-
Life Sciences Dec 2023Diabetic kidney disease (DKD) is a leading diabetic complication causing significant mortality among people around the globe. People with poor glycemic control... (Review)
Review
Diabetic kidney disease (DKD) is a leading diabetic complication causing significant mortality among people around the globe. People with poor glycemic control accompanied by hyperinsulinemia, dyslipidemia, hypertension, and obesity develop diabetic complications. These diabetic patients develop epigenetic changes and suffer from diabetic kidney complications even after subsequent glucose control, the phenomenon that is recognized as metabolic memory. DNA methylation is an essential epigenetic modification that contributes to the development and progression of several diabetic complications, including DKD. The aberrant DNA methylation pattern at CpGs sites within several genes, such as mTOR, RPTOR, IRS2, GRK5, SLC27A3, LCAT, and SLC1A5, associated with the accompanying risk factors exacerbate the DKD progression. Although drugs such as azacytidine and decitabine have been approved to target DNA methylation for diseases such as hematological malignancies, none have been approved for the treatment of DKD. More importantly, no DNA hypomethylation-targeting drugs have been approved for any disease conditions. Understanding the alteration in DNA methylation and its association with the disease risk factors is essential to target DKD effectively. This review has discussed the abnormal DNA methylation pattern and the kidney tissue-specific expression of critical genes involved in DKD onset and progression. Moreover, we also discuss the new possible therapeutic approach that can be exploited for treating DNA methylation aberrancy in a site-specific manner against DKD.
Topics: Humans; Diabetic Nephropathies; DNA Methylation; Kidney; Diabetes Complications; Epigenesis, Genetic; Diabetes Mellitus; Minor Histocompatibility Antigens; Amino Acid Transport System ASC
PubMed: 37949210
DOI: 10.1016/j.lfs.2023.122256 -
Terapevticheskii Arkhiv Dec 2023With the discovery and introduction of insulin, the "palette" of life-threatening conditions for patients with diabetes mellitus has changed dramatically: from diabetic... (Review)
Review
With the discovery and introduction of insulin, the "palette" of life-threatening conditions for patients with diabetes mellitus has changed dramatically: from diabetic coma of the "pre-insulin era" to severe vascular complications in the modern period. The key risk factors for diabetic angiopathies in diabetes mellitus are poor glycemic control in combination with a long course of the disease. Over the past 30 years, there has been a downward trend in the incidence of late vascular complications of diabetes both worldwide and in Russia. In particular, the frequency of cardiovascular events (myocardial infarctions, strokes, amputations) decreased, and the incidence of several other complications, such as diabetic retinopathy and neuropathy, stabilized. However, the incidence of chronic kidney disease and chronic heart failure is still increasing. The Joslin Medal, awarded to patients over 50, 75 and even 80 years of life with diabetes, reflects success in the fight against this disease.
Topics: Humans; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Retinopathy; Hyperglycemia; Incidence; Insulin; Risk Factors
PubMed: 38158936
DOI: 10.26442/00403660.2023.12.202498 -
Acta Diabetologica Oct 2023Glucose variability (GV) is increasingly considered an additional index of glycemic control. Growing evidence indicates that GV is associated with diabetic vascular... (Review)
Review
AIMS AND DATA SYNTHESIS
Glucose variability (GV) is increasingly considered an additional index of glycemic control. Growing evidence indicates that GV is associated with diabetic vascular complications, thus being a relevant point to address in diabetes management. GV can be measured using various parameters, but to date, a gold standard has not been identified. This underscores the need for further studies in this field also to identify the optimal treatment.
CONCLUSIONS
We reviewed the definition of GV, the pathogenetic mechanisms of atherosclerosis, and its relationship with diabetic complications.
Topics: Humans; Diabetes Mellitus, Type 2; Blood Glucose; Glucose; Glycated Hemoglobin; Cardiovascular Diseases; Risk Factors; Diabetic Angiopathies
PubMed: 37341768
DOI: 10.1007/s00592-023-02097-w -
Clinical Infectious Diseases : An... Aug 2023
Topics: Humans; Communicable Diseases; Diabetes Complications; Vascular Diseases; Diabetic Foot; Diabetes Mellitus
PubMed: 37579721
DOI: 10.1093/cid/ciad429 -
Frontiers in Endocrinology 20241,5-Anhydroglucitol (1,5-AG) is sensitive to short-term glucose fluctuations and postprandial hyperglycemia, which has great potential in the clinical application of... (Review)
Review
1,5-Anhydroglucitol (1,5-AG) is sensitive to short-term glucose fluctuations and postprandial hyperglycemia, which has great potential in the clinical application of diabetes as a nontraditional blood glucose monitoring indicator. A large number of studies have found that 1,5-AG can be used to screen for diabetes, manage diabetes, and predict the perils of diabetes complications (diabetic nephropathy, diabetic cardiovascular disease, diabetic retinopathy, diabetic pregnancy complications, diabetic peripheral neuropathy, etc.). Additionally, 1,5-AG and β cells are also associated with each other. As a noninvasive blood glucose monitoring indicator, salivary 1,5-AG has much more benefit for clinical application; however, it cannot be ignored that its detection methods are not perfect. Thus, a considerable stack of research is still needed to establish an accurate and simple enzyme assay for the detection of salivary 1,5-AG. More clinical studies will also be required in the future to confirm the normal reference range of 1,5-AG and its role in diabetes complications to further enhance the blood glucose monitoring system for diabetes.
