Clinical Phenotypes and the Clinical Course of Bullous Pemphigoid Receiving Dipeptidyl Pepitidase-4 Inhibitor Treatment: An Analysis of Cases in a Single Japanese Center.

Objective Several studies have shown an increased risk of bullous pemphigoid (BP) when receiving dipeptidyl pepitidase-4 inhibitor (DPP-4i) treatment. The present study explored the associations of DPP-4i treatment with the clinical phenotypes and clinical course of BP. Methods We analyzed data of 146 patients with BP at Tokai University School of Medicine from December 1, 2009, to December 31, 2021. We obtained data by a retrospective medical record review and compared the bullous pemphigoid disease area index (BPDAI) between diabetes patients receiving DPP-4i treatment and those not receiving DPP-4i treatment. We employed multivariable linear regression models to explore the association between the DPP-4i treatment and the BPDAI scores. Results Among 53 BP patients with diabetes, 33 had developed BP during treatment with DPP-4i agents, among which vildagliptin was the most frequently used. The urticaria/erythema scores of the BPDAI were significantly lower in patients who developed BP while receiving DPP-4i treatment than among others. Of note, 69.2% of the patients who stopped DPP-4i treatment experienced complete remission, and the clinical course was more favorable in patients with lower scores for urticaria/erythema than among others. Conclusion These findings suggest that, in patients who developed BP while receiving DPP-4i treatment, a noninflammatory phenotype may indicate a high likelihood that DPP-4i treatment contributes to the development of BP. The discontinuation of DPP-4i should be carefully considered in close consultation with dermatologists.

Importance of the Evaluation of Renal Function for the Prevention of Hypoglycemia in Elderly Diabetes Patients.

OBJECTIVE: The Japan Diabetes Society and the Japan Gerontological Society Collaborative Committee recently released guidelines for the management of elderly diabetes patients. In these guidelines, patients are classified into categories I-III depending on age, cognitive function, activities of daily living (ADL), and presence or absence of multiple functional impairments. The target control value of HbA1c is set for each category. Low (< 30 mL/min/1.73 m2) estimated glomerular filtration rate (eGFR) is an independent highrisk factor for severe hypoglycemia, yet it is not included in the categorization factors. We surveyed elderly diabetes patients with normal cognitive function and ADL (Category I) who were admitted to the emergency department with severe hypoglycemia, retrospectively studied eGFR at the onset of hypoglycemic episode, and checked whether the HbA1c levels matched the guidelines. METHODS: Among 129 diabetes patients aged ≥ 65 years admitted to the Tokai University hospital for hypoglycemic emergencies, 73 had normal cognitive function and ADL. HbA1c level and eGFR at the onset of hypoglycemic attack were obtained from the medical records of these subjects. RESULTS: All subjects were prescribed anti-diabetes agents with high-risk of severe hypoglycemia, including insulin. Sixty-one patients showed eGFR ≥ 30 mL/min/1.73 m2. Among them, 31 (50.8%) had HbA1c levels below the recommended range. Among 12 patients whose eGFR < 30 mL/min/1.73 m2, 6 (50%) had HbA1c levels below the recommended range. CONCLUSION: Even with normal cognitive function and ADL, eGFR < 30 mL/min/1.73 m2 a lone i s a s trong risk factor for hypoglycemia in elderly diabetes patients. We propose that the target control HbA1c level in elderly patients with eGFR < 30 mL/min/1.73 m2 should be 7.5-8.4 %, which is equivalent to that of category III patients.

Corrigendum to "A Liquid-Based Cytology System, without the Use of Cytocentrifugation, for Detection of Podocytes in Urine Samples of Patients with Diabetic Nephropathy".

[This corrects the article DOI: 10.1155/2019/9475637.].

Glycemic Control After Kidney Transplantation Using Sensor-augmented Insulin Pump Therapy in a Patient with Slowly Progressive Type 1 Diabetes Mellitus.

