ELUCIDATE Trial: A Single-Center Randomized Controlled Study.

BACKGROUND: Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, is an epochal oral antidiabetic drug that improves cardiorenal outcomes. However, the effect of early dapagliflozin intervention on left ventricular (LV) remodeling in patients with type 2 diabetes free from cardiovascular disease remains unclear. METHODS AND RESULTS: The ELUCIDATE trial was a prospective, open-label, randomized, active-controlled study that enrolled 76 patients with asymptomatic type 2 diabetes with LV ejection fraction ≥50%, randomized to the dapagliflozin 10 mg/day add-on or standard-of-care group. Speckle-tracking echocardiography-based measurements of the cardiac global longitudinal strain were performed at baseline and 24 weeks after treatment initiation. Patients who received dapagliflozin had a greater reduction in LV dimension (1.68 mm [95% CI, 0.53-2.84]; P=0.005), LV end-systolic volume (5.51 mL [95% CI, 0.86-10.17]; P=0.021), and LV mass index (4.25 g/m2.7 [95% CI, 2.42-6.09]; P<0.0001) compared with standard of care in absolute mean differences. Dapagliflozin add-on therapy led to a significant LV global longitudinal strain increment (0.74% [95% CI, 1.00-0.49]; P<0.0001) and improved LV systolic and early diastolic strain rates (0.27/s [95% CI, 0.17-0.60]; and 0.11/s [95% CI, 0.06-0.16], respectively; both P<0.0001) but not in global circumferential strain. No significant changes were found in insulin resistance, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, or other biomarkers at 6 months after the dapagliflozin administration. CONCLUSIONS: Dapagliflozin add-on therapy could lead to more favorable cardiac remodeling accompanied by enhanced cardiac mechanical function among patients with asymptomatic type 2 diabetes. Our findings provide evidence of the efficacy of dapagliflozin use for the primary prevention of diabetic cardiomyopathy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03871621.

High left ventricular mass associated with increased risk of incident diabetes.

Evidence for the role of electrocardiography or echocardiography in determining left ventricular hypertrophy for the risk of diabetes is still controversial. We aimed to explore whether left ventricular mass, as measured by these methods, is associated with the risk of diabetes in a community population. We recruited 2696 participants aged 35 years or older without diabetes who had undergone screening with electrocardiography and echocardiography. Left ventricular mass index (LVMI) was calculated using a formula, and participants were divided into tertiles based on their LVMI tertiles. During a median follow-up period of median, 8.9 years, a total of 405 participants developed diabetes. The incidence and risk of diabetes significantly increased with higher LVMI tertiles. Multivariate Cox regression analysis demonstrated that individuals in the highest LVMI tertile had a greater likelihood of developing incident diabetes, with a hazard ratio of 1.40 (95% CI 1.06-1.91), even after adjusting related covariates. The highest risk of diabetes was observed in the presence of both the uppermost LVMI tertile and electrocardiographically determined left ventricular hypertrophy for the Chinese population. Left ventricular hypertrophy identified by either electrocardiography or echo may serve as a surrogate marker for identifying the risk of diabetes in clinical practice.

The Effect of Mobile eHealth Education to Improve Knowledge, Skills, Self-Care, and Mobile eHealth Literacies Among Patients With Diabetes: Development and Evaluation Study.

