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Liver International : Official Journal... Jul 2024We examined the impact of a co-diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D) on patient outcomes.
BACKGROUND AND AIMS
We examined the impact of a co-diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D) on patient outcomes.
METHODS
Using TriNetX, a global federated research network (n = 114 million), we undertook two retrospective cohort studies, using time-to-event analysis. Analysis 1 compared MASLD with T2D to MASLD alone; analysis 2 compared T2D with MASLD to T2D alone. Propensity score matching using greedy nearest neighbour (calliper .1) balanced the cohorts (1:1) for significant covariates. Primary outcomes were cardiovascular, liver, diabetes-related, and cancer events over 5 years.
RESULTS
Analysis 1 (n = 95 275): a co-diagnosis of T2D significantly increased the risk of ischaemic heart disease (IHD) (HR 1.39; CI: 1.34, 1.44), ischaemic stroke (HR 1.45; CI: 1.35, 1.56), heart failure (HR 1.42; CI: 1.36, 1.49), atrial fibrillation (HR 1.09; CI: 1.03, 1.16), hepatocellular carcinoma (HR 1.96; CI: 1.69, 2.27), pancreatic cancer (HR 1.25; CI: 1.06, 1.48) and liver-related complications over 5 years from MASLD diagnosis. Analysis 2 (n = 15 208): a co-diagnosis of MASLD significantly increased risk of all-cause mortality (HR 1.11; CI: 1.02, 1.22), IHD (HR 1.181; CI: 1.08, 1.29), hepatocellular (HR 50.31; CI: 6.94, 364.72), pancreatic (HR 1.78; CI: 1.12, 2.84), breast (HR 1.43; CI: 1.09, 1.88) and renal cancer (HR 2.01; CI: 1.24, 3.26), and diabetic neuropathy (HR 1.17; CI: 1.09, 1.27) over 5 years from metformin initiation.
CONCLUSIONS
T2D significantly potentiates the risk of cardiovascular, malignancy and liver-related outcomes in people with MASLD. The effect of MASLD on people with T2D, although less dramatic, still potentiated risk of death, IHD, malignancy and peripheral neuropathy.
PubMed: 38949295
DOI: 10.1111/liv.16016 -
World Journal of Diabetes May 2024In this editorial, we comment on the article by Liu published in the recent issue of the (Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with...
In this editorial, we comment on the article by Liu published in the recent issue of the (Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria). Type 2 diabetes mellitus (T2DM) is a chronic disorder characterized by dysregulated glucose homeostasis. The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications, including cardiovascular disease, re-tinopathy, neuropathy, and nephropathy. T2DM arises from a complex interplay between genetic, epigenetic, and environmental factors. Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM. Specifically, variations within the glucokinase regulatory protein (GCKR) gene have been linked to heightened susceptibility to T2DM and its associated complications. The clinical trial by Liu further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development. Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype. These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.
PubMed: 38766433
DOI: 10.4239/wjd.v15.i5.814 -
Alcohol (Fayetteville, N.Y.) Jun 2024Alcohol overconsumption is well known to cause damage to the peripheral nervous system, affecting both small and large nerve fibers. The aim of this descriptive study...
Alcohol-related peripheral neuropathy: Clinico-neurophysiological characteristics and diagnostic utility of the neuropathy symptoms score and the neuropathy impairment score.
Alcohol overconsumption is well known to cause damage to the peripheral nervous system, affecting both small and large nerve fibers. The aim of this descriptive study was to investigate peripheral nerve damage, and to correlate clinical, epidemiological and neurophysiological findings, in patients diagnosed with Alcohol Use Disorder (AUD). Ninety alcohol-dependent subjects on inpatient basis were enrolled in this prospective study over a 3-year period. Every subject was assessed by the Neuropathy Symptoms Score (NSS) questionnaire and the Neuropathy Impairment Score (NIS) clinical examination grading scale, followed by Nerve Conduction Studies, Quantitative Sensory Testing and Sympathetic Skin Response (SSR) testing. Peripheral neuropathy was diagnosed in 54 subjects (60%), by abnormal neurophysiological tests and presence of clinical signs or symptoms. Among them, pure large fiber neuropathy (LFN) was found in 18 subjects, pure small fiber neuropathy (SFN) in 12 subjects, and both large and small fiber neuropathy was diagnosed in 24 subjects. Using linear regression, we found that higher NSS and NIS scores correlated with lower amplitudes of the sural sensory nerve action potential and of the SSR. We also found a significant longer duration of alcohol abuse in subjects with neuropathy, using Student's t-test (p = 0.024). Additionally, applying NIS abnormal cut-off score ≥4, using ROC analysis, we predicted the majority of subjects with LFN, confirming 95.23% sensitivity and 93.75% specificity. Our study confirmed that peripheral neuropathy involving large and small nerve fibers, with a symmetrical length-dependent pattern, is common between patients with AUD and related to the duration of the disorder. We suggest that NSS and NIS scales could be used for the assessment of neuropathy in clinical practice, when the essential neurophysiological testing is not available.
