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Journal of Diabetes and Metabolic... Jun 2024In this extensive review work, the important role of AMP-activated protein kinase (AMPK) in causing of diabetes mellitus has been highlighted. Structural feature of AMPK... (Review)
Review
PURPOSE
In this extensive review work, the important role of AMP-activated protein kinase (AMPK) in causing of diabetes mellitus has been highlighted. Structural feature of AMPK as well its regulations and roles are described nicely, and the association of AMPK with the diabetic complications like nephropathy, neuropathy and retinopathy are also explained along with the connection between AMPK and β-cell function, insulin resistivity, mTOR, protein metabolism, autophagy and mitophagy and effect on protein and lipid metabolism.
METHODS
Published journals were searched on the database like PubMed, Medline, Scopus and Web of Science by using keywords such as AMPK, diabetes mellitus, regulation of AMPK, complications of diabetes mellitus, autophagy, apoptosis etc.
RESULT
After extensive review, it has been found that, kinase enzyme like AMPK is having vital role in management of type II diabetes mellitus. AMPK involve in enhance the concentration of glucose transporter like GLUT 1 and GLUT 4 which result in lowering of blood glucose level in influx of blood glucose into the cells; AMPK increases the insulin sensitivity and decreases the insulin resistance and further AMPK decreases the apoptosis of β-cells which result into secretion of insulin and AMPK is also involve in declining of oxidative stress, lipotoxicity and inflammation, owing to which organ damage due to diabetes mellitus can be lowered by activation of AMPK.
CONCLUSION
As AMPK activation leads to overall control of diabetes mellitus, designing and developing of small molecules or peptide that can act as AMPK agonist will be highly beneficial for control or manage diabetes mellitus.
PubMed: 38932895
DOI: 10.1007/s40200-024-01420-8 -
Journal of Diabetes and Metabolic... Jun 2024This study aimed to assess the relationship between metabolic control factors, socio-demographic characteristics, personality traits, and self-perceived health status in...
Correlation between socio-demographic characteristics, metabolic control factors and personality traits with self-perceived health status in patients with diabetes: A cross-sectional study.
PURPOSE
This study aimed to assess the relationship between metabolic control factors, socio-demographic characteristics, personality traits, and self-perceived health status in diabetes.
METHODS
This cross-sectional study included 318 patients with type 1 and 2 diabetes (DM). Participants completed a questionnaire-based survey, which included the NEO Personality Inventory-Revised to measure five personality dimensions and the SF-12 survey to assess self-perceived health status. Binary logistic regression was performed to analyze the data, with socio-demographic characteristics, clinical data, and nutrition status as independent variables, and self-perceived health status (categorized as poor or good condition) as the dependent variable. Unadjusted and adjusted binary logistic regression analyses were used to examine the association between personality traits (high vs. low) and metabolic control factors (good control vs. bad control) with health status scores.
RESULTS
60.7% of the participants with diabetes in the study described their health as "good." The results indicated that female gender (OR: 0.314, 95%CI: 0.105-0.938, = 0.038), age > 60 years (OR: 0.263, 95%CI: 0.117-0.592, = 0.001), comorbidities (OR: 0.314, 95%CI: 0.178-0.556, = 0.001), DM complications (OR: 0.531, 95%CI: 0.337-0.838, = 0.007), diabetic neuropathy (OR: 0.562, 95%CI: 0.356-0.886, = 0.013), and diabetic ulcer (OR: 0.130, 95%CI: 0.023-0.747, = 0.022) were independent variables associated with a "poor" health status. However, regular physical activity (OR: 3.144, 95%CI: 1.209-8.175, = 0.019) and a healthy nutritional diet (OR: 2.456, 95%CI: 1.421-4.245, < 0.001) were associated with a higher likelihood of a "good" self-perceived health status.
CONCLUSION
Preventive programs and interventions aimed at improving self-perceived health among patients with diabetes should focus on increasing regular physical activity and promoting a healthy nutritional status. These actions should be particularly targeted towards female and older patients with higher neuroticism traits.
