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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 -
The Lancet. Neurology Apr 2024Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as...
BACKGROUND
Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.
METHODS
We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.
FINDINGS
Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378-521), affecting 3·40 billion (3·20-3·62) individuals (43·1%, 40·5-45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7-26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6-38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5-32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7-2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.
INTERPRETATION
As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Female; Humans; Infant, Newborn; Global Burden of Disease; Diabetic Neuropathies; Autism Spectrum Disorder; Premature Birth; Communicable Diseases; Risk Factors; Disease Progression; Global Health; COVID-19; Zika Virus; Zika Virus Infection; Quality-Adjusted Life Years; Life Expectancy
PubMed: 38493795
DOI: 10.1016/S1474-4422(24)00038-3 -
Diabetes Research and Clinical Practice Dec 2023This article summarizes the latest epidemiology of diabetic autonomic neuropathy (DAN), and provides a brief overview on epidemiology, current outcomes measures for... (Review)
Review
This article summarizes the latest epidemiology of diabetic autonomic neuropathy (DAN), and provides a brief overview on epidemiology, current outcomes measures for screening and diagnosis in research and clinical settings, the latest evidence on effective management, and novel perspectives on the impacts of social determinants of health in development and management of DAN. Among the various forms of diabetic neuropathy, distal symmetric polyneuropathy and diabetic autonomic neuropathies, particularly cardiovascular autonomic neuropathy, are by far the most studied. However, emerging data highlight the impact of other forms of autonomic neuropathies such as gastrointestinal and urogenital autonomic neuropathies, on healthcare and patients' reported outcomes [1].
Topics: Humans; Diabetic Neuropathies
PubMed: 38245325
DOI: 10.1016/j.diabres.2023.110762 -
Frontiers in Endocrinology 2023Previous observational studies have indicated an association between serum uric acid (SUA) and diabetic neuropathy (DN), but confounding factors and reverse causality...
BACKGROUND
Previous observational studies have indicated an association between serum uric acid (SUA) and diabetic neuropathy (DN), but confounding factors and reverse causality have left the causality of this relationship uncertain.
METHODS
Univariate Mendelian randomization (MR), multivariate MR and linkage disequilibrium score (LDSC) regression analysis were utilized to assess the causal link between SUA and DN. Summary-level data for SUA were drawn from the CKDGen consortium, comprising 288,648 individuals, while DN data were obtained from the FinnGen consortium, with 2,843 cases and 271,817 controls. Causal effects were estimated primarily using inverse variance weighted (IVW) analysis, supplemented by four validation methods, with additional sensitivity analyses to evaluate pleiotropy, heterogeneity, and result robustness.
RESULTS
The LDSC analysis revealed a significant genetic correlation between SUA and DN (genetic correlation = 0.293, P = 2.60 × 10). The primary methodology IVW indicated that each increase of 1 mg/dL in SUA would increase DN risk by 17% (OR = 1.17, 95% CI 1.02-1.34, P = 0.02), while no causal relationship was found in reverse analysis (OR = 1.00, 95% CI 0.98~1.01, = 0.97). Multivariate MR further identified that the partial effect of SUA on DN may be mediated by physical activity, low density lipoprotein cholesterol (LDL-C), insulin resistance (IR), and alcohol use.
CONCLUSION
The study establishes a causal link between elevated SUA levels and an increased risk of DN, with no evidence for a reverse association. This underscores the need for a comprehensive strategy in DN management, integrating urate-lowering interventions with modulations of the aforementioned mediators.
Topics: Humans; Diabetic Neuropathies; Mendelian Randomization Analysis; Uric Acid; Alcohol Drinking; Cholesterol, LDL; Diabetes Mellitus
PubMed: 38034019
DOI: 10.3389/fendo.2023.1277984 -
Diabetes Research and Clinical Practice Dec 2023Diabetic neuropathy is a common complication of diabetes that affects up to 50% of patients during the course of the disease; 20-30% of the patients also develop...
Diabetic neuropathy is a common complication of diabetes that affects up to 50% of patients during the course of the disease; 20-30% of the patients also develop neuropathic pain. The mechanisms underlying neuropathy are not known in detail, but both metabolic and vascular factors may contribute to the development of neuropathy. The development of the most common type of neuropathy is insidious, often starting distally in the toes and feet and gradually ascending up the leg and later also involving fingers and hands. The symptoms are mainly sensory with either sensory loss or positive symptoms with different types of paresthesia or painful sensations. In more advanced cases motor dysfunction may occur, causing gait disturbances and falls. The diagnosis of neuropathy is based on history and a careful examination, which includes a sensory examination of both large and small sensory nerve fiber function, as well as an examination of motor function and deep tendon reflexes of the lower limbs. Attention needs to be paid to the feet including examination of the skin, joints, and vascular supply. Nerve conduction studies are rarely needed to make a diagnosis of neuropathy. In patients with clear motor deficit or with an asymmetrical presentation, additional electrophysiological examination may be necessary. Early detection of diabetic neuropathy is important to avoid further irreversible injury to the peripheral nerves.
Topics: Humans; Diabetic Neuropathies; Neural Conduction; Peripheral Nerves; Neuralgia; Hand; Diabetes Mellitus
PubMed: 38245319
DOI: 10.1016/j.diabres.2023.110753 -
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 -
BMJ Open Diabetes Research & Care Nov 2023Diabetic foot ulcer (DFU) stands as a severe diabetic lower extremity complication, characterized by high amputation rates, mortality, and economic burden. We propose...