BACKGROUND: The promotion of mobile health (mHealth) and eHealth technologies as tools for managing chronic diseases, particularly diabetes mellitus, is on the rise. Nevertheless, individuals with diabetes frequently face a literacy gap that hinders their ability to fully leverage the benefits offered by these resources. Enhancing technology literacy to facilitate the adoption of mobile eHealth services poses a significant challenge in numerous countries. OBJECTIVE: This study aims to develop an educational mobile eHealth literacy (eHL) program for patients with diabetes and to evaluate its effect on patients' outcomes. METHODS: This study designed a mobile eHL education program comprising 2 modules specifically tailored for individuals with type 2 diabetes (T2D). These modules focused on guiding participants through the process of effectively navigating reliable health websites and utilizing diabetes-related apps. Using a pre- and posttest experimental design, the study featured an intervention group and a control group. Participants were recruited from 3 outpatient departments in hospitals, and assessments were conducted both before and after the intervention, along with a follow-up measure at the 3-month mark. The evaluation encompassed sociodemographic characteristics, computer and internet proficiency, mobile app usage, mobile eHL, and patient outcomes such as self-care behaviors and glycated hemoglobin (HbA1c) levels. RESULTS: The analysis included a total of 132 eligible participants. Significant differences were observed in the mean scores of knowledge (P<.001) and skills (P<.001) related to computers, the web, and mobile devices at the initiation of the study and after the intervention. During the 3-month follow-up, the findings indicated a significant improvement in mobile eHL (t114=3.391, P=.001) and mHealth literacy (mHL, a subconcept of mobile eHL; t114=3.801, P<.001) within the intervention group, whereas no such improvement was observed in the control group. The chi-square values from the McNemar test underscored that individuals with uncontrolled diabetes (HbA1c≥7%) in the intervention group exhibited more improvement compared with the control group. The generalized estimating equations model unveiled a significant difference in the change of general mHL in the intervention group (ß=1.91, P=.047) and self-care behavior in the control group from T0 to T2 (ß=-8.21, P=.015). Despite being small, the effect sizes for mobile eHL (d=0.49) and HbA1c (d=0.33) in the intervention group were greater than those in the control group (d=0.14 and d=0.16, respectively). CONCLUSIONS: The implementation of a mobile eHL education intervention demonstrates a positive influence on the familiarity of patients with T2D regarding health technology, leading to favorable glycemic outcomes. While additional studies are warranted for a more comprehensive understanding, this program emerges as a promising solution for enhancing patients' uptake of digital health technology.

Comparison of two titration programmes for adding insulin detemir to oral antidiabetic drugs in patients with poorly controlled type 2 diabetes mellitus.

AIM: To explore the effect of active insulin titration versus usual titration on glycaemic control in patients with type 2 diabetes mellitus uncontrolled with oral antidiabetic drugs (OADs). METHODS: In a 24-week, prospective and randomized study, 172 patients with uncontrolled type 2 diabetes were randomly assigned to either active titration or usual titration. Efficacy and safety outcomes included changes in glycated haemoglobin (HbA1c) and fasting plasma glucose, percentage of individuals achieving HbA1c<53 mmol/mol, and hypoglycaemic events. RESULTS: At Week 24, change in HbA1c was -1.08% ± 1.60% in the active titration group and -0.95% ± 1.34% in the usual titration group (P = 0.569). The percentages of individuals achieving HbA1c<53 mmol/mol were 29.4% and 16.1% in the active and usual titration groups, respectively (P = 0.037). There was no significant difference in the incidence of hypoglycaemia between the two groups. Multivariate logistic regression indicated that, with active titration, baseline HbA1c levels and postprandial glucose excursion were significantly associated with achieving HbA1c<53 mmol/mol. CONCLUSION: Addition of basal insulin using active titration for 24 weeks provided a higher rate of HbA1c target achievement without significant hypoglycaemia compared to usual titration in individuals with uncontrolled type 2 diabetes.

Risk associated with estimated glomerular filtration rate and albuminuria for PAD among patients with type 2 diabetes.

Chronic kidney disease (CKD) is significantly associated with peripheral arterial disease (PAD) in some studies, but data on the association of the risk of PAD across a broad range of kidney function in patients with type 2 diabetes are limited. Between October 17, 2013 and February 7, 2015, all consecutive outpatients with type 2 diabetes underwent ankle-brachial index (ABI) examination. We investigated the association of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) with the risk of PAD. A total of 1254 patients were cross-classified into 12 groups based on ACR category (normoalbuminuria, microalbuminuria and macroalbuminuria) and eGFR stage (≥90, 60-89, 30-59 and <30 mL/min/1.73 m2). Logistic regression analysis was used to investigate the association of eGFR and ACR with PAD. Within each ACR category, a lower eGFR stage was associated with PAD. Similarly, within each eGFR group, a higher ACR category was also associated with PAD. The OR for PAD was highest in patients with eGFR <30 mL/min/1.73 m2 and macroalbuminuria (OR 14.42, 95% CI 4.60 to 45.31) when compared with the reference group of subjects with eGFR ≥90 mL/min/1.73 m2 and normoalbuminuria. Our study found that cross-classification of eGFR with ACR revealed a more comprehensive association with risk of PAD than eGFR or ACR alone.

