Diabetes Disease Management Research Articles

Application of Bioactive Molecules in the Treatment and Management of Type-1 Diabetic Disease

Application of Bioactive Molecules in the Treatment and Management of Type-1 Diabetic Disease

The Prevalence of Chronic Kidney Disease and Albuminuria in Patients With Type 1 and Type 2 Diabetes Attending a Single Centre.

Background Diabetes is the leading cause of chronic kidney disease worldwide. Diabetic kidney disease is one of the microvascular complications of diabetes and it involves changes in glomerular hemodynamics, interstitial fibrosis, and tubular atrophy. Early detection and management of Diabetic kidney disease (DKD) help to reduce morbidity and mortality. This study aims to assess the prevalence of nephropathy and albuminuria in the diabetic population attending an Irish tertiary care center. Methods Retrospective data collection and analysis of patients diagnosed with Type 1 diabetes mellitus(T1DM) and Type 2 diabetes mellitus (T2DM) through the Development and Integration of Accurate Mathematical Operations in Numerical Data-Processing (DIAMOND) database in a single Irish tertiary care center. An audit tool was used to collect patients' information including gender, age, type of diabetes, serum creatinine, urinary albumin excretion, albumin creatinine ratio (ACR), body mass index, and last available glycated hemoglobin (HbA1c). Results Out of 7394 subjects with T2DM, 3139 (42%) were identified with chronic kidney disease (CKD).There were 1866 subjects with positive ACR out of 3139 subjects with CKD in the T2DM cohort.This shows that 25% of subjects have diabetic kidney disease and 17% have CKD of undetermined etiology.In the T1DM cohort with 1166 subjects, 209 (18%) were identified with CKD.Out of these 209 subjects with CKD, 164 (14%) were ACR-positive.The prevalence of CKD and albuminuria were related to age in both T1DM and T2DM populations. Albuminuria showed a linear relationship with age in subjects with no known CKD, which shows that age causally relates to albuminuria independent of type and duration of diabetes. Conclusion CKD is more prevalent in patients with T2DM as compared to T1DM, whereas the prevalence of albuminuria is higher in the T1DM population.

Continuous glucose monitoring reveals similar glycemic variability in individuals with obesity despite increased HOMA-IR.

Continuous glucose monitoring is a well-tolerated and versatile tool for management of diabetes and metabolic disease. While its use appears to be feasible to monitor glycemic profiles in diabetics, there is a paucity of data in individuals with obesity and normal glucose tolerance. The aim of this study is to investigate glucose fluctuations and insulin resistance patterns in normoglycemic participants with obesity vs. without obesity and contextualize these results against leading models for obesity. We designed a prospective, observational pilot study of two cohorts including 14 normoglycemic participants with obesity and 14 normoglycemic participants without obesity. Participants were monitored with continuous glucose monitoring (CGM) for five consecutive days. Insulin resistance levels were measured and glucometric data were extracted from CGM for all participants. Fasting serum insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly higher in the group with obesity (P < 0.05). While the group with obesity had a higher mean blood glucose (MBG), mean amplitude of glycemic excursions (MAGE), and continuous overall glycemic action-1 h (CONGA-1), these differences were not significant. On univariate linear regression, insulin resistance (HOMA-IR) was associated with body mass index (BMI), waist circumference (WC), cohort with obesity, cohort consuming a high glycemic diet, hemoglobin A1c (HbA1c), and fasting insulin levels. WC and fasting insulin levels remained predictors of HOMA-IR in our multivariable model. While there is much excitement surrounding the use of commercial CGM products in obesity management, our results suggest that fasting insulin and HOMA-IR values may be more clinically useful than CGM data alone.

Recurrent Out-of-Hospital Sudden Cardiac Arrest: Prevalence and Clinical Factors.

