Retraction: α-GalCer ameliorates listeriosis by accelerating infiltration of Gr-1+ cells into the liver.

Retraction: Emoto, M., Emoto, Y., Yoshizawa, I., Kita, E., Shimizu, T., Hurwitz, R., Brinkmann, V. and Kaufmann, S.H.E. (2010), α-GalCer ameliorates listeriosis by accelerating infiltration of Gr-1+ cells into the liver. Eur. J. Immunol., 40: 1328-1341. DOI: https://doi.org/10.1002/eji.200939594 The above article, published online on 16 February 2010 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the Chairman of the Executive Committee of the European Journal of Immunology and Wiley-VCH Verlag GmbH & Co. KGaA. The retraction has been agreed following an investigation carried out by Gunma University (http://www.gunma-u.ac.jp/wp-content/uploads/2017/10/chosakekka29.pdf). The investigation was unable to determine the validity of the images for which Professor Emoto, the article's corresponding author, was responsible. As a result, the journal has made the decision to retract the article.

Impaired residual renal function predicts denosumab-induced serum calcium decrement as well as increment of bone mineral density in non-severe renal insufficiency.

Denosumab treatment of osteoporotic patients, except those with severe renal insufficiency, reduced cCa levels. Low baseline cCa, low estimated glomerular filtration rate, and high bone turnover increased the risk of lower cCa, while increasing bone mineral density. Pretreatment with antiresorptive agents was beneficial in reducing the risk of hypocalcemia. INTRODUCTION: Although denosumab-induced hypocalcemia has been frequently observed in patients with chronic kidney disease (CKD) stages 4-5D being treated with denosumab for osteoporosis, few studies have assessed the risk factors for serum-corrected calcium (cCa) reductions in patients with non-severe renal insufficiency. This study assessed the risk factors for reduced cCa concentration following denosumab administration and analyzed factors predictive of changes in bone mineral density (BMD). METHODS: Seventy-seven osteoporotic patients, not including those with CKD stages 4-5D, were treated with 60 mg denosumab once every 6 months. Biochemical parameters and BMD were analyzed from prior to the initial dose until 1 month after the second dose. RESULTS: Following the first administration of denosumab, cCa levels decreased, reaching a minimum on day 7. Multiple linear regression analyses showed that baseline cCa, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, tartrate-resistant acid phosphatase-5b (TRACP-5b), and bone alkaline phosphatase (BAP) or pretreatment with antiresorptive agents were significant factors independently associated with the absolute reduction in cCa from baseline to day 7 (ΔcCa0-7 days). ΔcCa0-7 days after the second dose of denosumab was significantly lower than that after the first dose. After 6 months of denosumab treatment, both LS-BMD and FN-BMD significantly increased from baseline. LS-BMD and FN-BMD correlated significantly with baseline TRACP-5b or BAP and eGFR, respectively. CONCLUSIONS: Both low eGFR and high bone turnover were independent risk factors for denosumab-induced cCa decrement, and for increases in BMD. Pretreatment with antiresorptive agents may reduce the risk of hypocalcemia.

POTENTIAL ADVANTAGE OF REPAGLINIDE MONOTHERAPY IN GLYCEMIC CONTROL IN PATIENTS WITH TYPE 2 DIABETES AND SEVERE RENAL IMPAIRMENT.

CONTEXT: Oral anti-diabetic drugs (OADs) are leading option for treatment of type 2 diabetes (T2D). However, availability of OADs are limited in the presence of renal impairment (RI). OBJECTIVE: In this study, we examined the efficacy of repaglinide, which is mainly metabolized and excreted via non-renal route, in patients with T2D and severe RI that consists mainly of chronic kidney disease (CKD) stage 4. DESIGN SUBJECTS AND METHODS: This was an open label, single arm, interventional study by repaglinide monotherapy. The primary efficacy end point was HbA1c change from baseline to week 12. RESULTS: Repaglinide treatment significantly reduced HbA1c levels from 7.7 ± 0.7% to 6.1 ± 0.3% (p<0.001) in 9 patients with severe RI (mean estimated glomerular filtration rate was 26.4 ± 7.5 mL/min/1.73m2). Focusing on 4 patients who received DPP-4 inhibitor monotherapy at enrolment, switching to repaglinide also significantly improved HbA1c levels. No hypoglycemic symptoms or severe hypoglycemia was reported in patients who completed the period of 12 weeks. CONCLUSIONS: We demonstrated the efficacy of repaglinide in patients with T2D and severe RI. In case that DPP-4 inhibitors are not enough to achieve targeted range of glycemic control, repaglinide is another good candidate.

