A Case of Type 1 Diabetes Mellitus with Diabetic Ketoacidosis Presenting with Transient Severe Fatty Liver and Subsequent Liver Dysfunction.

Patients often present with severe fatty liver (FL) due to insulin deficiency at the onset of diabetic ketoacidosis (DKA). On the other hand, glycogenic hepatopathy (GH) is a possible cause of liver dysfunction in patients with DKA. We herein report a case of type 1 diabetes mellitus with severe FL at the onset of DKA, who demonstrated subsequent marked liver dysfunction after achieving an improvement of FL. As liver dysfunction persisted even after the FL improved, GH was suspected to be the cause of liver dysfunction. FL and GH have different prognoses and should therefore be differentiated using imaging studies and biopsies.

Effectiveness of DialBetesPlus, a self-management support system for diabetic kidney disease: Randomized controlled trial.

We evaluated the effectiveness of a mobile health (mHealth) intervention for diabetic kidney disease patients by conducting a 12-month randomized controlled trial among 126 type 2 diabetes mellitus patients with moderately increased albuminuria (urinary albumin-to-creatinine ratio (UACR): 30-299 mg/g creatinine) recruited from eight clinical sites in Japan. Using a Theory of Planned Behavior (TPB) behavior change theory framework, the intervention provides patients detailed information in order to improve patient control over exercise and dietary behaviors. In addition to standard care, the intervention group received DialBetesPlus, a self-management support system allowing patients to monitor exercise, blood glucose, diet, blood pressure, and body weight via a smartphone application. The primary outcome, change in UACR after 12 months (used as a surrogate measure of renal function), was 28.8% better than the control group's change (P = 0.029). Secondary outcomes also improved in the intervention group, including a 0.32-point better change in HbA1c percentage (P = 0.041). These improvements persisted when models were adjusted to account for the impacts of coadministration of drugs targeting albuminuria (GLP-1 receptor agonists, SGLT-2 inhibitors, ACE inhibitors, and ARBs) (UACR: -32.3% [95% CI: -49.2%, -9.8%] between-group difference in change, P = 0.008). Exploratory multivariate regression analysis suggests that the improvements were primarily due to levels of exercise. This is the first trial to show that a lifestyle intervention via mHealth achieved a clinically-significant improvement in moderately increased albuminuria.

Effects of hybrid closed-loop system on glycemic control and psychological aspects in persons with type 1 diabetes treated with sensor-augmented pump: A prospective single-center observational study.

AIMS/INTRODUCTION: This study evaluated the effects of the Medtronic MiniMed 770G hybrid closed-loop system on glycemic control and psychological aspects in persons with type 1 diabetes mellitus. MATERIALS AND METHODS: This 3-month prospective observational study included 22 participants with type 1 diabetes mellitus who used the Medtronic MiniMed 640G predictive low-glucose suspend system and were switched to the 770G system. Time in the range of 70-180 mg/dL and glycated hemoglobin levels were evaluated; satisfaction, emotional distress and quality of life were assessed using self-reported questionnaires, including the Diabetes Treatment Satisfaction Questionnaire Status, Problem Area in Diabetes and Diabetes Therapy-Related Quality of Life. RESULTS: Time in the range of 70-180 mg/dL increased (63.5 ± 13.4 to 73.0 ± 10.9% [mean ± standard deviation], P = 0.0010), and time above the range of 181-250 mg/dL decreased (26.9 ± 8.9 to 19.6 ± 7.1%, P < 0.0005). Glycated hemoglobin levels decreased (7.7 ± 1.0 to 7.2 ± 0.8%, P = 0.0021). The percentage of participants with time below the range of 54-69 mg/dL <4% of readings increased from 91% to 100% (P < 0.0005). No significant changes were detected in the satisfaction, emotional distress and quality of life levels, but increased sensor calibration might be related to worsened emotional distress and quality of life. CONCLUSIONS: The hybrid closed-loop system decreased hyperglycemia and minimized hypoglycemia, but did not improve psychological aspects compared with the predictive low-glucose suspend system, probably because sensor calibration was increased.

Sleep duration and food intake in people with type 2 diabetes mellitus and factors affecting confectionery intake.