Despite improvements in management following survival from sudden cardiac arrest (SCA) and wide availability of implantable cardioverter defibrillators for secondary prevention, a subgroup of individuals will suffer multiple distinct episodes of SCA. The objective of this study was to characterize and evaluate the burden of recurrent out-of-hospital SCA among survivors of SCA in a single large US community. SCA cases were prospectively ascertained in the Oregon Sudden Unexpected Death Study. Individuals that experienced recurrent SCA were identified both prospectively and retrospectively. We ascertained 6649 individuals with SCA (2002-2020) and 924 (14%) survived to hospital discharge. Of these, 88 survivors (10%) experienced recurrent SCA. Of the nonsurvivors (n=5725), 35 had suffered a recurrent SCA. Of the total 123 SCA cases with recurrent SCA, >60% occurred at least 1 year after the initial SCA (median 23 months, range: 6 days to 31 years). SCA occurred despite a secondary prevention implantable cardioverter defibrillator in 22% (n=26). Prevalence of coronary disease (36% versus 25%), hypertension (69% versus 43%), diabetes (44% versus 21%), and chronic kidney disease (35% versus 14%) was significantly higher in recurrent SCA versus single SCA survivors (n=80, P=0.01). Among individuals with no secondary prevention implantable cardioverter defibrillators before recurrent SCA, the majority had apparently reversible etiologies identified at initial SCA, with one-quarter undergoing coronary revascularization and over half diagnosed with noncoronary cardiac etiologies. At least 10% of SCA survivors had recurrent SCA, and a large subgroup suffered their repeat SCA despite treatment for an apparently reversible etiology. A renewed focus on careful assessment of cardiac substrate as well as management of coronary disease, hypertension, diabetes, and chronic kidney disease in SCA survivors could reduce recurrent SCA.

Abstract 13358: A Platform for the Personalized Management of Diabetes and Cardiovascular Disease at Population Scale With Data From Multiple Sensors

Introduction: The American Heart Association has identified the design of mobile health (mHealth) tools to improve the management of diabetes and cardiovascular disease and to prevent unplanned hospital readmissions as a priority. Methods: We developed HEART, an open source platform for personalized telehealth at population scale based on data from internet-connected health sensors and data extracted from the electronic medical record (EMR). Health sensors include scales, blood pressure monitors, activity monitors, continuous glucose monitors, and insulin pumps. EMR data include gender, age, race, reason for admission, all surgical procedures performed, and all medications prescribed upon discharge. We collected admission and readmission data for all cardiology patients at an academic pediatric medical center over the last 7 years. Results: HEART has five independent modules (Figure): 1) a data processing module that pulls data in from a variety of devices and EHR feeds, 2) an algorithm module that identifies reasons why a provider may want to contact a patient and ranks patients for contact, 3) a visual interface module that summarizes population data and provides additional details for patients selected by the provider, 4) an intervention module that facilitates messages being sent to providers and documented in the EMR, and 5) a user tracking module that monitors providers use. HEART ranks the entire population cared for by a clinic and allows providers to identify easily those patients who may benefit most from a secure message, telemedicine contact, or in-person visit. There were 5,011 admissions to cardiology among 2,916 patients, with 1000 urgent readmissions for 512 patients and 35,300 outpatient clinic visits. Conclusions: HEART is a population-level framework to facilitate personalized mHealth with data from a variety of sensors and EMR data feeds. It may facilitate outpatient monitoring as part of an effort to prevent unplanned hospital readmission.

Multi-modality cardiac imaging in the management of diabetic heart disease.

Diabetic heart disease is a major healthcare problem. Patients with diabetes show an excess of death from cardiovascular causes, twice as high as the general population and those with diabetes type 1 and longer duration of the disease present with more severe cardiovascular complications. Premature coronary artery disease and heart failure are leading causes of morbidity and reduced life expectancy. Multimodality cardiac imaging, including echocardiography, cardiac computed tomography, nuclear medicine, and cardiac magnetic resonance play crucial role in the diagnosis and management of different pathologies included in the definition of diabetic heart disease. In this review we summarise the utility of multi-modality cardiac imaging in characterising ischaemic and non-ischaemic causes of diabetic heart disease and give an overview of the current clinical practice. We also describe emerging imaging techniques enabling early detection of coronary artery inflammation and the non-invasive characterisation of the atherosclerotic plaque disease. Furthermore, we discuss the role of MRI-derived techniques in studying altered myocardial metabolism linking diabetes with the development of diabetic cardiomyopathy. Finally, we discuss recent data regarding the use of artificial intelligence applied to large imaging databases and how those efforts can be utilised in the future in screening of patients with diabetes for early signs of disease.

