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Diabetes Therapy : Research, Treatment... Dec 2021Pentoxifylline (Px) has protean effects that can be utilized in the therapy of diabetes and its complications. There have been well-documented but often inconclusive... (Review)
Review
Pentoxifylline (Px) has protean effects that can be utilized in the therapy of diabetes and its complications. There have been well-documented but often inconclusive improvements in peripheral arterial disease, foot ulcers, peripheral neuropathy, nephropathy, retinopathy, ischemic heart disease and cerebrovascular disease. In addition, non-alcoholic steatosis and steatohepatitis, which are closely associated with insulin resistance and type 2 diabetes, have been shown to improve with pentoxifylline. Surprisingly, pentoxifylline modestly improves insulin resistance through improvements in capillary blood flow as well as beta cell function and decreased hepatic glucose production. The therapeutic effects of pentoxifylline are complementary to the effects of drugs such as blockers of the renin-angiotensin-aldosterone system when utilized in the therapy of diabetic nephropathy.
PubMed: 34647189
DOI: 10.1007/s13300-021-01168-x -
Diabetes Therapy : Research, Treatment... Oct 2021Patients with diabetes and distal symmetrical polyneuropathy (DSP) are routinely evaluated for etiologies other than diabetes, including vitamin B12 deficiency,...
Patients with diabetes and distal symmetrical polyneuropathy (DSP) are routinely evaluated for etiologies other than diabetes, including vitamin B12 deficiency, paraproteinemia, hypothyroidism and drug or autoimmune-induced neuropathy. However, the most common cause of DSP, next to that of diabetes, is alcohol intake, which is almost never evaluated. In addition to assessment of alcohol intake based on patient history, which often leads to an underestimation of alchohol intake, markers of a high alcohol intake (elevated liver enzymes, uric acid, triglycerides, low magnesium or low folic acid levels) should be obtained. However, the test that is most likely to detect surreptitious alcohol intake is urinary ethyl glucuronide (EtG), which will detect the intake of alcohol within the previous 90 h. Detection of alcohol use is important since if alcohol consumption is not discontinued, DSP, whatever the etiology, will not improve. In addition, the use of drugs to improve symptoms of DSP (tricyclics, anti-epileptics, serotonin, norepinephrine reuptake inhibitors and analgesics) may in combination with alcohol excessively suppress respiration and cognitive function such that these drugs should not be prescribed or utilized if use of alcohol continues. In the future, all patients with DSP, and especially those with symptomatic DSP, should be biochemically screened for excessive alcohol intake and appropriate action taken.
PubMed: 34409562
DOI: 10.1007/s13300-021-01131-w -
Neuroscience Letters Sep 2021Complex Regional Pain Syndrome (CRPS) is a musculoskeletal pain condition that often develops after limb injury and/or immobilization. Although the exact mechanisms...
Complex Regional Pain Syndrome (CRPS) is a musculoskeletal pain condition that often develops after limb injury and/or immobilization. Although the exact mechanisms underlying CRPS are unknown, the syndrome is associated with central and autonomic nervous system dysregulation and peripheral hyperalgesia symptoms. These symptoms also manifest in alcoholic neuropathy, suggesting that the two conditions may be pathophysiologically accretive. Interestingly, people assigned female at birth (AFAB) appear to be more sensitive to both CRPS and alcoholic neuropathy. To better understand the biobehavioral mechanisms underlying these conditions, we investigated a model of combined CRPS and alcoholic neuropathy in female rats. Animals were pair-fed either a Lieber-DeCarli alcohol liquid diet or a control diet for ten weeks. CRPS was modeled via unilateral hind limb cast immobilization for seven days, allowing for the other limb to serve as a within-subject control for hyperalgesia measures. To investigate the role of circulating ovarian hormones on pain-related behaviors, half of the animals underwent ovariectomy (OVX). Using the von Frey procedure to record mechanical paw withdrawal thresholds, we found that cast immobilization and chronic alcohol drinking separately and additively produced mechanical hyperalgesia observed 3 days after cast removal. We then examined neuroadaptations in AMPA GluR1 and NMDA NR1 glutamate channel subunits, extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) in bilateral motor and cingulate cortex across all groups. Consistent with increased pain-related behavior, chronic alcohol drinking increased GluR1, NR1, ERK, and CREB phosphorylation in the cingulate cortex. OVX did not alter any of the observed effects. Our results suggest accretive relationships between CRPS and alcoholic neuropathy symptoms and point to novel therapeutic targets for these conditions.