OBJECTIVE: Patients with advanced diabetic nephropathy benefit from kidney transplantation. We report a patient who showed improved glycemic control after kidney transplantation followed by sensor-augmented pump (SAP) therapy. METHODS: The patient was a 67-year-old man on hemodialysis for diabetic nephropathy associated with slowly-progressive type 1 diabetes mellitus. He underwent living-donor kidney transplantation, followed by introduction of SAP therapy for strict glycemic control. RESULTS: SAP therapy improved glycated hemoglobin and glycated albumin levels from 7.8% and 24.2% to 7.0% and 19.2%, respectively, and reduced the frequency of hypoglycemic episodes. CONCLUSION: The case illustrates the usefulness of SAP therapy for post-kidney transplantation glycemic control.

Relation between Blood Pressure Management and Renal Effects of Sodium-Glucose Cotransporter 2 Inhibitors in Diabetic Patients with Chronic Kidney Disease.

AIM: The renoprotective effect of sodium-glucose cotransporter 2 inhibitors is thought to be due, at least in part, to a decrease in blood pressure. The aim of this study was to determine the renal effects of these inhibitors in low blood pressure patients and the dependence of such effect on blood pressure management status. METHODS: The subjects of this retrospective study were 740 patients with type 2 diabetes mellitus and chronic kidney disease who had been managed at the clinical facilities of the Kanagawa Physicians Association. Data on blood pressure management status and urinary albumin-creatinine ratio were analyzed before and after treatment. RESULTS: Changes in the logarithmic value of urinary albumin-creatinine ratio in 327 patients with blood pressure < 130/80 mmHg at the initiation of treatment and in 413 patients with BP above 130/80 mmHg were -0.13 ± 1.05 and -0.24 ± 0.97, respectively. However, there was no significant difference between the two groups by analysis of covariance models after adjustment of the logarithmic value of urinary albumin-creatinine ratio at initiation of treatment. Changes in the logarithmic value of urinary albumin-creatinine ratio in patients with mean blood pressure of <102 mmHg (n = 537) and those with ≥102 mmHg (n = 203) at the time of the survey were -0.25 ± 1.02 and -0.03 ± 0.97, respectively, and the difference was significant in analysis of covariance models even after adjustment for the logarithmic value of urinary albumin-creatinine ratio at initiation of treatment (p < 0.001). CONCLUSION: Our results confirmed that blood pressure management status after treatment with SGLT2 inhibitors influences the extent of change in urinary albumin-creatinine ratio. Stricter blood pressure management is needed to allow the renoprotective effects of sodium-glucose cotransporter 2 inhibitors.

A Liquid-Based Cytology System, without the Use of Cytocentrifugation, for Detection of Podocytes in Urine Samples of Patients with Diabetic Nephropathy.

OBJECTIVE: Podocytes have highly differentiated functions and are extremely difficult to grow; thus, damage of podocytes is associated with glomerular dysfunction. Desquamated podocytes can be detected in urine of patients with severe renal impairment. Unlike the rapidly progressive glomerular damage in glomerulonephritis, only a few desquamated podocytes are usually detected in diabetic nephropathy (DN). It is not clear whether the low podocyte count in DN is due to limitation of the conventional method or true pathological feature. The aim of this study was to compare the conventional method with a newly modified method in detecting podocytes in morning urine samples of patients with DN. MATERIALS AND METHODS: The study subjects were patients with type 2 diabetes. Urine samples from these patients were analyzed by the conventional method (Cytospin®) and the modified method (SurePath™). We determined the rate of detection of urinary podocytes and the number of detected cells. RESULTS: The detection rate and podocyte count were significantly higher by the modified method than by the conventional method. The differences in the detection rates and numbers of podocytes were not significant between patients with normoalbuminuria and those with macroalbuminuria. However, they were significant in patients with microalbuminuria. The number of podocytes in the urine correlated significantly with the albumin-to-creatinine ratio, but not with the estimated glomerular filtration rate. CONCLUSIONS: The true number of urinary podocytes, as measured by the modified SurePath™-based method, in patients with DN is much higher than that estimated by the conventional method.

Detection of Autonomic Nervous System Abnormalities in Diabetic Patients by 24-hour Ambulatory Blood Pressure Monitoring.