INCREASED DISTANCE FROM THE CLINIC LEADS TO HIGHER LOSS TO FOLLOW-UP AFTER PARS PLANA VITRECTOMY IN DIABETIC PATIENTS.

The importance of consistent outpatient follow-up for management of diabetic eye disease has been well-established. The objective of this study was to identify patient factors associated with being lost to follow-up in postsurgical patients after undergoing pars plana vitrectomy for diabetic eye disease. The charts of diabetic patients undergoing pars plana vitrectomy for nonclearing vitreous hemorrhage at an academic medical center by a single surgeon between 2012 and 2019 were reviewed. The rates of loss to follow-up during the postoperative period were compared based on patient distance from the clinic and insurance status. A total of 144 patients met inclusion criteria. A total of 45 patients (31.25%) were lost to follow-up during the 3-month postoperative period. The rate of loss to follow-up increased with every postoperative visit and was significantly higher for patients living greater than 30 miles from the clinic versus patients living within 30 miles from the clinic. There was no statistically significant difference in loss to follow-up based on insurance status. Increased distance from the clinic presents a challenge to providing safe and effective postsurgical care to diabetic patients. This presents opportunities for comanagement or other creative strategies to improve postsurgical follow-up rates for at-risk patients.

Patients' Perceptions of Reasons Contributing to Delay in Seeking Help at the Onset of a Diabetic Foot Ulcer: A Grounded Theory Study.

The purpose of this study was to explore patients' perception of reasons contributing to delay in seeking help and referral to a wound care specialist at the onset of a diabetic foot ulcer (DFU). Constructivist grounded theory study. The sample comprised 30 individuals with active DFU attending a wound care clinic in southeastern Ontario, Canada. Participants were selected through purposive and theoretical sampling. Semistructured interviews were conducted with participants until no new properties of the patterns emerged. All interviews were transcribed, coded, and analyzed using methods informed by constructivist grounded theory. The reasons contributing to delay to seek help and referral to a wound care specialist were (1) limited knowledge about foot care, (2) unaware of diabetic foot problems, (3) underestimation of ulcer presentation, (4) I thought I could fix it myself, (5) inaccurate diagnosis, and (6) trial and error approach by a nonspecialized wound care provider. Study findings suggest that patients and primary healthcare providers need additional education regarding the management of diabetic foot disease and DFU.

A procurement-based classification of pharmaceutical supplies for diabetes disease management.

Background and AimsDiabetes is among the most prevalent noncommunicable chronic diseases globally and carries a substantial expense in worldwide health care. Pharmaceutical supplies related to diabetes management account for 20%–40% of the disease's management cos, and this percentage continues to increase. This study examines the pharmaceutical expenses associated with one of the most common chronic diseases: diabetes. Specifically, we measure the extent to which patient health and demographic factors drive the annual cost of pharmaceutical supplies for diabetes management. Second, the study applied a procurement‐centric classification scheme to pharmaceutical items involved in diabetes treatment.MethodsData on 98,648 pharmaceutical‐dispensing transactions (related to 2828 patients) over 1 year were collected from a specialized diabetes health center. Pharmaceutical prices from the sample were compared internationally to ensure that the findings apply to other countries. The association between the item cost and the number of unique patients prescribed pharmaceutical products was estimated at the category and subcategory levels.ResultsApproximately 80% of total pharmaceutical expenditures were attributed to 20% of patients. Two of 20 pharmaceutical categories—anti‐diabetes drugs and insulin—accounted for 34% of products dispensed and 57% of total pharmaceutical expenditures. Age, body mass index, and diabetes type were essential factors in predicting supply cost per patient.ConclusionApplying the portfolio purchasing model also suggested that some clinically similar items, like insulin types, are best procured through divergent procurement strategies or vendors for optimal cost efficiency. A better understanding of the diverse array of diabetes supplies can reveal opportunities for better strategic supply management. This supply classification approach can also be applied in other supply‐intensive specialties, such as orthopedics.

