RESUMEN
Versican is a large chondroitin sulfate proteoglycan in the extracellular matrix. It plays a pivotal role in the formation of the provisional matrix. S100a4, previously known as fibroblast-specific protein, functions as a calcium channel-binding protein. To investigate the role of versican expressed in fibroblasts, we generated conditional knockout mice in which versican expression is deleted in cells expressing S100a4. We found that S100a4 is expressed in adipose tissues, and these mice exhibit obesity under a normal diet, which becomes apparent as early as five months. The white adipose tissues of these mice exhibited decreased expression levels of S100a4 and versican and hypertrophy of adipocytes. qRT-PCR showed a reduced level of UCP1 in their white adipose tissues, indicating that the basic energy metabolism is diminished. These results suggest that versican in adipose tissues maintains the homeostasis of adipose tissues and regulates energy metabolism.
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Tejido Adiposo , Metabolismo Energético , Homeostasis , Ratones Noqueados , Versicanos , Animales , Versicanos/metabolismo , Versicanos/genética , Ratones , Tejido Adiposo/metabolismo , Obesidad/metabolismo , Obesidad/genética , Tejido Adiposo Blanco/metabolismo , Ratones Endogámicos C57BL , Masculino , Adipocitos/metabolismoRESUMEN
Individuals suffering from diabetic polyneuropathy (DPN) experience debilitating symptoms such as pain, paranesthesia, and sensory disturbances, prompting a quest for effective treatments. Dipeptidyl-peptidase (DPP)-4 inhibitors, recognized for their potential in ameliorating DPN, have sparked interest, yet the precise mechanism underlying their neurotrophic impact on the peripheral nerve system (PNS) remains elusive. Our study delves into the neurotrophic effects of DPP-4 inhibitors, including Diprotin A, linagliptin, and sitagliptin, alongside pituitary adenylate cyclase-activating polypeptide (PACAP), Neuropeptide Y (NPY), and Stromal cell-derived factor (SDF)-1a-known DPP-4 substrates with neurotrophic properties. Utilizing primary culture dorsal root ganglia (DRG) neurons, we meticulously evaluated neurite outgrowth in response to these agents. Remarkably, all DPP-4 inhibitors and PACAP demonstrated a significant elongation of neurite length in DRG neurons (PACAP 0.1 µM: 2221 ± 466 µm, control: 1379 ± 420, p < 0.0001), underscoring their potential in nerve regeneration. Conversely, NPY and SDF-1a failed to induce neurite elongation, accentuating the unique neurotrophic properties of DPP-4 inhibition and PACAP. Our findings suggest that the upregulation of PACAP, facilitated by DPP-4 inhibition, plays a pivotal role in promoting neurite elongation within the PNS, presenting a promising avenue for the development of novel DPN therapies with enhanced neurodegenerative capabilities.
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Neuropatías Diabéticas , Inhibidores de la Dipeptidil-Peptidasa IV , Ganglios Espinales , Proyección Neuronal , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , Animales , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/farmacología , Proyección Neuronal/efectos de los fármacos , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/metabolismo , Ratones , Neuropéptido Y/metabolismo , Neuropéptido Y/farmacología , Quimiocina CXCL12/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Linagliptina/farmacología , Dipeptidil Peptidasa 4/metabolismo , Fosfato de Sitagliptina/farmacología , Células Cultivadas , Neuritas/efectos de los fármacos , Neuritas/metabolismo , OligopéptidosRESUMEN
Autophagy is the process by which intracellular components are degraded by lysosomes. It is also activated by oxidative stress; hence, autophagy is thought to be closely related to oxidative stress, one of the major causes of diabetic neuropathy. We previously reported that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) induced antioxidant enzymes and protected Schwann cells from oxidative stress. However, the relationship between autophagy and oxidative stress-induced cell death in diabetic neuropathy has not been elucidated. Treatment with tert-butyl hydroperoxide (tBHP) decreased the cell survival rate, as measured by an MTT assay in immortalized Fischer rat Schwann cells 1 (IFRS1). A DHA pretreatment significantly prevented tBHP-induced cytotoxicity. tBHP increased autophagy, which was revealed by the ratio of the initiation markers, AMP-activated protein kinase, and UNC51-like kinase phosphorylation. Conversely, the DHA pretreatment suppressed excessive tBHP-induced autophagy signaling. Autophagosomes induced by tBHP in IFRS1 cells were decreased to control levels by the DHA pretreatment whereas autolysosomes were only partially decreased. These results suggest that DHA attenuated excessive autophagy induced by oxidative stress in Schwann cells and may be useful to prevent or reduce cell death in vitro. However, its potentiality to treat diabetic neuropathy must be validated in in vivo studies.