AIMS/INTRODUCTION: We carried out a cross-sectional study of people with type 2 diabetes mellitus to elucidate the association between sleep duration and food intake. MATERIALS AND METHODS: Overall, 2,887 participants with type 2 diabetes mellitus (mean age 63.0 years; 61.1% men; mean glycated hemoglobin level 7.5%) were included in this study. The participants' self-reported dietary habits and sleep duration were evaluated using a brief self-administered dietary history questionnaire and Pittsburgh Sleep Quality Index, respectively. The participants were categorized into the following four groups based on sleep duration: <6, 6-6.9, 7-7.9 (reference) and ≥8 h. RESULTS: No significant differences were observed between the groups regarding energy intake (kcal/day), absolute intake (g/day) or relative intake (% energy) of carbohydrates, total fat, proteins and fibers. However, confectionery intake was higher in the <6 h group and lower in the ≥8 h group than in the reference group after adjustment for confounding factors. In multivariate analysis, sleep durations <6 h and ≥8 h significantly correlated with increased (95% confidence interval 0.55 to 3.6; P = 0.0078) and decreased (95% confidence interval -4.0 to -0.32; P = 0.021) confectionery intake, respectively. Confectionery intake was positively correlated with female sex, glycated hemoglobin level and dyslipidemia, whereas it was negatively correlated with alcohol consumption and current smoking status. CONCLUSIONS: Short sleep duration is associated with high confectionery intake in people with type 2 diabetes mellitus; this might disturb their glycemic control. Therefore, short sleepers with type 2 diabetes mellitus could improve their glycemic control by avoiding confectionery intake and maintaining adequate sleep duration.

Association of continuous positive airway pressure therapy on cardiac hypertrophy in patients with sleep apnea comorbid with type 2 diabetes mellitus.

Previous reports indicated the therapeutic effect of chronic continuous positive airway pressure (CPAP) therapy on cardiac hypertrophy due to sleep apnea syndrome. However, little is known for cases involving diabetic complications. This retrospective observational study examined the effects of CPAP therapy on left ventricular hypertrophy (LVH) in patients with obstructive sleep apnea syndrome (OSAS) and type 2 diabetes mellitus (T2DM). For all cases, the observation period was 3 years from the time when the patient was introduced to CPAP therapy. Overall, 123 patients were divided into a good CPAP group (CPAP ≥4 h/day, n = 63) and non-adherence group (CPAP <4 h/day, n = 60). The mean CPAP usage times were 5.58 ± 1.23 and 1.03 ± 1.17 h/day in the good CPAP and non-adherence groups, respectively. Regression tendencies of the thickness of the left ventricular posterior (-0.30 ± 1.19 mm) and interventricular septal walls (-0.48 ± 1.22 mm) were observed in the good CPAP group. Hypertrophic tendencies of the left ventricular posterior wall (+0.59 ± 1.44 mm) and interventricular septal wall thickness (+0.59 ± 1.43) were observed in the non-adherence group. Left ventricular posterior wall thickness (coefficient: -0.254, p = 0.0376) and interventricular septal wall thickness (coefficient: -0.426, p = 0.0006) were more likely to be greater in the non-adherence group than in the good CPAP group. Patients in the non-adherence group with an apnea hypopnea index ≥30 had increased left ventricular posterior wall thickness (coefficient: -0.263, p = 0.0673) and interventricular septal wall thickness (coefficient: -0.450, p = 0.0011). In conclusion, appropriate CPAP therapy is an effective treatment for LVH in patients with T2DM and OSAS, especially for severe cases.

The METRO study: a retrospective analysis of the efficacy of metformin for type 2 diabetes in Japan.

Metformin monotherapy as first-line treatment for patients with type 2 diabetes (T2D) has been shown to effectively improve blood glucose levels and motivation to undergo treatment and prevent complications. However, no studies have reported its effect when combined with other drugs or compared the effect based on administration time. This study aimed to investigate the effect of metformin administration in Japanese patients with T2D, examine how the introduction line impacts the effect of metformin, and examine the characteristics of patients demonstrating improved blood glucose levels. Data on characteristics of patients who were newly prescribed metformin with no shifting of hypoglycemic agents in the subsequent 24-week observation period, and their age [mean, 56.8 years], body mass index [mean, 27.5 kg/m2], glycated hemoglobin [HbA1c] [mean, 8.1%], and duration of diabetes [mean, 3.0 years] were obtained from the medical records of 201 patients. The changes in HbA1c by introduction line after 24 weeks were -1.59%, -0.91%, -0.89%, and -0.65% in the first, second, third, and fourth induction lines, respectively; earlier introduction more significantly improved blood glucose. The factors significantly associated with HbA1c changes were early introduction, high baseline HbA1c, high estimated glomerular filtration rate, decreased insulin secretion, short estimated duration of diabetes, and increased metformin dose. Furthermore, factors contributing to the largest HbA1c improvement by metformin were high baseline HbA1c and early administration. Metformin is expected to lower blood glucose levels in Japanese patients with T2D, even in those with decreased insulin secretion, due to its early introduction as a first-line drug.