Finerenone, a Novel and Safer Approach toward Management of Diabetic Kidney Disease with Heart Failure

Diabetes is the major cause of chronic and end-stage renal disease worldwide. Despite recent breakthroughs in diabetic kidney disease (DKD) therapy, there is still a significant need for more choices to enhance renal and cardiovascular outcomes. Mineralocorticoid overactivity adds to inflammation and fibrosis, which leads to the advancement of DKD. The mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone slow the course of DKD as well as the risk of hospitalizations and death in patients with heart failure (HF) with reduced ejection fraction but their potential of causing hyperkalemia, particularly in individuals with renal dysfunction, restricts their usage. Finerenone, a new non-steroidal MRA, has showed potential cardiac and renoprotective advantages in DKD as well as has a better affinity for the mineralocorticoid receptor (MR) than eplerenone and higher selectivity for the MR than spironolactone. Studies have shown that the selective non-steroidal MRA finerenone reduces the risk of cardiovascular events and chronic kidney disease (CKD) progression in individuals with CKD and type 2 diabetes mellitus. Finerenone selectivity and higher binding affinity to the MR may lower the risk of hyperkalemia and renal dysfunction, overcoming the reluctance to initiate MRAs in patients with HF and DKD.

Protective effects of Artemisia herba-alba in diabetic peripheral artery disease mediated via inhibition of advanced glycation end products

The rationale for undertaking this study is lethality of diabetes mellitus as predicted by 6.7 million deaths in 2021 and immense pharmacological potential of Artemisa herba-alba. The current research examined how Artemisia herba-alba extract (AHE) affects the peripheral artery disease in diabetic rats through lowering of advanced glycation end products (AGEs). The in-vitro AGE inhibiting potential of AHE was determined by spectrofluorimetric method. The blood glucose levels and HbA1c (A1C) of the rats from each group were determined by automatic analyser. The levels of AGEs in vascular smooth muscle cells (VSMCs) of different rat groups were observed through western blotting. Expression of COX-1 and COX-2 were determined by qRT-PCR. The AHE inhibition of AGEs formation was reported in vitro and exhibited an IC50 of 45 μg/mL which was significantly lower than that of standard AGEs inhibitor aminoguanidine (IC50: 60 μg/mL). Analysis of metabolic profiles revealed that AHE normalised the blood glucose, cholesterol, and triglycerides with no apparent changes on Hb1Ac levels. Western blot analysis showed that AHE exhibited protective effects in VSMCs of diabetic rats by inhibiting fabrication of AGEs. Moreover, the manifestation of COX-2 was inhibited by AHE in diabetic rats. However, the expression of COX-1 remained unaltered. Collectively, the results revealed AHE inhibits AGEs formation in vitro and in VSMCs of diabetic rats. These findings point towards the prospective of AHE applications towards the management of diabetic peripheral artery disease.

Evaluation of type 2 diabetes care management in nine primary care practices before and after implementation of the Criteria of Good Disease Management of Diabetes established by the Swiss Society of Endocrinology and Diabetology.

