Nonalbuminuric diabetic kidney disease (DKD) has become the prevailing phenotype in patients with type 2 diabetes. However, it remains unclear whether its prognosis is poorer than that of other DKD phenotypes. RESEARCH DESIGN AND METHODSA total of 2,953 Japanese patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) ‡30 mL/min/1.73 m 2 , enrolled in an observational cohort study in 2004, were followed until 2015. On the basis of albuminuria (>30 mg/g creatinine) and reduced eGFR (<60 mL/min/1.73 m 2 ) at baseline, participants were classified into the four DKD phenotypesdno-DKD, albuminuric DKD without reduced eGFR, nonalbuminuric DKD with reduced eGFR, and albuminuric DKD with reduced eGFRdto assess the risks of mortality, cardiovascular disease (CVD), and renal function decline. RESULTSDuring the mean follow-up of 9.7 years, 113 patients died and 263 developed CVD. In nonalbuminuric DKD, the risks of death or CVD were not higher than those in no-DKD (adjusted hazard ratio 1.02 [95% CI 0.66, 1.60]) and the annual decline in eGFR was slower than in other DKD phenotypes. The risks of death or CVD in nonalbuminuric DKD without prior CVD were similar to those in no-DKD without prior CVD, whereas the risks in nonalbuminuric DKD with prior CVD as well as other DKD phenotypes were higher. CONCLUSIONSNonalbuminuric DKD did not have a higher risk of mortality, CVD events, or renal function decline than the other DKD phenotypes. In nonalbuminuric DKD, the presence of macrovascular complications may be a main determinant of prognosis rather than the renal phenotype.

Objective-The association between insulin resistance (IR) and coronary artery calcification (CAC) has been uncertain after adjustment for metabolic syndrome components. We aimed to evaluate whether IR is associated with CAC prevalence or progression independently of metabolic syndrome components. Approach and Results-We conducted a population-based study in a random sample of Japanese men aged 40 to 79 years and determined IR using the homeostasis model assessment of insulin resistance (HOMA-IR).

Aims/Introduction Sodium–glucose cotransporter 2 inhibitors reduce bodyweight (BW) by creating a negative energy balance. Previous reports have suggested that this BW reduction is mainly loss of body fat and that ~20% of the reduction is lean mass. However, the effects of sodium–glucose cotransporter 2 inhibitors on BW and body composition remain unclear. We examined these effects in Japanese patients with type 2 diabetes mellitus treated with insulin. Materials and Methods In this open‐label, randomized controlled trial, 49 overweight patients (body mass index ≥23 kg/m 2 ) with inadequate glycemic control (hemoglobin A1c >7.0%) receiving insulin treatment were randomly assigned to receive add‐on ipragliflozin or no additional treatment (control group). Patients were followed for 24 weeks. The goal for all patients was to achieve glycated hemoglobin <7.0% without hypoglycemia. The primary end‐point was a change in BW from baseline to week 24. Body composition was assessed with dual‐energy X‐ray absorptiometry and bioelectrical impedance analysis. Results BW change was significantly larger in the ipragliflozin group than in the control group (−2.78 vs −0.22 kg, P < 0.0001). Total fat mass was reduced evenly in the arms, lower limbs and trunk in the ipragliflozin group. Total muscle mass and bone mineral content were maintained, but muscle mass in the arms might have been affected by ipragliflozin treatment. Conclusions Ipragliflozin treatment for 24 weeks resulted in reduced BW, mainly from fat mass loss. Muscle mass and bone mineral content were maintained. Further study is necessary to elucidate the long‐term effects of ipragliflozin.

Abstract:In hemodialysis (HD) patients the glycated hemoglobin (HbA1c) level may underestimate glycemic control. The aim of this study is to estimate accurate glycemic control in type 2 diabetic patients on HD. Type 2 diabetes patients (N = 87) who had been receiving maintenance HD for at least one year were enrolled. HbA1c and the percentage of glycated albumin relative to total the serum albumin (%GA) were measured in blood samples and the factors that affected the %GA/HbA1c ratio were examined. There were significant and positive correlations between the plasma glucose and either the HbA1c levels (r = 0.539, P < 0.01) or the %GA level (r = 0.520, P < 0.01). No relationship between the serum albumin levels and %GA levels was observed. A weekly dose of erythropoietin (EPO) was positively correlated with the ratio of %GA/HbA1c and hematocrit (Ht) correlated negatively. There was no significant correlation between the %GA/ HbA1c level and the EPO dose in patients with Ht Ն 30%, although a significant correlation was found between those parameters in the Ht < 30% group. The mean of the %GA/ HbA1c ratios in patients with Ht Ն 30%, with Ht < 30% and treated with EPO < 100 IU/kg/week, and with Ht < 30% and treated with EPO Ն 100 IU/kg/week were 3.41, 3.56 and 4.13, respectively. In HD patients, accurate glycemic control may be estimated as: HbA1c ¥ 1.14 if Ht Ն 30%; HbA1c ¥ 1.19 if Ht < 30% and treated with low dosages of EPO; and HbA1c ¥ 1.38 if Ht < 30% and treated with high dosages of EPO.

