglycemic stimulus but also plasma insulin concentration were important determinants responsible for glucagon secretion in insulin-induced hypoglycemia. Secondly, effect of strict glycemic control was studied. Short-acting insulin at a dose of 0.1 U/kg was injected in an intravenous bolus form into 12 insulin-dependent (IDDM) and 9 non-insulin-dependent (NIDDM) diabetics before and 1–3 months after strict glycemic control with multiple insulin injections therapy. Before strict glycemic regulations in IDDM, no significant rise in plasma glucagon concentrations was observed during the insulin-induced hypoglycemia. In NIDDM, a rise in plasma glucagon concentrations was observed, though the response was delayed. After strict glycemic regulations, in patients with residual endogenous insulin secretion, the glucagon response to hypoglycemia improved considerably in IDDM and normalized in NIDDM. In IDDM and NIDDM, improvement in glucagon response to hypoglycemia related positively to daily urinary secretion rate of C-peptide. From these experiments, it is clearly shown that blunted hypoglycemia induced glucagon secretion in diabetics is secondary to poor glycemic control, and that the existence of endogenous insulin secretion is essential to glucagon response to hypoglycemia.