-
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 -
Annals of Medicine Dec 2023Obesity is a chronic disease characterised by excess adiposity, which impairs health. The high prevalence of obesity raises the risk of long-term medical complications... (Review)
Review
Obesity is a chronic disease characterised by excess adiposity, which impairs health. The high prevalence of obesity raises the risk of long-term medical complications including type 2 diabetes and chronic kidney disease. Several studies have focused on patients with obesity, type 2 diabetes and chronic kidney disease due to the increased prevalence of diabetic kidney disease. Several randomized controlled trials on sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 analogues, and bariatric surgery in diabetic kidney disease showed renoprotective effects. However, further research is critical to address the treatment of patients with obesity and chronic kidney disease to lessen morbidity.Key messageObesity is a driver of chronic kidney disease, and type 2 diabetes, along with obesity, accelerates chronic kidney disease.Several randomized controlled trials on sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 analogues, and bariatric surgery in diabetic kidney disease demonstrate the improvement of renal outcomes.There is a need to address the treatment of patients with obesity and CKD to lessen morbidity.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Hypoglycemic Agents; Obesity; Renal Insufficiency, Chronic; Glucagon-Like Peptide 1; Glucose; Sodium
PubMed: 37086110
DOI: 10.1080/07853890.2023.2203517 -
Cell Reports. Medicine Oct 2023Neurovascular dysfunction is a preclinical manifestation of diabetic complications, including diabetic retinopathy (DR). Herein, we report that a transfer RNA-derived...
Neurovascular dysfunction is a preclinical manifestation of diabetic complications, including diabetic retinopathy (DR). Herein, we report that a transfer RNA-derived RNA fragment, tRF-3001a, is significantly upregulated under diabetic conditions. tRF-3001a downregulation inhibits Müller cell activation, suppresses endothelial angiogenic effects, and protects against high-glucose-induced retinal ganglion cell injury in vitro. Furthermore, tRF-3001a downregulation alleviates retinal vascular dysfunction, inhibits retinal reactive gliosis, facilitates retinal ganglion cell survival, and preserves visual function and visually guided behaviors in STZ-induced diabetic mice and db/db diabetic mice. Mechanistically, tRF-3001a regulates neurovascular dysfunction in a microRNA-like mechanism by targeting GSK3B. Clinically, tRF-3001a is upregulated in aqueous humor (AH) samples of DR patients. tRF-3001a downregulation inhibits DR-induced human retinal vascular endothelial cell and Müller cell dysfunction in vitro and DR-induced retinal neurovascular dysfunction in C57BL/6J mice. Thus, targeting tRF-3001a-mediated signaling is a promising strategy for the concurrent treatment of vasculopathy and neuropathy in diabetes mellitus.
Topics: Mice; Humans; Animals; Diabetes Mellitus, Experimental; Mice, Inbred C57BL; Retina; Diabetic Retinopathy; Hyperglycemia
PubMed: 37757825
DOI: 10.1016/j.xcrm.2023.101209 -
Renal Failure Dec 2023The safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors in elderly patients with diabetic kidney disease (DKD) is still controversial. This study aimed to... (Meta-Analysis)
Meta-Analysis Review
Comparative safety of sodium-glucose co-transporter 2 inhibitors in elderly patients with type 2 diabetes mellitus and diabetic kidney disease: a systematic review and meta-analysis.
The safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors in elderly patients with diabetic kidney disease (DKD) is still controversial. This study aimed to analyze the safety of SGLT2 inhibitors in elderly patients with type 2 diabetes mellitus (T2DM) and DKD. We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to March 2023. Randomized controlled trials (RCTs) were included. Data including patient characteristics and interesting outcomes were extracted, and the dichotomous data and continuous variables were evaluated using risk ratio (RR) with 95% confidence intervals (CIs) and mean difference (MD) with 95% CIs, respectively. A total of 14 RCTs with 59874 participants were finally included. There were 38,252 males (63.9%) and 21,622 females (36.1%). The patients' mean age was > 64.6 years. SGLT2 inhibitors could delay the further decline of estimated glomerular filtration rate (eGFR) when eGFR ≥ 60 ml/min/1.73m (MD: 2.36; 95%CI [1.15-3.57]). SGLT2 inhibitors in elderly patients with eGFR < 60 ml/min/1.73m (RR: 0.86; 95%CI [0.67-1.11]) may have a relatively increased risk of acute kidney injury compared to eGFR ≥ 60 ml/min/1.73m. SGLT2 inhibitors increased the incidence of genital mycotic infections (RR: 3.47; 95%CI [2.97-4.04]) and diabetic ketoacidosis (RR: 2.25; 95%CI [1.57-3.24]). Except for genital mycotic infections and diabetic ketoacidosis, other adverse reactions were few, indicating that SGLT2 inhibitors are relatively safe for elderly patients with T2DM and DKD. Safety and renoprotection may be diminished when SGLT2 inhibitors are used in elderly patients with eGFR < 60 ml/min/1.73m.
Topics: Male; Female; Humans; Aged; Middle Aged; Sodium-Glucose Transporter 2 Inhibitors; Diabetic Nephropathies; Diabetic Ketoacidosis; Diabetes Mellitus, Type 2; Symporters; Glucose; Sodium; Hypoglycemic Agents
PubMed: 37246403
DOI: 10.1080/0886022X.2023.2217287 -
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 -
Frontiers in Endocrinology 2023A causal relationship concerning coffee intake and diabetic nephropathy (DN) is controversial. We conducted a Mendelian randomization study to assess the causal nature...
