Association of urinary liver-type fatty acid-binding protein with renal functions and antihyperglycemic drug use in type 2 diabetic nephropathy patients.

PURPOSE: In diabetic nephropathy exacerbation, a reduction in the estimated glomerular filtration rate (eGFR) without raised albuminuria or proteinuria has been frequently observed. This study aimed to clarify the clinical usefulness of urinary liver-type fatty acid-binding protein (L-FABP) in the exacerbation of diabetic nephropathy in type 2 diabetes. METHODS: A cross-sectional study and a retrospective observational study of 227 patients with type 2 diabetes were conducted to investigate the relationship between urinary L-FABP and renal dysfunction. Changes in urinary L-FABP with or without additional administration of antihyperglycemic drugs were examined in 63 patients. RESULTS: Baseline urinary L-FABP was significantly associated with baseline eGFR (ρ = -0.34, p < 0.001) and baseline albuminuria (ρ = 0.64, p < 0.001). In multivariate regression analysis, baseline urinary L-FABP was a significant independent factor for eGFR reduction [ß = -0.348, 95% confidence interval (CI) = -0.482 to -0.214, p < 0.001]. Cox regression analysis showed that patients with a baseline urinary L-FABP above 6.5 µg/g creatinine exhibited a higher hazard ratio (HR) for the renal dysfunction surrogate end point (HR = 15.00, 95% CI 3.640-61.40, p < 0.001). In logistic regression analysis, administration of sodium glucose cotransporter-2 inhibitors was associated with a statistically significant reduction in urinary L-FABP levels, independent of changes in systolic blood pressure, glycosylated hemoglobin, and eGFR (odds ratio = 0.75, 95% CI 0.56-0.99, p = 0.04). CONCLUSION: Urinary L-FABP may be associated with the future decrease in renal functions in type 2 diabetic nephropathy patients. Additionally, urinary L-FABP could be used as a marker of the effectiveness of diabetic nephropathy treatment.

Evaluation of cold snare polypectomy for small pedunculated (Ip) polyps with thin stalks: a prospective clinical feasibility study.

BACKGROUND: Although the use of cold snare polypectomy (CSP) has spread rapidly, no prospective studies evaluating the safety of CSP for pedunculated (Ip) polyps have been carried out. AIM: We performed this study to provide an accurate evaluation of the safety of CSP for Ip polyps. METHODS: This is a prospective study (UMIN000035687). From January 2019 to February 2021, the safety of CSP for use on Ip polyps <10 mm with thin stalks was evaluated at our hospital. The primary outcome measure was the incidence of bleeding (delayed post-polypectomy bleeding (DPPB) and immediate bleeding). RESULTS: During the study period, 89 consecutive patients (including 92 colonoscopies and 114 polyps) were prospectively enrolled. The en-bloc resection rate was 100%. The rate of DPPB after CSP was 0%, however, DPPB after conversion to HSP occurred in 1 case (33.3% (1/3)). The rate of immediate bleeding during CSP was 28.9% (33/114). Polyps with diameters ≥6 mm (OR (95% CI): 2.77 (1.041-7.376); p = .041) were extracted as independent risk factors for immediate bleeding during CSP for Ip polyps. In all, 104 (91.2%) polyps were low-grade adenomas, and the percentage of cases with negative pathological margins was 96.5% (110/114). CONCLUSIONS: CSP for Ip polyps was safe and had good outcomes. We believe that Ip polyps could be included as an indication for CSP, and that CSP may become the next step in the 'cold revolution.' To confirm our results and verify CSP's inclusion in future guidelines, prospective, randomized studies are necessary.

Management of Less Than 10-mm-Sized Pedunculated (Ip) Polyps with Thin Stalk: Hot Snare Polypectomy Versus Cold Snare Polypectomy.

BACKGROUND: Although the use of cold snare polypectomy (CSP) has spread rapidly, its safety for pedunculated (Ip) polyps remains controversial. In particular, the outcomes of hot snare polypectomy (HSP) and CSP for Ip polyps have not been previously compared. AIMS: This study evaluated whether the rate of delayed postpolypectomy bleeding (DPPB) after CSP for Ip polyps was higher than that after HSP for Ip polyps and compared other outcomes (the rates of immediate bleeding and pathological margins) between the HSP and CSP procedures. METHODS: A total of 5905 colorectal polyps in 4920 patients were resected at Omori Red Cross Hospital between October 2012 and June 2019. The polyps were divided into two groups: the HSP group (86 polyps, 64 patients) and the CSP group (102 polyps, 87 patients). The primary outcome measure was the incidence of DPPB. The secondary outcome measures were the incidences of immediate bleeding during the procedure and pathological margins of the resected specimen. RESULTS: The rate of immediate bleeding during CSP was significantly higher than that for the HSP group [38.2% (39/102) versus 3.5% (3/86); p < 0.001]. However, the rate of DPPB was significantly higher in the HSP group than in the CSP group [4.7% (4/86) versus 0% (0/102); p < 0.001]. The rate of DPPB after CSP was 0%. CONCLUSIONS: This is the first study to compare the outcomes of HSP and CSP for Ip polyps. CSP is safer than HSP for Ip polyps measuring < 10 mm in diameter.