Decreased cortical thickness, as estimated by a newly developed ultrasound device, as a risk for vertebral fracture in type 2 diabetes mellitus patients with eGFR of less than 60 mL/min/1.73 m2.

UNLABELLED: Cortical porosity is increasingly recognized as an important risk for fracture in DM patients. The present study demonstrated that decreased cortical thickness, assessed using a newly developed quantitative ultrasonic bone densitometry, is a significant risk factor for vertebral fractures in type 2 diabetes mellitus patients with stage 3 or higher chronic kidney disease, but not in those without. INTRODUCTION: Cortical porosity is increasingly recognized as an important risk factor for fracture in type 2 diabetes mellitus (T2DM) patients as well as in stage 3 chronic kidney disease (CKD) patients in whom serum parathyroid hormone (PTH) starts to increase. The present study aimed to clarify whether the coexistence of CKD might affect the relationship of decreased cortical thickness (CoTh) in the development of vertebral fractures (VF) in T2DM patients. METHODS: In this cross-sectional study, trabecular bone mineral density (TrBMD), elastic modulus of trabecular bone (EMTb), and CoTh were estimated with a new quantitative ultrasound bone densitometry in 173 T2DM patients. VFs were identified radiographically. RESULTS: Thirty-nine patients (22.5%) had VF. Those with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) (low eGFR) showed a significantly higher VF rate (32.4%) than those with eGFR ≥60 mL/min/1.73 m(2) (high eGFR, 16.2%). Serum PTH was significantly higher with low eGFR than with high eGFR. In those with high eGFR, EMTb was significantly lower in VF(+) than VF(-). In those with low eGFR, TrBMD, EMTb, and CoTh were significantly lower in VF(+) than in VF(-). In a multivariate logistic regression analysis, EMTb was independently and significantly associated with VF in T2DM patients with a high eGFR, in contrast to those with only CoTh with VF in T2DM with low eGFR. CONCLUSION: This study demonstrated CoTh as a factor independently associated with VF in T2DM patients with low eGFR and increasing serum PTH levels.

Receiver circuit improvement of dual frequency-comb ka-band Doppler backscattering system in the large helical device (LHD).

Doppler-backscattering (DBS) has been used in several fusion plasma devices because it can measure the perpendicular velocity of electron density perturbation v⊥, the radial electric field Er, and the perpendicular wavenumber spectrum S(k⊥) with high wavenumber and spatial resolution. In particular, recently constructed frequency comb DBS systems enable observation of turbulent phenomena at multiple observation points in the radial direction. A dual-comb microwave DBS system has been developed for the large helical device plasma measurement. Since it is desirable to control the gain of each frequency-comb separately, a frequency-comb DBS system was developed with a function to adjust the gain of the scattered signal intensity of each channel separately. A correction processing method was also developed to correct the amplitude ratio and the phase difference between the in-phase and quadrature-phase signals of the scattered signals. As a result, the error in Doppler-shift estimation required to observe vertical velocity and the radial electric field was reduced, which enables more precise measurements.

Analysis of the Motional Stark Effect (MSE) diagnostic to measure the rotational transform and current profile in the Large Helical Device.