RATIONALE AND OBJECTIVE
A causal relationship concerning coffee intake and diabetic nephropathy (DN) is controversial. We conducted a Mendelian randomization study to assess the causal nature of these associations.
METHODS
40 independent single nucleotide polymorphisms (SNPs) associated with coffee intake were selected from the UK Biobank study. Summary-level data for diabetic nephropathy were obtained from publicly available genome-wide association studies (GWAS) and the FinnGen consortium. Inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods were used to examine a causal association. Sensitivity analyses included Cochran's Q test, the intercept of MR-Egger, MR-PRESSO, and the Outlier method. Leave-One-Out sensitivity analyses were also conducted to reduce the heterogeneity.
RESULTS
Our current study demonstrated positive associations of genetically predicted coffee intake with diabetic nephropathy (OR=1.939; = 0.045 and type 2 diabetes with renal complications (OR = 2.787, = 0.047). These findings were robust across several sensitivity analyses.
CONCLUSIONS
This study found a positive correlation between coffee consumption and the risk of diabetic nephropathy using genetic data. For a more accurate and trustworthy conclusion, subgroup analysis on coffee intake, including preparing method, variety of coffee, and quantity, is required.
Topics: Humans; Diabetic Nephropathies; Coffee; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Mendelian Randomization Analysis
PubMed: 37469984
DOI: 10.3389/fendo.2023.1169933 -
Investigative Ophthalmology & Visual... Oct 2023Microaneurysm (MA) plays an important role in the pathogenesis of diabetic macular edema (DME) progression and response to anti-vascular endothelial growth factor (VEGF)...
PURPOSE
Microaneurysm (MA) plays an important role in the pathogenesis of diabetic macular edema (DME) progression and response to anti-vascular endothelial growth factor (VEGF) therapy. This study aimed to investigate the effect of faricimab, a bispecific antibody against angiopoietin-2 and VEGF, on the number of MAs and their turnover in the treatment of DME.
METHODS
We included that patients with DME who underwent three monthly injections of faricimab in one eye, with the other eye as control. We examined central retinal thickness (CRT) based on optical coherence tomography (OCT) and best-corrected visual acuity. Turnover, including loss and newly formed MAs, and the total number of MAs were counted based on merged images of the OCT map and fluorescein angiography.
RESULTS
We enrolled 28 patients with DME. After 3 monthly injections of faricimab, CRT significantly improved, 66.0 ± 16.2% of MAs disappeared, and 6.71 ± 5.6% of new MAs were generated, resulting in total reduction to 40.7 ± 15.2%. In the treated eyes, MA disappearance (P < 0.0001) and turnover (P = 0.007) were significantly greater, and new formation was smaller (P < 0.0001) than in non-treated eyes. The size of the retained MAs decreased after treatment. Microaneurysm turnover was not significantly different between areas with and without edema before treatment.
CONCLUSIONS
In the process of improving edema in DME with faricimab, MAs shrink and disappear, and formation of MAs are inhibited, resulting in decreased total number of MAs. Intravitreal administration of faricimab suppresses vascular permeability and improves vascular structure.
Topics: Humans; Macular Edema; Diabetic Retinopathy; Vascular Endothelial Growth Factor A; Angiogenesis Inhibitors; Microaneurysm; Intravitreal Injections; Edema; Tomography, Optical Coherence; Diabetes Mellitus
PubMed: 37856112
DOI: 10.1167/iovs.64.13.31 -
Frontiers in Endocrinology 2023Diabetes is a global health problem which is accompanied with multi-systemic complications. It is of great significance to elucidate the pathogenesis and to identify... (Review)
Review
Diabetes is a global health problem which is accompanied with multi-systemic complications. It is of great significance to elucidate the pathogenesis and to identify novel therapies of diabetes and diabetic complications. Sestrin2, a stress-inducible protein, is primarily involved in cellular responses to various stresses. It plays critical roles in regulating a series of cellular events, such as oxidative stress, mitochondrial function and endoplasmic reticulum stress. Researches investigating the correlations between Sestrin2, diabetes and diabetic complications are increasing in recent years. This review incorporates recent findings, demonstrates the diverse functions and regulating mechanisms of Sestrin2, and discusses the potential roles of Sestrin2 in the pathogenesis of diabetes and diabetic complications, hoping to highlight a promising therapeutic direction.
Topics: Humans; Nuclear Proteins; Diabetes Mellitus; Endoplasmic Reticulum Stress; Oxidative Stress; Diabetes Complications
PubMed: 37920252
DOI: 10.3389/fendo.2023.1274686 -
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 Apr 2024This review summarises the present knowledge of acute foot attacks in patients with diabetes. Diagnosis and treatment of acute foot attacks in patients with diabetes are... (Review)
Review
This review summarises the present knowledge of acute foot attacks in patients with diabetes. Diagnosis and treatment of acute foot attacks in patients with diabetes are often delayed, which increases the risk of amputations. To prevent this, urgent action is necessary, as it is for acute myocardial infarction and stroke, to ensure that patients are seen by competent specialists in a multidisciplinary team within hours. By following evidence-based guidelines, such as the National Treatment Guideline for diabetic foot disease from the Danish Endocrine Society, and seeking immediate medical attention, the risk of amputation and complications can be significantly reduced.
Topics: Humans; Diabetic Foot; Amputation, Surgical; Acute Disease; Practice Guidelines as Topic
PubMed: 38704714
DOI: 10.61409/V09230598