Topics: Humans; Male; Female; Middle Aged; Adult; Prospective Studies; Alcoholic Neuropathy; Neural Conduction; Alcoholism; Severity of Illness Index; Peripheral Nervous System Diseases; Surveys and Questionnaires
PubMed: 38580031
DOI: 10.1016/j.alcohol.2024.04.001 -
Cureus Feb 2024Acute pancreatitis is a pancreatic inflammatory disorder that often leads to multi-organ dysfunction associated with systemic inflammatory response. Optic neuropathy is...
Acute pancreatitis is a pancreatic inflammatory disorder that often leads to multi-organ dysfunction associated with systemic inflammatory response. Optic neuropathy is an extremely rare ocular manifestation that can occur especially in alcoholic pancreatitis most likely due to ischemic complications and is a vision-threatening condition that has to be recognized early as it can cause permanent vision loss. In this case report, a 51-year-old lady, an occasional consumer of alcohol, post-cholecystectomy status, presented with severe abdominal pain of four days' duration associated with multiple episodes of vomiting. She was diagnosed with moderate to severe acute pancreatitis and needed ionotropic support initially. She had improvement in gastrointestinal symptoms. However, she had left peri-orbital pain and lacrimation with blurring of vision on Day 11 of illness. Subsequently, an ophthalmic evaluation revealed optic disc oedema and a mild decrease in visual acuity but normal visual field and colour vision. Therefore, left optic neuropathy was diagnosed and a high-dose oral steroid was started on a tapering dose. Follow-ups after four and 12 weeks showed significant improvement in optic disc oedema and other symptoms. Therefore, though optic neuropathy is rarely reported in acute pancreatitis, it has to be considered in clinical practice along with Purtscher-like retinopathy, which presents with ocular symptoms in acute pancreatitis.
PubMed: 38496136
DOI: 10.7759/cureus.54234 -
Neurology International Feb 2024Wernicke-Korsakoff Syndrome (WKS) is a severe neurological disorder resulting from thiamine deficiency, commonly associated with alcohol consumption but also stemming...
Wernicke-Korsakoff Syndrome (WKS) is a severe neurological disorder resulting from thiamine deficiency, commonly associated with alcohol consumption but also stemming from dietary imbalances or other clinical conditions. Cognitive deficits, affecting memory and executive functions, pose a serious concern, with partial recovery often not complete. A 28-year-old woman underwent surgery for acute necrotizing hemorrhagic pancreatitis, leading to admission for post-acute intensive treatment due to prolonged bed rest syndrome. Clinical examinations revealed sensory-motor neuropathy, denervation in the active phase, mammillary body hyperintensity, and cognitive impairment. The patient exhibited poor orientation, lacked awareness of her clinical condition, and experienced impaired nonverbal memory, practical constructive issues, and planning difficulties-consistent with WKS. The patient received high-dose thiamine (300 mg TDS), coupled with daily physiokinesitherapy and occupational therapy. A final neuropsychological evaluation three months later showed substantial remission of executive and memory difficulties, improved spatial-temporal orientation, and enhanced awareness. The complex case required timely multidisciplinary intervention for accurate diagnosis and effective rehabilitation. The patient experienced rapid clinical improvement and cognitive recovery with high-dose thiamine and physiotherapy.
PubMed: 38392959
DOI: 10.3390/neurolint16010018 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2023The aim: To study the peculiarities of diabetic polyneuropathy in patients with type 2 diabetes mellitus and concomitant NAFLD.
OBJECTIVE
The aim: To study the peculiarities of diabetic polyneuropathy in patients with type 2 diabetes mellitus and concomitant NAFLD.