PubMed: 38932851
DOI: 10.1007/s40200-023-01354-7 -
Journal of Diabetes and Metabolic... Jun 2024This article critically reviews the recent search on the use of Small Interfering RNA (siRNA) in the process of gene regulation that has been harnessed to silence... (Review)
Review
OBJECTIVE
This article critically reviews the recent search on the use of Small Interfering RNA (siRNA) in the process of gene regulation that has been harnessed to silence specific genes in various cell types, including those involved in diabetes complications.
SIGNIFICANCE
Diabetes, a prevalent and severe condition, poses life-threatening risks due to elevated blood glucose levels. It results from inadequate insulin production by the pancreas or ineffective insulin utilization by the body. Recent research suggests siRNA could hold promise in addressing diabetes complications.
METHODS
In this review, we discussed several subjects, including diabetes; its function, and common treatment options. An in-depth analysis of gene silencing method for siRNA and role of siRNA in diabetes, focusing on its impact on glucose homeostasis, diabetic retinopathy, wound healing, diabetic nephropathy and peripheral neuropathy, diabetic foot ulcers, diabetic atherosclerosis, and diabetic cardiomyopathy.
RESULT
siRNA-based treatment has the potential to target specific genes without disrupting several other endogenous pathways, which decreases the risk of off-target effects. In addition, siRNA has the capability to provide long-term efficacy with a single dose which will reduce treatment options and enhance patient compliance.
CONCLUSION
In the context of diabetic complications, siRNA has been explored as a potential therapeutic tool to modulate the expression of genes involved in various processes associated with diabetes-related issues such as Diabetic Retinopathy, Neuropathy, Nephropathy, wound healing. The use of siRNA in these contexts is still largely experimental, and challenges such as delivery to specific tissues, potential off-target effects, and long-term safety need to be addressed. Additionally, the development of siRNA-based therapies for clinical use in diabetic complications is an active area of research.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-024-01405-7.
PubMed: 38932822
DOI: 10.1007/s40200-024-01405-7 -
Pharmaceuticals (Basel, Switzerland) Jun 2024(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At...
(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At the present time, the exploration of novel therapies for alleviating diabetic-neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect the sildenafil (phosphodiesterase-5 inhibitor)-metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats. (2) Methods: This study involved a cohort of 70 diabetic rats and 10 non-diabetic rats. Diabetic neuropathy was induced by a single dose of 130 mg/kg alloxan. The rats were submitted to thermal stimulus test using a hot-cold plate and to tactile stimulus test using von Frey filaments. Moreover, at the end of the experiment, the animals were sacrificed and their brains and livers were collected to investigate the impact of this combination on TNF-α, IL-6, nitrites and thiols levels. (3) Results: The results demonstrated that all sildenafil-metformin combinations decreased the pain sensitivity in the von Frey test, hot plate test and cold plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil-metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect on alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion.
PubMed: 38931450
DOI: 10.3390/ph17060783 -
International Journal of Environmental... Jun 2024This study aims to examine the association between the occurrence of diabetic foot and air quality (SO, CO, NO, O). Open data were collected to conduct a big data study....
This study aims to examine the association between the occurrence of diabetic foot and air quality (SO, CO, NO, O). Open data were collected to conduct a big data study. Patient information was gathered from the National Health Insurance Service, and the National Institute of Environmental Science's air quality data were used. A total study population of 347,543 cases were reviewed (case = 13,353, control = 334,190). The lag period from air quality changes to the actual amputation operation was calculated for each factor. The frequency of diabetic foot amputation in each region was identified and analyzed using a distributed lag non-linear model. Gangwon-do showed the highest relative risks (RRs) for SO and CO, while Chungcheongnam-do exhibited the highest RR for NO. Jeju had the highest RR for O. Regions like Incheon, Busan, and the capital region also showed significant risk increases. These findings emphasize the importance of tailored air quality management to address diabetic foot complications effectively.
