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Aim: Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear., Materials and Methods: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease)., Results: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (β = -0.609, p = .039; β = -2.298, p < .001; β = -0.936, p = .048; β = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001)., Conclusions: The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes., (© 2024 John Wiley & Sons Ltd.)

Background: This study investigated the sex differences in the risk of end-stage kidney disease (ESKD) and mortality, as well as the effect modification of sex on associated factors in patients with type 2 diabetes., Methods: This multicenter observational cohort study included 4328 patients with type 2 diabetes. Hazard ratios (HRs) with 95% confidence intervals (CIs) of sex for ESKD and death were estimated using Cox proportional regression with adjustment for baseline covariates. For assessing risk modification, HRs and incidence rates for ESKD and death were compared between sexes across patient characteristics using Cox proportional and Poisson regression models., Results: During a median follow-up of 7 years, 276 patients (70% men) developed ESKD, and 241 patients (68% men) died. Men had higher risks of ESKD (HR 1.34; 95% CI 1.02-1.75; p = .034) and death (HR 1.64; 95% CI 1.24-2.16; p = .001) versus women after adjusting for multiple covariates. Among patients with microalbuminuria, men had a substantially higher risk of ESKD versus women, compared to those with normo- and macroalbuminuria (p for interaction .04). Incidence rates were also increased in men versus women with albuminuria of around 300 mg/g. No differences were detected in the association of sex and death across baseline patient subgroups., Conclusions: In type 2 diabetes, men had an increased risk of ESKD and death versus women. Moderately increased albuminuria was strongly associated with sex difference in developing ESKD., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Few studies have examined the effect of immediate breast reconstruction (IBR) on the overall progression of breast cancer therapy. This study examins the effect of IBR on the breast cancer therapy. 142 patients underwent mastectomy in our department (With IBR group, n = 17; Without IBR group, n = 125). We examined the number of days from diagnosis to surgery, operation time, length of postoperative stay, number of days from surgery to postoperative therapy, and complications in patients with or without breast reconstruction and by type of reconstruction. In the IBR group, the operation time was longer (P < 0.001), postoperative hospital stay was longer when adjusted for multivariate analysis (P = 0.008), and complications were significantly more common (P < 0.001), but there was no significant difference when limited to grade ≥3 complications. There was no difference until the start of postoperative treatment. The results reveal that IBR requires coordination between the surgical and operating room staff, and does not affect the transition to postoperative treatment but does affect an increased incidence of minor complications and length of postoperative stay.

In radiological examinations of patients, we often take stacked images and three-dimensional (3D) images of human bone radiological images such as X-ray images and CT images. In general, learning of bone structure using specialized anatomy books is currently performed at medical radiological technologist education facilities. In the anatomy education of the medical school, in order to understand the structure of human and the individual bone shapes in detail, a real human bone specimen is used to gain knowledge of skeleton, bone shape, bone name and bone function. But it is actually difficult for a radiological technologist to obtain such learning opportunities. Therefore, we had to depend on two-dimensional information from an anatomical atlas so far. Therefore, as a method to solve this, we devised this stereo-paired bone anatomical chart by stereoscopic photography of a real human bone specimen that is available only in the anatomy laboratory. In classical anatomy textbooks, there are no figures that enable us to view 3D structures of human bones. Our stereo-paired bone anatomical charts make it possible to observe accurate bone structures three-dimensionally. In addition, we saved the data as a PDF file and uploaded to an internet server so that we can freely download and readily observe 3D images of human bones at all times and all places with a tablet or a PC monitor.

