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The Journal of Clinical Endocrinology... Jul 2023The worldwide increase in the prevalence of diabetes mellitus has raised the demand for new therapeutic strategies targeting diabetic symptoms and its chronic... (Review)
Review
The worldwide increase in the prevalence of diabetes mellitus has raised the demand for new therapeutic strategies targeting diabetic symptoms and its chronic complications. Among different treatment options for diabetes, adipose-derived mesenchymal stem cells (ADMSCs) therapy attract the most attention. The therapeutic effects of ADMSCs are based primarily on their paracrine release of immunomodulatory, anti-inflammatory, and trophic factors. Animal models of diabetes as well as human clinical trials have shown that ADMSCs can effectively facilitate endogenous β cell regeneration, preserve residual β cell mass, reduce islet graft rejection, regulate the immune system, and ultimately improve insulin sensitivity or ameliorate insulin resistance in peripheral tissues. Nevertheless, transplantation of mesenchymal stem cells is associated with certain risks; therefore recently much attention has been devoted to ADMSCs derivatives, such as exosomes or conditioned media, as therapeutic agents for the treatment of diabetes. Compared to ADMSCs, cell-free therapy has even better therapeutic potential. This narrative review summarizes recent outcomes and molecular mechanisms of ADMSCs action in the treatment for both type 1 DM and type 2 DM, as well as shows their feasibility, benefits, and current limitations.
Topics: Humans; Diabetes Mellitus; Adipose Tissue; Mesenchymal Stem Cells; Insulin Resistance
PubMed: 36916961
DOI: 10.1210/clinem/dgad142 -
Redox Biology Aug 2023Brain and muscle arnt-like protein 1 (Bmal1) is a crucial transcription factor, regulating circadian rhythm and involved in multiple heart diseases. However, it is...
Brain and muscle arnt-like protein 1 (Bmal1) is a crucial transcription factor, regulating circadian rhythm and involved in multiple heart diseases. However, it is unknown whether Bmal1 promotes diabetic cardiomyopathy (DCM) pathogenesis. The objective of this investigation was to ascertain the vital role of Bmal1 in the progression of DCM. Mice with T2D and H9c2 cardiomyoblasts exposed to high glucose and palmitic acid (HGHP) were used. Cardiomyocyte-specific knockout mouse of Bmal1 (CKB) was also generated, and cardiac Bmal1 was overexpressed in type 2 diabetes (T2D) mice using an adeno-associated virus. Bmal1 gene recombinant adenovirus was used to either knockdown or overexpress in H9c2 cardiomyoblasts. Bmal1 expression was significantly altered in diabetic mice hearts. Bmal1 downregulation in CKB and T2D mice heart accelerated cardiac hypertrophy and diastolic dysfunction, while Bmal1 overexpression ameliorated these pathological changes in DCM mice. Furthermore, DCM mice had significant mitochondrial ultrastructural defects, reactive oxygen species accumulation, and apoptosis, which could be alleviated by overexpressing Bmal1. In H9c2 cardiomyoblasts, genetic downregulation of Bmal1 or HGHP markedly decreased the binding of Bcl2 to IP3R, thus increasing Ca release to mitochondria through mitochondria-associated endoplasmic reticulum membranes. Importantly, chromatin immunoprecipitation revealed Bmal1 could bind directly to the Bcl2 gene promoter region. Bmal1 overexpression augmented the Bmal1/Bcl2 binding, enhancing the inhibition of Bcl2 on IP3R activity, thus alleviating mitochondrial Ca overload and subsequent cell apoptosis. These results show that Bmal1 is involved in the DCM development through Bcl2/IP3R-mediated mitochondria Ca overload. Therapy targeting the circadian clock (Bmal1) can treat DCM.
Topics: Animals; Mice; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Down-Regulation; Mice, Knockout; Mitochondria
PubMed: 37356134
DOI: 10.1016/j.redox.2023.102788 -
BMC Medicine Sep 2023Diabetes mellitus (DM) is a chronic metabolic disease that could produce severe complications threatening life. Its early detection is thus quite important for the...