Diagnostic accuracy of home sleep apnea testing using peripheral arterial tonometry for sleep apnea: A systematic review and meta-analysis.

This study aimed to evaluate the diagnostic accuracy of home sleep apnea testing using peripheral arterial tonometry for sleep apnea as an alternative to polysomnography. We conducted a systematic review and meta-analysis of observational studies, randomized controlled trials, and diagnostic case-control studies examining the diagnostic accuracy of peripheral arterial tonometry by searching the CENTRAL, MEDLINE, EMBASE, ICTRP and ClinicalTrials.gov databases on 5 October 2021. We assessed the risk of bias of the included studies using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A bivariate random-effects model was generated to derive the summary point estimates of sensitivity and specificity with 95% confidence intervals at different apnea-hypopnea index cutoffs. This meta-analysis included 13 studies (1227 participants, median prevalence of sleep apnea with apnea-hypopnea index ≥ 5 events per hr: 85%). The risk of bias in the included studies was low to moderate. The pooled sensitivity and specificity estimates were 96% (95% confidence interval: 93%-97%) and 44% (95% confidence interval: 32%-56%) at apnea-hypopnea index ≥ 5 events per hr, 88% (85%-91%) and 74% (63%-83%) at apnea-hypopnea index ≧ 15 events per hr, and 80% (66%-89%) and 90% (83%-95%) at apnea-hypopnea index ≧ 30 events per hr, respectively. Peripheral arterial tonometry resulted in a significant number of false negatives and false positives at any apnea-hypopnea index cutoff when applied to the median prevalence setting of the included studies. The inadequate sensitivity and specificity of peripheral arterial tonometry render it an unsuitable alternative to polysomnography for detecting sleep apnea for apnea-hypopnea index ≧ 5, 15 and 30 events per hr.

Comparing the course and delivery outcomes of Japanese twin pregnancies with and without gestational diabetes mellitus: a single-center retrospective analysis.

Singleton pregnant women with gestational diabetes mellitus (GDM) are at an increased risk of adverse maternal and neonatal outcomes. Multiple pregnancies are associated with increased risks of perinatal complications; however, the impact of GDM on maternal and neonatal outcomes in multiple pregnancies is unknown, and there are currently few reports on GDM status in twin pregnancies. This study aimed to compare the background and perinatal outcomes between Japanese twin pregnancies with and without GDM at a perinatal center in Japan. Additionally, the clinical course of GDM was investigated. In this retrospective cohort study, women with twin pregnancies underwent GDM screening at Yokohama City University Medical Center from January 2011 to December 2016. Overall, 307 twin pregnancies were divided into GDM (47 cases, 15.3%) and non-GDM (260 cases, 84.7%) groups. GDM-associated pregnancy complications, GDM status, and pregnancy outcomes were ascertained. Women with GDM were older and had a higher pre-pregnancy body mass index than those without GDM. Glycemic control was good in all patients, and there was no difference in delivery outcomes between the two groups. Gestational weight gain was lower in pregnant women with GDM (+8.0 kg) than in those without GDM (+11.8 kg), suggesting the impact of strict nutritional guidance on twin pregnancies with GDM. In conclusion, twin pregnancies with GDM did not have different delivery outcomes compared to those without GDM. To manage twin pregnancies with GDM, this study suggests that it is important to monitor patients' weight and blood glucose levels.

Recurrent Subacute Thyroiditis in a Patient With Human Leukocyte Antigen-associated Predisposition to Graves Disease.

