Progression Of Diabetic Disease Research Articles

Breakdown and Repair of Peripheral Immune Tolerance in Type 1 Diabetes.

Failures in peripheral immune tolerance mechanisms create a permissive environment for autoimmune diabetes initiation and disease progression. Biomarker analyses provide tools that allow recognition of this loss of tolerance, reflecting a serial acquisition of pathogenic characteristics causally linked to islet β-cell dysfunction and death. Autoimmune effector cell activation and expansion, ineffective immune regulation, and tissue response to injury during active disease each represent challenges to homeostasis; however, they also represent targets for therapeutic intervention, with the potential for restoration of tolerance. Limited success in recent clinical trials demonstrates that tolerance in type 1 diabetes (T1D) is achievable, but currently occurs in few subjects and is not durable in most. Combining therapeutic agents to rebuild multiple immune components to restore tolerance, particularly addressing both effector and regulatory T-cell dysfunction, is needed.

Nε-carboxymethyl-lysine and inflammatory cytokines, markers and mediators of coronary artery disease progression in diabetes

This editorial refers to the article “Comparative analysis of Nε-carboxymethyl-lysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients”, published in the recent issue of the World Journal of Diabetes 2023 is based on glucose metabolism, advanced glycation end products (AGEs), inflammation and adiposity on diabetes and coronary artery disease (CAD). This study has included CAD patients who were stratified according to glycosylated hemoglobin higher than 6.5 and sex-matched. A higher prevalence of hypertension, dyslipidemia, and non-vegetarian diet were found in the diabetic group. These risk factors might influence body weight and adiposity and explain the increment of the left atrium. Although this data was not supported by the study. The diet can also explain the non-enzymatic reactions on lipids, proteins, or nucleic acids and consequently an increment of AGEs. These molecules can emit fluorescence. However, one of the non-fluorescent and most abundant AGEs is Nε-carboxymethyl-lysine (CML). Its association with coronary artery stenosis and severity in the diabetic group might suggest its role as a player in CAD progression. Thus, CML, after binding with its receptor (RAGE), can induce calcification cascade through reactive oxygen species and mitogen-activated protein kinase. Moreover, this interaction AGE-RAGE can cause activation of the transcription nuclear factor-kb and induce inflammatory cytokines. It might explain the relationship between CML and pro-inflammatory cytokines in diabetic and CAD patients. Although this is a population from one center, the determination of CML and inflammatory cytokines might improve the diagnosis of severe and progressive CAD. Future and comparative studies among glycosylated hemoglobin, CML, and other AGE levels according to diagnosis and prognosis value might modify the clinical practice. Although these molecules are irreversible, they can act through a specific receptor inducing a signal transduction that might be modu-lated by inhibitors, antibodies, or siRNA. Further mechanistic studies might improve the development of future preventive therapies for diabetic patients.

The Association of Sickle-Cell Disorders With Diabetic Retinopathy: A Large Database Study

PurposeTo evaluate the association of sickle-cell disease (SCD) and sickle-cell trait (SCT) disease with diabetic retinopathy (DR) in patients with diabetes mellitus (DM). DesignPopulation-based, retrospective cohort study utilizing data from the TriNetX Research Network, including 119 million patients across 80 healthcare organizations worldwide. ParticipantsDM patients (Type 1 (T1DM) or 2 (T2DM)), with or without SCD and SCT, were included. Three cohorts were analyzed, including (1) DM patients without SCD, SCT, or Sickle-cell/Hb-C; (2) DM with SCD; and (3) DM with SCT. MethodsAll patients with DM were categorized into three cohorts based on the presence of SCD and SCT. Each cohort underwent 1:1 propensity score matching for demographics, blood glucose levels, hemoglobin A1C, and other relevant comorbidities. Main Outcome MeasuresRisk of DR in DM patients with and without SCD or SCT. ResultsThere was no significant difference in the risk of any T1DR between those with and without SCD. However, for those with SCT, there was a notable 2-fold increased risk for T1-PDR (RR: 2.03; 95% CI: 1.33-3.01). In contrast, there was an elevated risk for any T2DR in patients with SCD (RR: 1.50; 95% CI: 1.19-1.88), particularly due to higher proliferative DR risks in T2DM patients (RR: 1.83; 95% CI: 1.29-2.60). The risk of mild to moderate T2DM non-proliferative DR was also found to be higher in patients with SCT. ConclusionsThe risk of any DR was increased in T2DM patients with SCD or SCT, with increased risks for proliferative DR in patients with SCT and T1DM. This indicates there may be a potential role of SC disorders in diabetic eye disease progression.