Little is known about the quality of diabetes management of patients with type 2 diabetes mellitus (T2DM) in Swiss primary care. Based on the recommendations of the National Council Quality Assurance Programme, an interprofessional working group of the Swiss Society of Endocrinology and Diabetology (SSED) established population-based national criteria for good disease management of T2DM in primary health care (the diabetes score). The objective of this study was to assess whether the implementation of these criteria improve diabetes management in primary care. The diabetes score comprises eight criteria including three biometric measurements, two lifestyle-specific items and screening of three diabetes-associated complications. Practices can evaluate adherence to the criteria based on a point system, with the recommended aim to achieve ≥70/100 points. Group practices and single practices were included in this study and started implementing the SSED criteria in January 2018. The resulting score was compared with data retrospectively obtained for 2017. The primary endpoint was the overall change in Diabetes Score between 2017 and 2018 at each practice, further stratified by practice type. The absolute effect on individual diabetes score criteria was assessed by pooling all patient-level data. Nine practices (six single and three group) participated in the study. In 2017 and 2018, the primary care practices treated 727 and 704 patients with T2DM, respectively, of whom 676 were treated both years. Around half of the patients were cared for in group practices and half in single practices. Between 2017 and 2018 the median (interquartile range) diabetes score improved from 40 (35, 65) to 55 (45, 70; p = 0.078). One practice (single) obtained a score ≥70 in 2017, three practices (all single) achieved this target in 2018. Pooling patient-level data, we observed a significant absolute improvement in the following criteria: number of regular diabetes check ups, body mass index, glycated haemoglobin, blood pressure, low density lipoprotein cholesterol and screenings for diabetes-associated complications (all p <0.05). However, the extent of the improvements were often insufficient to reach the prefixed targets of the diabetes score criteria on the practice level. Overall, the implementation of the SSED criteria in the current setting led to a modest, nonsignificant improvement of the diabetes score. Only three (all single practices) out of the nine practices reached the recommended 70-point target, indicating that further strategies are needed to improve diabetes care in primary care practice. Trial registration: ClinicalTrials.gov (ID NCT04216875).

Advances in the management of diabetic kidney disease: beyond sodium-glucose co-transporter 2 inhibitors.

Progress in the treatment of diabetic kidney disease (DKD) has been modest since the early trials on renin-angiotensin-aldosterone system inhibitors (RAASis). Although sodium-glucose co-transporter 2 inhibitors (SGLT2is) have revolutionized the management of DKD by lowering proteinuria and protecting organs, other novel treatment approaches with good evidence and efficacy that can be used in conjunction with a RAASi or SGLT2i in managing DKD have emerged in the past few years. This review discusses the evidence for glucagon-like peptide-1 receptor agonist, selective mineralocorticoid receptor antagonist, and selective endothelin A receptor antagonist, emerging treatment options for DKD beyond SGLT2 inhibition.

A Review of National Level Guidelines for Risk Management of Cardiovascular and Diabetic Disease.

Cardiovascular diseases and diabetes are among the leading preventable causes of morbidity and mortality. Cardiovascular disease risk reduction aimed to address the significant modifiable risk factors, including lifestyle-related risk factors, hypertension, hyperlipidemia, and diabetes. Given the severity and disease burden, many insurances, including Medicare, cover the annual counseling for risk reduction of cardiovascular disease. Although numerous national-level guidelines are available for managing these conditions, most of them focus on disease management. Given the broad areas covered in these recommendations, a concise review summarizing the measures addressing the preventive approach in these conditions is not readily available. Herewith, we review and outline the currently available guidelines from national-level publications with principal attention to the primary prevention measures to provide a broad overview and assist providers with the risk reduction counseling.

EE190 Cost-Effectiveness of Dapagliflozin Alone or in Combination with Saxagliptin Added to Standard of Care for the Management of Diabetic Kidney Disease in the United States

Angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor inhibitors (ARBs) have been used as standard of care (SoC) for the treatment of diabetes nephropathy (DN) in the United States. Dapagliflozin and saxagliptin have shown to reduce progression of diabetes kidney disease when they are added to the SoC. The present study aimed to determine the cost-effectiveness of dapagliflozin or dapagliflozin plus saxagliptin added to the SoC in diabetes patients with diabetic kidney disease.

Impact of a diabetes disease management program on guideline-adherent care, hospitalization risk and health care costs: a propensity score matching study using real-world data