Effects of SGLT2 inhibitors on stroke and its subtypes in patients with type 2 diabetes: a systematic review and meta-analysis.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown impressive effects in reducing major vascular events in several randomized controlled trials (RCTs). The purpose of this study was to perform a meta-analysis to evaluate the effect of SGLT2 inhibitors on the risk of stroke and its subtypes. All data from prospective RCTs up to 20 October 2020 involving SGLT2 inhibitors that reported stroke events as the primary endpoint or safety in subjects with type 2 diabetes were subjected to meta-analysis. Five eligible RCTs (EMPA-REG, CANVAS, DECLARE-TIMI 58, CREDENCE and VERTIS CV) involving 46,969 participants were included. Pooled analysis of the RCTs showed no significant effect of SGLT2 inhibitors on total stroke [risk ratio (RR) = 0.95; 95% confidence interval (CI) 0.79-1.13, P = 0.585]. Subgroup analysis indicated that SGLT2 inhibitors had no significant effect against fatal stroke, non-fatal stroke, ischemic stroke or transient ischemic attack. When only hemorrhagic stroke was included, SGLT2 inhibitors were associated with a significant 50% reduction compared with placebo (RR = 0.49, 95% CI 0.30-0.82, P = 0.007). This meta-analysis shows that SGLT2 inhibitors have a neutral effect on the risk of stroke and its subtypes but a potential protective effect against hemorrhagic stroke.

High pulse wave velocity is associated with the severity of diabetic retinopathy in patients with type 2 diabetes.

Pulse wave velocity (PWV) is a non-invasive test for assessing arterial stiffness, and brachial-ankle PWV has been used as an index of peripheral arterial stiffness. This study aimed to investigate the association between the PWV value and severity of diabetic retinopathy (DR). 846 patients with type 2 diabetes (T2DM) consecutively underwent brachial-ankle PWV, and the degree of PWV was defined by tertile. The severity of DR was categorized as no diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) based on the Early Treatment Diabetic Retinopathy Study Scale. Multinomial logistic regression analyses were utilized not only to explore the association between the degree of PWV and severity of DR but also to examine the association of a high-tertile PWV with PDR. PWV levels, diabetes duration and blood pressure were all significantly higher in subjects with NPDR or PDR as compared with individuals with NDR. In the univariate analysis, the highest tertile of PWV (>19.6 m/s) was significantly associated with both NPDR (p<0.001) and PDR (p<0.001) as compared with NDR. After adjusting for confounding factors, the highest tertile of PWV remained significantly associated with PDR (p=0.005), but not with NPDR (p=0.107). Furthermore, the highest tertile of PWV was more significantly associated with PDR (OR=6.15, 95%CI 1.38 to 27.38) as compared with the lowest tertile. In our study, an increasing degree of PWV was positively associated with the severity of DR. High PWV was strongly associated with the risk of severe DR, especially PDR.

Addition of Metabolic Syndrome to Albuminuria Provides a New Risk Stratification Model for Diabetic Kidney Disease Progression in Elderly Patients.

Elderly patients with type 2 diabetes (T2DM) are more prone to developing diabetic kidney disease (DKD). Patients with DKD can develop albuminuria, and some studies have suggested an association between metabolic syndrome and albuminuria. The prevalence of both metabolic syndrome and albuminuria increases with age. We evaluated the association of these risk factors with worsening renal function and albuminuria progression in 460 T2DM patients with a mean age of 72 years. During the 5-year follow-up period, progression of albuminuria and worsening of renal function were observed in 97 (21.2%) and 23 (5.1%) patients, respectively. After adjusting for confounding factors, the group with metabolic syndrome had a higher multivariable-adjusted hazard ratio (HR) for worsening renal function (P = 0.038) and albuminuria progression (P = 0.039) than the group without metabolic syndrome. When patients were divided into four groups according to the presence of metabolic syndrome and/or albuminuria, the HR gradually increased. The group with both albuminuria and metabolic syndrome exhibited the highest cumulative incidence of worsening renal function (P = 0.003). When we redefined metabolic syndrome to exclude the blood pressure (BP) component, similar results were obtained. We concluded that the presence of metabolic syndrome independently predicts the progression of renal disease in elderly patients with T2DM. The use of both metabolic syndrome and albuminuria provides a better risk stratification model for DKD progression than albuminuria alone.