Transcriptome and Pathway Analysis Reveals that Adipose-derived Stem Cells Target Inflammatory Factors and Delay the Progression of Diabetic Liver Disease.

Diabetic liver disease is one of the main complications that leads to the aggravation of diabetes, but it has not received sufficient attention. This study aimed to provide a better understanding of the altered molecular networks in in diabetic rats with liver damage after stem cell therapy. To a certain extent, our research would be instructive, since almost no studies of this kind have been performed on patients with diabetic liver disease after stem cell therapy. Streptozotocin-induced diabetic rats were treated with adipose-derived stem cells. RNA-Seq analysis was performed on the liver tissues of these animals, and key pathway factors were further identified and validated. RNA-Seq analysis revealed numerous affected signaling pathways and functional categories. The results showed that the network of dual specificity phosphatase 1 (DUSP1), an oxidative stress-related gene, was prominently activated in the liver after stem cell therapy, and the enrichment of genes associated with liver damage, steatosis and fibrosis was also detected. The extracellular regulated protein kinase (ERK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway may be involved in this process by regulating the nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. These data provide novel insights into liver biology, suggest common alterations in the molecular networks during diabetic liver damage, and show the advantages of stem cell therapy, indicating its further application potential for early treatment of diabetic liver damage and delaying the progression of liver fibrosis in the later stage.

Exploring Technology Domains for Diabetes Care and Management under Pandemic: A preliminary scoping review

Objective: Technology innovation emerged in diabetic care and management during COVID-19. To tackle emerging opportunities, this scoping review aims to analyze current technology used for diabetic care by employing WHO technology initiatives to reveal technology use potentials for future research and development. Materials and Methods: We conducted a review following PRISMA. We initiated a search of related terms for peer-reviewed publications in PubMed and Web of Science, including those themed in diabetic care and management and published in English. Results: We reviewed 42 articles following the guidance of WHO technology conceptualization, including mHealth (12%), eHealth (76%), and dHealth (12%). These initiatives are used to reveal six areas of technology utilization for diabetes care during the pandemic, including (1) social media; (2) sensor; (3) teleconference; (4) virtual care; (5) artificial intelligence; and (6) data mining. Discussion: Based on the identified dimensions related to technology and health, we presented seven diabetes-related health events and their associations with technologies. Implications such as technology’s association with diabetes disease progression, technology diagramming for interdisciplinary collaboration, and technology features for health outcomes provide direction for future research and development. Conclusion: This review illustrates current technology utilization in diabetes care during the pandemic. It also uncovers innovation opportunities across technology and diabetic healthcare domains and provides direction for future pursuits in academia and practice.

Call for Cultural and Language-Concordant Diabetes Care, Nutrition Education, and Self-Management for South Asian Individuals Living in the US

Ethnic South Asian Americans have the highest relative risk of type 2 diabetes mellitus in the US. Culturally tailored and language-concordant diabetes care and nutrition interventions can potentially promote South Asian diabetes management and disease progression. From our perspective, the extent of their use and evaluation in the US settings remains limited. This Perspective characterizes and evaluates the necessity and outcomes of culturally and linguistically adapted lifestyle interventions targeted toward type 2 diabetes mellitus indicators among South Asian individuals in the US. Suggestions for how this education could be modified include emphasizing the cultural and linguistic knowledge and self-awareness of diabetes educators and the sociological and historical factors that influence the cultural and linguistic orientation of diabetes care professionals and their clients. Such strategies could ensure better diabetes education and self-management among South Asian individuals.