The analysis method of the Motional Stark Effect (MSE) diagnostic to measure the rotational transform and current profiles in the Large Helical Device has been improved. This was done by using the Variational Moments Equilibrium Code to calculate an equilibrium database for various pressure profiles and current profiles. This method looks for the radial profile of the rotational transform in the equilibrium database that gives the best fit to the polarization angle profiles measured with the MSE diagnostic. This analysis improves the measurements of rotational transform, especially near the magnetic axis, where the sensitivity of the polarization angle measurements becomes low and the uncertainty due to error in the estimation of the Pfirsch-Schlüter current becomes large. The radial profiles of the rotational transform and current profiles for Electron Cyclotron Current Drive and Neutral Beam Current Drive are obtained in the new analysis method with a sufficiently high accuracy to discuss the discrepancy of the current density profiles between the measurements and the calculations.

W-band millimeter-wave back-scattering system for high wavenumber turbulence measurements in LHD.

A 90 GHz W-band millimeter-wave back-scattering system is designed and installed for measuring electron scale turbulence (k⊥ρs ∼ 40). A metal lens relay antenna is used for in-vessel beam focusing, and a beam diameter of less than 40 mm is achieved in the plasma core region. This antenna can be steered at an angle of 159° ± 6°, which almost covers the plasma radius. The estimated size of the scattering volume is ∼105 mm at the edge and 135 mm at the core, respectively. A 60 m corrugated waveguide is used to achieve a low transmission loss of ∼8 dB. A heterodyne detection system for millimeter-wave circuits with probing power modulation can distinguish the scattered signal from background noise.

Induction of gamma/delta T cells in murine salmonellosis by an avirulent but not by a virulent strain of Salmonella choleraesuis.

To elucidate the relationship between the virulence of intracellular bacterium and its ability to induce gamma/delta T cells in the host during infection, we examined the differences in appearance of gamma/delta T cells in mice infected with Salmonella choleraesuis virulent strain RF-1 carrying a virulence plasmid of 50 kb, and with avirulent strain 31N-1 cured of the 50-kb plasmid. The number of gamma/delta T cells in the peritoneal cavity was increased to a significant level on day 3 after an intraperitoneal infection with a sublethal dose (5 x 10(4) colony-forming units) of avirulent strain 31N-1. On the other hand, no increase in the number of gamma/delta T cells was evident in the peritoneal cavity at any stage after infections with various doses of virulent strain RF-1, although the numbers of the bacteria were drastically increased. Similar to that seen in the peritoneal cavity, the number of gamma/delta T cells in the liver was significantly increased after an intraperitoneal infection with avirulent strain 31N-1 but not with virulent strain RF-1. The early appearing gamma/delta T cells during salmonellosis with avirulent stain 31N-1, which preferentially used V gamma 1/V delta 6, showed blastogenesis in response to purified protein derivative (PPD) derived from Mycobacterium tuberculosis. The gamma/delta T cells also responded to the peritoneal adherent cells in mice infected with avirulent strain 31N-1 6 d previously, which expressed a high level of endogenous heat-shock protein (hsp) homologous to the mycobacterial 65-kD hsp. The expression of the hsp, however, was not prominent in the adherent cells in mice infected with virulent strain RF-1. These results suggest that the gamma/delta T cells specific for PPD may play important roles in host defense against murine salmonellosis, and that the virulence of Salmonella may be inversely correlated with its ability to induce endogenous hsp in the infected macrophages, which in turn stimulate the gamma/delta T cells in the host during salmonellosis.

Non-oxidative glucose disposal is reduced in type 2 diabetes, but can be restored by aerobic exercise.