Effect of acupressure at Sanyinjiao on albuminuria in patients with early diabetic nephropathy: A single-blind, randomized, controlled preliminary study.

BACKGROUND: Elevated urinary albumin excretion is a clinical manifestation of early-stage diabetic nephropathy (DN). PURPOSE: To investigate effect of acupressure at Sanyinjiao on albuminuria in patients with early DN. METHODS: Total included 53 patients with DN and albuminuria; 21 were assigned to the sham group without acupressure, and 32 were assigned to the experimental group with acupressure at Sanyinjiao (SP6) for 8weeks. The experimental group was divided into experiment A (acupressure <45 days) and experiment B (acupressure ≥45 days). The primary outcome measure was the urine albuminuria/creatinine ratio (UACR) or logarithmic transformed urine microalbumin creatinine ratio (log-UACR) changes, and the secondary outcome measures were the estimated glomerular filtration rate and hemoglobin A1c. RESULTS: The difference in UACR and log-UACR before and after the study was higher in the experiment B group than in the experiment A and sham groups. CONCLUSION: Acupressure at Sanyinjiao for 8 weeks may reduce albuminuria in patients with DN. However, this study was a preliminary design.

Risk factors in metabolic syndrome predict the progression of diabetic nephropathy in patients with type 2 diabetes.

BACKGROUND: While metabolic syndrome can independently predict the development of diabetic kidney disease (DKD) in patients with type 2 diabetes, the risk factors for DKD progression have rarely been discussed. The purpose of this study is to evaluate the association between metabolic syndrome and the progression of DKD in patients with type 2 diabetes. MATERIAL AND METHODS: This retrospective observational cohort study lasted approximately five years. We defined metabolic syndrome using the criteria of the National Cholesterol Education Program Adult Treatment Panel III with the Asian definition of obesity. The progression of DKD was demonstrated by either the progression of albuminuria or worsening renal function. Progression of albuminuria was defined by the transition from normoalbuminuria (<30 mg/g) to microalbuminuria (30-300 mg/g) or from micro- to macroalbuminuria (>300 mg/g). Worsening renal function was defined by a reduction of eGFR to 50% of the baseline or the doubling of serum creatinine. We adopted multivariate Cox-regression analysis to determine the risk factors associated with DKD progression. RESULTS: This study consisted of 935 type 2 diabetic patients with a mean age of 64.62 years. We found progression of albuminuria in 172 patients (18.4%) and worsened renal function in 41 patients (4.4%). After Cox regression analysis, the multivariable-adjusted HR for the progression of albuminuria and worsened renal function was 1.65 (95% C.I.:1.07-2.53 P = 0.022) and 2.62 (95% C.I.:1.01-6.79 P = 0.047) respectively, for those with metabolic syndrome compared to those without metabolic syndrome. CONCLUSION: The presence of metabolic syndrome independently predicts DKD progression in patients with type 2 diabetes.

Characterization of thyroid nodules using the proposed thyroid imaging reporting and data system (TI-RADS).

BACKGROUND: The Thyroid Imaging Reporting and Data System (TI-RADS) was proposed based on a scheme similar to Breast Imaging Reporting and Data System (BI-RADS) lexicon used in breast lesions. The purpose of this study was to evaluate its interobserver variability and accuracy. METHODS: We included 498 nodules in 437 patients undergoing thyroidectomy. Two endocrine surgeons and 2 endocrinologists independently reviewed sonographic images. RESULTS: There was moderate to substantial interobserver agreement for final assessment category (kappa = 0.61). The overall sensitivity, specificity, and negative predictive value (NPV) were 94%, 43%, and 96%, respectively. Positive predictive values (PPVs) for categories 4 and 5 were 32% and 60%. The sensitivity was 92%, 99%, 96%, and 89%, whereas the specificity was 25%, 37%, 41%, and 62% for tumor sizes of <2, 2 to 3, 3 to 4, and >4 cm, respectively. CONCLUSION: TI-RADS is a helpful but not optimal reporting tool in characterizing thyroid lesions. Tumor size has a considerable impact on interobserver concordance and diagnostic performance.