Background: Subacute thyroiditis (SAT) followed by Graves disease (GD) is a rare condition. We report the case of a patient with recurrent SAT with human leukocyte antigen (HLA)-associated predisposition to GD. Case Report: A 28-year-old Japanese woman presented with neck pain and hyperthyroidism symptoms. We observed elevated C-reactive protein and thyroid hormone levels, along with a high erythrocyte sedimentation rate. Further, anti-thyroid-stimulating hormone receptor antibody was undetected, and thyroid glands were heterogeneous and hypoechoic. These findings confirmed a diagnosis of SAT. The patient was treated with prednisone (starting dose, 30 mg), and clinical and laboratory data suggested an improvement. Six months later, the patient presented with recurrent clinical and biochemical features of hyperthyroidism (thyroid-stimulating hormone level, 0.003 mIU/mL; free thyroxine level, 3.14 ng/dL; and TSH receptor-stimulating autoantibodies, 220%). The patient was diagnosed with GD and was successfully treated with methimazole. Eleven years later, the patient was diagnosed with simultaneous SAT and GD. HLA-typing revealed that the patient possessed characteristic alleles associated with susceptibility to GD, such as HLA-DRB1∗04:03 and ∗15:01, DQB1∗03:02:01 and 06:02:01, and HLA DPB1∗05:01 alleles. Discussion: The occurrence of SAT may trigger thyroid antigen release and lead to the onset of GD in patients who are genetically predisposed to this autoimmune disorder. Conclusion: For certain patients, the diagnosis of GD should be considered in case of recurrent hyperthyroidism and history of resolved SAT.

Angiogenesis and Anastomosis on Graft Retina after Autologous Retinal Transplantation.

Anastomosis on graft retina was studied after autologous retinal transplantation (ART) on 26 eyes with primary and refractory macular holes. Angiogenesis and anastomosis were seen in 35% of the eyes with successful ART, likely contributing to the survival of the transplanted retina.

Efficacy of education on injection technique for patients diagnosed with diabetes with lipohypertrophy: systematic review and meta-analysis.

OBJECTIVES: This study aimed to investigate the efficacy of providing education on injection technique to patients with diabetes with lipohypertrophy (LH). DESIGN: We conducted a systematic review and meta-analysis. METHODS: We included patients with diabetes who use insulin and have LH, and excluded patients without LH. We performed a literature search on CENTRAL, MEDLINE, EMBASE, ICTRP and ClinicalTrials.gov in November 2021 for randomised controlled trials (RCTs). We used the revised Cochrane Risk of Bias 2 tool to evaluate the risk of bias in each outcome in each study. We then pooled the data using a random-effects model and evaluated the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. OUTCOME MEASURES: The primary endpoints were change in total daily dose (TDD) of insulin, change in HbA1c levels and prevalence of hypoglycaemia. RESULTS: We screened 580 records and included three RCTs (637 participants) in the meta-analysis. Education on injection technique may slightly increase the change of TDD of insulin (three studies, 637 participants: mean difference (MD) -6.26; 95% CI -9.42 to -3.10; p<0.001; I2=38%; low certainty of evidence) and may have little to no effect on change in HbA1c but the evidence is very uncertain compared with that in the control group (three studies, 637 participants: MD -0.59; 95% CI -1.71 to 0.54; p=0.31; I2=98%; very low certainty of evidence). Providing education about injection technique may have little to no effect on the prevalence of hypoglycaemia (three studies, 637 participants: risk ratio 0.44; 95% CI 0.06 to 3.13; p=0.41; I2=90%; very low certainty of evidence). CONCLUSIONS: The present meta-analysis suggests that injection technique education may result in a slight reduction in the TDD of insulin. However, the effect of education on HbA1c, hypoglycaemia and cured LH is uncertain. PROTOCOL REGISTRATION: DOI: dx.doi.org/10.17504/protocols.io.btiinkce.

A cross-sectional study of the relationship between quality of life and sleep quality in Japanese patients with type 1 diabetes mellitus.

This study aimed to reveal the relationship between quality of life (QOL) and sleep quality in patients with type 1 diabetes mellitus (T1DM). Overall, 202 patients with T1DM were registered in our study, and 192 were eligible for analysis. Baseline characteristics and laboratory values were determined. Patients completed the Japanese versions of the Pittsburgh Sleep Quality Index (PSQI) and Diabetes Therapy-Related QOL (DTR-QOL) questionnaires. We investigated the relationship between the global PSQI and DTR-QOL total scores by using linear regression analysis. In univariate regression analysis, DTR-QOL total scores were associated with body mass index, alcohol consumption, hypertension, hemoglobin A1c (HbA1c), and global PSQI score (all p-value <0.05) but not with sleep duration. When the association between PSQI subscales and DTR-QOL total scores was examined, DTR-QOL total scores were significantly related to subjective sleep quality and daytime dysfunction. In a multivariate regression analysis, the global PSQI score was negatively related to DTR-QOL total scores. Patients with an HbA1c concentration ≥8.0% had significantly lower DTR-QOL total scores. We revealed a relationship between QOL and sleep quality in T1DM patients and showed that the relationship between QOL and PSQI subscales in T1DM patients may be different from that in patients with type 2 diabetes mellitus. Assessing and managing sleep quality may be necessary for patients with diabetes to improve QOL.