Safety and efficacy of cold snare polypectomy for pedunculated (Ip) polyps measuring less than 10 mm in diameter.

BACKGROUND: Although cold snare polypectomy (CSP) has spread rapidly, it still remains controversial whether CSP is safe for pedunculated (Ip) polyps. PURPOSE: The aim of this study was to evaluate whether CSP for Ip polyps measuring less than 10 mm in diameter might be associated with an increased rate of delayed post-polypectomy bleeding (DPPB). METHODS: A total of 1641 colorectal polyps in 634 patients were resected at Omori Red Cross Hospital between April 2018 and December 2018. The polyps were divided into two groups depending on the morphology: the Ip group (90 polyps), and the non-Ip group (1551 polyps). RESULTS: Among the 1641 polyps, there was no case of DPPB, including in the Ip group. Immediate bleeding occurred in a total of 101 (6.2%) cases. Polyp location in the rectum (OR (95% CI), 3.61 (1.843-7.092); p < 0.001), polyp diameter ≥ 6 mm (OR (95% CI), 2.65 (1.702-4.132); p < 0.001), Ip morphology (OR (95% CI), 15.66 (9.262-26.49); p < 0.001), and treatment with antithrombotic agents (OR (95% CI), 2.18 (1.358-3.501); p = 0.0012) were identified as significant risk factors for immediate bleeding. CONCLUSIONS: This is the first study conducted to examine the safety of CSP for Ip polyps measuring less than 10 mm in diameter. CSP can be performed with a high level of safety even for Ip polyps. Based on our findings, we believe that Ip polyps could be included as an indication for CSP. However, prospective, randomized studies are necessary to confirm our results.

Safety of Cold Snare Polypectomy in Patients Receiving Treatment with Antithrombotic Agents.

BACKGROUND: With the aging of the population and rising incidence of thromboembolic events, the clinical use of antithrombotic agents is also increasing. There are few reports yet on the management of antithrombotic agent use in patients undergoing cold snare polypectomy (CSP). AIMS: The aim of this study was to evaluate whether continued administration of antithrombotic agents in patients undergoing CSP would be associated with an increased rate of delayed post-polypectomy bleeding (DPPB). METHODS: A total of 1177 colorectal polyps in 501 patients were resected at Omori Red Cross Hospital between October 2017 and March 2018. The polyps were divided into two groups depending on whether the patients received antithrombotic agent treatment or not: the antithrombotic group (911 polyps) and the no-antithrombotic group (266 polyps). RESULTS: Among the 1177 polyp resections, there was no case of DPPB, including in the antithrombotic group. Immediate bleeding occurred in a total of 63 (5.4%) cases. Polyp location in the rectum (OR (95% CI) 2.64 (1.223-5.679); p = 0.013), polyp size ≥ 6 mm (OR (95% CI) 4.64 (2.719-7.933); p < 0.001), polypoid growth pattern (OR (95% CI) 2.78 (1.607-4.793); p < 0.001), and antithrombotic agent use (OR (95% CI) 2.98 (1.715-5.183); p < 0.001) were identified as significant risk factors of immediate bleeding. CONCLUSIONS: Continued use of antithrombotic agents does not increase the risk of DPPB, even in those receiving multiple antithrombotic agents. Thus, it is safe to perform CSP even in multiple agent users. Prospective, randomized studies are necessary to confirm our results.

Leptin is associated with vascular endothelial function in overweight patients with type 2 diabetes.

