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JCI Insight Sep 2023Diabetic cardiomyopathy, an increasingly global epidemic and a major cause of heart failure with preserved ejection fraction (HFpEF), is associated with hyperglycemia,...
Diabetic cardiomyopathy, an increasingly global epidemic and a major cause of heart failure with preserved ejection fraction (HFpEF), is associated with hyperglycemia, insulin resistance, and intracardiomyocyte calcium mishandling. Here we identify that, in db/db mice with type 2 diabetes-induced HFpEF, abnormal remodeling of cardiomyocyte transverse-tubule microdomains occurs with downregulation of the membrane scaffolding protein cardiac bridging integrator 1 (cBIN1). Transduction of cBIN1 by AAV9 gene therapy can restore transverse-tubule microdomains to normalize intracellular distribution of calcium-handling proteins and, surprisingly, glucose transporter 4 (GLUT4). Cardiac proteomics revealed that AAV9-cBIN1 normalized components of calcium handling and GLUT4 translocation machineries. Functional studies further identified that AAV9-cBIN1 normalized insulin-dependent glucose uptake in diabetic cardiomyocytes. Phenotypically, AAV9-cBIN1 rescued cardiac lusitropy, improved exercise intolerance, and ameliorated hyperglycemia in diabetic mice. Restoration of transverse-tubule microdomains can improve cardiac function in the setting of diabetic cardiomyopathy and can also improve systemic glycemic control.
Topics: Animals; Mice; Blood Glucose; Diabetic Cardiomyopathies; Heart Failure; Calcium; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Stroke Volume; Anti-Arrhythmia Agents; Cardiotonic Agents; Myocytes, Cardiac; Hyperglycemia; Adaptor Proteins, Signal Transducing; Amino Acids; Enzyme Inhibitors; Genetic Therapy
PubMed: 37639557
DOI: 10.1172/jci.insight.166713 -
Aging Jun 2024Prostate cancer is one of the most common types of cancer in the US, and it has a high mortality rate. Diabetes mellitus is also a dangerous health condition. While some... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prostate cancer is one of the most common types of cancer in the US, and it has a high mortality rate. Diabetes mellitus is also a dangerous health condition. While some studies have examined the relationship between diabetes mellitus and the risk of prostate cancer, there is still some debate on the matter. This study aims to carefully assess the relationship between prostate cancer and diabetes from both real-world and genetic-level data.
METHODS
This meta-analysis was conducted following the PRISMA 2020 reporting guidelines. The study searched three databases including Medline, Embase and Cochrane. The studies about the incidence risk of prostate cancer with diabetes mellitus were included and used to evaluate the association. The odds ratio (OR), risk ratio (RR) and 95% confidence intervals (95% CI) were estimated using Random Effects models and Fixed Effects models. Mendelian randomization study using genetic variants was also conducted.
RESULTS
A total of 72 articles were included in this study. The results showed that risk of prostate cancer decreased in diabetes patients. And the influence was different in different regions. This study also estimated the impact of body mass index (BMI) in the diabetes populations and found that the risk decreased in higher BMI populations. The MR analysis found that diabetes mellitus exposure reduced the risk of prostate cancer in the European population and Asia populations. Conclusions The diabetes mellitus has a protective effect on prostate cancer. And the influence of obesity in diabetes mellitus plays an important role in this effect.
Topics: Humans; Male; Prostatic Neoplasms; Mendelian Randomization Analysis; Diabetes Mellitus; Body Mass Index; Risk Factors
PubMed: 38836754
DOI: 10.18632/aging.205886 -
Diabetologia Jun 2024Dyslipidaemias are major cardiovascular risk factors, especially in people with diabetes. In this area, next-generation therapies targeting circulating lipoparticle... (Review)
Review
Dyslipidaemias are major cardiovascular risk factors, especially in people with diabetes. In this area, next-generation therapies targeting circulating lipoparticle metabolism (LDL, VLDL, chylomicrons, HDL) have recently been approved by the European and US medical agencies, including anti- proprotein convertase subtilisin/kexin 9 (PCSK9) antibodies; an siRNA targeting PCSK9; bempedoic acid, which targets ATP citrate lyase; an antisense oligonucleotide targeting apolipoprotein C-III; an anti-angiopoietin-like 3 antibody; and a purified omega-3 fatty acid, icosapent ethyl. Other therapies are in different phases of development. There are several important considerations concerning the link between these new lipid-lowering therapies and diabetes. First, since concerns were first raised in 2008 about an increased risk of new-onset diabetes mellitus (NODM) with intensive statin treatment, each new lipid-lowering therapy is being evaluated for its associated risk of NODM, particularly in individuals with prediabetes (impaired fasting glucose and/or impaired glucose tolerance). Second, people with diabetes represent a large proportion of those at high or very high cardiovascular risk in whom these lipid-lowering drugs are currently, or will be, prescribed. Thus, the efficacy of these drugs in subgroups with diabetes should also be closely considered, as well as any potential effects on glycaemic control. In this review, we describe the efficacy of next-generation therapies targeting lipoprotein metabolism in subgroups of people with diabetes and their effects on glycaemic control in individuals with diabetes and prediabetes and in normoglycaemic individuals.
