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A post-hoc exploratory analysis of the PIONEER 9 and 10 trials evaluated the effect of baseline age (<65 and ≥65 years) on the efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes. In PIONEER 9 and 10, patients were randomized to once-daily oral semaglutide (3, 7 or 14 mg) or a comparator (placebo or once-daily subcutaneous liraglutide 0.9 mg [PIONEER 9]; once-weekly subcutaneous dulaglutide 0.75 mg [PIONEER 10]) for 52 weeks, with 5 weeks' follow-up. In total, 701 patients were included (PIONEER 9: N = 243; PIONEER 10: N = 458). Glycaemic efficacy of oral semaglutide was similar in Japanese patients aged <65 years compared with those ≥65 years, and there did not appear to be a clear pattern between age subgroup and body weight changes. Across treatment arms, adverse events generally occurred in greater proportions of patients aged ≥65 versus <65 years. There was generally a higher rate of premature trial product discontinuation because of adverse events in the older age group. These results indicate that oral semaglutide is efficacious in Japanese patients irrespective of age.
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Diabetes Mellitus Tipo 2 , Administração Oral , Idoso , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/efeitos adversos , Japão/epidemiologiaRESUMO
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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Neuropatias Diabéticas , Ácidos Docosa-Hexaenoicos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Autofagia , Morte Celular , Neuropatias Diabéticas/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Estresse Oxidativo , Ratos , Ratos Endogâmicos F344 , Células de Schwann/metabolismo , Transdução de Sinais , terc-Butil Hidroperóxido/toxicidadeRESUMO
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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Neuropatias Diabéticas/etiologia , Peptídeos Semelhantes ao Glucagon/deficiência , Animais , Neuropatias Diabéticas/genética , Neuropatias Diabéticas/patologia , Modelos Animais de Doenças , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Glucagon/deficiência , Glucagon/genética , Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/deficiência , Peptídeo 1 Semelhante ao Glucagon/genética , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Peptídeos Semelhantes ao Glucagon/genética , Peptídeos Semelhantes ao Glucagon/metabolismo , Hiperalgesia/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fibras Nervosas Mielinizadas/patologia , Condução Nervosa , Crescimento Neuronal , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Glucagon/genética , Receptores de Glucagon/metabolismoRESUMO
AIMS: To investigate the efficacy and safety of insulin degludec/liraglutide (IDegLira) compared with 50 U insulin degludec (degludec) or less in Japanese individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: In this 26-week, double-blind, multicentre, treat-to-target trial, Japanese individuals with T2D that was uncontrolled with basal or pre-mix insulin (20-50 units) were randomized (1:1) to receive IDegLira or degludec, both with metformin. The maximum dose was 50 dose steps (IDegLira) or 50 units (degludec). The primary endpoint was change from baseline in HbA1c with IDegLira vs degludec after 26 weeks of treatment. RESULTS: In total, 210 Japanese individuals were randomized to IDegLira or degludec and completion rates were 100% and 93%, respectively. IDegLira was superior to degludec with respect to change from baseline in HbA1c: estimated treatment difference (ETD) (95% confidence interval), -13.98 mmol/Mol (-16.41; -11.55); P < 0.0001. The change in mean HbA1c was from 70.6 by -21.3 mmol/Mol with IDegLira and from 70.1 by -7.1 mmol/Mol with degludec. Mean change in body weight was -0.7 kg with IDegLira and 0.7 kg with degludec: ETD (95% CI) -1.41 kg (-2.26; -0.56); P = 0.0012. Mean daily total insulin dose was significantly lower with IDegLira (37.6 U) as compared to that with degludec (41.2 U) at Week 26. Overall rates of severe or blood glucose-confirmed hypoglycaemia and adverse events were comparable between treatment groups. CONCLUSIONS: IDegLira provided superior reductions in HbA1c compared with ≤50 U degludec, with weight loss and similar hypoglycaemia rates and no unexpected safety or tolerability issues. These results suggest that this treatment could be an attractive intensification option for Japanese subjects with T2D that was uncontrolled with basal or pre-mixed insulin.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas/análise , Hipoglicemiantes/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Liraglutida/uso terapêutico , Idoso , Glicemia/análise , Método Duplo-Cego , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/efeitos adversos , Japão , Liraglutida/administração & dosagem , Liraglutida/efeitos adversos , Masculino , Pessoa de Meia-IdadeRESUMO
The aim of this study was to evaluate the efficacy and safety of pemafibrate in people with type 2 diabetes and hypertriglyceridaemia over a 52-week period. Participants were randomly assigned to receive treatment with placebo or pemafibrate at a dose of 0.2 or 0.4 mg/d for 24 weeks (treatment period 1). The main results from treatment period 1 have been reported previously. The assigned treatment was continued up to week 52, except that the placebo was changed to pemafibrate 0.2 mg/d after week 24 (treatment period 2). The percentage changes in fasting serum triglyceride (TG) levels at week 52 (last observation carried forward) were -48.2%, -42.3%, and -46.4% in the placebo/pemafibrate 0.2 mg/d (n = 57), pemafibrate 0.2 mg/d (n = 54), and pemafibrate 0.4 mg/d (n = 55) groups, respectively. Levels of TG, non-HDL cholesterol and total cholesterol stably decreased, whereas levels of HDL cholesterol increased with pemafibrate treatments over 52 weeks. Pemafibrate was well tolerated throughout the study period. The present study is the first to show that pemafibrate treatment substantially ameliorated lipid abnormalities and was well tolerated for 52 weeks in people with type 2 diabetes and hypertriglyceridaemia.
