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.].

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.

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.

The Prevalence of 25-hydroxyvitamin D Deficiency in Japanese Patients with Diabetic Nephropathy.

Objective The purpose of this study was to measure serum 25-hydroxyvitamin D [25(OH)D] levels in Japanese patients with diabetic nephropathy and determine the relationship between 25(OH)D concentrations and various factors. Methods The study subjects included 442 patients with type 2 diabetes. Their serum levels of creatinine, HbA1c, intact-parathyroid hormone, urinary albumin, 25(OH)D, and 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured and their estimated glomerular filtration rate (eGFR) was determined. The patients were divided into four groups based on the risk for progression to chronic kidney disease (CKD): low, moderate, high, very high, based on their eGFR and their level of albuminuria. Results The median 25(OH)D level was 14.6 ng/mL; 11% of the patients had 25(OH)D deficiency (<10 ng/mL), and 2% of patients had active vitamin D deficiency, as defined by a 1,25(OH)2D level of <22 pg/mL. The serum 25(OH)D level was correlated with the serum 1,25(OH)2D level in patients with a very high risk for CKD, but not in those with a moderate or high risk for CKD. Conclusion Although the vitamin D levels of the Japanese patients with diabetic nephropathy and CKD were low, the prevalence of vitamin D deficiency, as defined by the 1,25(OH)2D level, was low. Albuminuria, younger age, and female gender were associated with a low 25(OH)D level. The serum level of 25(OH)D should be monitored to assess the vitamin D status of patients with nephropathy and CKD.

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.

Effects of liraglutide, a human glucagon-like peptide-1 analogue, on body weight, body fat area and body fat-related markers in patients with type 2 diabetes mellitus.

OBJECTIVE: To evaluate the effects of six-month liraglutide treatment on body weight, visceral and subcutaneous fat and related markers in Japanese type 2 diabetic patients. METHODS: A total of 59 patients with type 2 diabetes were treated with liraglutide (0.3 mg/day for ≥1 week and then 0.6 mg/day for ≥1 week, gradually increasing the dose to 0.9 mg/day) for six months. Changes in body weight, body mass index (BMI), HbA1c, the fasting blood glucose level, visceral and subcutaneous fat areas, hepatic and renal CT values and the associated markers proinsulin, adiponectin and pentraxin (PTX) 3 were measured. RESULTS: The study included one treatment-naïve patient, 10 patients who were switched from oral antidiabetic drugs and 35 patients who were switched from insulin therapy. At six months after treatment, the preprandial blood glucose levels were higher (148.8±40.5 mg/dL) than the baseline values (130.8±36.7, p<0.05); however, body weight, BMI and abdominal circumference were lower, and the liver/kidney CT ratio improved significantly from 1.64±0.44 at baseline to 1.78±0.42. An analysis of the patients who were not pretreated with insulin resistance ameliorators showed that six months of liraglutide treatment significantly decreased the subcutaneous but not visceral fat areas, significantly decreased the serum adiponectin levels and significantly increased the serum PTX3 levels. CONCLUSION: In addition to its glucose-lowering effects, liraglutide exhibits weight loss promotion actions, reducing subcutaneous fat areas in particular. The weight and total fat area reduction properties of liraglutide are likely to be beneficial when this medication is used in combination with other oral antidiabetic drugs and insulin.

Long-term glycemic control in Japanese type 2 diabetes patients after switching treatment from twice-daily premixed insulin to once daily insulin glargine.

OBJECTIVE: To examine the clinical utility of once-daily insulin glargine, we studied the clinical course of patients who were switched to from twice-daily premixed insulin to once daily insulin glargine. METHODS: The study was conducted at Tokai University hospital in 20 patients with type 2 diabetes, whose treatment regimens were switched from twice-a-day premixed insulin formulation to once-a-day insulin glargine. Changes in various clinical indexes were studied during a 3-year period after the switch. We also compared the well-controlled group (hemoglobin A1c, HbA1c, levels maintained at less than 6.9%) and poorly-controlled group (HbA1c levels at 7.4% or higher). RESULTS: During the 3-year period, all patients showed significant decrease in HbA1c levels and tendency for reduced daily dose of insulin. Although both BMI and insulin dose tended to decrease in the well-controlled group, they increased in the poorly controlled group. CONCLUSION: The findings suggest that in type 2 diabetes, once-a-day insulin glargine could be more useful than twice-a-day premixed insulin formulation. Poor adherence was observed in the poorly-controlled group, namely lack of thoroughness in self-monitoring of blood glucose and adherence to diet and exercise therapy, thus emphasizing the importance of diabetes education.

Efficacy of long-acting insulin analog insulin glargine at high dosage for basal-bolus insulin therapy in patients with type 2 diabetes.

OBJECTIVE: Attempts to achieve strict glycemic control with basal-bolus insulin therapy required increased dosages of neutral protamine Hagedorn (NPH) insulin. However, high dosage of NPH insulin often occurs nocturnal hypoglycemia. Insulin glargine can simulate normal basal insulin secretion with its flat time-action profiles. To confirm the efficacy of insulin glargine we investigated the type 2 diabetic patients on basal-bolus insulin therapy whose basal insulin was switched from NPH insulin to insulin glargine. METHODS: The Japanese 400 patients with type 2 diabetes on basal-bolus insulin therapy whose basal insulin was switched from NPH insulin to insulin glargine were followed-up. After the switching, the basal insulin was increased with reference to the self-monitoring of blood glucose results, with the aim of maintaining fasting blood sugar (FBS) level at 110 mg/dL, and simultaneously reducing the bolus insulin dosage to maintain the total daily insulin dosage. RESULTS: We were able to lower FBS significantly with almost no serious hypoglycemia. HbA1c also improved significantly. The improvements in FBS and HbA1c levels did not require a significant increase in the total insulin dosage. CONCLUSION: Our results suggest that basal insulin supplementation using insulin glargine is a useful method to control not only FBS but also HbA1c.

Effectiveness of basal-supported oral therapy (BOT) using insulin glargine in patients with poorly controlled type 2 diabetes.

OBJECTIVE: To determine the clinical usefulness of basal-supported oral therapy (BOT) using insulin glargine in Japanese patients with type 2 diabetes. METHODS: We compared HbA1c levels, body weight, and insulin doses before the introduction of BOT and in the final month of the observation period in 122 patients with type 2 diabetes who received BOT with insulin glargine between October 2007 and July 2009. To exclude the possible effects of seasonal changes in glycemic control, 57 of the 122 patients were followed-up for one year and examined for changes in HbA1c levels, body weight, and insulin dose. RESULTS: Examination of all cases (n=122) showed a significant decrease in HbA1c (before BOT: 8.7±1.8, after: 7.1±1.1%), but no significant change in body weight (before: 63.1±16.1, after: 63.8±17.0 kg). The mean observation period was 10.5±6.4 months. Insulin doses were significantly increased during the study. HbA1c levels improved significantly in patients on non-insulin-secreting drugs (biguanide, α-glucosidase inhibitor and thiazolidine derivatives) than those on insulin-secreting drugs (SU agents and glinides). CONCLUSION: BOT with insulin glargine is a useful strategy that can achieve good glycemic control in clinical practice without causing serious hypoglycemia. The introduction of BOT before exhaustion of pancreatic ß cells may increase its effectiveness.