Associations of impaired glucose tolerance and sleep disorders with mortality among the US general population.

INTRODUCTION: Sleep disorders and short sleep duration are common symptoms among people with diabetes. However, the evidence is limited about the associations of post-challenge hyperglycemia and sleep quality or quantity with all-cause mortality in the US general population. RESEARCH DESIGN AND METHODS: Our study included 8795 adults from the National Health and Nutrition Examination Survey 2005-2014. Mortality data were ascertained through 2015. Multivariable Cox proportional-hazards models were used to estimate adjusted HRs (aHRs) for all-cause mortality according to 2-hour plasma glucose levels during the 75 g oral glucose tolerance test-normal glucose tolerance (NGT), <140 mg/dL; impaired glucose tolerance (IGT), 140-199 mg/dL; and diabetes, ≥200 mg/dL. We then examined the associations of glucose tolerance status and self-reported physician-diagnosed sleep disorders (yes vs no) or sleep duration (<7 vs ≥7 hours) with all-cause mortality. RESULTS: During follow-up (median, 5.6 years), the diabetes group had a higher risk of all-cause mortality compared with the NGT group (aHR (95% CI)=1.93 (1.41 to 2.64)), but not the IGT group (aHR (95% CI)=1.19 (0.90 to 1.59)). When we categorized participants according to glucose tolerance status and sleep disorders, the IGT group with sleep disorders had a higher risk of all-cause mortality (aHR (95% CI)=2.03 (1.24 to 3.34)) compared with the NGT group without sleep disorders. Both diabetes groups with and without sleep disorders also showed high mortality risks. The results were consistent when we used sleep duration instead of sleep disorders. CONCLUSIONS: Using the most updated US national data, we found a high risk of all-cause mortality among individuals with IGT having sleep disorders or short sleep duration as well as those with diabetes. Future investigations are needed to identify whether and what kind of sleep management is beneficial for people with impaired glucose metabolism to prevent early death.

Efficacy of the Self-management Support System DialBetesPlus for Diabetic Kidney Disease: Protocol for a Randomized Controlled Trial.

BACKGROUND: Diabetic kidney disease (DKD) is one of the main complications of type 2 diabetes mellitus (T2DM). DKD is a known risk factor for end-stage renal disease, cardiovascular disease, and all-cause death. Effective intervention for early-stage DKD is vital to slowing down the progression of kidney disease and improve prognoses. Mobile health (mHealth) is reportedly effective in supporting patients' self-care and improving glycemic control, but the impact of mHealth on DKD has yet to be shown. OBJECTIVE: The purpose of this study is to evaluate the efficacy of standard therapy with the addition of a self-management support system, DialBetesPlus, in patients with DKD and microalbuminuria. METHODS: This study is a prospective, randomized, open-label, multicenter clinical trial. The target population consists of 160 patients diagnosed with T2DM accompanied by microalbuminuria. We randomly assigned the patients to 2 groups-the intervention group using DialBetesPlus in addition to conventional therapy and the control group using conventional therapy alone. DialBetesPlus is a smartphone application that supports patients' self-management of T2DM. The study period was 12 months, with a follow-up survey at 18 months. The primary outcome was a change in albuminuria levels at 12 months. Secondary outcomes included changes in physical parameters, blood test results (glycemic control, renal function, and lipid metabolism), lifestyle habits, self-management scores, medication therapy, and quality of life. RESULTS: The study was approved in April 2018. We began recruiting patients in July 2018 and completed recruiting in August 2019. The final 18-month follow-up was conducted in March 2021. We recruited 159 patients and randomly allocated 70 into the intervention group and 61 into the control group, with 28 exclusions due to withdrawal of consent, refusal to continue, or ineligibility. The first results are expected to be available in 2021. CONCLUSIONS: This is the first randomized controlled trial assessing the efficacy of mHealth on early-stage DKD. We expect that albuminuria levels will decrease significantly in the intervention group due to improved glycemic control with ameliorated self-care behaviors. TRIAL REGISTRATION: UMIN-CTR UMIN000033261; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000037924. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31061.