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BackgroundSmoking is an overwhelming, but preventable, risk factor for cardiovascular diseases (CVD), although smoking prevalence remains high in developed and developing countries in East Asia.Methods and ResultsIn a population‐based sample of 1019 Japanese men aged 40 to 79 years, without CVD, we examined cross‐sectional associations of smoking status, cumulative pack‐years, daily consumption, and time since cessation, with subclinical atherosclerosis at 4 anatomically distinct vascular beds, including coronary artery calcification, carotid intima‐media thickness (CIMT) and plaque, aortic artery calcification (AoAC), and ankle‐brachial index. Current, former, and never smoking were present in 32.3%, 50.0%, and 17.7%, respectively. Compared to never smokers, current smokers had significantly higher risks of subclinical atherosclerosis in all 4 circulations (eg, odds ratios for coronary artery calcification >0, 1.79 [95% CIs, 1.16–2.79]; CIMT >1.0 mm, 1.88 [1.02–3.47]; AoAC >0, 4.29 [2.30–7.97]; and ankle‐brachial index <1.1, 1.78 [1.16–2.74]) and former smokers did in carotid and aortic circulations (CIMT >1.0 mm, 1.94 [1.13–3.34]; and AoAC >0, 2.55 [1.45–4.49]). Dose–response relationships of pack‐years and daily consumption, particularly with CIMT, carotid plaque, AoAC, and ankle‐brachial index, were observed among both current and former smokers, and even a small amount of pack‐years or daily consumption among current smokers was associated with coronary artery calcification and AoAC, whereas time since cessation among former smokers was linearly associated with lower burdens of all atherosclerotic indices.ConclusionsCigarette smoking was strongly associated with subclinical atherosclerosis in multiple vascular beds in Japanese men, and these associations attenuated with time since cessation.

Studies from Western countries suggest that smokers tend to display greater abdominal obesity than non-smokers, despite showing lower weight. Whether this holds true in a leaner population requires clarification. Using indices of abdominal obesity including visceral adipose tissue, we examined whether lifetime cigarette smoking is associated with unfavorable fat distribution among Japanese men.From 2006 to 2008, we conducted a cross-sectional investigation of a community-based sample of Japanese men at 40–64 years old, free of cardiovascular diseases and cancer. Areas of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated using computed tomography. We divided participants into four groups: never-smokers; and tertiles of pack-years of smoking among ever-smokers. Using multivariable linear regression, we calculated adjusted means of obesity indices (VAT, SAT, VAT-SAT ratio [VSR], and waist-hip ratio [WHR]) for each group, and mean differences between consecutive groups.We analyzed 513 men (median age, 58.2 years; current smokers, 40.1%). Two-thirds showed body mass index (BMI) < 25 kg/m2 (median, 23.5 kg/m2). Overall, greater lifetime smoking group was associated with greater WHR and VSR. On average, one higher smoking group was associated with 0.005 higher WHR (95% CI, 0.001–0.008; P = 0.005) and 0.041 greater VSR (95% CI, 0.009–0.073; P = 0.012) after adjustment for potential confounders, including BMI. In this sample of relatively lean Japanese men, greater lifetime smoking was associated with a metabolically more adverse fat distribution. Although smoking is commonly associated with lower BMI, minimizing the amount of lifetime smoking should be advocated.

Aim: Although renal dysfunction has been identified as a novel risk factor affecting stroke prognosis, few have analyzed the association within large-scale population-based setting, using wide-range estimated glomerular filtration rate (eGFR) category. We aimed to determine the association of admission eGFR with acute stroke outcomes using data from a registry established in Shiga Prefecture, Japan.Methods: Following exclusion of patients younger than 18 years, with missing serum creatinine data, and with onset more than 7 days prior to admission, 2,813 acute stroke patients registered in the Shiga Stroke Registry year 2011 were included in the final analysis. The Japanese Society of Nephrology equation was used to estimate GFR. Multivariable logistic regression was performed to analyze the association of eGFR with all-cause in-hospital death (modified Rankin Scale [mRS] 6), and atdischarge death/disability (mRS 2–6). Separate analyses were conducted within stroke subtypes.Results: Compared to eGFR 60–89 mL/min/1.73 m2, adjusted odds ratios (ORs) and 95% confidence interval [95% CI] for in-hospital death (in the order of eGFR < 45, 45–59, and ≥ 90 mL/min/1.73 m2) were 1.54 [1.04–2.27], 1.07 [0.72–1.58], and 1.04 [0.67–1.59]. Likewise, adjusted ORs [95% CI] for at-discharge death/disability were 1.54 [1.02–2.32], 0.97 [0.73–1.31], and 1.48 [1.06–2.05]. Similar pattern was further evident in the eGFR < 45 mL/min/1.73 m2 group for both outcomes within acute ischemic stroke patients.Conclusions: Our study has ascertained that in acute stroke, particularly ischemic stroke, low eGFR was significantly associated with in-hospital death and at-discharge death/disability. Additionally, high eGFR was found to be associated with at-discharge death/disability.