PATIENTS AND METHODS
Materials and methods: We examined 75 patients with type 2 diabetes mellitus, including 31 (41.3%) women and 44 (58.7%) men. The main group included 35 patients with NAFLD (46.7%), and the control group included 40 patients without NAFLD (53.3%). The severity of polyneuropathy was assessed using the Toronto clinical neuropathy score. The presence of neuropathic pain syndrome in patients allowed us to divide patients into groups with painful or painless forms of diabetic polyneuropathy. The electroneuromyographic examination was used to study nerve conduction parameters, namely peroneal motor nerve conduction velocity (PMNCV), sensory nerve action potential (SNAP), and sensory nerve conduction velocity (SNCV).
RESULTS
Results: The proportion of patients who did not have diabetic polyneuropathy in the NAFLD group was 12.5%, and in the group without NAFLD - 87.2%. The frequency of diabetic polyneuropathy was higher in the main group, namely: mild, moderate, and severe polyneuropathy was 80%, 56% and 59.3%, respectively, compared to the control group - 20%, 44%, 40.7% (p=0.02). The painful form of DPN was more common in patients of the main group than in the control group, respectively 69.8% and 30.2% (p=0.01). The degree of liver fibrosis did not affect the course of DPN. The study of nerve conduction by PMNCV, SNAP, and SNCV parameters showed that PMNCV was higher in the NAFLD group, and SNAP and SNCV - in the control group, but without statistical significance (p>0.05).
CONCLUSION
Conclusions: In patients with type 2 diabetes mellitus, the presence of NAFLD affects the severity of diabetic polyneuropathy and increases the risk of painful DPN. The degree of liver fibrosis did not show an effect on the development of diabetic polyneuropathy. ENMG parameters did not demonstrate a statistically significant difference in the study groups.
Topics: Male; Humans; Female; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Non-alcoholic Fatty Liver Disease; Polyneuropathies; Liver Cirrhosis
PubMed: 38112355
DOI: 10.36740/WLek202311109 -
Journal of Ethnopharmacology Mar 2024Tinospora cordifolia (T. cordifolia) (Willd.) Miers, a member of the Menispermaceae, family documented in the ancient textbooks of the Ayurveda System of Medicine, has...
ETHNOPHARMACOLOGICAL RELEVANCE
Tinospora cordifolia (T. cordifolia) (Willd.) Miers, a member of the Menispermaceae, family documented in the ancient textbooks of the Ayurveda System of Medicine, has been used in the management of sciatica pain and diabetic neuropathy.
AIM
The study has been designed to evaluate the antinociceptive potential of various extracts of T. cordifolia stem in Paclitaxel (PT)-generated neuropathic pain model in albino rats and explore its possible mechanism employing molecular docking studies.
METHODS
Stems of T. cordifolia were shade dried, grinded in fine powder, and extracted separately with different solvents viz. ethanol, water & hydro-alcoholic and characterized using LCMS/MS. The antinociceptive property of T. cordifolia stem (200 and 400 mg/kg) was examined in albino rats using a PT-induced neuropathic pain model. Further, the effect of these extracts was also observed using different behavioral assays viz. cold allodynia, mechanical hyperalgesia (pin-prick test), locomotor activity test, walking track test, and Sciatic Functional Index (SFI) in rats. Tissue lysate of the sciatic nerve was used to determine various biochemical markers such as GSH, SOD, TBARS, tissue protein, and nitrite. Further to explore the possible mechanism of action, the most abundant and therapeutically active compounds available in aqueous extract were analyzed for binding affinity towards soluble epoxide hydrolase (sEH) enzyme (PDB ID: 3wk4) employing molecular docking studies.
RESULTS
The results of the LCMS/MS study of different extracts of T. cordifolia indicated presence of alkaloids, glycosides, terpenoids, sterols and sugars such as amritoside A, tinocordin, magnoflorine, N-methylcoclaurine, coridine, 20β-hydroxyecdysone and menaquinone-7 palmatin, cordifolioside A and tinosporine etc. Among all the three extracts, the hydroalcoholic extract (400 mg/kg) showed the highest response followed by aqueous and ethanolic extracts as evident in in vivo behavioral and biochemical evaluations. Furthermore, docking studies also exposed that these compounds viz. N-methylcoclaurine tinosporin, palmatine, tinocordin, 20β-hydroxyecdysone, and coridine exhibited well to excellent affinity towards target sEH protein.