Experimental diabetic animal models to study diabetes and diabetic complications

Diabetes is an endocrine illness involving numerous physiological systems. To understand the intricated pathophysiology and disease progression in diabetes, small animals are still the most relevant model systems, despite the availability and progression in numerous invitro and insilico research methods in recent years. In general, experimental diabetes is instigated mainly due to the effectiveness of animal models in illuminating disease etiology. Most diabetes trials are conducted on rodents, while some research is conducted on larger animals. This review will discuss the methodology and mechanisms in detail for preparing diabetic animal models, considering the following important points. The exact pathophysiology of the disease may or may not be replicated in animal models, the correct induction doses must be given and the combination of different approaches for the models is recommended to get desired results.•Animal models are essential to understand diabetes etiology and pathophysiology.•Diabetic models can be developed in both rodents and non-rodents.•Chemically induced and genetic models of diabetes are widely used to study diabetes and diabetic complications.

Understanding the Role of the Gut Microbiome in Diabetes and Therapeutics Targeting Leaky Gut: A Systematic Review.

The gut microbiota has been studied and continues to be a developing area in the pathognomic development of metabolic diseases like diabetes. Treatment with diet changes, the addition of supplements like prebiotics/probiotics, and the impact of fecal microbial transplantation can be correlated to targeting changes in dysbiosis. Understanding the impacts of various anti-hyperglycemic agents such as metformin and the implications of post-bariatric surgery on the gut microbiota diversity has emerged. These areas of study are crucial to understanding the pathognomic aspects of diabetes disease progression at the microbial level of metabolic and inflammatory mechanisms, which may give more insight into focusing on the role of diet prebiotic/probiotic supplements as potential forms of prospective management in diabetes and the development of more agents that target gut microbiota, which harbors low-grade inflammation. Intestinal dysbiosis was consistently observed in the mechanism of gut microbial change in diabetic individuals, contributing to reduced insulin sensitivity and poor glycemic control. This systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 checklist. We performed a literature search using the PubMed, Google Scholar and Science Direct databases in accordance with the eligibility criteria and ultimately selected 14 articles for final analysis. The Scale for the Assessment of Narrative Review Articles (SANRA) and the PRISMA 2020 checklist were used to assess the quality of selected articles for cross-sectional studies, traditional literature reviews, and systematic reviews, respectively. We collected papers from 2012 to 2022 for this review. We gathered articles from databases, such as this study, which show there is a strong connection between microbiota and diabetes that appears to exist. The objective is to assess and identify any dietary and therapeutic agents that may alter the microbiota and potentially target and modulate insulin sensitivity. This review article will discuss the pathophysiological effects of gut microbiota in diabetes management and the impact of various gut biodiversity therapeutics that can aid in reversing insulin sensitivity.

Assessment of Parafoveal Diabetic Macular Ischemia on Optical Coherence Tomography Angiography Images to Predict Diabetic Retinal Disease Progression and Visual Acuity Deterioration