BACKGROUND
Diabetes mellitus (DM) is a chronic metabolic disease that could produce severe complications threatening life. Its early detection is thus quite important for the timely prevention and treatment. Normally, fasting blood glucose (FBG) by physical examination is used for large-scale screening of DM; however, some people with normal fasting glucose (NFG) actually have suffered from diabetes but are missed by the examination. This study aimed to investigate whether common physical examination indexes for diabetes can be used to identify the diabetes individuals from the populations with NFG.
METHODS
The physical examination data from over 60,000 individuals with NFG in three Chinese cohorts were used. The diabetes patients were defined by HbA1c ≥ 48 mmol/mol (6.5%). We constructed the models using multiple machine learning methods, including logistic regression, random forest, deep neural network, and support vector machine, and selected the optimal one on the validation set. A framework using permutation feature importance algorithm was devised to discover the personalized risk factors.
RESULTS
The prediction model constructed by logistic regression achieved the best performance with an AUC, sensitivity, and specificity of 0.899, 85.0%, and 81.1% on the validation set and 0.872, 77.9%, and 81.0% on the test set, respectively. Following feature selection, the final classifier only requiring 13 features, named as DRING (diabetes risk of individuals with normal fasting glucose), exhibited reliable performance on two newly recruited independent datasets, with the AUC of 0.964 and 0.899, the balanced accuracy of 84.2% and 81.1%, the sensitivity of 100% and 76.2%, and the specificity of 68.3% and 86.0%, respectively. The feature importance ranking analysis revealed that BMI, age, sex, absolute lymphocyte count, and mean corpuscular volume are important factors for the risk stratification of diabetes. With a case, the framework for identifying personalized risk factors revealed FBG, age, and BMI as significant hazard factors that contribute to an increased incidence of diabetes. DRING webserver is available for ease of application ( http://www.cuilab.cn/dring ).
CONCLUSIONS
DRING was demonstrated to perform well on identifying the diabetes individuals among populations with NFG, which could aid in early diagnosis and interventions for those individuals who are most likely missed.
Topics: Humans; Fasting; Diabetes Mellitus; Risk Factors; Machine Learning; Glucose
PubMed: 37674168
DOI: 10.1186/s12916-023-03045-9 -
Frontiers in Immunology 2023The incidence of Diabetes Mellitus is increasing globally. Individuals who have been burdened with diabetes for many years often develop complications as a result of... (Review)
Review
The incidence of Diabetes Mellitus is increasing globally. Individuals who have been burdened with diabetes for many years often develop complications as a result of hyperglycemia. More and more research is being conducted highlighting inflammation as an important factor in disease progression. In all kinds of diabetes, hyperglycemia leads to activation of alternative glucose metabolic pathways, resulting in problematic by-products including reactive oxygen species and advanced glycation end products. This review takes a look into the pathogenesis of three specific diabetic complications; retinopathy, nephropathy and neuropathy as well as their current treatment options. By considering recent research papers investigating the effects of immunotherapy on relevant conditions in animal models, multiple strategies are suggested for future treatment and prevention of diabetic complications with an emphasis on molecular targets associated with the inflammation.
Topics: Animals; Prospective Studies; Diabetes Complications; Diabetes Mellitus; Hyperglycemia; Inflammation; Immunotherapy
PubMed: 37483613
DOI: 10.3389/fimmu.2023.1219598 -
Journal of Diabetes Science and... Nov 2023Diabetes technology is a dynamically evolving field. Sometimes the pace of evaluation of new diabetes technologies does not keep pace with its dynamic development. This...
Diabetes technology is a dynamically evolving field. Sometimes the pace of evaluation of new diabetes technologies does not keep pace with its dynamic development. This leads to a dilemma: either the evaluation lags behind the developing technologies or diabetes technologies are used without sufficient evaluation. This situation is known as the Catch 22 dilemma. The aim of this paper is a discussion of ideas for a timely assessment, taking account of the speed of technological development and the need for evidence and safety improvement.