Association between ANGPTL3, 4, and 8 and lipid and glucose metabolism markers in patients with diabetes.

Lipid management, especially with respect to triglyceride (TG) metabolism, in patients with diabetes is not sufficient with current therapeutic agents, and new approaches for improvement are needed. Members of the angiopoietin-like protein (ANGPTL) family, specifically ANGPTL3, 4, and 8, have been reported as factors that inhibit lipoprotein lipase (LPL) activity and affect TGs. The present study investigated the association between lipid and glucose metabolism markers and the mechanism by which these proteins affect lipid metabolism. A total of 84 patients hospitalized for diabetes treatment were evaluated. Lipid and glucose metabolism markers in blood samples collected before breakfast, on the day after hospitalization, were analyzed. ANGPTL8 showed a significant positive correlation with TG values. HDL-C values displayed a significant positive correlation with ANGPTL3 but a negative correlation with ANGPTL4 and ANGPTL8. The results did not indicate a significant correlation among ANGPTL3, 4, and 8 levels. Thus, it is possible that the distribution of these proteins differs among patients. When patients were divided into groups according to the levels of ANGPTL3 and ANGPTL8, those with high levels of both ANGPTL3 and ANGPTL8 also had high levels of TG and small dense LDL-C/LDL-C (%). Multiple regression analysis indicated that low LPL, high ApoC2, high ApoC3, high ApoE, and high ANGPTL8 levels were the determinants of fasting hypertriglyceridemia. By contrast, no clear association was observed between any of the ANGPTLs and glucose metabolism markers, but ANGPTL8 levels were positively correlated with the levels of HOMA2-IR and BMI. Patients with high levels of both ANGPTL3 and ANGPTL8 had the worst lipid profiles. Among ANGPTL3, 4, and 8, ANGPTL8 is more important as a factor determining plasma TG levels. We anticipate that the results of this research will facilitate potential treatments targeting ANGPTL8 in patients with diabetes.

Assessment of the accuracy of an intermittent-scanning continuous glucose monitoring device in patients with type 2 diabetes mellitus undergoing hemodialysis (AIDT2H) study.

FreeStyle Libre has been approved for use in patients undergoing hemodialysis (HD) in Japan, unlike Europe and the United States; however, evidence regarding its accuracy in such patients is sparse. Forty-one participants with type 2 diabetes undergoing HD were recruited. The overall mean absolute relative difference and mean absolute difference were 23.4% and 33.9 mg/dL, respectively. Sensor glucose levels and capillary glucose levels were significantly correlated (r = 0.858, P < .01), although the sensor glucose levels were significantly lower than the capillary glucose levels. The accuracy of FreeStyle Libre in patients undergoing HD became deteriorated with the days of usage. The percentage of sensor results in Zones A and B in the consensus error grid analysis and in the Clarke error grid analysis were 99.7% and 99.0%, respectively. Its insufficient accuracy necessitates adjunct usage of FreeStyle Libre with self-monitoring of blood glucose in patients undergoing HD.

Relationship between basal sodium intake and the effects of dapagliflozin in albuminuric diabetic kidney disease.

We investigated the impact of basal dietary sodium intake on the dapagliflozin-induced changes in albuminuria and blood pressure (BP) measured at home in patients with diabetic kidney disease (DKD).This was a secondary analysis of the Y-AIDA Study, in which DKD patients with estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine were administered dapagliflozin for 24 weeks, and dapagliflozin significantly improved albuminuria levels and home BP profiles. The effects on UACR, home-measured BP, and eGFR were compared between high- and low-sodium intake groups (HS and LS groups), which were created using baseline urinary sodium-to-creatinine ratio of 84 participants with available basal sodium-to-creatinine ratios. At baseline, clinic-/home-measured BPs, UACR, and eGFR, were comparable in the two groups. After 24 weeks, the reductions from baseline in ln-UACR were comparable in the two groups. In contrast, the reductions in evening home systolic BP and eGFR from baseline were larger in HS than in LS (BP: - 13 ± 2.08 vs. - 6 ± 1.88, P = 0.020; eGFR: - 3.33 ± 1.32 vs. 0.37 ± 1.29, P = 0.049). The home BP-lowering effects of dapagliflozin are larger in HS than LS, concomitant with a larger reduction in eGFR, suggesting a dapagliflozin-induced improvement in glomerular relative hyperfiltration in HS.

