OBJECTIVETo investigate the association between aortic stiffness and incident albuminuria and the decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.RESEARCH DESIGN AND METHODSWe investigated 461 Japanese type 2 diabetic patients, comprising 199 women and 262 men, with a mean age of 59 ± 11 years. Patients were divided into two groups according to the median value of carotid-femoral pulse wave velocity (cf-PWV), which was used to evaluate aortic stiffness. The end point was defined as the transition from normo- to microalbuminuria or micro- to macroalbuminuria. The Cox proportional hazard model was used to calculate the hazard ratio (HR) and 95% CI. The correlation between cf-PWV and rate of change in eGFR was also determined by linear regression analysis.RESULTSThe baseline mean (± SD) cf-PWV was 9.6 ± 2.4 m/s. During a median follow-up period of 5.9 years (range 0.3–8.6), progression of albuminuria was observed in 85 patients. The 5-year cumulative incidence of the end point in patients with cf-PWV below and above the median was 8.5 and 19.4%, respectively (P = 0.002, log-rank test). cf-PWV was significantly associated with incident albuminuria (HR 1.23, 95% CI 1.13–1.33, P < 0.001) by multivariate Cox regression analysis. A significant association between cf-PWV and annual change in eGFR was also suggested by multiple linear regression analysis (standardized estimate −0.095, P = 0.031).CONCLUSIONSAortic stiffness is associated with incident albuminuria and the rate of decline in glomerular filtration rate in type 2 diabetic patients.

It is unclear whether albuminuria and reduced glomerular filtration rate (GFR) independently increase the risk of incident stroke and coronary artery disease (CAD) in Japanese patients with diabetes. We investigated the independent effects of albuminuria and estimated GFR (eGFR) on the first occurrence of stroke and CAD in patients with type 2 diabetes mellitus (T2DM). We studied 1002 T2DM patients with eGFR (ml min À1 per 1.73 m 2 ) X15 and had no previous cardiovascular disease (CVD) history. GFR was estimated using the modified three-variable equation for the Japanese. Patients were divided into four eGFR categories: X90, 60-89, 30-59 and 15-29. The end point was an incident stroke and CAD events. The Cox proportional hazard model was used to calculate hazard ratio and 95% confidence interval. During a mean follow-up period of 5.2±2.1 years, 72 episodes of stroke and 90 of CAD were observed. Multivariate Cox analysis revealed no significant association between the eGFR category and incident stroke. The stroke hazard ratio (95% confidence interval) in reference to patients with an eGFR X90 was 0.78 (0.40-1.56) for patients with an eGFR of 60-89, 1.47 (0.70-3.10) for patients with an eGFR of 30-59 and 1.14 (0.39-3.35) for patients with an eGFR of 15-29. Reduced eGFR was a significant risk factor for CAD, with hazard ratios (95% confidence interval) for patients with an eGFRs of 60-89, 30-59 and 15-29 at 1.81 (1.01-3.57), 2.03 (1.04-4.40) and 3.01 (1.13-8.02), respectively. Reduced eGFR is independently associated with incident CAD but not stroke in Japanese patients with T2DM.

Aims/Introduction:  To reveal whether visit‐to‐visit variability in HbA1c is associated with higher risk of cardiovascular disease (CVD) in patients with type 2 diabetes.Materials and Methods:  The study was conducted on 689 Japanese patients with type 2 diabetes [295 women, 394 men; mean (±standard deviations (SD)) age 65 ± 11 years]. Variability in HbA1c was evaluated as the intrapersonal SD of serial measurements of HbA1c during the follow‐up period for at least 12 months. Patients were divided into quartiles according to the SD of HbA1c, and the primary endpoint was defined as incident CVD. Cox’s proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI).Results:  During a median follow‐up period of 3.3 years (range 1.0–6.3 years), 26 ± 14 measurements of HbA1c were obtained per patient and 61 episodes of incident CVD were recorded. The 5‐year cumulative incidence of CVD in patients across the first, second, third, and fourth quartiles of SD in HbA1c was 4.9, 8.7, 17.1, and 26.2%, respectively (P < 0.001, log‐rank test). Multivariate Cox regression analysis revealed that the incidence of CVD was significantly higher in patients in the fourth quartile of SD in HbA1c compared with those in the first quartile (HR 3.38; 95% CI 1.07–10.63; P = 0.039), independent of mean HbA1c and other traditional cardiovascular risk factors.Conclusions:  Variability of HbA1c may be a potent predictor of incident CVD in Japanese patients with type 2 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00155.x, 2011)

Lower HDL cholesterol levels seem to be associated with the progression of DKD in men but not in women.

Abstract. Production of hyaluronan (hyaluronic acid: HA) was demonstrated in denuded mouse oocytes (DOs) by the enzyme-linked immunosorbent assay, and the role of HA in enlargement of the perivitelline space in the oocytes was examined. The incidence of polyspermy following insemination was also observed in DOs in which HA synthesis was inhibited. HA was not detected in culture medium containing DOs immediately after collection. After culture for 7 h, 4.75 pg of HA per DO was detected in the medium, and the mean amount of HA significantly increased to 20.78 pg 14 h after culture. When DOs were cultured in medium containing 0.25 mM 4-methylumbelliferone (MU), an inhibitor of HA synthase, the mean amount of HA in the culture medium with DOs was 8.61 pg, which was significantly smaller than the amount in the control medium with non-treated DOs (21.59 pg). The mean size of the perivitelline space in oocytes cultured with cumulus cells (5.40 μm) did not differ from that (5.08 μm) of DOs. The mean size of the perivitelline space was significantly smaller in the MU-treated DOs (3.58 μm) than in the control DOs (4.65 μm). The fertilization rate did not differ between the MU-treated DOs (84.9%) and control DOs (81.0%), whereas the incidence of polyspermy was significantly higher in the MU-treated DOs (13.3%) compared with the control DOs (2.1%). These findings clarified that the HA involved in enlargement of the perivitelline space in oocytes is synthesized and secreted by the oocytes themselves. They also suggest that there is a close relationship between the size of perivitelline space and the incidence of polyspermy in mouse oocytes. Key words: Enzyme-linked immunosorbent assay, Hyaluronan production, Incidence of polyspermy, Mouse oocyte, Size of perivitelline space (J. Reprod. Dev. 55: [496][497][498][499][500][501] 2009) he perivitelline space is the gap between the plasma membrane and zona pellucida in oocytes. Recently, it has been reported that the incidence of polyspermy in porcine and mouse oocytes with larger perivitelline space is significantly lower than that in oocytes with a smaller perivitelline space [1][2][3][4]. Therefore, it has been suggested that there could be a relationship between the size of the perivitelline space and the incidence of polyspermy in porcine and mouse oocytes.It is known that glycosaminoglycans including hyaluronan (hyaluronic acid: HA) synthesized in cumulus cells by the stimulation of FSH and LH are secreted [5,6] and that the extracellular matrix in cumulus cells is occupied by the secreted HA [7][8][9][10]. HA has been found to also exist in the perivitelline space [11][12][13][14], and one of its properties is retention of large volumes of water [14]. Therefore, when HA accumulates in the perivitelline space, its role is to absorb water, which causes the perivitelline space to enlarge.On the other hand, with regard to the secretory source of HA in the perivitelline space, Salustri et al. [15] used [ 3 H] glucosamine as a metabolic precursor to examine the production of H...