-
Endocrine Reviews Mar 2024Chronic complications of diabetes are due to myriad disorders of numerous metabolic pathways that are responsible for most of the morbidity and mortality associated with... (Review)
Review
Chronic complications of diabetes are due to myriad disorders of numerous metabolic pathways that are responsible for most of the morbidity and mortality associated with the disease. Traditionally, diabetes complications are divided into those of microvascular and macrovascular origin. We suggest revising this antiquated classification into diabetes complications of vascular, parenchymal, and hybrid (both vascular and parenchymal) tissue origin, since the profile of diabetes complications ranges from those involving only vascular tissues to those involving mostly parenchymal organs. A major paradigm shift has occurred in recent years regarding the pathogenesis of diabetes complications, in which the focus has shifted from studies on risks to those on the interplay between risk and protective factors. While risk factors are clearly important for the development of chronic complications in diabetes, recent studies have established that protective factors are equally significant in modulating the development and severity of diabetes complications. These protective responses may help explain the differential severity of complications, and even the lack of pathologies, in some tissues. Nevertheless, despite the growing number of studies on this field, comprehensive reviews on protective factors and their mechanisms of action are not available. This review thus focused on the clinical, biochemical, and molecular mechanisms that support the idea of endogenous protective factors, and their roles in the initiation and progression of chronic complications in diabetes. In addition, this review also aimed to identify the main needs of this field for future studies.
Topics: Humans; Protective Factors; Diabetic Angiopathies; Diabetes Mellitus; Risk Factors; Diabetes Mellitus, Type 2
PubMed: 37638875
DOI: 10.1210/endrev/bnad030 -
The Lancet. Diabetes & Endocrinology Nov 2023Diabetes is a highly heterogeneous condition; yet, it is diagnosed by measuring a single blood-borne metabolite, glucose, irrespective of aetiology. Although... (Review)
Review
Diabetes is a highly heterogeneous condition; yet, it is diagnosed by measuring a single blood-borne metabolite, glucose, irrespective of aetiology. Although pragmatically helpful, disease classification can become complex and limit advances in research and medical care. Here, we describe diabetes heterogeneity, highlighting recent approaches that could facilitate management by integrating three disease models across all forms of diabetes, namely, the palette model, the threshold model and the gradient model. Once diabetes has developed, further worsening of established diabetes and the subsequent emergence of diabetes complications are kept in check by multiple processes designed to prevent or circumvent metabolic dysfunction. The impact of any given disease risk factor will vary from person-to-person depending on their background, diabetes-related propensity, and environmental exposures. Defining the consequent heterogeneity within diabetes through precision medicine, both in terms of diabetes risk and risk of complications, could improve health outcomes today and shine a light on avenues for novel therapy in the future.
Topics: Humans; Diabetes Mellitus, Type 2; Precision Medicine; Diabetes Complications; Glucose
PubMed: 37804855
DOI: 10.1016/S2213-8587(23)00159-6 -
Continuum (Minneapolis, Minn.) Oct 2023This article provides an up-to-date review of the diagnosis and management of the most common neuropathies that occur in patients with diabetes.
OBJECTIVE
This article provides an up-to-date review of the diagnosis and management of the most common neuropathies that occur in patients with diabetes.
LATEST DEVELOPMENTS
The prevalence of diabetes continues to grow worldwide and, as a result, the burden of diabetic neuropathies is also increasing. Most diabetic neuropathies are caused by hyperglycemic effects on small and large fiber nerves, and glycemic control in individuals with type 1 diabetes reduces neuropathy prevalence. However, among people with type 2 diabetes, additional factors, particularly metabolic syndrome components, play a role and should be addressed. Although length-dependent distal symmetric polyneuropathy is the most common form of neuropathy, autonomic syndromes, particularly cardiovascular autonomic neuropathy, are associated with increased mortality, whereas lumbosacral radiculoplexus neuropathy and treatment-induced neuropathy cause substantial morbidity. Recent evidence-based guidelines have updated the recommended treatment options to manage pain associated with distal symmetric polyneuropathy of diabetes.
ESSENTIAL POINTS
Identifying and appropriately diagnosing the neuropathies of diabetes is key to preventing progression. Until better disease-modifying therapies are identified, management remains focused on diabetes and metabolic risk factor control and pain management.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Risk Factors; Polyneuropathies; Pain
PubMed: 37851036
DOI: 10.1212/CON.0000000000001291 -
Frontiers in Endocrinology 2023Diabetic nephropathy (DN) and diabetic retinopathy (DR) are the most serious and common diabetes-associated complications. DN and DR are all highly prevalent and... (Review)
Review
Diabetic nephropathy (DN) and diabetic retinopathy (DR) are the most serious and common diabetes-associated complications. DN and DR are all highly prevalent and dangerous global diseases, but the underlying mechanism remains to be elucidated. Ferroptosis, a relatively recently described type of cell death, has been confirmed to be involved in the occurrence and development of various diabetic complications. The disturbance of cellular iron metabolism directly triggers ferroptosis, and abnormal iron metabolism is closely related to diabetes. However, the molecular mechanism underlying the role of ferroptosis in DN and DR is still unclear, and needs further study. In this review article, we summarize and evaluate the mechanism of ferroptosis and its role and progress in DN and DR, it provides new ideas for the diagnosis and treatment of DN and DR.
