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Frontiers in Medicine 2024Type 1 diabetes mellitus (T1DM) is frequently associated with various infections, including mycoses; however, the direct link between T1DM and fungal infections remains...
BACKGROUND
Type 1 diabetes mellitus (T1DM) is frequently associated with various infections, including mycoses; however, the direct link between T1DM and fungal infections remains under-researched. This study utilizes a Mendelian randomization (MR) approach to investigate the potential causal relationship between T1DM and mycoses.
METHODS
Genetic variants associated with T1DM were sourced from the European Bioinformatics Institute database, while those related to fungal infections such as candidiasis, pneumocystosis, and aspergillosis were obtained from the Finngen database, focusing on European populations. The primary analysis was conducted using the inverse variance weighted (IVW) method, with additional insight from Mendelian randomization Egger regression (MR-Egger). Extensive sensitivity analyses assessed the robustness, diversity, and potential horizontal pleiotropy of our findings. Multivariable Mendelian randomization (MVMR) was employed to adjust for confounders, using both MVMR-IVW and MVMR-Egger to evaluate heterogeneity and pleiotropy.
RESULTS
Genetically, the odds of developing candidiasis increased by 5% in individuals with T1DM, as determined by the IVW method (OR = 1.05; 95% CI 1.02-1.07, = 0.0001), with a Bonferroni-adjusted -value of 0.008. Sensitivity analyses indicated no significant issues with heterogeneity or pleiotropy. Adjustments for confounders such as body mass index, glycated hemoglobin levels, and white blood cell counts further supported these findings (OR = 1.08; 95% CI:1.03-1.13, = 0.0006). Additional adjustments for immune cell counts, including CD4 and CD8 T cells and natural killer cells, also demonstrated significant results (OR = 1.04; 95% CI: 1.02-1.06, = 0.0002). No causal associations were found between T1DM and other fungal infections like aspergillosis or pneumocystosis.
CONCLUSION
This MR study suggests a genetic predisposition for increased susceptibility to candidiasis in individuals with T1DM. However, no causal links were established between T1DM and other mycoses, including aspergillosis and pneumocystosis.
PubMed: 38947239
DOI: 10.3389/fmed.2024.1408297 -
Cureus Jun 2024Hyperosmolar hyperglycemic state (HHS) is the most serious emergency in patients with uncontrolled diabetes mellitus. It has been associated with a prothrombotic state...
Hyperosmolar hyperglycemic state (HHS) is the most serious emergency in patients with uncontrolled diabetes mellitus. It has been associated with a prothrombotic state that increases the risk for ischemia in affected patients. Despite the literature on the risk of ischemic stroke in patients with chronic hyperglycemia being vast, there is not enough documentation on the risk of developing a stroke during a hyperglycemic crisis. We present a rare case of an 86-year-old male who was admitted with HHS whose hospital course was further complicated by multiple embolic strokes. Prompt recognition of cerebral infarction when it intertwines with HHS remains a challenging task. This case emphasizes the value of clinical vigilance in patients with this hyperglycemic crisis. Further research is needed to better understand what this prothrombotic state truly entails in these patients.
PubMed: 38947137
DOI: 10.7759/cureus.63331 -
Journal of Pain Research 2024Chronic peripheral neuropathic pain (PNP) is a debilitating condition that is associated with many types of injury/diseases, including diabetes mellitus. Patients with...
BACKGROUND & OBJECTIVE
Chronic peripheral neuropathic pain (PNP) is a debilitating condition that is associated with many types of injury/diseases, including diabetes mellitus. Patients with longstanding diabetes develop diabetic PNP (DPNP), which is resilient to currently available drugs. The underlying molecular mechanisms of DPNP are still illusive, but K7 channels that have been implicated in the pathogenesis of various types of chronic pain are likely to be involved. Indeed, using the streptozotocin (STZ) rat model of DPNP, we have previously shown that K7 activation with their non-selective activator retigabine attenuated neuropathic pain behavior suggesting that these channels are implicated in DPNP pathogenesis. Here, we evaluated, in the same STZ model, whether the more potent and more selective K7 channel openers flupirtine and ML213 attenuate STZ-induced pain hypersensitivity.
METHODS
Male Sprague Dawley rats (250-300 g) were used. The STZ model involved a single injection of STZ (60 mg/kg, i.p.). Behavioral testing for mechanical and heat pain sensitivity was performed using a dynamic plantar aesthesiometer and Hargreaves analgesiometer, respectively.