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Benzoxazóis , Butiratos , Diabetes Mellitus Tipo 2/complicações , Hipertrigliceridemia , Hipolipemiantes , Benzoxazóis/efeitos adversos , Benzoxazóis/uso terapêutico , Butiratos/efeitos adversos , Butiratos/uso terapêutico , Humanos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/tratamento farmacológico , Hipolipemiantes/efeitos adversos , Hipolipemiantes/uso terapêutico , Triglicerídeos/sangueRESUMO
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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Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/terapia , Transplante de Células-Tronco/métodos , Animais , Humanos , Camundongos , Ratos , Medicina Regenerativa/métodos , Engenharia Tecidual/métodosRESUMO
The light propagation and scattering in monolithic transparent nanoporous materials such as Vycor glasses exhibit two optical turbidities, both of which are slightly deviated from the λ-4 Rayleigh wavelength dependence in the visible region: one is a transient white turbidity τf, characterized by the convex-upward dependence on the inverse fourth power of wavelength, and the other is turbidity τsp inherent to the structural inhomogeneity, characterized by the convex-downward dependence. The former is attributed to a fractal-like percolation network of imbibed or drained pores as a consequence of transient imbibition or drainage of wetting fluid into or from the pore space. The latter is attributed to the structural inhomogeneities inherent to the original dry porous glass, which are produced by spinodal decomposition. In this paper, we develop a general scheme to estimate the transmittance spectra of Vycor through the turbidities τf and τsp in the visible region on the basis of the theory of dielectric constant fluctuations. We show the applicability and its limitation of the turbidity analysis of the photospectroscopically measured data as a method to study the correlation functions that characterize the pore space and the structural features of isotropic transparent nanoporous media, on the presupposition that there exists no light attenuation other than the scattering.
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The light scattering and absorption of monolithic nanoporous Vycor glass during imbibition and drainage of wetting fluid such as water exhibit the following two optical hysteretic characteristics: one is the hysteretic response of the transient white turbidity in the visible (Vis) region and the other the hysteretic response of the absorbance peak in the near-infrared (NIR) region. We analyzed the effect of increasing and decreasing humidity in ambient air on the transmission in the glass with emphasis on its response to the humidity change, with or without holding at the maximum constant humidity, and its response to the humidity change up to various values of maximum attained humidity. We show that both the light scattering in the Vis region and the absorption in the NIR region are strongly affected by the duration and the maximum values of humidity, which implies that the amount of water in the pore space determines saturated and unsaturated responses of optical hystereses in both regions. We also show that the duration decreases the white turbidity while the immediate change of humidity from increasing to decreasing rather increases the turbidity. These facts verify that the nonequilibrium inhomogeneous distribution of the imbibed water in the pore space results in the optical inhomogeneity that causes the scattering, which is subsequently observed as the transient white turbidity, and that hysteresis loops of absorption are caused by the imbibed water in the pore space of Vycor glass. The existence of a threshold humidity of about 40% relative humidity (or corresponding pore-filling fraction of about 0.4) below which the two optical hystereses are suppressed and the fact that the maximum of optical turbidity occurs at about f=0.6 where the capillary condensation takes places imply that the appearance of a long-range capillary bridge between pores causes the transient white turbidity phenomenon.
RESUMO
We use light scattering to study spatial correlations in the pore space of Vycor glass upon draining a wetting fluid. We analyze the transmission spectrum of forward-scattered light on the basis of the theory of dielectric constant fluctuation, whereas conventional light scattering analyzes the scattered light at small angles of monochromatic incident light. Assuming that the drained pores, which are surrounded by filled pores, exhibit long-range correlations of a fractal dimension of 2.5, we analytically derive the corresponding turbidity. The slight deviation from the λ(-4) Rayleigh wavelength dependence directly provides the correlation length of the interconnected network of drained pores. The estimated length, ranging from 0.5 to 18 nm at most, is almost the same order as that indirectly estimated from our previous simple effective Rayleigh scatterer model.