OBJECTIVE: To determine the relationship between 24-hr blood pressure (BP) fluctuations and autonomic nervous system dysfunction in diabetic patients using non-invasive ambulatory blood-pressure monitoring (ABPM) system. METHODS: The subjects were 39 diabetic patients free of cardiovascular diseases. 24-hr BP was monitored by a non-invasive ABPM system. The relationships among 24-hr BP fluctuations and various clinical parameters relevant to diabetes and hypertension were analyzed. RESULTS: Patients were divided into the diurnal hypertension (DH, n=4), diurnal and nocturnal hypertension (DNH, n=9), normotension (N, n=14), and nocturnal hypertension (NH, n=12) groups. DH and/or NH was observed in 25 (64%) patients: 13 had DH (≥135/85 mmHg), 21 had NH (≥120/70 mmHg), and 9 had both. Furthermore, 4 patients with DH but no NH (diurnal/nocturnal+/ - ); 9 (+/+); 14 ( - / - ); and 12 ( - /+). The R-R interval coefficient of variation on the EKG (CV-RR) was significantly different among the groups (N>NH>DNH>DH). CONCLUSION: Autonomic nervous system dysfunction in diabetic patients had a negative influence on 24-hr fluctuations in BP. Monitoring nighttime hypertension and daily BP variation using ABPM diabetic is a potentially useful approach for identifying autonomic nervous system dysfunction and associated abnormal BP patterns that cannot be detected by routine check-ups.

Exercise Therapy for Management of Type 2 Diabetes Mellitus: Superior Efficacy of Activity Monitors over Pedometers.

We compared the efficacy of activity monitor (which displays exercise intensity and number of steps) versus that of pedometer in exercise therapy for patients with type 2 diabetes. The study subjects were divided into the activity monitor group (n = 92) and pedometer group (n = 95). The primary goal was improvement in hemoglobin A1c (HbA1c). The exercise target was set at 8,000 steps/day and 20 minutes of moderate-intensity exercise (≥3.5 metabolic equivalents). The activity monitor is equipped with a triple-axis accelerometer sensor capable of measuring medium-intensity walking duration, number of steps, walking distance, calorie consumption, and total calorie consumption. The pedometer counts the number of steps. Blood samples for laboratory tests were obtained during the visits. The first examination was conducted at the start of the study and repeated at 2 and 6 months. A significant difference in the decrease in HbA1c level was observed between the two groups at 2 months. The results suggest that the use of activity level monitor that displays information on exercise intensity, in addition to the number of steps, is useful in exercise therapy as it enhances the concept of exercise therapy and promotes lowering of HbA1c in diabetic patients.

Upregulation of α3ß1-Integrin in Podocytes in Early-Stage Diabetic Nephropathy.

Background. Podocyte injury plays an important role in the onset and progression of diabetic nephropathy (DN). Downregulation of α3ß1-integrin expression in podocytes is thought to be associated with podocyte detachment from the glomerular basement membrane, although the mechanisms remain obscure. To determine the mechanism of podocyte detachment, we analyzed the expression levels of α3ß1-integrin in podocytes in early and advanced stages of DN. Methods. Surgical specimens from DN patients were examined by in situ hybridization, and the expression levels of α3- and ß1-integrin subunits in glomeruli of early (n = 6) and advanced (n = 8) stages were compared with those of normal glomeruli (n = 5). Heat-sensitive mouse podocytes (HSMP) were cultured with TGF-ß1 to reproduce the microenvironment of glomeruli of DN, and the expression levels of integrin subunits and the properties of migration and attachment were examined. Results. Podocytes of early-stage DN showed upregulation of α3- and ß1-integrin expression while those of advanced stage showed downregulation. Real-time PCR indicated a tendency for upregulation of α3- and ß1-integrin in HSMP cultured with TGF-ß1. TGF-ß1-stimulated HSMP also showed enhanced in vitro migration and attachment on collagen substrate. Conclusions. The results suggested that podocyte detachment during early stage of DN is mediated through upregulation of α3ß1-integrin.