BACKGROUND: The adipocyte-derived hormone leptin plays a key role in the regulation of appetite and body weight. Recent studies have suggested that leptin is also involved in the pathogenesis of obesity-related atherosclerosis and cardiovascular disease. In this study, we investigated the association of plasma leptin levels with vascular endothelial function in lean and overweight patients with type 2 diabetes. METHODS: One hundred seventy-one type 2 diabetic patients, of which 85 were overweight (body mass index (BMI) ≥ 25 kg/m2), were enrolled in this cross-sectional study. Plasma leptin concentrations were measured by enzyme-linked immunosorbent assay. Flow-mediated dilatation (FMD) of the brachial artery was measured to evaluate vascular endothelial function using ultrasound. RESULTS: No significant difference in FMD was found between the lean and overweight groups (7.0 ± 3.8% and 6.5 ± 3.6%, respectively; p = 0.354). FMD was negatively correlated with age (r = -0.371, p < 0.001) and serum creatinine levels (r = -0.236, p = 0.030), but positively correlated with BMI (r = 0.330, p = 0.002) and plasma leptin levels (r = 0.290, p = 0.007) in the overweight group. FMD was not associated with any parameters in the lean group. Multiple regression analysis including possible atherosclerotic risk factors revealed that the plasma leptin level (ß = 0.427, p = 0.013) was independently associated with FMD in the overweight group (R2 = 0.310, p = 0.025), but not the lean group. CONCLUSION: Plasma leptin levels are associated with vascular endothelial function in overweight patients with type 2 diabetes.

Clinical assessment of delayed gastric emptying and diabetic complications using gastric emptying scintigraphy: involvement of vascular disorder.

AIM: Delayed gastric emptying, including gastroparesis, is a common complication in diabetes mellitus. The association between delayed gastric emptying and overall diabetic complications remains to be studied in detail. We analysed this association. METHODS: We performed gastric emptying scintigraphy of (99m) Tc-diethylenetriaminepentaacetic acid in 34 patients with diabetes to measure the gastric emptying half-times (T1/2) of the whole stomach (WS), proximal stomach (PS) and distal stomach (DS). We assessed T1/2, diabetic-related factors and complications. RESULTS: The prevalence of autonomic neuropathy was higher in the group with delayed T1/2 of the WS than in the normal group. Analysis of intima-media thickness (IMT) and ankle brachial pressure index (ABI), which are risk indicators for vascular disorder, showed that IMT of the carotid bulb was greater in the group with delayed T1/2 of the WS than in the normal group (2·41 mm [1·50-2·81] versus 1·40 mm [0·81-2·08], P = 0·015). T1/2 of the WS correlated positively with IMT of the carotid bulb (r = 0·391, P = 0·027) and negatively with ABI (r = -0·389, P = 0·028). These correlations were mainly attributed to PS and were the same in patients without autonomic neuropathy. In seven of nine patients who received scintigraphy again after diabetic treatment, glycosylated haemoglobin (HbA1c) levels decreased and T1/2 of the WS shortened compared with before treatment. CONCLUSION: Vascular disorder, among other cofactors such as autonomic neuropathy, could be involved in the pathophysiology of delayed gastric emptying. Medium- to long-term glycaemic control was associated with gastric emptying.

Clinical impact of the leptin to soluble leptin receptor ratio on subclinical carotid atherosclerosis in patients with type 2 diabetes.

AIM: The adipocyte-derived hormone leptin plays a key role in the regulation of food intake and energy expenditure. Recent studies have suggested that leptin is also involved in the pathogenesis of obesity-associated atherosclerosis and cardiovascular disease. In this study, we investigated the associations of leptin and the soluble leptin receptor (sOb-R) with atherosclerosis in patients with type 2 diabetes. METHODS: Three hundred seventeen type 2 diabetic subjects were enrolled in this cross-sectional study. Fasting plasma leptin and sOb-R concentrations were measured by enzyme-linked immunosorbent assays. The intima-media thickness (IMT) of the common carotid artery was measured by ultrasound. RESULTS: The IMT was significantly associated with sOb-R concentrations, age, diabetes duration, serum creatinine (sCre) levels, and systolic blood pressure (SBP), but not with leptin concentrations or the leptin/sOb-R ratio. The concentrations of leptin (r=0.478, p<0.001) and the sOb-R (r= -0.404, p<0.001) and the leptin/sOb-R ratio (r=0.501, p<0.001) were strongly correlated with IMT in subjects treated with insulin for glycemic control, but not in those treated with diet alone or oral hypoglycemic agents. Multiple regression analysis, including age, sex, diabetes duration, body mass index, SBP, HbA1c, triglycerides, LDL-cholesterol, sCre, smoking, and insulin therapy, revealed that plasma leptin and the leptin/sOb-R ratio were independently associated with IMT in subjects treated with insulin. CONCLUSIONS: Plasma leptin and the leptin/sOb-R ratio are associated with atherosclerosis in patients with type 2 diabetes on insulin therapy, and these associations were independent of obesity and other cardiovascular risk factors.