Whole-body glucose utilization consists of mitochondrial glucose oxidation and non-oxidative glycogen synthesis. We examined whether reduction of both non-oxidative glucose disposal and glucose oxidation contributes to insulin resistance in type 2 diabetes. We also examined the effects of exercise on these two components. Whole-body glucose disposal rate (GDR, mg/kg/min) was evaluated in 37 type 2 diabetic (T2DM) and 17 non-diabetic (non-DM) subjects as the mean of glucose infusion rate during steady state in the euglycaemic-hyperinsulinaemic clamp study. Glucose oxidation rates were assessed by indirect calorimetry, and non-oxidative GDR was calculated by subtracting glucose oxidation rate from GDR. Intramyocellular lipid (IMCL) content of the soleus muscle was measured using (1)H-magnetic resonance spectroscopy. In 10 T2DM subjects, the changes in oxidative and non-oxidative glucose disposal during clamp were examined after 3-month exercise intervention. GDR (2.93 +/- 1.55 vs. 4.55 +/- 1.83, p = 0.001) and non-oxidative GDR (1.45 +/- 1.52 vs. 3.01 +/- 1.87, p = 0.002) were significantly lower in T2DM than in non-DM subjects. Glucose oxidation rate was comparable in the two groups, and inversely correlated with IMCL (n = 15, r =-0.565, p = 0.028). GDR (2.28 +/- 1.67 to 4.63 +/- 2.42, p = 0.021) and non-oxidative GDR (0.72 +/- 1.27 to 2.26 +/- 1.91, p = 0.047) were increased after exercise intervention, although the change in glucose oxidation rate was not significant. In summary, reduction of non-oxidative glucose disposal may contribute to decreased whole-body glucose utilization. In addition, exercise improves insulin resistance mainly by increasing non-oxidative glucose disposal in type 2 diabetes.

Microwave frequency comb Doppler reflectometer applying fast digital data acquisition system in LHD.

We succeeded in increasing the radial observation points of the microwave frequency comb Doppler reflectometer system from 8 to 20 (or especially up to 45) using the high sampling rate of 40 GS/s digital signal processing. For a new acquisition system, the estimation scheme of the Doppler shifted frequency is constructed and compared with the conventional technique. Also, the fine radial profile of perpendicular velocity is obtained, and it is found that the perpendicular velocity profile is consistent with the E × B drift velocity one.

Novel analysis technique for measuring edge density fluctuation profiles with reflectometry in the Large Helical Device.

A new method for measuring density fluctuation profiles near the edge of plasmas in the Large Helical Device (LHD) has been developed utilizing reflectometry combined with pellet-induced fast density scans. Reflectometer cutoff location was calculated by proportionally scaling the cutoff location calculated with fast far infrared laser interferometer (FIR) density profiles to match the slower time resolution results of the ray-tracing code LHD-GAUSS. Plasma velocity profile peaks generated with this reflectometer mapping were checked against velocity measurements made with charge exchange spectroscopy (CXS) and were found to agree within experimental uncertainty once diagnostic differences were accounted for. Measured density fluctuation profiles were found to peak strongly near the edge of the plasma, as is the case in most tokamaks. These measurements can be used in the future to inform inversion methods of phase contrast imaging (PCI) measurements. This result was confirmed with both a fixed frequency reflectometer and calibrated data from a multi-frequency comb reflectometer, and this method was applied successfully to a series of discharges. The full width at half maximum of the turbulence layer near the edge of the plasma was found to be only 1.5-3 cm on a series of LHD discharges, less than 5% of the normalized minor radius.

Troglitazone treatment increases plasma vascular endothelial growth factor in diabetic patients and its mRNA in 3T3-L1 adipocytes.

Troglitazone is one of the thiazolidinediones, a new class of oral antidiabetic compounds that are ligands of peroxisome proliferator-activated receptor-gamma. This study on vascular endothelial growth factor (VEGF), also known as vascular permeability factor, was prompted by our clinical observation that the characteristics of troglitazone-induced edema were very similar to those caused by vascular hyperpermeability. When Japanese diabetic patients were screened for plasma VEGF, we found levels to be significantly (P < 0.001) increased in troglitazone-treated subjects (120.1 +/- 135.0 pg/ml, n = 30) compared with those treated with diet alone (29.2 +/- 36.1 pg/ml, n = 10), sulfonylurea (25.8 +/- 22.2 pg/ml, n = 10), or insulin (24.6 +/- 19.0 pg/ml, n = 10). Involvement of troglitazone in increased VEGF levels was further supported by the plasma VEGF levels in five patients before treatment (20.2 +/- 7.0 pg/ml), after 3 months of troglitazone treatment (83.6 +/- 65.9 pg/ml), and 3 months after discontinuation (28.0 +/- 11.6 pg/ml). We further demonstrated that troglitazone, as well as rosiglitazone, at the plasma concentrations observed in patients, increased VEGF mRNA levels in 3T3-L1 adipocytes. VEGF is an angiogenic and mitogenic factor and is currently considered the most likely cause of neovascularization and hyperpermeability in diabetic proliferative retinopathy. Although increased VEGF may be beneficial for subjects with macroangiopathy and troglitazone is currently not available for clinical use, vascular complications, especially diabetic retinopathy, must be followed with great caution in subjects treated with thiazolidinediones.