The presence of diabetic macular ischemia (DMI) on optical coherence tomography angiography (OCTA) images predicts diabetic retinal disease progression and visual acuity (VA) deterioration, suggesting an OCTA-based DMI evaluation can further enhance diabetic retinopathy (DR) management. To investigate whether an automated binary DMI algorithm using OCTA images provides prognostic value on DR progression, diabetic macular edema (DME) development, and VA deterioration in a cohort of patients with diabetes. In this cohort study, DMI assessment of superficial capillary plexus and deep capillary plexus OCTA images was performed by a previously developed deep learning algorithm. The presence of DMI was defined as images exhibiting disruption of fovea avascular zone with or without additional areas of capillary loss, while absence of DMI was defined as images presented with intact fovea avascular zone outline and normal distribution of vasculature. Patients with diabetes were recruited starting in July 2015 and were followed up for at least 4 years. Cox proportional hazards models were used to evaluate the association of the presence of DMI with DR progression, DME development, and VA deterioration. Analysis took place between June and December 2022. DR progression, DME development, and VA deterioration. A total of 321 eyes from 178 patients were included for analysis (85 [47.75%] female; mean [SD] age, 63.39 [11.04] years). Over a median (IQR) follow-up of 50.41 (48.16-56.48) months, 105 eyes (32.71%) had DR progression, 33 eyes (10.28%) developed DME, and 68 eyes (21.18%) had VA deterioration. Presence of superficial capillary plexus-DMI (hazard ratio [HR], 2.69; 95% CI, 1.64-4.43; P < .001) and deep capillary plexus-DMI (HR, 3.21; 95% CI, 1.94-5.30; P < .001) at baseline were significantly associated with DR progression, whereas presence of deep capillary plexus-DMI was also associated with DME development (HR, 4.60; 95% CI, 1.15-8.20; P = .003) and VA deterioration (HR, 2.12; 95% CI, 1.01-5.22; P = .04) after adjusting for age, duration of diabetes, fasting glucose, glycated hemoglobin, mean arterial blood pressure, DR severity, ganglion cell-inner plexiform layer thickness, axial length, and smoking at baseline. In this study, the presence of DMI on OCTA images demonstrates prognostic value for DR progression, DME development, and VA deterioration.

Potential Protective Link Between Type I Diabetes and Parkinson's Disease Risk and Progression.

Epidemiological studies suggested an association between Parkinson's disease (PD) and type 2 diabetes, but less is known about type 1 diabetes (T1D) and PD. This study sought to explore the association between T1D and PD. We used Mendelian randomization, linkage disequilibrium score regression, and multi-tissue transcriptome-wide analysis to examine the association between PD and T1D. Mendelian randomization showed a potentially protective role of T1D for PD risk (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.94-0.99; P = 0.039), as well as motor (OR, 0.94; 95% CI, 0.88-0.99; P = 0.044) and cognitive progression (OR, 1.50; 95% CI, 1.08-2.09; P = 0.015). We further found a negative genetic correlation between T1D and PD (rg = -0.17; P = 0.016), and we identified eight genes in cross-tissue transcriptome-wide analysis that were associated with both traits. Our results suggest a potential genetic link between T1D and PD risk and progression. Larger comprehensive epidemiological and genetic studies are required to validate our findings. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Hybrid confidence intervals for informative uniform asymptotic inference after model selection

Abstract I propose a new type of confidence interval for correct asymptotic inference after using data to select a model of interest without assuming any model is correctly specified. This hybrid confidence interval is constructed by combining techniques from the selective inference and post-selection inference literatures to yield a short confidence interval across a wide range of data realizations. I show that hybrid confidence intervals have correct asymptotic coverage, uniformly over a large class of probability distributions that do not bound scaled model parameters. I illustrate the use of these confidence intervals in the problem of inference after using the lasso objective function to select a regression model of interest and provide evidence of their desirable length and coverage properties in small samples via a set of Monte Carlo experiments that entail a variety of different data distributions as well as an empirical application to the predictors of diabetes disease progression.

Recent Advancements of Microspheres for The Management of Diabetes

Diabetes is a chronic metabolic disorder that is accompanied by the inability of the body to regulate blood sugar level. The prevalent lifestyle and diet habits have increased the number of diabetic individuals to a large number. The novel treatment options have been explored to manage diabetes and overcome the risks associated with the existing therapy. Some of the recent researchers have prepared advanced microspheres either for the delivery of anti-diabetic drugs and insulin or for diagnostic purposes. These microspheres allow the development of controlled or sustained delivery products with rapid onset of action and improved bioavailability. The fabrication of surface-modified microspheres has shown significant promise in achieving the therapeutic goal of diabetes. Glucose-sensitive microspheres can control the release of insulin for a longer duration and improve the hypoglycemic effect of the product. Apart from these, specially designed microspheres were utilized for early detection of diabetes and study disease progression. This review is aimed at providing a perspective over some of the important recent researches with regards to treatment and diagnosis of diabetes. Microspheres have offered a lot of potential for integrating innovative strategies in the treatment and diagnosis of diabetes. The scalability and real-life interventions of these approaches might still be a challenge that need to be addressed.