Topics: Humans; Diabetic Foot; Republic of Korea; Air Pollution; Female; Air Pollutants; Male; Middle Aged; Aged; Adult
PubMed: 38929021
DOI: 10.3390/ijerph21060775 -
International Journal of Molecular... Jun 2024The exact mechanism by which diabetic neuropathy develops is still not fully known, despite our advances in medical knowledge. Progressing neuropathy may occur with a... (Review)
Review
The exact mechanism by which diabetic neuropathy develops is still not fully known, despite our advances in medical knowledge. Progressing neuropathy may occur with a persistently favorable metabolic status in some patients with diabetes mellitus, while, in others, though seldom, a persistently unfavorable metabolic status is not associated with significant neuropathy. This might be significantly due to genetic differences. While recent years have brought compelling progress in the understanding of the pathogenetic background-in particular, accelerated progress is being made in understanding molecular biological mechanisms-some aspects are still not fully understood. A comparatively small amount of information is accessible on this matter; therefore, by summarizing the available data, in this review, we aim to provide a clearer picture of the current state of knowledge, identify gaps in the previous studies, and possibly suggest directions for future studies. This could help in developing more personalized approaches to the prevention and treatment of diabetic neuropathy, while also taking into account individual genetic profiles.
Topics: Humans; Diabetic Neuropathies; Genetic Predisposition to Disease; Genetic Variation; Animals
PubMed: 38928135
DOI: 10.3390/ijms25126429 -
Biomedicines Jun 2024Diabetes mellitus (DM) is a chronic metabolic disorder marked by hyperglycemia due to defects in insulin secretion, action, or both, with a global prevalence that has... (Review)
Review
Diabetes mellitus (DM) is a chronic metabolic disorder marked by hyperglycemia due to defects in insulin secretion, action, or both, with a global prevalence that has tripled in recent decades. This condition poses significant public health challenges, affecting individuals, healthcare systems, and economies worldwide. Among its numerous complications, ocular surface disease (OSD) is a significant concern, yet understanding its pathophysiology, diagnosis, and management remains challenging. This review aims to explore the epidemiology, pathophysiology, clinical manifestations, diagnostic approaches, and management strategies of diabetes-related OSD. The ocular surface, including the cornea, conjunctiva, and associated structures, is vital for maintaining eye health, with the lacrimal functional unit (LFU) playing a crucial role in tear film regulation. In DM, changes in glycosaminoglycan metabolism, collagen synthesis, oxygen consumption, and LFU dysfunction contribute to ocular complications. Persistent hyperglycemia leads to the expression of cytokines, chemokines, and cell adhesion molecules, resulting in neuropathy, tear film abnormalities, and epithelial lesions. Recent advances in molecular research and therapeutic modalities, such as gene and stem cell therapies, show promise for managing diabetic ocular complications. Future research should focus on pathogenetically oriented therapies for diabetic neuropathy and keratopathy, transitioning from animal models to clinical trials to improve patient outcomes.
PubMed: 38927510
DOI: 10.3390/biomedicines12061303 -
American Journal of Kidney Diseases :... Jun 2024Social disconnection has been associated with poor cardiometabolic health. This study sought to investigate the associations of social isolation and loneliness with...
RATIONALE & OBJECTIVE
Social disconnection has been associated with poor cardiometabolic health. This study sought to investigate the associations of social isolation and loneliness with diabetic microvascular complications (DMC) among individuals with type 2 diabetes mellitus (T2DM) and compare these associations to those related to traditional risk factors.
STUDY DESIGN
Prospective cohort study.
SETTING & PARTICIPANTS
A total of 24,297 UK Biobank participants with T2DM and no DMC at baseline.
EXPOSURE
Social isolation and loneliness measured using self-reported questionnaires.
OUTCOME
The incidence of DMC defined as a composite of diabetic kidney disease, diabetic retinopathy, or diabetic neuropathy.
ANALYTICAL APPROACH
Multivariable cause-specific hazards regression. To compare the relative importance of social disconnection with other established factors, the R values of the Cox models were calculated.