Topics: Humans; Diabetic Nephropathies; Ferroptosis; Retinal Diseases; Diabetic Retinopathy; Iron; Diabetes Mellitus
PubMed: 37600716
DOI: 10.3389/fendo.2023.1215292 -
Cell Metabolism Sep 2023The pathogenic mechanisms underlying distal symmetric polyneuropathy (DSPN), a common neuropathy in patients with diabetes mellitus (DM), are not fully understood.... (Randomized Controlled Trial)
Randomized Controlled Trial
The pathogenic mechanisms underlying distal symmetric polyneuropathy (DSPN), a common neuropathy in patients with diabetes mellitus (DM), are not fully understood. Here, we discover that the gut microbiota from patients with DSPN can induce a phenotype exhibiting more severe peripheral neuropathy in db/db mice. In a randomized, double-blind, and placebo-controlled trial (ChiCTR1800017257), compared to 10 patients who received placebo, DSPN was significantly alleviated in the 22 patients who received fecal microbiota transplants from healthy donors, independent of glycemic control. The gut bacterial genomes that correlated with the Toronto Clinical Scoring System (TCSS) score were organized in two competing guilds. Increased guild 1, which had higher capacity in butyrate production, and decreased guild 2, which harbored more genes in synthetic pathway of endotoxin, were associated with improved gut barrier integrity and decreased proinflammatory cytokine levels. Moreover, matched enterotype between transplants and recipients showed better therapeutic efficacy with more enriched guild 1 and suppressed guild 2. Thus, changes in these two competing guilds may play a causative role in DSPN and have the potential for therapeutic targeting.
Topics: Diabetic Neuropathies; Gastrointestinal Microbiome; Polyneuropathies; Humans
PubMed: 37451270
DOI: 10.1016/j.cmet.2023.06.010 -
Redox Biology Aug 2023Diabetic vascular complications can affect both microvascular and macrovascular. Diabetic microvascular complications, such as diabetic nephropathy, diabetic... (Review)
Review
Diabetic vascular complications can affect both microvascular and macrovascular. Diabetic microvascular complications, such as diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, and diabetic cardiomyopathy, are believed to be caused by oxidative stress. The Nox family of NADPH oxidases is a significant source of reactive oxygen species and plays a crucial role in regulating redox signaling, particularly in response to high glucose and diabetes mellitus. This review aims to provide an overview of the current knowledge about the role of Nox4 and its regulatory mechanisms in diabetic microangiopathies. Especially, the latest novel advances in the upregulation of Nox4 that aggravate various cell types within diabetic kidney disease will be highlighted. Interestingly, this review also presents the mechanisms by which Nox4 regulates diabetic microangiopathy from novel perspectives such as epigenetics. Besides, we emphasize Nox4 as a therapeutic target for treating microvascular complications of diabetes and summarize drugs, inhibitors, and dietary components targeting Nox4 as important therapeutic measures in preventing and treating diabetic microangiopathy. Additionally, this review also sums up the evidence related to Nox4 and diabetic macroangiopathy.
Topics: Humans; NADPH Oxidase 4; NADPH Oxidases; Reactive Oxygen Species; Oxidative Stress; Diabetic Nephropathies; Diabetic Angiopathies; Diabetes Mellitus
PubMed: 37321060
DOI: 10.1016/j.redox.2023.102781 -
Reviews in Endocrine & Metabolic... Aug 2023Emerging evidence suggests that treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) could be an interesting treatment strategy to reduce neurological... (Review)
Review
Emerging evidence suggests that treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) could be an interesting treatment strategy to reduce neurological complications such as stroke, cognitive impairment, and peripheral neuropathy. We performed a systematic review to examine the evidence concerning the effects of GLP-1 RAs on neurological complications of diabetes. The databases used were Pubmed, Scopus and Cochrane. We selected clinical trials which analysed the effect of GLP-1 RAs on stroke, cognitive impairment, and peripheral neuropathy. We found a total of 19 studies: 8 studies include stroke or major cardiovascular events, 7 involve cognitive impairment and 4 include peripheral neuropathy. Semaglutide subcutaneous and dulaglutide reduced stroke cases. Liraglutide, albiglutide, oral semaglutide and efpeglenatide, were not shown to reduce the number of strokes but did reduce major cardiovascular events. Exenatide, dulaglutide and liraglutide improved general cognition but no significant effect on diabetic peripheral neuropathy has been reported with GLP-1 RAs. GLP-1 RAs are promising drugs that seem to be useful in the reduction of some neurological complications of diabetes. However, more studies are needed.
