Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus : A randomized, crossover trial

Aims: We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range. Methods: This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR; <70 mg/dL). Results: The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001). Conclusions: The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM

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

Regulation of Renin Expression by Β1-Integrin in As4.1 Juxtaglomerular Line Cells

(1) Background: Renal dysfunction and hypertension are mutually aggravating factors; however, the details of their interaction remain unclear. In a study using renal tissue from diabetic rats, we found that β1-integrin, a cell-substrate adhesion molecule, is specifically phosphorylated in juxtaglomerular cells that secrete renin, a blood pressure regulator. (2) Methods: A mouse juxtaglomerular cell line (As4.1 cells) was used for the following experiments: drug-induced promotion of β1-integrin phosphorylation/dephosphorylation; knockdown of β1-integrin and the cell adhesion molecule connexin-40 (a candidate for the main body of baroreceptor); and pressurization to atmospheric pressure + 100 mmHg. culture in hypotonic liquid medium. The expression of renin under these conditions was measured by qRT-PCR. (3) Results: Phosphorylation of β1-integrin suppressed the expression of renin, while dephosphorylation conversely promoted it. β1-integrin and connexin-40 knockdown both promoted the expression of renin. Pneumatic pressurization and hypotonic medium culture both decreased the expression of renin, which was restored by the knockdown of β1-integrin. (4) Conclusions: β1-integrin plays an inhibitory role in the regulation of the expression of renin, which may be controlled by phosphorylation and dephosphorylation. It is hypothesized that β1-integrin and other adhesion factors regulate the expression of renin by altering the sensitivity of baroreceptors on the plasma membrane

Regulation of Renin Expression by &Beta;1-Integrin in As4.1 Juxtaglomerular Line Cells

(1) Background: Renal dysfunction and hypertension are mutually aggravating factors; however, the details of their interaction remain unclear. In a study using renal tissue from diabetic rats, we found that &beta;1-integrin, a cell-substrate adhesion molecule, is specifically phosphorylated in juxtaglomerular cells that secrete renin, a blood pressure regulator. (2) Methods: A mouse juxtaglomerular cell line (As4.1 cells) was used for the following experiments: drug-induced promotion of &beta;1-integrin phosphorylation/dephosphorylation; knockdown of &beta;1-integrin and the cell adhesion molecule connexin-40 (a candidate for the main body of baroreceptor); and pressurization to atmospheric pressure + 100 mmHg. culture in hypotonic liquid medium. The expression of renin under these conditions was measured by qRT-PCR. (3) Results: Phosphorylation of &beta;1-integrin suppressed the expression of renin, while dephosphorylation conversely promoted it. &beta;1-integrin and connexin-40 knockdown both promoted the expression of renin. Pneumatic pressurization and hypotonic medium culture both decreased the expression of renin, which was restored by the knockdown of &beta;1-integrin. (4) Conclusions: &beta;1-integrin plays an inhibitory role in the regulation of the expression of renin, which may be controlled by phosphorylation and dephosphorylation. It is hypothesized that &beta;1-integrin and other adhesion factors regulate the expression of renin by altering the sensitivity of baroreceptors on the plasma membrane

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

Upregulation of α3β1-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 α3β1-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 α3β1-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 β1-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-β1 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 β1-integrin expression while those of advanced stage showed downregulation. Real-time PCR indicated a tendency for upregulation of α3- and β1-integrin in HSMP cultured with TGF-β1. TGF-β1-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 α3β1-integrin