RESULTS
STZ rats exhibited behavioral signs of mechanical and heat hypersensitivity as indicated by significant decreases in the mean paw withdrawal threshold (PWT) and mean paw withdrawal latency (PWL), respectively, at 35 days post-STZ treatment. Single injections of flupirtine (10 mg/kg, i.p.) and ML213 (5 mg/kg, i.p.) to STZ rats (35-days after STZ treatment) caused significant increases in the mean PWT, but not PWL, indicating attenuation of mechanical, but not heat hypersensitivity. Both flupirtine and ML213 were as effective as the positive control gabapentin (10/kg, i.p.), and their anti-allodynic effects were prevented by the K7 channel-specific blocker XE991 (3 mg/kg, i.p.).
CONCLUSION
The findings suggest that K7 channels are involved in the mechanisms of mechanical but not heat hypersensitivity associated with DPNP, and that their activation may prove to be effective in alleviating DPNP symptoms.
PubMed: 38947132
DOI: 10.2147/JPR.S467535 -
The Yale Journal of Biology and Medicine Jun 2024Nodal regions, areas of intensive contact between Schwann cells and axons, may be exceptionally vulnerable to diabetes-induced changes because they are exposed to and...
Nodal regions, areas of intensive contact between Schwann cells and axons, may be exceptionally vulnerable to diabetes-induced changes because they are exposed to and impacted by the metabolic implications of diabetes. Insulin receptors, glucose transporters, Na and K channels, and mitochondria are abundant in nodes, all of which have been linked to the development and progression of Diabetic Peripheral Neuropathy (DPN) and Type 1 Diabetes Mellitus (T1DM)-associated cognitive impairment. Our study aimed to evaluate if the administration of (NS) and (CA) prevented diabetes-associated nervous system deficits in hyperglycemic mice. We developed T1DM mice through Streptozotocin (STZ) injections and validated the elevations in blood glucose levels. NS and CA were administered immediately upon the induction of diabetes. Behavioral analysis, histopathological evaluations, and assessment of molecular biomarkers (NR2A, MPZ, NfL) were performed to assess neuropathy and cognitive impairment. Improvements in memory, myelin loss, and the expression of synaptic proteins, even with the retention of hyperglycemia, were evident in the mice who were given a dose of herbal products upon the detection of hyperglycemia. NS was more beneficial in preventing memory impairments, demyelination, and synaptic dysfunction. The findings indicate that including these herbs in the diets of diabetic as well as pre-diabetic patients can reduce complications associated with T1DM, notably diabetic peripheral neuropathy and cognitive deficits associated with T1DM.
Topics: Animals; Diabetic Neuropathies; Nigella sativa; Mice; Cognitive Dysfunction; Male; Diabetes Mellitus, Experimental; Plant Extracts; Plants, Medicinal; Senna Plant
PubMed: 38947105
DOI: 10.59249/UQLO8012 -
Diabetes, Metabolic Syndrome and... 2024Growing evidence indicates that there is a close relationship between type 2 diabetes mellitus (T2DM) and sarcopenia, and T2DM patients are often accompanied by obesity....
Importance of Assessing Sarcopenia in Patients with Type 2 Diabetes Mellitus Based on Body Fat Percentage Measured by Dual-Energy X-Ray Absorptiometry in Different Genders.
BACKGROUND
Growing evidence indicates that there is a close relationship between type 2 diabetes mellitus (T2DM) and sarcopenia, and T2DM patients are often accompanied by obesity. However, research exploring the connection between body fat percentage (BFP) and sarcopenia is currently limited.
METHODS
This was a cross-sectional study that included 676 patients with T2DM over 50 years old. The appendicular skeletal muscle mass index (ASMI), handgrip strength, and 5-time chair stand test (5-TCST) were measured, and sarcopenia was diagnosed according to the Asian Working Group on Sarcopenia (AWGS). Spearman's coefficient was used to evaluate the correlation of BFP and body mass index (BMI) with the diagnostic elements of sarcopenia, and BFP and other relevant covariates were included in the binary logistic regression model. The subgroup performed an interaction test for statistically significant population baseline information.