Topics: Humans; Hyperlipidemias; Hypolipidemic Agents; Diabetes Mellitus, Type 2; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Diabetes Mellitus
PubMed: 38376536
DOI: 10.1007/s00125-024-06100-z -
Acta Diabetologica Nov 2023Glucagon-like peptide-1 receptor agonists are effective treatments for type 2 diabetes, effectively lowering glucose without weight gain and with low risk for...
AIMS
Glucagon-like peptide-1 receptor agonists are effective treatments for type 2 diabetes, effectively lowering glucose without weight gain and with low risk for hypoglycemia. However, their influence on the retinal neurovascular unit remains unclear. In this study, we analyzed the effects of the GLP-1 RA lixisenatide on diabetic retinopathy.
METHODS
Vasculo- and neuroprotective effects were assessed in experimental diabetic retinopathy and high glucose-cultivated C. elegans, respectively. In STZ-diabetic Wistar rats, acellular capillaries and pericytes (quantitative retinal morphometry), neuroretinal function (mfERG), macroglia (GFAP western blot) and microglia (immunohistochemistry) quantification, methylglyoxal (LC-MS/MS) and retinal gene expressions (RNA-sequencing) were determined. The antioxidant properties of lixisenatide were tested in C. elegans.
RESULTS
Lixisenatide had no effect on glucose metabolism. Lixisenatide preserved the retinal vasculature and neuroretinal function. The macro- and microglial activation was mitigated. Lixisenatide normalized some gene expression changes in diabetic animals to control levels. Ets2 was identified as a regulator of inflammatory genes. In C. elegans, lixisenatide showed the antioxidative property.
CONCLUSIONS
Our data suggest that lixisenatide has a protective effect on the diabetic retina, most likely due to a combination of neuroprotective, anti-inflammatory and antioxidative effects of lixisenatide on the neurovascular unit.
Topics: Rats; Animals; Diabetic Retinopathy; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Glucagon-Like Peptide-1 Receptor; Caenorhabditis elegans; Chromatography, Liquid; Rats, Wistar; Diabetes Mellitus, Experimental; Tandem Mass Spectrometry; Antioxidants; Glucose
PubMed: 37423944
DOI: 10.1007/s00592-023-02135-7 -
Frontiers in Endocrinology 2023
Topics: Humans; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1
PubMed: 37800146
DOI: 10.3389/fendo.2023.1291637 -
Biosensors Jul 2023We present a critical review of the current progress in wearable insulin biosensors. For over 40 years, glucose biosensors have been used for diabetes management.... (Review)
Review
We present a critical review of the current progress in wearable insulin biosensors. For over 40 years, glucose biosensors have been used for diabetes management. Measurement of blood glucose is an indirect method for calculating the insulin administration dosage, which is critical for insulin-dependent diabetic patients. Research and development efforts aiming towards continuous-insulin-monitoring biosensors in combination with existing glucose biosensors are expected to offer a more accurate estimation of insulin sensitivity, regulate insulin dosage and facilitate progress towards development of a reliable artificial pancreas, as an ultimate goal in diabetes management and personalised medicine. Conventional laboratory analytical techniques for insulin detection are expensive and time-consuming and lack a real-time monitoring capability. On the other hand, biosensors offer point-of-care testing, continuous monitoring, miniaturisation, high specificity and sensitivity, rapid response time, ease of use and low costs. Current research, future developments and challenges in insulin biosensor technology are reviewed and assessed. Different insulin biosensor categories such as aptamer-based, molecularly imprinted polymer (MIP)-based, label-free and other types are presented among the latest developments in the field. This multidisciplinary field requires engagement between scientists, engineers, clinicians and industry for addressing the challenges for a commercial, reliable, real-time-monitoring wearable insulin biosensor.