Topics: Humans; Hypoglycemic Agents; Liraglutide; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide 1; Cardiovascular Diseases; Stroke; Diabetes Complications
PubMed: 37231200
DOI: 10.1007/s11154-023-09807-3 -
Diabetes/metabolism Research and Reviews Nov 2023To assess the prevalence of diabetic peripheral neuropathy (DPN) and its risk factors in the type 2 diabetes mellitus (T2DM) population.
AIMS
To assess the prevalence of diabetic peripheral neuropathy (DPN) and its risk factors in the type 2 diabetes mellitus (T2DM) population.
METHODS
This cross-sectional study enroled patients with T2DM between July and December 2017 from 24 provinces in China. Diabetic peripheral neuropathy and its severity were assessed by the Toronto clinical scoring system, neuropathy symptoms score (NSS) and neuropathy disability score. The prevalence of DPN and its risk factors were analysed.
RESULTS
A total of 14,908 patients with T2DM were enroled. The prevalence of DPN was 67.6%. Among 10,084 patients with DPN, 4808 (47.7%), 3325 (33.0%), and 1951 (19.3%) had mild, moderate, and severe DPN, respectively. The prevalence of DPN in females was higher than in males (69.0% vs. 66.6%, P = 0.002). The prevalence of DPN increased with age and course of diabetes and decreased with body mass index (BMI) and education level (all P for trend <0.05). The comorbidities and complications in patients with DPN were higher than in those without DPN, including hypertension, myocardial infarction, diabetic retinopathy, and diabetic nephropathy (all P < 0.001). Age, hypertension, duration of diabetes, diabetic retinopathy, diabetic nephropathy, glycated haemoglobin, high-density lipoprotein cholesterol, and lower estimated glomerular filtration rate were positively associated with DPN, while BMI, education level, fasting C-peptide, and uric acid were negatively associated with DPN.
CONCLUSIONS
Among patients with T2DM in China, the prevalence of DPN is high, especially in the elderly, low-income, and undereducated patients.
Topics: Male; Female; Humans; Aged; Diabetes Mellitus, Type 2; Cross-Sectional Studies; Diabetic Neuropathies; Prevalence; Risk Factors; Diabetic Retinopathy; Hypertension; Diabetic Nephropathies
PubMed: 37490047
DOI: 10.1002/dmrr.3702 -
Clinical Infectious Diseases : An... Aug 2023
Topics: Humans; Diabetes Complications; Communicable Diseases; Skin Diseases; Vascular Diseases; Diabetic Foot; Diabetes Mellitus
PubMed: 37306693
DOI: 10.1093/cid/ciad255 -
JPMA. the Journal of the Pakistan... Jul 2023Diabetic foot ulcer disease is the combination of vasculopathy, neuropathy and infection. It is important to identify the main aetiology and to treat it for optimal... (Review)
Review
Diabetic foot ulcer disease is the combination of vasculopathy, neuropathy and infection. It is important to identify the main aetiology and to treat it for optimal ulcer healing so that limb amputation may be prevented. A literature review spanning five years (2018-2021) was performed to assess the current understanding of these aetiologies and management options for their treatment. Peripheral artery disease is prevalent in patients with diabetes. Before performing any amputations, whether minor or major, vascular supply in these patients needs to be evaluated and, if needed, improved. Diabetic neuropathy is a long-term complication of uncontrolled diabetes. Patients' education is very important with respect to selfcare and prevention of foot complications arising out of minor trauma in diabetic population. Better foot care and regular use of off-loading shoe wear can prevent neuropathic diabetic foot ulcers. Infection in diabetic patients is mostly polymicrobial and it can present as superficial or deep infections. Early diagnosis, use of broad-spectrum antibiotics, and aggressive debridement, when needed, is advocated to prevent foot amputation. Contemporary treatment armamentarium provides many options for treating diabetic foot ulcers. Nevertheless, one must exhaust all preventive strategies to avoid ulcers in the first place. Once an ulcer has developed, it should be managed aggressively with appropriate soft tissue and, if required, with bony procedures. The current narrative review was planned to explore the current understanding about the main aetiologies of diabetic foot ulcers and about the available treatment options.
Topics: Humans; Diabetic Foot; Diabetic Neuropathies; Foot; Risk Factors; Amputation, Surgical; Diabetes Mellitus
PubMed: 37469062
DOI: 10.47391/JPMA.6634