Contribution of interferon gamma and membrane-associated interleukin 1 to the resistance to murine typhoid of Ityr mice.

Resistance of mice to Salmonella typhimurium in the early phase of infection is known to be controlled by the expression of chromosome 1 locus Ity. To clarify the mechanism by which the genetically resistant (Ityr) mice can overcome the first phase of salmonellosis, the early response in DBA/2 (Ityr) and BALB/c (Itys) mice was compared after a subcutaneous injection of S. typhimurium. In both strains, the growth of S. typhimurium was controlled in livers and Kupffer cells until day 3, but thereafter the bacteria multiplied rapidly in BALB/c mice. Over the first 2 days nonspecific responses (changes in levels of blood leukocytes, plasma iron, and alpha 1-antitrypsin) were not significantly different between the strains, and the capacity of Kupffer cells isolated from infected mice of both strains to produce interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) was of the same degree. Thereafter, only DBA/2 Kupffer cells were able to produce membrane-associated IL-1 (ma IL-1) as well as TNF-alpha. Moreover, only DBA/2 splenocytes were able to produce interferon gamma (IFN-gamma) upon stimulation with Salmonella antigens, although concanavalin A-stimulated splenocytes of both strains produced the same level of interleukin 2. Furthermore, administration of recombinant murine IFN-gamma and DBA/2 Kupffer cells of day 6 to BALB/c mice 3 days after infection resulted in a significant level of protection, whereas neither of these materials alone induced protection. Injection of anti-TNF-alpha antibodies did not affect the resistance of DBA/2 mice. Thus, these findings suggest that the early resistance of Ityr mice is partly attributable to their capacity to produce IFN-gamma and ma IL-1 after infection.

Alterations of host resistance to mouse typhoid infection by sex hormones.

The effect on mouse typhoid infection of a 3-day treatment of female virgin mice with 1 mg/day of female sex hormones (estrogen or progesterone), maintaining the same hormonal levels observed in pregnant mice for 30 days, was investigated in order to clarify the mechanisms of altered resistance during pregnancy. Estrogen-exposed mice were more susceptible to the intraperitoneal challenge with Salmonella typhimurium as compared with the vehicle control mice, while progesterone treatment increased the survival times of mice. Estrogen exposure increased the number of peritoneal cells after treatment, but the inflammatory cellular response after infection was significantly suppressed. Although the estrogen-treated and vehicle control mice had the same degrees of peritoneal cellular responses after infection, the death rates in the estrogen-treated mice were higher than those in the vehicle control mice against challenge with 1 LD50 of S. typhimurium. On the other hand, progesterone treatment resulted in the marked influx of peritoneal cells after treatment was terminated, and also it induced a significant increase in the number of peritoneal cells after infection. Although survival times in the progesterone group were higher than those in other groups, all progesterone-treated mice died after a challenge with 1,000 LD50 of S. typhimurium. These results suggest that progesterone enhances nonspecific resistance by increasing the influx of peritoneal cells after infection, while estrogen affects the acute inflammatory responses.

Decrease in glomerular filtration rate in Japanese patients with type 2 diabetes is linked to atherosclerosis.