Topics: Alcohol Drinking; Animals; Central Nervous System Stimulants; Cyclic AMP Response Element-Binding Protein; Ethanol; Female; Gyrus Cinguli; Hindlimb Suspension; Hyperalgesia; MAP Kinase Signaling System; Motor Cortex; Nociception; Rats; Rats, Inbred F344; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate
PubMed: 34280506
DOI: 10.1016/j.neulet.2021.136119 -
Indian Journal of Psychiatry 2021Thiamine is essential for the activity of several enzymes associated with energy metabolism in humans. Chronic alcohol use is associated with deficiency of thiamine... (Review)
Review
Thiamine is essential for the activity of several enzymes associated with energy metabolism in humans. Chronic alcohol use is associated with deficiency of thiamine along with other vitamins through several mechanisms. Several neuropsychiatric syndromes have been associated with thiamine deficiency in the context of alcohol use disorder including Wernicke-Korsakoff syndrome, alcoholic cerebellar syndrome, alcoholic peripheral neuropathy, and possibly, Marchiafava-Bignami syndrome. High-dose thiamine replacement is suggested for these neuropsychiatric syndromes.
PubMed: 34194054
DOI: 10.4103/psychiatry.IndianJPsychiatry_440_20 -
Brain & NeuroRehabilitation Jul 2021Marchiafava-Bignami disease (MBD), Wernicke encephalopathy (WE) and alcoholic polyneuropathy (AP) are distinct diseases and all have strong relationship with chronic...
Marchiafava-Bignami disease (MBD), Wernicke encephalopathy (WE) and alcoholic polyneuropathy (AP) are distinct diseases and all have strong relationship with chronic alcoholism. A 70-year-old male who had altered mentality and ataxia of both lower limbs and had past history of WE 3 years previously admitted with 6 months history of impaired walking. He also had a symptom of altered sensorium by impaired consciousness for 2 days. In brain magnetic resonance imaging, the body, splenium of corpus callosum and bilateral frontal cortex were involved. The patient was diagnosed with MBD on the basis of the clinical features and the brain imaging findings. The electrodiagnostic findings implied demyelinating neuropathy in all extremities. He failed to recover his mentality and the function of the limbs remained poor finishing several treatment options including medications and physical therapy. The poor prognosis of this patient is thought to be associated with cortical involvement of MBD. We reported this very rare case who was affected by 3 distinct diseases of MBD, AP, and WE as complications of chronic alcohol abuse. Moreover, the case was relevant to a rare clinical presentation of MBD with cortical involvement which was associated with poor prognosis.
PubMed: 36743432
DOI: 10.12786/bn.2021.14.e19 -
Experimental Eye Research Jul 2021Peroxisome Proliferator-Activated Receptors (PPARs) are a family of nuclear receptors that play essential roles in modulating cell differentiation, inflammation, and... (Review)
Review
Peroxisome Proliferator-Activated Receptors (PPARs) are a family of nuclear receptors that play essential roles in modulating cell differentiation, inflammation, and metabolism. Three subtypes of PPARs are known: PPAR-alpha (PPARα), PPAR-gamma (PPARγ), and PPAR-beta/delta (PPARβ/δ). PPARα activation reduces lipid levels and regulates energy homeostasis, activation of PPARγ results in regulation of adipogenesis, and PPARβ/δ activation increases fatty acid metabolism and lipolysis. PPARs are linked to various diseases, including but not limited to diabetes, non-alcoholic fatty liver disease, glaucoma and atherosclerosis. In the past decade, numerous studies have assessed the functional properties of PPARs in the eye and key PPAR mechanisms have been discovered, particularly regarding the retina and cornea. PPARγ and PPARα are well established in their functions in ocular homeostasis regarding neuroprotection, neovascularization, and inflammation, whereas PPARβ/δ isoform function remains understudied. Naturally, studies on PPAR agonists and antagonists, associated with ocular pathology, have also gained traction with the development of PPAR synthetic ligands. Studies on PPARs has significantly influenced novel therapeutics for diabetic eye disease, ocular neuropathy, dry eye, and age-related macular degeneration (AMD). In this review, therapeutic potentials and implications will be highlighted, as well as reported adverse effects. Further investigations are necessary before any of the PPARs ligands can be utilized, in the clinics, to treat eye diseases. Future research on the prominent role of PPARs will help unravel the complex mechanisms involved in order to prevent and treat ocular diseases.