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Neuropatías Diabéticas , Ácidos Docosahexaenoicos , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Autofagia , Muerte Celular , Neuropatías Diabéticas/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Ácidos Docosahexaenoicos/farmacología , Estrés Oxidativo , Ratas , Ratas Endogámicas F344 , Células de Schwann/metabolismo , Transducción de Señal , terc-Butilhidroperóxido/toxicidadRESUMEN
Although diabetic polyneuropathy (DPN) is the commonest diabetic complication, its pathology remains to be clarified. As previous papers have suggested the neuroprotective effects of glucagon-like peptide-1 in DPN, the current study investigated the physiological indispensability of glucagon gene-derived peptides (GCGDPs) including glucagon-like peptide-1 in the peripheral nervous system (PNS). Neurological functions and neuropathological changes of GCGDP deficient (gcg-/-) mice were examined. The gcg-/- mice showed tactile allodynia and thermal hyperalgesia at 12-18 weeks old, followed by tactile and thermal hypoalgesia at 36 weeks old. Nerve conduction studies revealed a decrease in sensory nerve conduction velocity at 36 weeks old. Pathological findings showed a decrease in intraepidermal nerve fiber densities. Electron microscopy revealed a decrease in circularity and an increase in g-ratio of myelinated fibers and a decrease of unmyelinated fibers in the sural nerves of the gcg-/- mice. Effects of glucagon on neurite outgrowth were examined using an ex vivo culture of dorsal root ganglia. A supraphysiological concentration of glucagon promoted neurite outgrowth. In conclusion, the mice with deficiency of GCGDPs developed peripheral neuropathy with age. Furthermore, glucagon might have neuroprotective effects on the PNS of mice. GCGDPs might be involved in the pathology of DPN.
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Neuropatías Diabéticas/etiología , Péptidos Similares al Glucagón/deficiencia , Animales , Neuropatías Diabéticas/genética , Neuropatías Diabéticas/patología , Modelos Animales de Enfermedad , Ganglios Espinales/metabolismo , Ganglios Espinales/patología , Glucagón/deficiencia , Glucagón/genética , Glucagón/metabolismo , Péptido 1 Similar al Glucagón/deficiencia , Péptido 1 Similar al Glucagón/genética , Péptido 1 Similar al Glucagón/metabolismo , Péptidos Similares al Glucagón/genética , Péptidos Similares al Glucagón/metabolismo , Hiperalgesia/etiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fibras Nerviosas Mielínicas/patología , Conducción Nerviosa , Proyección Neuronal , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Glucagón/genética , Receptores de Glucagón/metabolismoRESUMEN
PURPOSE OF REVIEW: After a prolonged warm-up period of basic research, several modalities of cell replacement therapies are under development for diseases with no available cure. Diabetic polyneuropathy (DPN) is one of the most prevalent chronic diabetes complications that causes sensorimotor dysfunction, subsequent high risks for lower limb amputations, and high mortality. Currently, no disease modifying therapy exists for DPN. RECENT FINDINGS: Several types of well-documented stem/progenitor cells have been utilized for cell transplantation therapies in DPN model rodents: mesenchymal stromal cells (MSCs), endothelial progenitor cells (EPCs), and cells with similar characteristics of MSCs or EPCs derived from embryonic stem cells or induced pluripotent stem cells. Some recent experimental studies reported that these immature cells may have beneficial effects on DPN. Although the role of nerve regeneration in the pathology of DPN has not been sufficiently elucidated, many intervention studies attempting regenerative therapy of DPN have been reported. Further studies are needed to better evaluate the potential of regeneration in reversing the pathology of DPN.