Risk of cardiovascular disease, death, and renal progression in diabetes according to albuminuria and estimated glomerular filtration rate

AimWe aimed to examine risks of major cardiovascular events (MACEs), renal outcomes, and all-cause mortality in type 2 diabetes mellitus (T2DM) patients with different diabetic kidney disease (DKD) subtypes. MethodsA total of 36,509 participants with T2DM recruited from 20 community sites across mainland China were followed up during 2011-2016. DKD subtypes were categorized based on albuminuria (urinary albumin-to-creatinine ratio, UACR ≥ 30 mg/g) and reduced estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m2) as Alb−/eGFR−, Alb+/eGFR−, Alb−/eGFR+, and Alb+/eGFR+. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of developing clinical outcomes in DKD subtypes. ResultsMore than half (53.5%) of participants with diabetes and reduced eGFR had normal UACR levels (Alb−/eGFR+), termed as non-albuminuria DKD. These patients had a modest increase in the risks of MACEs (hazard ratio, HR 1.42 [95% CI 1.08;1.88]) and mortality (HR 1.42 [1.04;1.92]) compared with patients without DKD, whereas CKD progression was not significantly increased (HR 0.97 [0.60;1.57]). Participants with albuminuria (Alb+/eGFR− or Alb+/eGFR+) had higher risks of clinical outcomes. Subgroup analysis revealed that the associations between non-albuminuria DKD and risks of MACEs and mortality were more evident in those aged <65 years. ConclusionNon-albuminuria DKD accounts for more than half of DKD cases with low eGFR in Chinese diabetes patients. Diabetes patients with albuminuria are at higher risks of developing clinical outcomes and warrant early intervention, as well as patients with non-albuminuria DKD with age < 65 years.

The effect of comorbid factors and amputation level on mortality in geriatric patients with diabetic foot.

The aim of this study was to evaluate the factors that influenced one-year and five-year mortality and to compare major and minor amputations in diabetic patients with comorbidities. Between February 2008 and November 2014, a total of 201 type 2 diabetic foot patients (147 males, 54 females; median age: 65.99 years; range, 50 to 92 years) who underwent amputation were retrospectively analyzed. The patients were divided into two groups according to their initial amputation level: Group 1 (n=100), minor amputation group, which included the distal region of the ankle joint and Group 2 (n=101), major amputation group, which included trans-tibial amputation, trans-femoral amputation and hip disarticulation. Clinical data including patients' demographic features, re-amputation degree, length of hospitalization, hyperbaric oxygen therapy, comorbidities, blood parameters, and survival rates were recorded. The regression analysis of one-year mortality found that the presence of cerebrovascular disease increased death by 2.463 times (p=0.002). Minor amputation increased mortality by 2.284 (p=0.006), and each unit increase in patient age increased mortality by 1.05 (p=0.008). Chronic renal failure increased death by 3.164 times (p<0.001) in the five-year mortality regression analysis. Minor amputations have an effect on one-year mortality, as do cerebrovascular disease and age. On the other hand, chronic renal failure has a negative impact on five-year mortality. Minor amputations may have a detrimental effect on mortality due to the ongoing progression of diabetic foot disease and the involvement of comorbidities. Comorbidities associated with amputations of the diabetic foot have a significant impact on mortality.