OBJECTIVE: We assessed the effects of atherosclerosis on the glomerular filtration rate (GFR) in patients with type 2 diabetes and who had micro- or normoalbuminuria. RESEARCH DESIGN AND METHODS: A total of 61 Japanese patients with type 2 diabetes were recruited from inpatients of Osaka City University Hospital. They ranged in age from 40 to 69 years (28 men and 33 women). Each subject collected a 24-h urine sample for quantitative analysis of albumin. Absence of albuminuria was defined as a urinary albumin excretion level of <30 mg/24 h (n = 36) and microalbuminuria as a level of 30-300 mg/24 h. The GFR was estimated using 99mTc diethylenetriamine pentaacetic renogram method. As indexes of atherosclerosis, we measured the intimal-medial thickness (IMT) and distensibility of the carotid artery using high-resolution B-mode ultrasonagraphy and an echo-tracking system. We measured the resistance index (RI) of the renal interlobar arteries by pulsed Doppler sonography. RESULTS: The clinical characteristics of type 2 diabetic patients with and without microalbuminuria did not differ except for duration of diabetes, which was longer in the patients with microalbuminuria. GFR also did not differ between the patients with and without microalbuminuria. GFR was significantly correlated with the patient's age (r = -0.256, P < 0.05), carotid IMT (r = -0.326, P < 0.05), carotid stiffness beta (r = -0.449, P < 0.001), and renal arterial RI (r = -0.365, P < 0.05). In multiple regression analysis, independent factors associated with GFR were carotid IMT (R2 = 0.108, P = 0.0102), carotid stiffness beta (R2 = 0.208, P = 0.0003), and renal artery RI (R2 = 0.130, P = 0.0043). CONCLUSIONS: The decline in GFR in type 2 diabetic patients in the early stages of nephropathy may be due in part to atherosclerosis.

Correlation between the intima-media thickness of the carotid artery and aortic pulse-wave velocity in patients with type 2 diabetes. Vessel wall properties in type 2 diabetes.

OBJECTIVE: The aim of this study was to assess the relationship between atherotic (structural) and sclerotic (functional) changes in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Aortic distensibility and carotid intimal-media thickness (IMT) were evaluated using carotid-femoral aortic pulse-wave velocity (a-PWV) and high-resolution B-mode ultrasonography in 271 patients with type 2 diabetes and 285 age-matched control subjects. RESULTS: a-PWV and carotid IMT were significantly higher in the patients than in the control subjects in all age-groups (P < 0.0001, respectively). The carotid IMT and a-PWV were significantly correlated with age in both the patients with type 2 diabetes and control subjects. There was a significant positive relationship between the carotid IMT and a-PWV in both the patients (r = 0.482, P < 0.0001) and control subjects (r = 0.424, P < 0.0001). The slope of the regression line for the carotid IMT to the a-PWV was significantly steeper in the diabetic patients than in the control subjects (P < 0.05). Multiple regression analysis in all subjects showed that age, diabetic state, and cigarette smoking were independently common risk factors for the increase in carotid IMT and a-PWV. In the diabetic patients, the independent risk factors associated with the carotid IMT were age, hyperlipidemia, and duration of diabetes (R2 = 0.232, P < 0.0001), while those associated with a-PWV were age and duration of diabetes (R2 = 0.334, P < 0.0001). CONCLUSIONS: The results indicated that diabetic patients showed more advanced changes in atherosis than that in sclerosis as compared with age- and sex-matched control subjects. Such atherotic changes in diabetic patients may be associated with hyperlipidemia.

Association of ACE gene polymorphism with arterial stiffness in patients with type 2 diabetes.

OBJECTIVE: To assess the relationship between the insertion (I)/deletion (D) polymorphism of the ACE gene and arterial distensibility in patients with type 2 diabetes and healthy control subjects. RESEARCH DESIGN AND METHODS: Aortic and carotid arterial distensibility were evaluated by measuring aortic pulse-wave velocity (a-PWV) and carotid stiffness beta using an echo-tracking system in 137 patients with type 2 diabetes and 260 age-matched control subjects. RESULTS: a-PWV and carotid stiffness beta were significantly higher in patients with type 2 diabetes than in age-matched control subjects (P < 0.05). Both stiffness beta and a-PWV were significantly higher in the patients with the II genotype than in those with the DD genotype (P < 0.001). In the control subjects, multiple regression analysis showed that age and decreased HDL cholesterol were independently associated with increased a-PWV (R2 = 0.244, P < 0.0001) and that age, systolic and diastolic blood pressure, and BMI were independently associated with increased carotid stiffness beta (R2 = 0.454, P < 0.0001). In the patients with type 2 diabetes, age, gene dose of the I allele, and systolic and diastolic blood pressure were independently associated with increased a-PWV (R2 = 0.545, P < 0.0001), and age, gene dose of the I allele, and systolic blood pressure were associated with increases in carotid stiffness beta (R2 = 0.314, P < 0.0001). CONCLUSIONS: These results suggested that ACE polymorphism is associated with the impairment of aortic and carotid distensibility in patients with type 2 diabetes.