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Neuropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/terapia , Trasplante de Células Madre/métodos , Animales , Humanos , Ratones , Ratas , Medicina Regenerativa/métodos , Ingeniería de Tejidos/métodosRESUMEN
BACKGROUND: Accurate glomerular filtration rate (GFR) evaluation is significant for drug dosing of carboplatin, anticancer drug excreted mainly from kidney. Serum cystatin-C (sCys-C) is a GFR marker with little affected by body muscle mass volume. And GFR equations based on serum creatinine (eGFRcreat) and sCys-C (eGFRcys) were developed; however, accuracy of eGFRcys has not been elucidated fully among patients with cancer. Therefore, we analyzed the performance of GFR equations among patients with cancer whose GFR values were measured by inulin clearance (Cin). METHODS: Study design was a cross-sectional study. Subjects were 41 patients with cancer whose GFR values were measured by Cin for drug dosing studies of carboplatin or S-1 in Nagoya University Hospital from 2007 to 2010 and 29 non-cancer patients. Correlation with Cin and slope of regression line were evaluated in eGFRcreat and eGFRcys. Single and multiple regression analyses were analyzed to identify associating factors with eGFRcreat/Cin or eGFRcys/Cin. RESULTS: Age, body weight, body mass index (BMI) and sCr were different between cancer patients and non-cancer patients, but sCys-C and Cin were consistent in 2 groups. The slope of the regression line for Cin vs. eGFRcys with zero intercept in cancer patients was 1.10 (95 % CI: 1.02-1.17), which was significantly different from 1.0. In multiple regression analysis revealed that BMI and urinary creatinine excretion were significantly associated with eGFRcreat/Cin, and cancer was only associating factor with eGFRcys/Cin. CONCLUSION: eGFRcys should not be used for evaluation of renal function in patients with cancer because it underestimates GFR.
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Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Pruebas de Función Renal/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/fisiopatología , Anciano , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Índice de Masa Corporal , Carboplatino/efectos adversos , Creatinina/sangre , Estudios Transversales , Cistatina C/sangre , Combinación de Medicamentos , Femenino , Tasa de Filtración Glomerular , Humanos , Inulina/metabolismo , Masculino , Persona de Mediana Edad , Ácido Oxónico/efectos adversos , Ácido Oxónico/uso terapéutico , Piridinas/efectos adversos , Piridinas/uso terapéutico , Tegafur/efectos adversos , Tegafur/uso terapéuticoRESUMEN
Diagnostic criteria of diabetic neuropathy that can be easily used at bedsides and have international consensus have not been established. The most important therapeutic strategy is to maintain strict glycemic control. In addition, treatment with an aldose reductase inhibitor that is innovated from the viewpoint of the pathogenesis of diabetic neuropathy would be useful for preventing the progression of diabetic neuropathy. For painful diabetic neuropathy, pregabalin and duloxetine effectively relieve the pain, and contribute to the improvement of the quality of life.
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Neuropatías Diabéticas/terapia , Algoritmos , Glucemia/metabolismo , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/metabolismo , Progresión de la Enfermedad , HumanosRESUMEN
Diabetic neuropathy is one of the major three diabetic complications, together with diabetic retinopathy and nephropathy. It develops early and with a high incidence after the onset of diabetes mellitus and influences the QOL and prognosis of patients with diabetes mellitus. Although the exact mechanism by which hyperglycemia causes nerve damage remains a subject of debate, metabolic and vascular disturbances due to hyperglycemia are assumed to cause nerve damage. The treatments of diabetic neuropathy aim at both the inhibition of its onset and progression (causative treatment) and the care for symptoms due to neuropathy such as pain(symptomatic treatment). In this paper, we describe the outlines of these two kinds of treatment for diabetic neuropathy.