RESULTS
During a median follow-up of 12.6 years, 5,530 patients were documented to develop DMC (3,458 with diabetic kidney disease, 2,255 with diabetic retinopathy, and 1,146 with diabetic neuropathy). The highest level of social isolation was associated with an increased risk of any DMC component (most vs. least: HR: 1.13; 95% CI: 1.05-1.22), especially diabetic kidney disease (HR: 1.14, 95% CI: 1.04-1.25) and neuropathy (HR: 1.31, 95% CI: 1.11-1.53). Any level of loneliness was associated with an increased risk of any DMC component (HR: 1.12; 95% CI: 1.02-1.23) and diabetic kidney disease (HR: 1.16, 95% CI: 1.03-1.30). Social isolation and loneliness exhibited associations with DMC comparable to other conventional risk factors including smoking, blood pressure, and physical activity.
LIMITATIONS
Limited generalizability related to the composition of participants in the UK Biobank Study.
CONCLUSIONS
Social isolation and loneliness were independently associated with a higher risk of incident DMC among individuals with T2DM, with comparable importance to other traditional risk factors. These findings underscore social isolation and loneliness as novel and potentially modifiable risk factors for DMC.
PubMed: 38925507
DOI: 10.1053/j.ajkd.2024.05.004 -
Endocrinology, Diabetes & Metabolism Jul 2024Diabetic foot ulcers in developing countries often become infected. The healthcare systems are often not equipped to conduct the culture and the sensitivity tests... (Review)
Review
BACKGROUND
Diabetic foot ulcers in developing countries often become infected. The healthcare systems are often not equipped to conduct the culture and the sensitivity tests required for prescribing a targeted antibiotic treatment for diabetic foot infection (DFI).
METHODS
We evaluate antibiotic stewardship programmes for DFIs, at every level of health care, with an emphasis on resource-poor settings such as in Africa.
RESULTS
The management of DFI very often is adapted to the financial and practical realities of the resource-poor regions. The application of the point-of-care Gram stain of deep tissue samples is efficient, rapid, low cost and ubiquitously available. Upon the identification of the predominant pathogen in the Gram stain, a semi-quantitative preemptive antibiotic treatment can be started in accordance with the World Health Organization Aware, Watch and Restrict Essential Medicine List. This list is catered to every country and is a powerful tool. However, some basic knowledge of the local microbiological epidemiology is necessary to choose the most appropriate agent. We report our experience on using the rapidly available Gram stain for narrowing the preemptive choice of listed antibiotic agents, as an economic tool for antibiotic stewardship in DFIs.
CONCLUSIONS
In the practical and resource-saving management of DFI, the 'therapeutic' use of Gram stains is not common in resource-rich countries but should be added to the arsenal of the general efforts for antibiotic stewardship.
Topics: Diabetic Foot; Humans; Antimicrobial Stewardship; Anti-Bacterial Agents; Developing Countries; Gentian Violet; Phenazines
PubMed: 38924696
DOI: 10.1002/edm2.503 -
Science Advances Jun 2024Chronic wounds are a common and costly complication of diabetes, where multifactorial defects contribute to dysregulated skin repair, inflammation, tissue damage, and...
Chronic wounds are a common and costly complication of diabetes, where multifactorial defects contribute to dysregulated skin repair, inflammation, tissue damage, and infection. We previously showed that aspects of the diabetic foot ulcer microbiota were correlated with poor healing outcomes, but many microbial species recovered remain uninvestigated with respect to wound healing. Here, we focused on , a Gram-negative bacterium that is frequently recovered from chronic wounds but rarely causes infection. Treatment of diabetic wounds with accelerated healing during early stages. We investigated the underlying mechanisms and found that treatment promotes reepithelialization of diabetic keratinocytes, a process that is necessary for healing but deficient in chronic wounds. Overexpression of matrix metalloproteinases in diabetes contributes to failed epithelialization, and we found that treatment balances this overexpression to allow proper healing. This work uncovers a mechanism of bacterial-driven wound repair and provides a foundation for the development of microbiota-based wound interventions.
Topics: Alcaligenes faecalis; Wound Healing; Animals; Keratinocytes; Humans; Matrix Metalloproteinases; Diabetic Foot; Mice; Re-Epithelialization; Male
PubMed: 38924411
DOI: 10.1126/sciadv.adj2020