Topics: Animals; Eye Diseases; Homeostasis; Humans; Ligands; Lipid Metabolism; Peroxisome Proliferator-Activated Receptors
PubMed: 34010603
DOI: 10.1016/j.exer.2021.108617 -
Journal of Diabetes Investigation Nov 2021Non-alcoholic fatty liver disease and type 2 diabetes mellitus are closely related, and often occur simultaneously in patients. Type 2 diabetes increases the risk of...
AIMS/INTRODUCTION
Non-alcoholic fatty liver disease and type 2 diabetes mellitus are closely related, and often occur simultaneously in patients. Type 2 diabetes increases the risk of diabetic peripheral neuropathy, resulting in intolerable pain and extremity amputation that reduces the quality of life. However, the role of non-alcoholic fatty liver disease in the pathogenesis of diabetic peripheral neuropathy remains unclear. Thus, we evaluated the correlation of liver fibrosis and steatosis, which are representative histological morphologies of non-alcoholic fatty liver disease, with diabetic peripheral neuropathy in type 2 diabetes patients.
MATERIALS AND METHODS
Five hundred twenty individuals with type 2 diabetes were recruited. All the patients were detected nerve conduction study for diabetic peripheral neuropathy and fibro touch for liver steatosis and fibrosis. Correlation of DPN with liver steatosis and fibrosis were analysed with binary logistic analysis.
RESULTS
Among the 520 patients, the prevalence of liver steatosis, fibrosis and diabetic peripheral neuropathy was 63.0% (n = 328), 18.1% (n = 94) and 52.1% (n = 271), respectively. The prevalence of diabetic peripheral neuropathy was significantly elevated in patients with liver steatosis (55.7 vs 44.9%, P = 0.03) and fibrosis (61.5 vs 50%, P = 0.04), and it increased as liver stiffness measurement increased. Additionally, both hepatic steatosis (odds ratio 1.48, 95% confidence interval 1.04-2.11, P = 0.03) and fibrosis (odds ratio 1.60, 95% confidence interval 1.02-2.51, P = 0.04) were correlated with diabetic peripheral neuropathy. After adjusting for age, sex, weight, height, body mass index, waist hip ratio, duration of type 2 diabetes, blood glucose, homeostatic model assessment of insulin resistance, blood pressure, serum lipid, liver enzyme, urea, uric acid, creatinine and inflammatory factors, liver fibrosis remained associated with diabetic peripheral neuropathy (odds ratio 2.24, 95% confidence interval 1.11-4.53, P = 0.02).
CONCLUSIONS
The prevalence of diabetic peripheral neuropathy was elevated in patients with liver steatosis and fibrosis. Liver fibrosis was also independently associated with an increased risk of diabetic peripheral neuropathy.
Topics: Aged; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Insulin Resistance; Liver Cirrhosis; Logistic Models; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Prevalence; Risk Factors
PubMed: 33943028
DOI: 10.1111/jdi.13562 -
Cell Metabolism Mar 2021The nervous system instructs the body's metabolism, including that in the liver. However, the neural anatomy of the liver under either normal or metabolically stressed...
The nervous system instructs the body's metabolism, including that in the liver. However, the neural anatomy of the liver under either normal or metabolically stressed conditions remains to be unequivocally assessed. Here, we examined neural distributions in the mouse, nonhuman primate, and human livers with advanced 3D imaging. We observed that neural innervations within the liver are predominantly sympathetic, but not parasympathetic, inputs. Moreover, we discovered the profound and reversible loss of such sympathetic innervations during metabolic challenges. This hepatic sympathetic neuropathy was caused by TNFα derived from CD11b F4/80 immune cells under high-fat-diet (HFD) condition. We further demonstrated that the Sarm1 deletion mitigated the hepatic sympathetic neuropathy and improved metabolic parameters in HFD-challenged mice. Mechanistically, the sympathetic neurotransmitter norepinephrine attenuated the immune-cell inflammation that would otherwise trigger the insulin insensitivity of hepatocytes. These results together reveal the previously unrecognized neuropathic event in the liver with metabolic relevance.