Background: According to studies by the National Kidney Foundation and Food and Drug Administration, 30% and 40% declines in estimated glomerular filtration rate (eGFR) could be used as surrogate endpoints of end-stage renal disease (ESRD). However, the benefits of using these endpoints in diabetic patients remain unclear., Methods: This cohort study comprised Japanese patients with type 2 diabetes; those with repeated serum creatinine measurements during a baseline period of 2 years (n = 1868) or 3 years (n = 2001) were enrolled. Subsequent risks of ESRD following eGFR declines were assessed., Results: In the 2-year baseline analysis, the cumulative prevalence of -20%, -30%, -40%, and -53% changes in eGFR were 23.9%, 11.1%, 6.8%, and 3.7%, respectively. There were 133 cases (7.1%) of subsequent ESRD during a median follow-up period of 6.5 years. In the 3-year baseline analysis, the corresponding proportions were 28.1%, 14.0%, 7.7%, and 3.9%, respectively, with 110 participants (5.5%) reaching ESRD during a median follow-up period of 5.5 years. The adjusted hazard ratios of subsequent ESRD following -53%, -40%, -30%, and -20% changes in eGFR during the 2-year baseline period were 22.9 (11.1-47.3), 12.8 (6.9-23.7), 8.2 (4.3-15.5), and 3.9 (2.2-7.0), respectively when compared with the no changes in eGFR. In the 3-year baseline analysis, the corresponding risks were 29.7 (10.8-81.9), 18.4 (7.6-44.7), 12.8 (5.2-32.2), and 5.4 (2.3-12.8), respectively. In the subgroup analysis, similar trends were observed in patients with macroalbuminuria at baseline., Conclusions: Declines in eGFR were strongly associated with subsequent risk of ESRD in Japanese type 2 diabetic patients. In addition to 30% and 40% declines, a 20% decline in eGFR over 2 years could be considered as a candidate surrogate endpoint of ESRD in diabetic kidney disease., Competing Interests: Takashi Wada was supported by Grant-in-Aids for Diabetic Nephropathy Research and for Diabetic Nephropathy and Nephrosclerosis Research, from the Ministry of Health, Labour and Welfare of Japan (https://www.mhlw.go.jp) and by the Ministry of Education, Science, Sports and Culture, Japan (http://www.mext.go.jp) under Grant Number 201121003B, 201413001B, and 24406028. He was also supported by Japan Agency for Medical Research and Development (AMED) under Grant Number JP17ek0310003 (https://www.amed.go.jp). Hirofumi Makino is a consultant for AbbVie, Astellas, and Teijin, receives speaker honoraria from Astellas, MSD, Takeda, and Tanabe Mitsubishi, and receives grant support from Astellas, Daiichi Sankyo, Dainippon Sumitomo, MSD, Novo Nodisk, and Takeda. These do not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Hypoxia causes proximal tubular cell damage in diabetes, even though proximal tubular cells have an adaptive system to combat hypoxia involving induction of hypoxia factor-1 (HIF-1) and inhibition of mechanistic target of rapamycin complex 1 (mTORC1). Here, we examined the interference effect of altered glucose and lipid metabolism on the hypoxia responses in proximal tubular cells. In culture, hypoxia alone induced HIF-1 and inhibited mTORC1, preventing death in proximal tubular cells. However, hypoxia with high glucose and palmitate increased mTORC1 activity and promoted apoptosis in proximal tubular cells, which was inhibited by pharmacological and genetic inactivation of mTORC1. Since inhibition of all mTORC1's physiological functions regulated by growth factors including insulin causes various adverse effects, we screened for a microRNA that can inhibit only pro-apoptotic effects of mTORC1 to discover a safe therapeutic target. This screen found microRNA-148b-3p was able to specifically inhibit mTORC1-dependent apoptosis in hypoxic proximal tubular cells exposed to high glucose and palmitate, without affecting insulin-dependent mTORC1 activation. Furthermore, tumor necrosis factor receptor (TNFR) 2 was the target of microRNA-148b-3p and its suppression inhibited apoptosis. Finally, enhanced apoptosis with TNFR2 overexpression was found in hypoxic and mTORC1-activated proximal tubular cells in diabetic rats. Thus, diabetes activated mTORC1 even in hypoxic proximal tubular cells, leading to apoptosis by reducing microRNA-148b-3p expression. Modulating this pathogenic pathway may be a novel therapy for proximal tubular cell damage in diabetes., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: A recent genome-wide association study for diabetic nephropathy in European type 1 diabetes identified 3 candidate loci for diabetic nephropathy. In this study, we examined the association of the 3 single nucleotide polymorphism (SNP) loci with susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes., Methods: We genotyped 3 SNPs, rs7583877 in AFF3, rs12437854 in the RGMA-MCTP2 locus and rs7588550 in ERBB4, for 2,300 Japanese patients with type 2 diabetes [initial study, 1,055 nephropathy cases with overt proteinuria or with end-stage renal disease (ESRD) and 1,245 control patients with normoalbuminuria]. The association of these SNPs with diabetic nephropathy was examined by using a logistic regression analysis., Results: We observed a significant association of rs7588550 in ERBB4 with diabetic nephropathy in the Japanese patients with type 2 diabetes, although the effect direction was not consistent with that in the European study [p = 0.0126, odds ratio (OR) = 0.79, 95 % confidence interval (CI): 0.65-0.95]. We further examined the association of rs7588550 with diabetic nephropathy in an independent Japanese cohort (596 nephropathy cases and 311 controls) and observed the same trend of the association with the initial study. We did not observe any association of the remaining 2 SNP loci with diabetic nephropathy in the present Japanese sample., Conclusion: The association of SNP loci derived from GWAS in European type 1 diabetes with diabetic nephropathy was not replicated in the Japanese patients with type 2 diabetes, although the ERBB4 locus may have some effect also in Japanese type 2 diabetes.