Topics: Humans; Insulin; Biosensing Techniques; Diabetes Mellitus; Glucose; Wearable Electronic Devices
PubMed: 37504117
DOI: 10.3390/bios13070719 -
Medicine Oct 2023Diabetes mellitus is a complex chronic metabolic disease characterized by hyperglycemia and various complications. According to the different pathophysiological... (Review)
Review
Diabetes mellitus is a complex chronic metabolic disease characterized by hyperglycemia and various complications. According to the different pathophysiological mechanisms, these complications can be classified as microvascular or macrovascular complications, which have long-term negative effects on vital organs such as the eyes, kidneys, heart, and brain, and lead to increased patient mortality. Diabetes mellitus is a major global health issue, and its incidence and prevalence have increased significantly in recent years. Moreover, the incidence is expected to continue to rise as more people adopt a Western lifestyle and diet. Thus, it is essential to understand the epidemiology, pathogenesis, risk factors, and treatment of vascular complications to aid patients in managing the disease effectively. This paper provides a comprehensive review of the literature to clarify the above content. Furthermore, this paper also delves into the correlation between novel risk factors, such as long noncoding RNAs, gut microbiota, and nonalcoholic fatty liver disease, with diabetic vascular complications.
Topics: Humans; Diabetes Mellitus; Diabetic Angiopathies; Risk Factors; Hyperglycemia; Cardiovascular Diseases
PubMed: 37800828
DOI: 10.1097/MD.0000000000035285 -
Frontiers in Endocrinology 2024
Topics: Humans; Young Adult; Diabetes Mellitus; Students; Universities; Disease Management
PubMed: 38660515
DOI: 10.3389/fendo.2024.1402133 -
JPMA. the Journal of the Pakistan... Oct 2023Diabetes and other cardiometabolic diseases occur across the world, and do not discriminate between populations. This communication reviews the epidemiology and etiology...
Diabetes and other cardiometabolic diseases occur across the world, and do not discriminate between populations. This communication reviews the epidemiology and etiology of diabetes in the transgender population, and highlights clinical issues that must be kept in mind while evaluating and managing the condition. It adds value to existing literature by equipping health care professionals with specific skills designed to enhance diabetes care delivery, and results, in transgender individuals.
Topics: Humans; Transgender Persons; Transsexualism; Diabetes Mellitus; Delivery of Health Care
PubMed: 37876084
DOI: 10.47391/JPMA.23-72 -
Medicina (Kaunas, Lithuania) Nov 2023Thyroid disorders (TD) and diabetes mellitus (DM) are the two endocrinopathies with the highest prevalence in the general population that frequently coexist. Thyroid... (Review)
Review
Thyroid disorders (TD) and diabetes mellitus (DM) are the two endocrinopathies with the highest prevalence in the general population that frequently coexist. Thyroid dysfunction is more common in people with type 2 diabetes mellitus (T2DM) compared to normoglycemic individuals. Untreated TD can impair glycemic control, increasing the risk of diabetes complications. Hyperinsulinemia can affect the morphology of the thyroid gland by promoting the proliferation of thyroid tissue and increasing the size of thyroid nodules. Metformin can confer benefits in both endocrinopathies, while other antidiabetics, such as sulfonylureas, can negatively affect thyroid function. Animal and human observational data suggest an increased risk of medullary thyroid carcinoma after treatment with glucagon-like peptide-1 receptor agonists. However, randomized trials have so far been reassuring. Furthermore, some observational studies suggest an association between thyroid cancer and T2DM, especially in women. This narrative review aims to shed light on the epidemiological, pathophysiological, and clinical aspects of the interplay between TD and T2DM. Taking into account the important clinical implications of the coexistence of T2DM and TD, proper screening and management strategies are needed for both endocrinopathies to ensure optimal patient care.
Topics: Animals; Humans; Female; Diabetes Mellitus, Type 2; Thyroid Diseases; Hypoglycemic Agents; Metformin
PubMed: 38004062
DOI: 10.3390/medicina59112013