ObjectiveTo evaluate the impact of a DMP for patients with diabetes mellitus in a Swiss primary care setting.MethodsIn a prospective observational study, we compared diabetes patients in a DMP (intervention group; N = 538) with diabetes patients receiving usual care (control group; N = 5050) using propensity score matching with entropy balancing. Using a difference-in-difference (DiD) approach, we compared changes in outcomes from baseline (2017) to 1-year (2017/18) and to 2-year follow-up (2017/19). Outcomes included four measures for guideline-adherent diabetes care, hospitalization risk, and health care costs.ResultsWe identified a positive impact of the DMP on the share of patients fulfilling all measures for guideline-adherent care [DiD 2017/18: 7.2 percentage-points, p < 0.01; 2017/19: 8.4 percentage-points, p < 0.001]. The hospitalization risk was lower in the intervention group in both years, but only statistically significant in the 1-year follow-up [DiD 2017/18: – 5.7 percentage-points, p < 0.05; 2017/19: – 3.9 percentage points, n.s.]. The increase in health care costs was smaller in the intervention than in the control group [DiD 2017/18: CHF – 852; 2017/19: CHF – 909], but this effect was not statistically significant.ConclusionThe DMP under evaluation seems to exert a positive impact on the quality of diabetes care, reflected in the increase in the measures for guideline-adherent care and in a reduction of the hospitalization risk in the intervention group. It also might reduce health care costs, but only a longer follow-up will show whether the observed effect persists over time.

The 2021–2022 position of Brazilian Diabetes Society on diabetic kidney disease (DKD) management: an evidence-based guideline to clinical practice. Screening and treatment of hyperglycemia, arterial hypertension, and dyslipidemia in the patient with DKD

BackgroundDiabetic kidney disease is the leading cause of end-stage renal disease and is associated with increased morbidity and mortality. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021–2022. This evidence-based guideline provides guidance on the correct management of Diabetic Kidney Disease (DKD) in clinical practice.MethodsThe methodology was published elsewhere in previous SBD guidelines and was approved by the internal institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated 14 experts to constitute the Central Committee, designed to regulate methodology, review the manuscripts, and make judgments on degrees of recommendations and levels of evidence. SBD Renal Disease Department drafted the manuscript selecting key clinical questions to make a narrative review using MEDLINE via PubMed, with the best evidence available including high-quality clinical trials, metanalysis, and large observational studies related to DKD diagnosis and treatment, by using the MeSH terms [diabetes], [type 2 diabetes], [type 1 diabetes] and [chronic kidney disease].ResultsThe extensive review of the literature made by the 14 members of the Central Committee defined 24 recommendations. Three levels of evidence were considered: A. Data from more than 1 randomized clinical trial or 1 metanalysis of randomized clinical trials with low heterogeneity (I2 < 40%). B. Data from metanalysis, including large observational studies, a single randomized clinical trial, or a pre-specified subgroup analysis. C: Data from small or non-randomized studies, exploratory analyses, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panelists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa 75–89% of agreement; IIb 50–74% of agreement, and III, when most of the panelist recommends against a defined treatment.ConclusionsTo prevent or at least postpone the advanced stages of DKD with the associated cardiovascular complications, intensive glycemic and blood pressure control are required, as well as the use of renin–angiotensin–aldosterone system blocker agents such as ARB, ACEI, and MRA. Recently, SGLT2 inhibitors and GLP1 receptor agonists have been added to the therapeutic arsenal, with well-proven benefits regarding kidney protection and patients’ survival.

Association Between Serum Aminotransferases and Risk of New-Onset Cardiometabolic Disease in a Healthy Chinese Population: A Cohort Study.

PurposeThis study aimed to investigate the association between serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and incident metabolic disease in a cohort of community-based older Chinese people.Patients and MethodsFive thousand healthy Gaohang residents who attended community health checks at the Shanghai East Hospital in 2013 were recruited. Biological, biochemical, and lifestyle variables were collected. The cohort was followed for new-onset metabolic disease in 2014 and 2017, with a final study population of 3,123 (63%) after follow-up. The study outcome included type-2 diabetes mellitus and metabolic syndrome.ResultsBaseline AST and ALT were associated with incident type-2 diabetes mellitus (HR 1.019, 95% CI 1.006–1.032, p = 0.003 and HR 1.016, 95% CI 1.008–1.025, p < 0.001 respectively). These associations persisted after adjusting for traditional risk factors including age, sex, income, waist circumference, systolic blood pressure, diastolic blood pressure, HbA1c, triglyceride, cholesterol, HDL and eGFR. Baseline AST and ALT were associated with incident metabolic syndrome in the crude analysis (HR 0.980, 95% CI 0.965–0.996, p = 0.012 and HR 0.992, 95% CI 0.988–0.997, p = 0.001, respectively). However, the association between AST and ALT with metabolic syndrome was non-significant after adjusting for biochemical parameters such as the lipid profile.ConclusionThis study demonstrated that serum AST and ALT are associated with new-onset type-2 diabetes mellitus, independent of traditional risk factors, in a cohort of older Chinese people. These findings may contribute to disease risk stratification and management in type-2 diabetes.