AUTOLOGOUS RETINAL TRANSPLANTATION AS A PRIMARY TREATMENT FOR LARGE CHRONIC MACULAR HOLES.

PURPOSE: To report the outcomes of autologous neurosensory retinal transplant as a primary treatment for patients with large chronic macular holes and evaluate the safety and feasibility of the procedure. DESIGN: Retrospective study, consecutive case series. METHODS: We reviewed seven patients with a primary chronic large macular hole, who underwent autologous neurosensory retinal transplant. Mean preoperative minimum and maximum hole diameters were 643 µm and 1214 µm, respectively. Changes in visual acuity were measured postsurgery, and optical coherence tomography, fluorescein angiography, and microperimetry-3 were analyzed after the procedure. RESULTS: Closure of the macular hole was achieved in all seven eyes in the study. At 1 year post-surgery, there was significant improvement in mean visual acuity (LogMAR 1.10 vs. 0.68, P = 0.001). Optical coherence tomography showed that all grafts had formed attachments to the retinal epithelial cells of the recipient retina. Mean preoperative ellipsoid zone defect was 1,089 ± 403.8 µm (range, 918-1,329 µm) which further decreased to 921 ± 129.1 µm (range, 670-1,201 µm) at final follow up (P = 0.09). Microperimetry-3 testing indicated retinal sensitivity in the graft in five eyes. CONCLUSION: Autologous retinal transplantation may help rebuild the macular structure resulting in functional improvement for eyes with primary chronic large macular hole.

Improved home BP profile with dapagliflozin is associated with amelioration of albuminuria in Japanese patients with diabetic nephropathy: the Yokohama add-on inhibitory efficacy of dapagliflozin on albuminuria in Japanese patients with type 2 diabetes study (Y-AIDA study).

BACKGROUND: The Y-AIDA study was designed to investigate the renal- and home blood pressure (BP)-modulating effects of add-on dapagliflozin treatment in Japanese individuals with type 2 diabetes mellitus (T2DM) and albuminuria. METHODS: We conducted a prospective, multicenter, single-arm study. Eighty-six patients with T2DM, HbA1c 7.0-10.0%, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2, and urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine (gCr) were enrolled, and 85 of these patients were administered add-on dapagliflozin for 24 weeks. The primary and key secondary endpoints were change from baseline in the natural logarithm of UACR over 24 weeks and change in home BP profile at week 24. RESULTS: Baseline median UACR was 181.5 mg/gCr (interquartile range 47.85, 638.0). Baseline morning, evening, and nocturnal home systolic/diastolic BP was 137.6/82.7 mmHg, 136.1/79.3 mmHg, and 125.4/74.1 mmHg, respectively. After 24 weeks, the logarithm of UACR decreased by 0.37 ± 0.73 (P < 0.001). In addition, changes in morning, evening, and nocturnal home BP from baseline were as follows: morning systolic/diastolic BP - 8.32 ± 11.42/- 4.18 ± 5.91 mmHg (both P < 0.001), evening systolic/diastolic BP - 9.57 ± 12.08/- 4.48 ± 6.45 mmHg (both P < 0.001), and nocturnal systolic/diastolic BP - 2.38 ± 7.82/- 1.17 ± 5.39 mmHg (P = 0.0079 for systolic BP, P = 0.0415 for diastolic BP). Furthermore, the reduction in UACR after 24 weeks significantly correlated with an improvement in home BP profile, but not with changes in other variables, including office BP. Multivariate linear regression analysis also revealed that the change in morning home systolic BP was a significant contributor to the change in log-UACR. CONCLUSIONS: In Japanese patients with T2DM and diabetic nephropathy, dapagliflozin significantly improved albuminuria levels and the home BP profile. Improved morning home systolic BP was associated with albuminuria reduction. Trial registration The study is registered at the UMIN Clinical Trials Registry (UMIN000018930; http://www.umin.ac.jp/ctr/index-j.htm ). The study was conducted from July 1, 2015 to August 1, 2018.