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Neuropatías Diabéticas/tratamiento farmacológico , Glucemia/análisis , Humanos , Incretinas/fisiologíaRESUMEN
The effect of spironolactone (SPIR) on lipopolysaccharide (LPS)-induced production of proinflammatory mediators was examined using RAW 264.7 macrophage-like cells and mouse peritoneal macrophages. SPIR significantly inhibited LPS-induced production of nitric oxide (NO), tumor necrosis factor-α and prostaglandin E2. The inhibition was not mediated by cell death. SPIR reduced the expression of an inducible NO synthase mRNA in response to LPS. SPIR significantly inhibited phosphorylation of p65 nuclear factor (NF)-κB in response to LPS. Furthermore, SPIR inhibited phosphorylation of IκB kinase (IKK) as an upstream molecule of NF-κB in response to LPS. LPS did not induce the production of aldosterone in RAW 264.7 cells. Taken together, SPIR is suggested to inhibit LPS-induced proinflammatory mediators via inactivation of IKK/NF-κB in LPS signaling.
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Mediadores de Inflamación/antagonistas & inhibidores , Lipopolisacáridos/farmacología , FN-kappa B/antagonistas & inhibidores , Espironolactona/farmacología , Aldosterona/biosíntesis , Animales , Células Cultivadas , Dinoprostona/biosíntesis , Quinasa I-kappa B/metabolismo , Mediadores de Inflamación/metabolismo , Ratones , Óxido Nítrico/biosíntesis , Fosforilación , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
This study aimed to investigate the prevalence and characteristics of diabetic symmetric sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes registered in the Japan Diabetes Complication and its Prevention Prospective study. In the study, 6,338 patients with diabetes who had been treated by diabetes specialists were registered in 2007-2009. Of these, patients with type 2 diabetes who could be evaluated for DSPN were analyzed using the t-test, χ2 -test and logistic regression analyses. DSPN was diagnosed using the Simple Diagnostic Criteria for Diabetic Polyneuropathy proposed by the Diabetic Neuropathy Study Group in Japan. Of the total participants, 5,451 patients (mean age 61.4 years, duration of diabetes 10.8 years) were analyzed. Based on the criteria, 35.8% of patients were diagnosed with DSPN. The prevalence of sensory symptoms was 25.8%. The following factors increased the risk for DSPN: age (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.42-1.73), duration of diabetes (OR 1.32, 95% CI 1.21-1.43), body mass index (OR 1.19, 95% CI 1.09-1.30), systolic blood pressure (OR 1.06, 95% CI 1.01-1.10), hemoglobin A1c (OR 1.15, 95% CI 1.09-1.22), biguanides (OR 1.22, 95% CI 1.06-1.39) and insulin therapy (OR 1.59, 95% CI 1.36-1.84). The following factors decreased the risk for DSPN: total cholesterol (OR 0.98, 95% CI 0.96-1.00) and exercise therapy (OR 0.85, 95% CI 0.73-0.98). The baseline survey clarified the prevalence and characteristics of DSPN in Japanese patients with type 2 diabetes. The survey also showed the risk factors of DSPN.