Topics: Humans; Deoxyglucose; Diabetes Complications; Blood Glucose; Diabetes Mellitus; Blood Glucose Self-Monitoring; Biomarkers
PubMed: 38803475
DOI: 10.3389/fendo.2024.1383483 -
Frontiers in Endocrinology 2023The triglyceride-glucose (TyG) index is an accessible and reliable surrogate indicator of insulin resistance and is strongly associated with diabetes. However, its... (Meta-Analysis)
Meta-Analysis
UNLABELLED
The triglyceride-glucose (TyG) index is an accessible and reliable surrogate indicator of insulin resistance and is strongly associated with diabetes. However, its relationship with diabetic retinopathy (DR) remains controversial. This meta-analysis aimed to assess the relationship between the TyG index and the prevalence of DR. Initial studies were searched from PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) electronic databases. The retrieval time range was from the establishment of the database to June 2023. Pooled estimates were derived using a random-effects model and reported as odds ratio (OR) with 95% confidence intervals (CIs). Two researchers independently assessed the methodological quality of the included studies. The Newcastle-Ottawa Quality Scale (NOS) was utilized to assess cohort studies or case-control studies. The Agency for Healthcare Research and Quality (AHRQ) methodology checklist was applied to assess cross-sectional studies. Ten observational studies encompassing 13716 patients with type 2 diabetes were included in the meta-analysis. The results showed that a higher TyG index increased the risk of DR compared with a low TyG index (OR: 2.34, 95% CI: 1.31-4.19, P < 0.05). When the index was analyzed as a continuous variable, consistent results were observed (OR: 1.48, 95% CI: 1.12-1.97, P < 0.005). There was no significant effect on the results of the sensitivity analyses excluding one study at a time (P all < 0.05). A higher TyG index may be associated with an increased prevalence of DR in patients with type 2 diabetes. However, high-quality cohort or case-control studies are needed to further substantiate this evidence.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023432747.
Topics: Humans; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Glucose; Triglycerides; United States; Observational Studies as Topic
PubMed: 38130393
DOI: 10.3389/fendo.2023.1302127 -
Frontiers in Endocrinology 2024Diabetes is a global health concern characterized by chronic hyperglycemia resulting from insulinopenia and/or insulin resistance. The rising prevalence of diabetes and... (Review)
Review
INTRODUCTION
Diabetes is a global health concern characterized by chronic hyperglycemia resulting from insulinopenia and/or insulin resistance. The rising prevalence of diabetes and its associated complications (ulcers, periodontitis, healing of bone defect, neuropathy, retinopathy, cardiopathy and nephropathy) necessitate innovative therapeutic approaches. Photobiomodulation (PBM), involves exposing tissues and cells to low-energy light radiation, leading to biological effects, largely via mitochondrial activation.
METHODS
This review evaluates preclinical and clinical studies exploring the potential of PBM in diabetes and its complications, as well all clinical trials, both planned and completed, available on ClinicalTrials database.
RESULTS
This review highlights the variability in PBM parameters across studies, hindering consensus on optimal protocols. Standardization of treatment parameters and rigorous clinical trials are needed to unlock PBM's full therapeutic potential. 87 clinical trials were identified that investigated PBM in diabetes mellitus (with 5,837 patients planned to be treated with PBM). Clinical trials assessing PBM effects on diabetic neuropathy revealed pain reduction and potential quality of life improvement. Studies focusing on wound healing indicated encouraging results, with PBM enhancing angiogenesis, fibroblast proliferation, and collagen density. PBM's impact on diabetic retinopathy remains inconclusive however, requiring further investigation. In glycemic control, PBM exhibits positive effects on metabolic parameters, including glucose tolerance and insulin resistance.
CONCLUSION
Clinical studies have reported PBM-induced reductions in fasting and postprandial glycemia without an increased hypoglycemic risk. This impact of PBM may be related to its effects on the beta cells and islets in the pancreas. Notwithstanding challenges, PBM emerges as a promising adjunctive therapy for managing diabetic neuropathy, wound healing, and glycemic control. Further investigation into its impact on diabetic retinopathy and muscle recovery is warranted.