Association of endothelial and vascular smooth muscle dysfunction with cardiovascular risk factors, vascular complications, and subclinical carotid atherosclerosis in type 2 diabetic patients.

AIM: Atherosclerosis and arteriosclerosis are mainly caused by the dysfunction of arterial components, namely, vascular endothelial cells, smooth muscle cells, and the extracellular matrix. Endothelial dysfunction is well established as a predictive surrogate marker of cardiovascular events; however, little is known regarding the clinical implications of vascular smooth muscle dysfunction for cardiovascular disease and microangiopathy. In the present study, we aimed to clarify the association of arterial dysfunction with micro-/macroangiopathy and conventional cardiovascular risk factors in 181 type 2 diabetic patients (T2DM; age ± SD, 64 ± 10 years; duration of diabetes, 12 ± 10 years). METHODS: Flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) were assessed to evaluate endothelial dysfunction and vascular smooth muscle dysfunction, respectively, by using a novel ultrasound device, UNEXEF18G (Unex Co. Ltd., Japan). RESULTS: The FMD and NMD were 6.4 ± 3.9% and 13.4 ± 6.6%, respectively. No significant differences in FMD were noted between T2DM with and without micro- or macroangiopathy; however, NMD in T2DM patients with micro- and macroangiopathy was significantly lower than that in T2DM patients without angiopathy. NMD decreased with the progression of chronic kidney disease (CKD) stage (p = 0.005), but not FMD (p = 0.071). On multiple regression analysis, significant independent contributors to FMD were age, smoking, systolic blood pressure, glycosylated hemoglobin, and serum total cholesterol, while those for NMD were age, systolic blood pressure, and waist circumference. CONCLUSION: The relationship of vascular complications and cardiovascular risk factors with NMD is different from that with FMD in type 2 diabetic patients.

Association of serum TRAIL levels with atherosclerosis in patients with type 2 diabetes mellitus.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) was originally isolated as an inducer of apoptosis. Recent cross-sectional and prospective studies suggest an inverse association of serum TRAIL levels with the severity of coronary artery disease (CAD) and with an adverse outcome in patients with CAD or heart failure. However, it is unknown whether TRAIL can inversely reflect the progression of atherosclerosis from its early stage. We therefore examined the association between TRAIL measured by ELISA and intima-media thickness (IMT) in carotid and femoral arteries evaluated by ultrasonography as a surrogate marker of atherosclerosis in 416 type 2 diabetic patients without any symptoms of CAD and heart failure. Concurrently, the existence of calcified plaque (CP) was examined. There was no significant association between TRAIL and carotid IMT (ρ=-0.096, p=0.052) or femoral IMT (ρ=-0.025, p=0.610), although TRAIL was associated with carotid IMT in a subset of patients with macrovascular diseases (ρ=-0.174, p=0.034). No difference in TRAIL levels was found between two groups with or without CP. TRAIL may not be a good candidate as a biomarker to evaluate early-stage atherosclerotic lesions.

Fetuin-A and atherosclerotic calcified plaque in patients with type 2 diabetes mellitus.

Fetuin-A is a multifunctional circulating glycoprotein. Among its roles, inhibition of ectopic calcification is a prominent feature. Low fetuin-A levels in dialysis patients are associated with cardiovascular mortality, possibly via accelerating vascular calcification. However, except for dialyzed conditions, a correlation between fetuin-A levels and vascular calcification remains controversial. Furthermore, any inhibitory effect of fetuin-A on atherosclerotic calcified plaques (CPs) remains unclear compared with its effect on medial artery calcification that is often found in dialyzed patients. Therefore, we examined the association between fetuin-A levels and atherosclerotic CPs. For this study, 416 consecutive patients with type 2 diabetes mellitus and without renal dysfunction were examined. We measured serum fetuin-A levels and investigated for the presence of CP in the common carotid and femoral arteries using ultrasonography. Fetuin-A levels were significantly lower in patients with CP than those without CP (262.6 +/- 56.7 and 281.5 +/- 64.6 microg/mL, respectively; P = .001). Multivariate logistic regression analysis showed that fetuin-A levels were inversely associated with the presence of CP (odds ratio = 0.753; 95% confidence interval, 0.608-0.933; P = .010). These results suggest that fetuin-A may inhibit the calcification of atherosclerotic plaques independently of the dialyzed condition.