Dumping syndrome, or rapid gastric emptying, is a frequent complication after gastric surgery. In this case, the patient was a 47-year-old woman who 10 years previously had undergone distal gastrectomy with Billroth I reconstruction for early-stage gastric cancer. She presented with symptoms of weakness, headache, palpitation, sweating, dizziness and significant fatigue between one and two hours after a meal. Because a 75 g oral glucose tolerance test (75 g-OGTT) induced both acute postprandial tachycardia (within 1 hour) and postprandial hypoglycemia, we diagnosed this patient with early and late dumping syndrome. Dietary measures and acarbose improved symptoms of late dumping syndrome but did not prevent the symptoms of early dumping syndrome such as postprandial tachycardia, weakness, headache, palpitation, and dizziness. We therefore used the somatostatin analogue octreotide, which has been reported as an effective therapy for early dumping syndrome. Octreotide prevented the symptoms of early dumping syndrome, especially postprandial tachycardia, but caused postprandial hyperglycemia. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were completely suppressed during the 75 g-OGTT following subcutaneous injection of octreotide. No change was observed in vasoactive intestinal polypeptide (VIP), which is the gastrointestinal peptide hormone generally responsible for early dumping syndrome, suggesting possible contribution of incretins in early dumping syndrome of this patient.

Objective: Epidemiological and family studies have demonstrated that susceptibility genes play an important role in the etiology of diabetic nephropathy, defined as persistent proteinuria or end-stage renal disease (ESRD) in type 1 diabetes., Research Design and Methods: To efficiently search for genomic regions harboring diabetic nephropathy genes, we conducted a scan using 5,382 informative single nucleotide polymorphisms on 100 sibpairs concordant for type 1 diabetes but discordant for diabetic nephropathy. In addition to being powerful for detecting linkage to diabetic nephropathy, this design allows linkage analysis on type 1 diabetes via traditional affected sibpair (ASP) analysis. In weighing the evidence for linkage, we considered maximum logarithm of odds score (maximum likelihood score [MLS]) values and corresponding allelic sharing patterns, calculated and viewed graphically using the software package SPLAT., Results: Our primary finding for diabetic nephropathy, broadly defined, is on chromosome 19q (MLS = 3.1), and a secondary peak exists on chromosome 2q (MLS = 2.1). Stratification of discordant sibpairs based on whether disease had progressed to ESRD suggested four tertiary peaks on chromosome 1q (ESRD only), chromosome 20p (proteinuria only), and chromosome 3q (two loci 58 cm apart, one for ESRD only and another for proteinuria only). Additionally, analysis of 130 ASPs for type 1 diabetes confirmed the linkage to the HLA region on chromosome 6p (MLS = 9.2) and IDDM15 on chromosome 6q (MLS = 3.1)., Conclusions: This study identified several novel loci as candidates for diabetic nephropathy, none of which appear to be the sole genetic determinant of diabetic nephropathy in type 1 diabetes. In addition, this study confirms two previously reported type 1 diabetes loci.