RESULTS
The prevalence of sarcopenia was 18.0% in males and 11.6% in females. Spearman correlation analysis showed that BFP was positively correlated with ASMI in women (=0.107, =0.029), but not in men. BFP was negatively correlated with grip strength (male: = -0.187, =0.003; female: =-0.108, =0.029). There was a positive correlation between BFP and 5-TCST (male: =0.199, =0.001; female: =0.144, =0.003). After adjusting for confounding factors, BFP was an independent risk factor for sarcopenia (men, OR: 1.33, 95% CI: 1.15-1.54; women, OR: 1.26, 95% CI: 1.13-1.41). This correlation was generally consistent, as demonstrated in further subgroup analyses.
CONCLUSION
High BFP was significantly associated with sarcopenia risk, and this association was independent of gender, age, and BMI.
PubMed: 38946913
DOI: 10.2147/DMSO.S461748 -
World Journal of Gastroenterology Jun 2024Metabolic dysfunction-associated fatty liver disease (MAFLD) is a hepatic manifestation of the metabolic syndrome. It is one of the most common liver diseases worldwide... (Review)
Review
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a hepatic manifestation of the metabolic syndrome. It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries. MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma. Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis. The mechanisms involved in maintaining gut-liver axis homeostasis are complex. One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gut-liver axis functionality. An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis. Moreover, alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of drugs developed for the treatment of type 2 diabetes mellitus. They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis. The mechanisms reported to be involved in this effect include an improved regulation of glycemia, reduced lipid synthesis, β-oxidation of free fatty acids, and induction of autophagy in hepatic cells. Recently, multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment. A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD. This review presents the current understanding of the role of the gut-liver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.
Topics: Humans; Glucagon-Like Peptide-1 Receptor; Gastrointestinal Microbiome; Liver; Non-alcoholic Fatty Liver Disease; Animals; Metabolic Syndrome; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Incretins; Intestinal Mucosa; Glucagon-Like Peptide-1 Receptor Agonists
PubMed: 38946874
DOI: 10.3748/wjg.v30.i23.2964 -
World Journal of Gastrointestinal... Jun 2024Glucagon-like peptide receptor agonists (GLP-1RA) are used to treat type 2 diabetes mellitus and, more recently, have garnered attention for their effectiveness in...
Glucagon-like peptide receptor agonists (GLP-1RA) are used to treat type 2 diabetes mellitus and, more recently, have garnered attention for their effectiveness in promoting weight loss. They have been associated with several gastrointestinal adverse effects, including nausea and vomiting. These side effects are presumed to be due to increased residual gastric contents. Given the potential risk of aspiration and based on limited data, the American Society of Anesthesiologists updated the guidelines concerning the preoperative management of patients on GLP-1RA in 2023. They included the duration of mandated cessation of GLP-1RA before sedation and usage of "full stomach" precautions if these medications were not appropriately held before the procedure. This has led to additional challenges, such as extended waiting time, higher costs, and increased risk for patients. In this editorial, we review the current societal guidelines, clinical practice, and future directions regarding the usage of GLP-1RA in patients undergoing an endoscopic procedure.
PubMed: 38946857
DOI: 10.4253/wjge.v16.i6.292 -
PRiMER (Leawood, Kan.) 2024Metformin is one of the primary pharmacologic agents for managing type 2 diabetes mellitus (T2DM). However, it has been associated with interference in vitamin B12...
BACKGROUND AND OBJECTIVES
Metformin is one of the primary pharmacologic agents for managing type 2 diabetes mellitus (T2DM). However, it has been associated with interference in vitamin B12 absorption and deficiency. Vitamin B12 deficiency and T2DM can present diagnostic challenges for polyneuropathy. Diagnosis is essential for guiding treatment, yet the use of vitamin B12 level testing in this population may have dwindled over time amid changing practice guidelines. This study examines trends over time in the use of vitamin B12 level testing among patients on metformin.
METHODS
This retrospective trend analysis used data from TriNetX, a real-world, longitudinal clinical database. Patients treated with metformin from 2000 to 2020 were identified using Rx Concept Unique Identifier codes. The number of patients who underwent vitamin B12 level testing at any time after 1 month from metformin initiation was tabulated. Patients were grouped by the year of B12 level testing. Trends in B12 level testing were assessed using the Jonckheere-Terpstra statistical test (<.05).
RESULTS
Out of 4,203,020 patients prescribed metformin, 1,055,995 (25.1%) underwent B12 level testing. The highest proportion of patients tested was in 2000 to 2002 (39.6%), while the lowest proportion was in 2018 to 2020 (20.1%). B12 testing utilization declined significantly by 19.5% from 2000-2002 to 2018-2020 (=.001).