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Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Polineuropatías , Humanos , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/diagnóstico , Estudios Prospectivos , Japón/epidemiología , Prevalencia , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/diagnóstico , Polineuropatías/epidemiología , Polineuropatías/etiologíaRESUMEN
Aim/introduction: This study aims to investigate the prevalence and characteristics of diabetic symmetric sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes registered in the Japan Diabetes Complication and its Prevention Prospective (JDCP) study. Materials and methods: In the study, 6338 patients with diabetes who had been treated by diabetes specialists were registered in 2007-2009. Of these, patients with type 2 diabetes who could be evaluated for DSPN were analyzed using t test, chi-square test, and logistic regression analyses. DSPN was diagnosed using the Simple Diagnostic Criteria for Diabetic Polyneuropathy proposed by the Diabetic Neuropathy Study Group in Japan. Results: Of the total participants, 5451 patients (mean age 61.4 years old and duration of diabetes 10.8 years) were analyzed. Based on the criteria, 35.8% of patients were diagnosed with DSPN. The prevalence of sensory symptoms was 25.8%. The following factors increased risk for DSPN: age [odds ratio (OR) 1.57, 95% confidence intervals (CI) 1.42-1.73], duration of diabetes (OR 1.32, 95% CI 1.21-1.43), body mass index (OR 1.19, 95% CI 1.09-1.30), systolic blood pressure (OR 1.06, 95% CI 1.01-1.10), hemoglobin A1c (OR 1.15, 95% CI 1.09-1.22), biguanides (OR 1.22, 95% CI 1.06-1.39), and insulin therapy (OR 1.59, 95% CI 1.36-1.84). The following factors decreased risk for DSPN: total cholesterol (OR 0.98, 95% CI 0.96-1.00) and exercise therapy (OR 0.85, 95% CI 0.73-0.98). Conclusions: The baseline survey clarified the prevalence and characteristics of DSPN in Japanese patients with type 2 diabetes. The survey also revealed the risk factors of DSPN.
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Increased low-density lipoprotein levels are risk factors for diabetic neuropathy. Diabetes mellitus is associated with elevated metabolic stress, leading to oxidised low-density lipoprotein formation. Therefore, it is important to investigate the mechanisms underlying the pathogenesis of diabetic neuropathy in diabetes complicated by dyslipidaemia with increased levels of oxidised low-density lipoprotein. Here, we examined the effects of hyperglycaemia and oxidised low-density lipoprotein treatment on Schwann cell death and its underlying mechanisms. Immortalised mouse Schwann cells were treated with oxidised low-density lipoprotein under normo- or hyperglycaemic conditions. We observed that oxidised low-density lipoprotein-induced cell death increased under hyperglycaemic conditions compared with normoglycaemic conditions. Moreover, hyperglycaemia and oxidised low-density lipoprotein treatment synergistically upregulated the gene and protein expression of toll-like receptor 4. Pre-treatment with TAK-242, a selective toll-like receptor 4 signalling inhibitor, attenuated hyperglycaemia- and oxidised low-density lipoprotein-induced cell death and apoptotic caspase-3 pathway. Our findings suggest that the hyperactivation of toll-like receptor 4 signalling by hyperglycaemia and elevated oxidised low-density lipoprotein levels synergistically exacerbated diabetic neuropathy; thus, it can be a potential therapeutic target for diabetic neuropathy.
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This algorithm was issued for the appropriate use of drugs for the treatment of type 2 diabetes mellitus in Japan. The revisions include safety considerations, fatty liver disease as a comorbidity to be taken into account and the position of tirzepatide.
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Algoritmos , Consenso , Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Japón , Hipoglucemiantes/uso terapéutico , Sociedades MédicasRESUMEN