Topics: Humans; Diabetic Retinopathy; Low-Level Light Therapy; Diabetic Neuropathies; Insulin Resistance; Quality of Life; Diabetes Mellitus
PubMed: 38567306
DOI: 10.3389/fendo.2024.1303638 -
Biomedicine & Pharmacotherapy =... Sep 2023Constipation is a major complications of diabetes mellitus. With the accelerating prevalence of diabetes worldwide and an aging population, there is considerable... (Review)
Review
Constipation is a major complications of diabetes mellitus. With the accelerating prevalence of diabetes worldwide and an aging population, there is considerable research interest regarding the altered function and structure of the gastrointestinal tract in diabetic patients. Despite current advances in hyperglycemic treatment strategies, the specific pathogenesis of diabetic constipation remains unknown. Patients with constipation, may be reluctant to eat regularly, which may worsen glycemic control and thus worsen symptoms associated with underlying diabetic bowel disease. This paper presents a review of the complex relationship between diabetes and constipation, exploring the morphological alterations and biomechanical remodeling associated with intestinal motility dysfunction, as well as alterations in intestinal neurons, cellular signaling pathways, and oxidative stress. Further studies focusing on new targets that may play a role in the pathogenesis of diabetic constipation may, provide new ideas for the development of novel therapies to treat or even prevent diabetic constipation.
Topics: Humans; Aged; Glycemic Control; Diabetes Mellitus; Constipation; Hyperglycemia; Gastrointestinal Diseases; Diabetes Complications
PubMed: 37506579
DOI: 10.1016/j.biopha.2023.115202 -
Endocrinology and Metabolism (Seoul,... Feb 2024Type 2 diabetes (T2D) is a progressive disease in which it is challenging to achieve long-term durable glycemic control. However, intensive glycemic control is crucial... (Review)
Review
Type 2 diabetes (T2D) is a progressive disease in which it is challenging to achieve long-term durable glycemic control. However, intensive glycemic control is crucial for preventing diabetes-related complications. Previous studies showed that monotherapy with a stepwise add-on approach was seldom effective for long-term durable glycemic control. Combination therapy, which refers to the use of two or more drugs to control hyperglycemia, has multiple benefits, including the ability to target a variety of pathophysiological processes underlying hyperglycemia. In clinical trials, initial combination therapy showed better glycemic control than monotherapy or a stepwise approach. Emerging evidence indicates that initial combination therapy is associated with preserved β-cell function and fewer complications in T2D. However, cost-effectiveness and adverse events with combination therapy are issues that should be considered. Therefore, initial combination therapy is an important option for patients with T2D that clinicians should consider with a view toward balancing benefits and potential harms. In this review, we summarize the literature addressing initial combination therapy in T2D, and we suggest optimal strategies based on clinical situations and patient characteristics.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Diabetes Complications; Combined Modality Therapy; Hyperglycemia
PubMed: 38031401
DOI: 10.3803/EnM.2023.1816 -
Diabetes Research and Clinical Practice Aug 2023Data on the long-term consequences of diabetic foot disease (DFD) are scarce. We examined the association between DFD and major clinical outcomes in patients with...
AIMS
Data on the long-term consequences of diabetic foot disease (DFD) are scarce. We examined the association between DFD and major clinical outcomes in patients with diabetes in the general population.
METHODS
We conducted a prospective cohort analysis of 1,428 participants with diabetes in the Atherosclerosis Risk in Communities Study. DFD and four clinical outcomes (nontraumatic lower-extremity amputation, cardiovascular disease, major fall, and death) were captured through 2018 using administrative data. We used Cox regression models to evaluate the association between incident DFD (modeled as a time-varying exposure) and the subsequent risk of clinical outcomes.
RESULTS
During over two decades of follow-up (1996-1998 to 2018), the cumulative incidence of DFD was 33.3%. Risk factors for DFD included older age, poor glycemic control, long diabetes duration, and prevalent vascular disease (chronic kidney disease, retinopathy, cardiovascular disease). Following incident DFD, the five-year cumulative incidence of major clinical outcomes was 38.9% for mortality, 25.2% for cardiovascular disease, 14.5% for nontraumatic lower-extremity amputation, and 13.2% for major fall. DFD remained associated with all four clinical outcomes after multivariable adjustment, with hazard ratios ranging from 1.5 (cardiovascular disease) to 34.7 (lower-extremity amputation).
CONCLUSIONS
DFD is common and confers substantial risk for major morbidity and mortality.
Topics: Humans; Diabetic Foot; Prospective Studies; Cardiovascular Diseases; Risk Factors; Hyperglycemia; Diabetes Mellitus
PubMed: 37321302
DOI: 10.1016/j.diabres.2023.110778