Urinary type IV collagen excretion predicts an increased urinary albumin-to-creatinine ratio in normoalbuminuric patients with diabetes

Aims: We evaluated whether urinary excretion of type IV collagen (U-COL) may predict an increase in the urinary albumin-to-creatinine ratio (ACR) and what factors regulate U-COL in 145 normoalbuminuric patients with type 2 diabetes. Methods: We measured HbA1c, systolic blood pressure (SBP), urinary 8-hydroxydeoxyguanosine (8-OHdG) and monocyte chemoattractant protein (MCP)-1 at start of this study (Baseline), ACR and U-COL in addition to these measurements at one year later (Evaluation-1), and ACR and SBP after two years of the Evaluation-1 (Evaluation-2). The relationships were investigated between the increase of ACR and the U-COL. The effect of angiotensin receptor blockers (ARB) treatment on the correlations between U-COL and ACR at Evaluation-2 on one hand, and between U-COL and percent change of ACR on the other, was also analyzed. Furthermore, we investigated whether the increase in 8-OHdG and in MCP-1 in a year prior to the Evaluation-1 were risk factors of the rise in U-COL levels. Results: Both U-COL and SBP at Evaluation-1, but not ARB treatment, were independent risk factors for an increased ACR after 2 years. ARB treatment significantly suppressed the increase in ACR after 2 years in patients with higher U-COL excretion. The percentage changes in 8-OHdG (%8-OHdG) and MCP-1 (%MCP-1) in one year prior to Evaluation-1 measurements are independent risk factors for U-COL. HbA1c and SBP values one year prior to Evaluation-1 are independent risk factors not only for %8-OHdG but also, for baseline U-COL. The %8-OHdG is an independent risk factor for %MCP-1. Conclusions: U-COL may predict an increase in the ACR. The U-COL seems to be increased with oxidative stress and inflammation induced by past hyperglycemia.

Compared with insulin glargine, insulin degludec narrows the day-to-day variability in the glucose-lowering effect rather than lowering blood glucose levels

Background: Changes in the day-to-day variability in the glucose-lowering effect of insulin [fluctuations of blood glucose levels (BG) seen during the same time period] that occur when insulin glargine (glargine) is replaced with insulin degludec (degludec) have not been sufficiently evaluated. Subjects: Five diabetics with unstable BG undergoing basal-bolus treatment using insulin glargine as basal insulin. Methods: Basal insulin was changed from glargine to same-dose degludec. The subjects’ HbA1c, glycoalbumin, and 1.5-anhydro-D-glucitol were measured before and after the switchover. Fasting blood glucose concentration (FBG) and predinner blood glucose concentration (PDBG) were measured continuously for 28 days immediately before the switchover, and 28 days immediately thereafter, to compare and evaluate 1) the changes in their mean values and standard deviations (SDs) before and after the switchover, and 2) the frequency of appearance of BG of over 180 mg/dL (BG ≥ 180) and under 70 mg/dL (BG Results: The levels of HbA1c, glycoalbumin, FBG’s mean value, SDs, BG ≥ 180 and BG Conclusion: The possibility was shown that degludec, to a greater extent than glargine, suppressed daily fluctuations of FBG and PDBG, suppressed the occurrence frequency of hyperglycemia and hypoglycemia, and exerted more steady hypoglycemic actions.

ARB affects nicotine-induced gene expression profile in human coronary artery endothelial cells

AIM: To investigate the effects of nicotine and nicotine plus angiotensin Ⅱ receptor blocker(ARB) on the gene expression profile of human coronary artery endothelial cells(HCAECs).METHODS: The changes in gene expression profiles in HCAECs treated with nicotine and nicotine plus ARB olmesartan were analyzed by DNA microarray. In nicotine-treated HCAECs, 432 genes selected by P < 0.01 were greater than 1.5-fold compared with the untreated cells. Data were analyzed using IPA(Ingenuity? Systems, www.ingenuity.com).RESULTS: The gene expression levels of tumor necrosis factor-α, collagen type 1, matrix metalloproteinase-10, and disintegrin and metalloprotease domain 8, which are related to "cardiovascular function and disease", were significantly increased. In canonical pathway analyses using IPA, "atherosclerosis signaling" was strongly affected by nicotine treatment and this effect was reduced by co-incubation with ARB olmesartan. These data indicate that the deleterious cardiovascular consequences of cigarette smoking may, at least in part, be due to the nicotine-induced gene expression profile related to "atherosclerosis signaling".CONCLUSION: The inhibitory effect of ARB against the nicotine-induced gene expression profile may possibly induce anti-atherosclerotic effects that are independent of those from lowering the blood pressure.