The Japan Diabetes Society (JDS) adopted a sweeping decision to release consensus statements on relevant issues in diabetes management that require updating from time to time and launched a "JDS Committee on Consensus Statement Development." In March 2020, the committee's first consensus statement on "Medical Nutrition Therapy and Dietary Counseling for People with Diabetes" was published. In September 2022, a second consensus "algorithm for pharmacotherapy in people with type 2 diabetes" was proposed. In developing an algorithm for diabetes pharmacotherapy in people with type 2 diabetes, the working concept was that priority should be given to selecting such medications as would appropriately address the diabetes pathology in each patient while simultaneously weighing the available evidence for these medications and the prescribing patterns in clinical practice in Japan. These consensus statements are intended to present the committee's take on diabetes management in Japan, based on the evidence currently available for each of the issues addressed. It is thus hoped that practicing diabetologists will not fail to consult these statements to provide the best available practice in their respective clinical settings. Given that the persistent dual GIP/GLP-1 receptor agonist tirzepatide was approved in April 2023, these consensus statements have been revised1). In this revision, specifically, tirzepatide was added to the end of [likely involving insulin resistance] of "Obese patients" in Step 1: "Select medications to address the diabetes pathology involved" in Fig. 2. While the sentence, "Insulin insufficiency and resistance can be assessed by referring to the various indices listed in the JDS 'Guide to Diabetes Management.' was mentioned in the previous edition as well, "While insulin resistance is analogized based on BMI, abdominal obesity, and visceral fat accumulation, an assessment of indicators (e.g., HOMA-IR) is desirable" was added as information in order to more accurately recognize the pathology. Regarding Step 2: "Give due consideration to safety," "For renal excretion" was added to the "Rule of thumb 2: Avoid glinides in patients with renal impairment." The order of the medications in "rule of thumb 3: Avoid thiazolidinediones and biguanides in patients with heart failure (in whom they are contraindicated)." to thiazolidinediones then biguanides. In the description of the lowest part of Fig. 2, for each patient failing to achieve his/her HbA1c control goal, "while reverting to step 1" was changed to "while reverting to the opening" and "including reassessment if the patient is indicated for insulin therapy" was added. In the separate table, the column for tirzepatides was added, while the two items, "Characteristic side effects" and "Persistence of effect" were added to the area of interest. The revision also carried additional descriptions of the figure and table such as tirzepatides and "Characteristic side effects" in the statement, and while not mentioned in the proposed algorithm figure, nonalcoholic fatty liver disease (NAFLD) is covered from this revision for patients with comorbidities calling for medical attention. Moreover, detailed information was added to the relative/absolute indication for insulin therapy, the Kumamoto Declaration 2013 for glycemic targets, and glycemic targets for older people with diabetes. Again, in this revision, it is hoped that the algorithm presented here will not only contribute to improved diabetes management in Japan, but will continue to evolve into a better algorithm over time, reflecting new evidence as it becomes available.
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AIMS/INTRODUCTION: This study aimed to investigate the diagnostic potential of two simplified tests, a point-of-care nerve conduction device (DPNCheck™) and a coefficient of variation of R-R intervals (CVR-R), as an alternative to traditional nerve conduction studies for the diagnosis of diabetic polyneuropathy (DPN) in patients with diabetes. MATERIALS AND METHODS: Inpatients with type 1 or type 2 diabetes (n = 167) were enrolled. The study population consisted of 101 men, with a mean age of 60.8 ± 14.8 years. DPN severity was assessed using traditional nerve conduction studies, and differentiated based on Baba's classification (BC). To examine the explanatory potential of variables in DPNCheck™ and CVR-R regarding the severity of DPN according to BC, a multiple regression analysis was carried out, followed by a receiver operating characteristic analysis. RESULTS: Based on BC, 61 participants (36.5% of the total) were categorized as having DPN severity of stage 2 or more. The multiple regression analysis yielded a predictive formula with high predictive power for DPN diagnosis (estimated severity of DPN in BC = 2.258 - 0.026 × nerve conduction velocity [m/s] - 0.594 × ln[sensory nerve action potential amplitude (µV)] + 0.528In[age(years)] - 0.178 × ln[CVR-R], r = 0.657). The area under the curve in receiver operating characteristic analysis was 0.880. Using the optimal cutoff value for DPN with severer than stage 2, the predictive formula showed good diagnostic efficacy: sensitivity of 83.6%, specificity of 79.2%, positive predictive value of 51.7% and negative predictive value of 76.1%. CONCLUSIONS: These findings suggest that DPN diagnosis using DPNCheck™ and CVR-R could improve diagnostic efficiency and accessibility for DPN assessment in patients with diabetes.