Topics: Animals; Armadillo Domain Proteins; Cytoskeletal Proteins; Diet, High-Fat; Humans; Liver; Lymphocytes; Macaca mulatta; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Non-alcoholic Fatty Liver Disease; Norepinephrine; Stress, Physiological; Tumor Necrosis Factor-alpha
PubMed: 33545051
DOI: 10.1016/j.cmet.2021.01.012 -
Oman Journal of Ophthalmology 2020Intentional ingestion of alcohol-based handrub (ABHR) or sanitizer solution is uncommon. The coronavirus disease-19 pandemic caused by severe acute respiratory syndrome...
Intentional ingestion of alcohol-based handrub (ABHR) or sanitizer solution is uncommon. The coronavirus disease-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 has led to lockdowns being put in place in many countries across the globe and resulted in a surge in ABHR usage to maintain hand hygiene. In this communication, we report the case of a 56-year-old male, a chronic alcoholic who presented during the lockdown period, with acute bilateral loss of vision following ingestion of ABHR. The handrub was found to be a nonstandardized sanitizer with no labels mentioning its constituents. Typically, the ingestion of ABHR solutions results in isopropanol or ethanol poisoning, both of which have low toxicity. Based on the clinical history and findings in our patient, a diagnosis of optic neuropathy due to accidental ingestion of sanitizer containing methyl alcohol as an unlisted ingredient was made. Our report underscores the need for strict guidelines, toxicovigilance, and surveillance systems to be in place to prevent such adulterated ABHRs from being commercially available.
PubMed: 33542609
DOI: 10.4103/ojo.OJO_277_2020 -
PeerJ 2021The relationship between serum uric acid (SUA) and several diabetic complications or co-morbidities remains a matter of debate. The study aims to explore the association...
BACKGROUND
The relationship between serum uric acid (SUA) and several diabetic complications or co-morbidities remains a matter of debate. The study aims to explore the association between SUA levels and the prevalence of non-alcoholic fatty liver disease (NAFLD), diabetic retinopathy (DR), diabetic nephropathy (DN) and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM).
METHODS
A total of 2,809 participants (1,784 males and 1,025 females) were included in this cross-sectional study. Clinical characteristics and the prevalence of each of the four diseases were analyzed based on gender-specific quartiles of SUA levels. The Pearson correlation analysis and linear-regression analysis were used to access the correlation between SUA levels and clinical characteristics. Furthermore, a binary logistic regression analysis was carried out to determine whether SUA was an independent risk factor for each of the four complications.
RESULTS
SUA levels were positively correlated to BMI, BUN, Scr and TG, but negatively associated with eGFR, HDL, FBG, 2h-PG and HbA1c% for the patients with T2DM. The prevalence of NAFLD and DN, but not DR or DPN, were increased with SUA levels from the first to the fourth quartile. Binary logistic regression further disclosed that SUA was an independent risk factor for NAFLD (ORs Male = 1.002, = 0.0013; ORs Female = 1.002, = 0.015) and DN (ORs Male = 1.006, < 0.001; ORs Female = 1.005, < 0.001), but not for DR and DPN. After adjustment for the confounders, SUA levels were significantly associated with NAFLD within the 3rd (ORs = 1.829, = 0.004) and 4th quartile (ORs = 2.064, = 0.001) for women, but not independently associated with SUA for man. On the other hand, our results revealed increased prevalence of DN for SUA quartile 2 (ORs = 3.643, = 0.039), quartile 3 (ORs = 3.967, = 0.024) and quartile 4 (ORs = 9.133, < 0.001) in men; however, SUA quartiles were significantly associated with DN only for quartile 4 (ORs = 4.083, = 0.042) in women.
CONCLUSION
For patients with T2DM, elevated SUA concentration is an independent risk factor for the prevalence of NAFLD and DN after adjustment for other indicators, but not DR or DPN.
PubMed: 33520463
DOI: 10.7717/peerj.10691