HIF-1α accumulation in response to transient hypoglycemia may worsen diabetic eye disease

Tight glycemic control (TGC), the cornerstone of diabetic management, reduces the incidence and progression of diabetic microvascular disease. However, TGC can also lead to transient episodes of hypoglycemia, which have been associated with adverse outcomes in patients with diabetes. Here, we demonstrate that low glucose levels result in hypoxia-inducible factor (HIF)-1-dependent expression of the glucose transporter, Glut1, in retinal cells. Enhanced nuclear accumulation of HIF-1α was independent of its canonical post-translational stabilization but instead dependent on stimulation of its translation and nuclear localization. In the presence of hypoxia, this physiologic response to low glucose resulted in a marked increase in the secretion of the HIF-dependent vasoactive mediators that promote diabetic retinopathy. Our results provide a molecular explanation for how early glucose control, as well as glycemic variability (i.e., oscillating serum glucose levels), contributes to diabetic eye disease. These observations have important implications for optimizing glucose management in patients with diabetes.

Efficacy and safety of external therapy of TCM for diabetic peripheral vascular disease: A protocol for systematic review and meta-analysis.

In modern society, the incidence of diabetes is increasing yearly, and poor glycemic control can accelerate the progression and severity of diabetic peripheral vascular disease. External treatment with traditional Chinese medicine (TCM) has been widely used in the treatment of diabetes, but there is no systematic review on the external treatment of TCM for diabetic peripheral vascular disease; therefore, this study aimed to conduct a meta-analysis on the clinical efficacy and safety of external treatment of TCM in the treatment of diabetic peripheral vascular diseases. We searched The Cochrane Library, PubMed, Web of Science, EMBASE, China Science and Technology Journal, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature Database, and other sources from their respective inception dates to October 20, 2022, to identify potentially eligible studies. We will use Review Manager 5.4 software provided by the Cochrane Collaborative Network for statistical analysis. We then assessed the quality and risk of the included studies and observed their outcome measures. Changes in the bilateral femoral artery, popliteal artery, dorsal artery diameter, blood flow, ankle/brachial index, and dorsal foot temperature: An overall reduction in symptoms (a reduction in diabetes-related symptoms that occur only during the intervention or as a result of the intervention, including peripheral vascular disease). The objective of this meta-analysis was to investigate the influence of external treatment of traditional Chinese medicine on diabetic peripheral vascular disease and to provide more methods for the clinical prevention and treatment of diabetic peripheral vascular disease.

Cellular Stress Assay in Peripheral Blood Mononuclear Cells: Factors Influencing Its Results.

Cellular stress is central to the understanding of pathological mechanisms and the development of new therapeutic strategies and serves as a biomarker for disease progression in neurodegeneration, diabetes, cancer, cardiovascular and other chronic diseases. The common cellular stress assay (CSA) based on Seahorse technology in peripheral blood mononuclear cells (PBMCs) shows inconsistent results, which prevents its use as a biomarker for the progression of chronic diseases. Therefore, the aim of this study was to investigate potential factors that affect the CSA in PBMCs. We measured the CSA parameters in PBMCs from study participants and compared the results according to the potential factors, namely, the PBMC isolation method, age, seasonal variation and the gender of the study participants. PBMCs were isolated by OptiPrep® and RobosepTM-S methods. PBMCs isolated with the OptiPrep method showed much higher extracellular acidification and higher respiration compared to Robosep-isolated cells. Moreover, OptiPrep-isolated cells showed a higher number of outliers for the proton production rate (PPR) and a high respiratory quotient, indicating impurities with other cells, such as platelets, and technical inconsistencies. PBMCs from older individuals showed higher maximal respiration, spare capacity and extracellular acidification than younger participants. Additionally, in winter, maximal respiration and spare capacity decreased. From spring until early autumn, spare capacity and maximal respiration continuously increased. Elderly males also showed higher basal respiration, spare capacity and extracellular acidification than females. In conclusion, the findings of this study clearly demonstrate that the results of CSA parameters measured in PBMCs are influenced by the PBMC isolation method, age, seasonal variation and gender. Therefore, we recommend that researchers and physicians properly interpret the results of CSA parameters in PBMCs by considering these factors. It is important to use separate CSA evaluation standards based on the isolation method, age, gender and season-dependent factors. To assess the cellular stress situation in PBMCs, both extracellular acidification and mitochondrial respiration should be taken into account. Further study of additional factors, such as mitochondrial mass, should be conducted to improve the measurement of CSA parameters for the assessment of the real mitochondrial fitness.