The Lower Limit of Reference of Urinary Albumin/Creatinine Ratio and the Risk of Chronic Kidney Disease Progression in Patients With Type 2 Diabetes Mellitus.

A urine albumin/creatinine ratio (UACR) <30 mg/g is considered to be normal, while increased risk of incident hypertension and cardiovascular disease mortality in subjects with high normal UACR level had been observed. However, a mild elevated but normal UACR level was associated with the risk of initiating chronic kidney disease (CKD) is uncertain. We investigated whether higher normal UACR is associated with the risk of developing CKD. A total of 4821 subjects with type 2 diabetes mellitus (T2DM), an estimated glomerular filtration rate >60 ml/min/1.73 m2 and UACR <30 mg/g enrolled in a diabetes disease management program between 2006 and 2020 were studied. The optimal cutoff point for baseline UACR as a predictor for progression to CKD according to the 2012 KDIGO definition was calculated using receiving operating characteristic curve analysis. After a mean of 4.9 years follow-up, the CKD risk progression increased in parallel with the quartiles of baseline UACR <30 mg/g (p for trend <0.0001). UACR cutoff points of 8.44 mg/g overall, 10.59 mg/g in males and 8.15 mg/g in females were associated with the risk of CKD progression. In multivariate Cox regression analysis, the hazard ratios for the association between UACR (>8.44 mg/g, >10.9 mg/g, >8.15 mg/g in overall, male, and female patients, respectively) and the risk of CKD progression were significant. This study demonstrated that a cutoff UACR value of >10 mg/g could significantly predict the cumulative incidence and progression of CKD in patients with T2DM.

Syzygium samarangense leaf extract exhibits distinct antidiabetic activities: Evidences from in silico and in vivo studies

The wax apple, Syzygium samarangense , is widely used in traditional medicine. We have previously described a plethora of biological activities from its leaf extract. These include antioxidant, anti-inflammatory, antiulcer, antitrypanosomal and hepatoprotective effects. Here, we explored the antidiabetic activities from the bioactive leaf extract in silico on two crucial receptors involved in the management of diabetes disease namely peroxisome proliferator activated receptor gamma (PPARɣ) and glucagon like peptide-1 (GLP-1) and in vivo against streptozotocin-induced diabetic rats. Altogether, 457 secondary metabolites belonging to 10 classes (phenolic acids (86 compounds), flavonoids (139 compounds), anthocyanins (61 compounds), alkylphenols (17 compounds), chalcone (15 compounds), stilbenes (9 compounds), lignans (29 compounds), tannins (29 compounds), tyrosols (13 compounds), and terpenes and others (59 compounds), were docked into the active site of PPARɣ and GLP-1 receptors. From the PDB codes used for each receptor, the co-crystallized ligand was extracted and docked together with a known reference ligand. This was done simultaneously with docking the extract’s compounds to serve as references for comparative purposes. Out of the docked candidates, the top 30 compounds affording the best docking scores were compiled for further inspection and they appeared to exhibit better scores than the respective co-crystallized and reference ligands, highlighting the antidiabetic potential of the tested extract. Nine compounds exhibited highly negative scores on both receptors, demonstrating their high probability of being potent antidiabetic agents through forming stable ligand-receptor complexes. These activities were also confirmed in STZ diabetic rats where the extract reduced the elevated levels of serum glucose and lipid peroxides and increased the declined serum insulin hormone level. Taking all together, S. samarangense can be a potential candidate for further investigations for the treatment of numerous health disorders including diabetes.