Glycemic control is a predictor of survival for diabetic patients on hemodialysis.

OBJECTIVE: To investigate the impact of glycemic control on the survival of diabetic subjects with end-stage renal disease (ESRD) starting hemodialysis treatment. RESEARCH DESIGN AND METHODS: This single-center prospective observational study enrolled 150 diabetic ESRD subjects (109 men and 41 women; age at hemodialysis initiation, 60.5 +/- 10.2 years) at start of hemodialysis between January 1989 and December 1997. The subjects were divided into groups according to their glycemic control level at inclusion as follows: good HbA1c <7.5%, n = 93 (group G), and poor HbA1c > or = 7.5%, n = 57 (group P); and survival was followed until December 1999, with a mean follow-up period of 2.7 years. RESULTS: Group G had better survival than group P (the control group) (P = 0.008). At inclusion, there was no significant difference in age, sex, systolic blood pressure (SBP), BMI, cardio-to-thoracic ratio (CTR) on chest X-ray, and serum creatinine (Cre) or hemoglobin (Hb) levels between the two groups. After adjustment for age and sex, HbA1c was a significant predictor of survival (hazard ratio 1. 133 per 1.0% increment of HbA1c, 95% CI 1.028-1.249, P = 0.012), as were Cre and CTR. CONCLUSIONS: Good glycemic control (HbA1c <7.5%) predicts better survival of diabetic ESRD patients starting hemodialysis treatment.

Relations between ACE gene and ecNOS gene polymorphisms and resistive index in type 2 diabetic patients with nephropathy.

OBJECTIVE: ACE and endothelial cell nitric oxide synthase (ecNOS) genotypes have been reported to be related to the incidence of renal diseases and coronary artery diseases. In order to assess the effect of the gene polymorphism of both ACE and ecNOS on renal hemodynamic abnormality, we examined 155 Japanese patients with type 2 diabetes with various stages of nephropathy. RESEARCH DESIGN AND METHODS: The patients ranged in age from 40 to 72 years (92 men and 63 women). They were divided into four groups: group 1 consisted of patients with urinary albumin excretion (UAE) <30 mg/day (n = 69), group 2 had 30 < or = UAE < 300 mg/day (n = 44), group 3 had UAE > or =300 mg/day and serum creatinine <1.5 mg/dl (n = 22), and group 4 had serum creatinine >1.5 mg/dl (n = 20). Intrarenal hemodynamics were studied by duplex Doppler sonography in patients with type 2 diabetes. The ACE and ecNOS gene polymorphisms were examined by polymerase chain reaction. RESULTS: There were no significant differences in sex, BMI, and blood glucose level, but there were differences in HbA(1c) and lipoprotein profiles among the four groups. There were no significant differences in the distribution of ACE genotype or in the frequency of the ecNOS 4a allele among the four groups. Resistive index (RI) values of the interlobar arteries of group 4 were significantly higher than those of groups 1, 2, and 3, whereas the RI values were not significantly different among groups 1, 2, and 3. Multiple regression analysis showed that age, duration of diabetes, systolic and diastolic blood pressure, and creatinine clearance were significantly associated with the increased RI values, but that there was no significant association between RI values and the ecNOS genotype (R(2) = 0.613, P < 0.0001). CONCLUSIONS: These results suggest that intrarenal hemodynamic abnormalities are present as a feature of the progression of nephropathy in type 2 diabetes, and that they are associated with age, duration of diabetes, decreased creatinine clearance, and blood pressure, but not with the genetic factors of the ACE and ecNOS gene polymorphism in nephropathy of type 2 diabetes.