INTRODUCTION
Diabetic foot ulcer (DFU) stands as a severe diabetic lower extremity complication, characterized by high amputation rates, mortality, and economic burden. We propose using Mendelian randomization studies to explore shared and distinct risk factors for diabetic lower extremity complications.
RESEARCH DESIGN AND METHODS
We selected uncorrelated genetic variants associated with 85 phenotypes in five categories at the genome-wide significance level as instrumental variables. Genetic associations with DFU, diabetic polyneuropathy (DPN), and diabetic peripheral artery disease (DPAD) were obtained from the FinnGen and UK Biobank studies.
RESULTS
Body mass index (BMI) emerged as the only significant risk factor for DPAD, DPN, and DFU, independent of type 2 diabetes, fasting glucose, fasting insulin, and HbA1c. Educational attainment stood out as the sole significant protective factor against DPAD, DPN, and DFU. Glycemic traits below the type 2 diabetes diagnosis threshold showed associations with DPAD and DPN. While smoking history exhibited suggestive associations with DFU, indicators of poor nutrition, particularly total protein, mean corpuscular hemoglobin, and mean corpuscular volume, may also signal potential DFU occurrence.
CONCLUSIONS
Enhanced glycemic control and foot care are essential for the diabetic population with high BMI, limited education, smoking history, and indicators of poor nutrition. By focusing on these specific risk factors, healthcare interventions can be better tailored to prevent and manage DFU effectively.
Topics: Humans; Diabetic Foot; Diabetes Mellitus, Type 2; Mendelian Randomization Analysis; Risk Factors
PubMed: 37989345
DOI: 10.1136/bmjdrc-2023-003523 -
Frontiers in Endocrinology 2024
Topics: Humans; Diabetic Neuropathies; Early Diagnosis; Drug Therapy, Combination
PubMed: 38868745
DOI: 10.3389/fendo.2024.1422734 -
Journal of Advanced Research Dec 2023Poor wound healing is a significant complication of diabetes, which is commonly caused by neuropathy, trauma, deformities, plantar hypertension and peripheral arterial... (Review)
Review
BACKGROUND
Poor wound healing is a significant complication of diabetes, which is commonly caused by neuropathy, trauma, deformities, plantar hypertension and peripheral arterial disease. Diabetic foot ulcers (DFU) are difficult to heal, which makes patients susceptible to infections and can ultimately conduce to limb amputation or even death in severe cases. An increasing number of studies have found that epigenetic alterations are strongly associated with poor wound healing in diabetes.
AIM OF REVIEW
This work provides significant insights into the development of therapeutics for improving chronic diabetic wound healing, particularly by targeting and regulating DNA methylation and demethylation in DFU. Key scientific concepts of review: DNA methylation and demethylation play an important part in diabetic wound healing, via regulating corresponding signaling pathways in different breeds of cells, including macrophages, vascular endothelial cells and keratinocytes. In this review, we describe the four main phases of wound healing and their abnormality in diabetic patients. Furthermore, we provided an in-depth summary and discussion on how DNA methylation and demethylation regulate diabetic wound healing in different types of cells; and gave a brief summary on recent advances in applying cellular reprogramming techniques for improving diabetic wound healing.
Topics: Humans; Diabetic Foot; DNA Methylation; Endothelial Cells; Wound Healing; Demethylation; Diabetes Mellitus
PubMed: 36706989
DOI: 10.1016/j.jare.2023.01.009 -
Saudi Medical Journal Oct 2023To compare the efficacy of negative pressure wound therapy (NPWT) and alginate dressings on wound bed preparation prior to split thickness skin graft (STSG) surgery for... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To compare the efficacy of negative pressure wound therapy (NPWT) and alginate dressings on wound bed preparation prior to split thickness skin graft (STSG) surgery for patients with chronic diabetic foot ulcers (DFUs).
METHODS
Between September 2022 and March 2023, we completed a randomized controlled trial in Nanjing First Hospital and PLA 454 Hospital. Patients were divided into 2 groups: i) the NPWT group (with vacuum-assisted closure, n=50); ii) the control group (with alginates dressings, n=50). Once DFU wound was filled with healthy granulation tissues, STSG surgery was performed. The time to STSG surgery was regarded as the primary outcome. The survival rates of skin graft, the wound blood perfusion, the wound neutrophil extracellular traps (NETs) formation, and polarization of M1 and M2 macrophages in DFU wounds were regarded ad secondary outcomes.
RESULTS
Patients in the NPWT group had less time to STSG surgery than the control group. The patients in the NPWT group had prominently increased survival rates of skin graft, increased wound blood perfusion, and decreased NET formation in comparison with the control group. The macrophages in DFU wounds switched from M1 to M2 phenotype in the NPWT group.
CONCLUSION
Negative pressure wound therapy is superior to conventional moist dressings in wound bed preparation prior to STSG surgery for patients with chronic DFUs.
Topics: Humans; Diabetic Foot; Negative-Pressure Wound Therapy; Wound Healing; Bandages; Skin Transplantation; Diabetes Mellitus
PubMed: 37777272
DOI: 10.15537/smj.2023.44.20230386