Topics: Humans; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus; Diabetes Mellitus, Type 1; Technology; Insulin; Hypoglycemic Agents
PubMed: 37129215
DOI: 10.1177/19322968231170884 -
Nutrients Oct 2023The alarming rise in obesity worldwide is a dramatic public health concern [...].
The alarming rise in obesity worldwide is a dramatic public health concern [...].
Topics: Humans; Risk Factors; Cardiovascular Diseases; Diabetes Mellitus; Diet; Obesity
PubMed: 37836567
DOI: 10.3390/nu15194283 -
Journal of Diabetes Jul 2023
Topics: Humans; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1
PubMed: 37310420
DOI: 10.1111/1753-0407.13434 -
Diabetes Research and Clinical Practice Dec 2023The diabetic neuropathies represent the commonest long-term complications of diabetes, and may be the presenting feature of Type 2 diabetes. In clinical practice, distal... (Review)
Review
The diabetic neuropathies represent the commonest long-term complications of diabetes, and may be the presenting feature of Type 2 diabetes. In clinical practice, distal symmetrical polyneuropathy (DSPN) and the autonomic neuropathies are the most frequently seen forms of diabetic neuropathy. The 2017 American Diabetes Association classification system for the neuropathies of diabetes are in general use. Treatment challenges remain and the need for revised recommendations and further discussion of management of severely painful DSPN that does not fully respond to conventional medical management is clear, especially in light of the recent opioid crisis in the USA.
Topics: Humans; Autonomic Nervous System; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Pain; Polyneuropathies
PubMed: 38245328
DOI: 10.1016/j.diabres.2023.110758 -
Ugeskrift For Laeger May 2024Assessment and treatment of hyperglycaemia in people with diabetes and chronic kidney disease (CKD) are challenging. In advanced CKD HbA1c can be unreliable, and... (Review)
Review
Assessment and treatment of hyperglycaemia in people with diabetes and chronic kidney disease (CKD) are challenging. In advanced CKD HbA1c can be unreliable, and treatment adjustments should be supported by other glucose measurements (e.g., continuous glucose monitoring (CGM) or blood glucose measurements). Glucose-lowering treatments should be evaluated based on CKD and an individualised assessment of risk factors especially hypoglycaemia. This review aims at providing an overview of the options for glycaemic monitoring and glucose-lowering treatments in people with diabetes and CKD.
Topics: Humans; Renal Insufficiency, Chronic; Hyperglycemia; Hypoglycemic Agents; Blood Glucose; Blood Glucose Self-Monitoring; Glycated Hemoglobin; Diabetes Mellitus, Type 2; Diabetes Mellitus; Diabetic Nephropathies; Risk Factors
PubMed: 38808757
DOI: 10.61409/V01240051 -
World Journal of Gastroenterology Aug 2023Diabetes is a highly prevalent disease that was initially simplified into three major types: Type 1, type 2 and gestational diabetes. With the global rise in incidence... (Review)
Review
Diabetes is a highly prevalent disease that was initially simplified into three major types: Type 1, type 2 and gestational diabetes. With the global rise in incidence of acute pancreatitis (AP), a lesser-known type of diabetes referred to as diabetes of the exocrine pancreas (DEP) is becoming more recognized. However, there is a poor understanding of the inherent relationship between diabetes and AP. There is established data about certain diseases affecting the exocrine function of the pancreas which can lead to diabetes. More specifically, there are well established guidelines for diagnosis and management of DEP caused be chronic pancreatitis. Conversely, the sequelae of AP leading to diabetes has limited recognition and data. The purpose of this review is to provide a comprehensive summary of the prevalence, epidemiology, pathophysiology and future research aims of AP-related diabetes. In addition, we propose a screening and diagnostic algorithm to aid clinicians in providing better care for their patients.
Topics: Humans; Acute Disease; Pancreas; Pancreatitis, Chronic; Diabetes Mellitus
PubMed: 37664150
DOI: 10.3748/wjg.v29.i31.4736