CONCLUSIONS
In this study, we found that the use of vitamin B12 level testing in patients on metformin has significantly declined over the years, potentially impacting early detection of B12 deficiency. Future studies with more granular data from real-life practice are recommended to understand the precise reasons and impact of this trend.
PubMed: 38946756
DOI: 10.22454/PRiMER.2024.278059 -
The Pan African Medical Journal 2024the utility of glycated haemoglobin (HbA1c) for the diagnosis and monitoring of diabetes in sub-Saharan Africa is uncertain due to limited data on the performance of the... (Comparative Study)
Comparative Study
Impact of haemoglobin variants on the diagnostic sensitivity of glycated haemoglobin (HbA1c) assay methodologies in sub-Saharan Africa: a laboratory-based method validation study.
INTRODUCTION
the utility of glycated haemoglobin (HbA1c) for the diagnosis and monitoring of diabetes in sub-Saharan Africa is uncertain due to limited data on the performance of the available HbA1c assay methods in this population, which has a high prevalence of haemoglobin variants. We aimed to compare the diagnostic accuracy of the major HbA1c methodologies (Boronate Affinity, Capillary Electrophoresis, High Performance Liquid Chromatography, Immunoassay) in an African population, and assess the impact of the common haemoglobin variant HbAS (sickle cell trait).
METHODS
whole blood samples were obtained from 182 individuals living with type 2 diabetes in Uganda. HbA1c values for each method were compared to average glucose measured over 14 days by continuous glucose monitoring (CGM). To determine concordance, the three HbA1c assay methods were compared to the capillary electrophoresis method.
RESULTS
there was a strong correlation between CGM average glucose levels and all four HbA1c methodologies (r=0.81-0.89) which did not differ in those with and without HbAS (present in 37/182 participants). The presence of HbAS did not alter the relationship between HbA1c and CGM glucose for any assay (p for interaction >0.2 for all methods). Diagnostic accuracy for CGM average glucose thresholds of 7 and 10mmol/L was similar across methods (area under the receiver operating characteristic curve 0.80-0.84 and 0.76-0.84 respectively). The maximum bias between the HbA1c assay methodologies was 2 mmol/mol (2.07%).
CONCLUSION
all major HbA1c technologies offer accurate and comparable HbA1c measurement even in this population with high prevalence of haemoglobin variants.
Topics: Humans; Glycated Hemoglobin; Diabetes Mellitus, Type 2; Electrophoresis, Capillary; Female; Blood Glucose; Male; Middle Aged; Sensitivity and Specificity; Chromatography, High Pressure Liquid; Uganda; Adult; Immunoassay; Blood Glucose Self-Monitoring; Aged; Hemoglobins, Abnormal
PubMed: 38946743
DOI: 10.11604/pamj.2024.48.10.41679 -
Journal of Cell Communication and... Jun 2024Obesity, a rapidly expanding epidemic worldwide, is known to exacerbate many medical conditions, making it a significant factor in multiple diseases and their associated... (Review)
Review
Obesity, a rapidly expanding epidemic worldwide, is known to exacerbate many medical conditions, making it a significant factor in multiple diseases and their associated complications. This threatening epidemic is linked to various harmful conditions such as type 2 diabetes mellitus, hypertension, metabolic dysfunction-associated steatotic liver disease, polycystic ovary syndrome, cardiovascular diseases (CVDs), dyslipidemia, and cancer. The rise in urbanization and sedentary lifestyles creates an environment that fosters obesity, leading to both psychosocial and medical complications. To identify individuals at risk and ensure timely treatment, it is crucial to have a better understanding of the pathophysiology of obesity and its comorbidities. This comprehensive review highlights the relationship between obesity and obesity-associated complications, including type 2 diabetes, hypertension, (CVDs), dyslipidemia, polycystic ovary syndrome, metabolic dysfunction-associated steatotic liver disease, gastrointestinal complications, and obstructive sleep apnea. It also explores the potential mechanisms underlying these associations. A thorough analysis of the interplay between obesity and its associated complications is vital in developing effective therapeutic strategies to combat the exponential increase in global obesity rates and mitigate the deadly consequences of this polygenic condition.
PubMed: 38946722
DOI: 10.1002/ccs3.12039