CONCLUSION
T. cordifolia stem could alleviate neuropathic pain via soluble epoxide hydrolase inhibitory activity.
Topics: Rats; Animals; Paclitaxel; Plant Extracts; Tinospora; Epoxide Hydrolases; Molecular Docking Simulation; Neuralgia; Analgesics
PubMed: 38072294
DOI: 10.1016/j.jep.2023.117559 -
Case Reports in Ophthalmology 2023A 56-year-old man with a medical history of alcoholic cirrhosis presented with acute bilateral loss of vision. On admission, the patient had pale skin and low arterial...
A 56-year-old man with a medical history of alcoholic cirrhosis presented with acute bilateral loss of vision. On admission, the patient had pale skin and low arterial pressure. Ophthalmic examination demonstrated a visual acuity of 6/9 in the right eye and the absence of light perception in the left. Automated perimetry revealed a superior altitudinal defect in the right eye. Optic disc swelling, flame-shaped hemorrhages, and several cotton-wool spots were evident in both eyes on fundoscopy. Lab results confirmed severe anemia. Following prompt correction of the anemia, the altitudinal defect remained unchanged. However, visual acuity in the right eye improved significantly in a few days. The potential association of anemia with both papilledema and non-arteritic anterior ischemic optic neuropathy (NA-AION) is discussed, with a focus on possible pathophysiological mechanisms. The necessity for routine anemia screening, encompassing complete blood count, serum iron, and vitamin B12 levels, and subsequent rapid correction in these patients, is emphasized.
PubMed: 37901626
DOI: 10.1159/000531999 -
Frontiers in Endocrinology 2023Worldwide, diabetes and its complications have seriously affected people's quality of life and become a serious public health problem. C-peptide is not only an indicator... (Review)
Review
Worldwide, diabetes and its complications have seriously affected people's quality of life and become a serious public health problem. C-peptide is not only an indicator of pancreatic β-cell function, but also a biologically active peptide that can bind to cell membrane surface signaling molecules and activate downstream signaling pathways to play antioxidant, anti-apoptotic and inflammatory roles, or regulate cellular transcription through internalization. It is complex how C-peptide is related to diabetic complications. Both deficiencies and overproduction can lead to complications, but their mechanisms of action may be different. C-peptide replacement therapy has shown beneficial effects on diabetic complications in animal models when C-peptide is deficient, but results from clinical trials have been unsatisfactory. The complex pattern of the relationship between C-peptide and diabetic chronic complications has not yet been fully understood. Future basic and clinical studies of C-peptide replacement therapies will need to focus on baseline levels of C-peptide in addition to more attention also needs to be paid to post-treatment C-peptide levels to explore the optimal range of fasting C-peptide and postprandial C-peptide maintenance.
Topics: Animals; Humans; C-Peptide; Quality of Life; Diabetes Complications; Diabetes Mellitus
PubMed: 37745697
DOI: 10.3389/fendo.2023.1256093 -
Pharmacological Research Oct 2023There is an increasing interest in the use of nutraceuticals and plant-derived bioactive compounds from foods for their potential health benefits. For example, as a... (Review)
Review
There is an increasing interest in the use of nutraceuticals and plant-derived bioactive compounds from foods for their potential health benefits. For example, as a major active ingredient found from cruciferous vegetables like broccoli, there has been growing interest in understanding the therapeutic effects of sulforaphane against diverse metabolic complications. The past decade has seen an extensive growth in literature reporting on the potential health benefits of sulforaphane to neutralize pathological consequences of oxidative stress and inflammation, which may be essential in protecting against diabetes-related complications. In fact, preclinical evidence summarized within this review supports an active role of sulforaphane in activating nuclear factor erythroid 2-related factor 2 or effectively modulating AMP-activated protein kinase to protect against diabetic complications, including diabetic cardiomyopathy, diabetic neuropathy, diabetic nephropathy, as well as other metabolic complications involving non-alcoholic fatty liver disease and skeletal muscle insulin resistance. With clinical evidence suggesting that foods rich in sulforaphane like broccoli can improve the metabolic status and lower cardiovascular disease risk by reducing biomarkers of oxidative stress and inflammation in patients with type 2 diabetes. This information remains essential in determining the therapeutic value of sulforaphane or its potential use as a nutraceutical to manage diabetes and its related complications. Finally, this review discusses essential information on the bioavailability profile of sulforaphane, while also covering information on the pathological consequences of oxidative stress and inflammation that drive the development and progression of diabetes.
PubMed: 37703962
DOI: 10.1016/j.phrs.2023.106918