Metabolic labeling unveils alterations in the turnover of HDL-associated proteins during diabetes progression in mice.

Several aspects of diabetes pathophysiology and complications result from hyperglycemia-induced alterations in the structure and function of plasma proteins. Furthermore, insulin has a significant influence on protein metabolism by affecting both the synthesis and degradation of proteins in various tissues. To understand the role of progressive hyperglycemia on plasma proteins, in this study, we measured the turnover rates of high-density lipoprotein (HDL)-associated proteins in control (chow diet), prediabetic [a high-fat diet (HFD) for 8 wk] or diabetic [HFD for 8 wk with low-dose streptozotocin (HFD + STZ) in weeks 5-8 of HFD] C57BL/6J mice using heavy water (2H2O)-based metabolic labeling approach. Compared with control mice, HFD and HFD + STZ mice showed elevations of fasting plasma glucose levels in the prediabetic and diabetic range, respectively. Furthermore, the HFD and HFD + STZ mice showed increased hepatic triglyceride (TG) levels, total plasma cholesterol, and plasma TGs. The kinetics of 40 proteins were quantified using the proteome dynamics method, which revealed an increase in the fractional synthesis rate (FSR) of HDL-associated proteins in the prediabetic mice compared with control mice, and a decrease in FSR in the diabetic mice. The pathway analysis revealed that proteins with altered turnover rates were involved in acute-phase response, lipid metabolism, and coagulation. In conclusion, prediabetes and diabetes have distinct effects on the turnover rates of HDL proteins. These findings suggest that an early dysregulation of the HDL proteome dynamics can provide mechanistic insights into the changes in protein levels in these conditions.NEW & NOTEWORTHY This study is the first to examine the role of gradual hyperglycemia during diabetes disease progression on HDL-associated protein dynamics in the prediabetes and diabetic mice. Our results show that the fractional synthesis rate of HDL-associated proteins increased in the prediabetic mice whereas it decreased in the diabetic mice compared with control mice. These kinetic changes can help to elucidate the mechanism of altered protein levels and HDL dysfunction during diabetes disease progression.

12 Using continuous glucose monitoring to predict disease progression and development of diabetes in youth with cystic fibrosis

12 Using continuous glucose monitoring to predict disease progression and development of diabetes in youth with cystic fibrosis

Aldosterone in chronic kidney disease and renal outcomes.

Randomized controlled trials have demonstrated the efficacy of mineralocorticoid receptor (MR) antagonism in delaying chronic kidney disease (CKD) progression in diabetes; however, they have not investigated the role of aldosterone or whether these beneficial effects could be achieved in individuals without diabetes. The association between serum aldosterone concentrations and kidney disease progression was investigated among 3680 participants in the Chronic Renal Insufficiency Cohort. The primary outcome was CKD progression [defined as the composite of 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, whichever occurred first]. The associations between serum aldosterone and kidney disease outcomes were assessed using Cox proportional hazard models. At baseline, higher aldosterone concentrations were associated with a lower eGFR, lower serum potassium, greater urinary potassium, and protein excretion. Over a median follow-up of 9.6 years, 1412 participants developed CKD progression. In adjusted models, each doubling of serum aldosterone was associated with a 11% increased risk of CKD progression [hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.04-1.18]. Individuals with the highest quartile of serum aldosterone had a 45% increased risk of CKD progression (HR 1.45, 95% CI 1.22-1.73) compared with the lowest quartile. The risk for CKD progression was similar regardless of whether patients had concomitant diabetes (P-interaction = 0.10). Higher serum aldosterone levels among individuals with CKD are independently associated with an increased risk for kidney disease progression, irrespective of concomitant diabetes. These findings provide mechanistic support for MR antagonists in delaying CKD progression and suggest that they may also have a role in those without diabetes.