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Neuropatías Diabéticas , Electrocardiografía , Conducción Nerviosa , Sistemas de Atención de Punto , Humanos , Neuropatías Diabéticas/diagnóstico , Masculino , Persona de Mediana Edad , Conducción Nerviosa/fisiología , Electrocardiografía/instrumentación , Electrocardiografía/métodos , Anciano , Femenino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnósticoRESUMEN
Aims: We aimed to identify patients who would benefit from basal insulin-supported oral therapy (BOT) with a glinide and an α-glucosidase inhibitor (a fixed-dose combination tablet of mitiglinide 10 mg and voglibose 0.2 mg) in Japanese type 2 diabetic patients. Methods: Patients who were hospitalized to improve hyperglycemia received basal-bolus insulin therapy. After the reduction of glucose toxicity, a 75 g oral glucose tolerance test and a glucagon test were performed. Thereafter, the basal-bolus insulin therapy was switched to BOT with mitiglinide, followed by further addition of voglibose. Interstitial glucose levels were continuously monitored throughout the study period. Diurnal glucose profile was recorded and analyzed. Patients were divided into two groups according to whether their percentage of time in range (TIR, 70-180 mg/dL) under BOT with mitiglinide/voglibose was higher than 70% or not, and the differences in clinical characteristics between the groups were analyzed. Results: Twenty patients were enrolled, and 19 of them completed the study. BOT with mitiglinide/voglibose achieved ≥ 70% of TIR in thirteen patients. The area under the curve of serum C-peptide levels during the oral glucose tolerance test was significantly higher in the patients with ≥ 70% of TIR. The daily insulin dosages and blood glucose profiles were comparable between the two groups. Conclusions: The efficacy of BOT with mitiglinide/voglibose depended on residual insulin secretory abilities. This therapy would be a useful therapeutic option for patients with type 2 diabetes.
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[This corrects the article DOI: 10.1007/s13340-022-00605-x.].
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Aims: Muscle atrophy is a diabetic complication, which results in a deterioration in glycemic control in type 2 diabetes mellitus (T2DM) individuals. The psoas muscle mass index (PMI) is a reliable indicator for estimating whole-body muscle mass. We aimed to examine the relationship between clinical parameters and the PMI to clarify the mechanism underlying muscle atrophy in diabetes. Methods: This retrospective, cross-sectional study examined 51 patients (31 men and 20 women) with T2DM and a mean HbA1c value of 9.9 ± 1.7%. These patients were admitted to Aichi Medical University Hospital and underwent abdominal computed tomography imaging from July 2020 to April 2021. Multiple clinical parameters were assessed with the PMI. Results: In a multiple regression analysis adjusted for age and sex, the PMI was correlated with body weight, body mass index, serum concentrations of corrected calcium, aspartate aminotransferase, alanine aminotransferase, creatine kinase, thyroid-stimulating hormone (TSH), urinary C-peptide concentrations, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, and the young adult mean score at the femur neck. Receiver operating characteristic curves were created using TSH concentrations and the FT3/FT4 ratio for diagnosing a low PMI. The area under the curve was 0.593 and 0.699, respectively. The cut-off value with maximum accuracy for TSH concentrations was 1.491 µIU/mL, sensitivity was 56.1%, and specificity was 80.0%. Corresponding values for the FT3/FT4 ratio were 1.723, 78.0, and 66.7%, respectively. Conclusion: TSH concentrations and the FT3/FT4 ratio are correlated with the PMI, and their thresholds may help prevent muscle mass loss in Japanese individuals with T2DM.
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Early radiation dermatitis develops after large doses of X-radiation. Inflammatory erythema develops within about a week. This may heal with desquamation and pigmentation. If the dose was high enough, painful blisters may develop at the site of erythema. In that case, healing usually takes place with atrophy, teleangiectasia, and irregular hyperpigmentation. Subsequent to very large doses, ulceration occurs, generally within 2 months. Such an ulcer may heal ultimately with severe atrophic scarring. Chronic radiation dermatitis occurs from a few months to many years. The skin shows atrophy, teleangiectasia, and irregular hyper- and hypopigmentation. Ulceration may be seen within the areas of atrophy. Radiation ulcerations should be studied by biopsy if they have been present for three or more months. After a long latent period, various malignant neoplasms may form. Most frequent is the basal cell carcinoma, followed by squamous cell carcinoma.