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Vidro , Luz , Nanotecnologia , Fenômenos Ópticos , Molhabilidade , Porosidade , Espalhamento de RadiaçãoRESUMO
BACKGROUND: Integration of disease-specific programmes into the primary health care (PHC) service has been attempted mostly in clinically oriented disease control such as HIV/AIDS and tuberculosis but rarely in vector control. Chagas disease is controlled principally by interventions against the triatomine vector. In Honduras, after successful reduction of household infestation by vertical approach, the Ministry of Health implemented community-based vector surveillance at the PHC services (health centres) to prevent the resurgence of infection. This paper retrospectively analyses the effects and process of integrating a Chagas disease vector surveillance system into health centres. METHODS: We evaluated the effects of integration at six pilot sites in western Honduras during 2008-2011 on; surveillance performance; knowledge, attitude and practice in schoolchildren; reports of triatomine bug infestation and institutional response; and seroprevalence among children under 15 years of age. The process of integration of the surveillance system was analysed using the PRECEDE-PROCEED model for health programme planning. The model was employed to systematically determine influential and interactive factors which facilitated the integration process at different levels of the Ministry of Health and the community. RESULTS: Overall surveillance performance improved from 46 to 84 on a 100 point-scale. Schoolchildren's attitude (risk awareness) score significantly increased from 77 to 83 points. Seroprevalence declined from 3.4% to 0.4%. Health centres responded to the community bug reports by insecticide spraying. As key factors, the health centres had potential management capacity and influence over the inhabitants' behaviours and living environment directly and through community health volunteers. The National Chagas Programme played an essential role in facilitating changes with adequate distribution of responsibilities, participatory modelling, training and, evaluation and advocacy. CONCLUSIONS: We found that Chagas disease vector surveillance can be integrated into the PHC service. Health centres demonstrated capacity to manage vector surveillance and improve performance, children's awareness, vector report-response and seroprevalence, once tasks were simplified to be performed by trained non-specialists and distributed among the stakeholders. Health systems integration requires health workers to perform beyond their usual responsibilities and acquire management skills. Integration of vector control is feasible and can contribute to strengthening the preventive capacity of the PHC service.
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Doença de Chagas , Prestação Integrada de Cuidados de Saúde , Vigilância da População , Atenção Primária à Saúde , Adolescente , Doença de Chagas/sangue , Criança , Pré-Escolar , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Honduras , Humanos , Masculino , Projetos Piloto , Atenção Primária à Saúde/organização & administração , Estudos Retrospectivos , Estudos Soroepidemiológicos , Serviço SocialRESUMO
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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Neuropatias Diabéticas/terapia , Algoritmos , Glicemia/metabolismo , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/metabolismo , Progressão da Doença , HumanosRESUMO
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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Neuropatias Diabéticas/tratamento farmacológico , Glicemia/análise , Humanos , Incretinas/fisiologiaRESUMO
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 da Inflamação/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , NF-kappa B/antagonistas & inibidores , Espironolactona/farmacologia , Aldosterona/biossíntese , Animais , Células Cultivadas , Dinoprostona/biossíntese , Quinase I-kappa B/metabolismo , Mediadores da Inflamação/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Fosforilação , Fator de Necrose Tumoral alfa/biossínteseRESUMO
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 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 , Neuropatias Diabéticas , Polineuropatias , Humanos , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Estudos Prospectivos , Japão/epidemiologia , Prevalência , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/diagnóstico , Polineuropatias/epidemiologia , Polineuropatias/etiologiaRESUMO
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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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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Neuropatias Diabéticas , Eletrocardiografia , Condução Nervosa , Sistemas Automatizados de Assistência Junto ao Leito , Humanos , Neuropatias Diabéticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Eletrocardiografia/instrumentação , Eletrocardiografia/métodos , Idoso , Feminino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnósticoRESUMO
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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Porous Vycor glass with nanopores is transparent in the visible region and is often used in colorimetric chemical sensing when impregnated with selectively reacting reagents. However, it has some disadvantages in sensing, since changes in the humidity of ambient air strongly affect its transmission. In this work, by combining a humidity-controlled thermostatic chamber and an ultraviolet-visible and near-infrared spectrophotometer through fiber optics, we analyzed the effect of increasing and decreasing humidity in the ambient air on the transparency change of the nanoporous glass. The transparency response in the visible region to changes in humidity is analyzed to correlate the turbidity response of the glass with the amount of water in it. The turbidity is found to be dependent on the inverse fourth power of the wavelength (1/λ4), which implies that Rayleigh-type scattering takes place for both adsorption and desorption of water. We show that measures of the extent of the optical inhomogeneity that causes the scattering, such as the effective radius of scatterers and their number density, exhibit a pronounced hysteretic characteristic for the imbibition and drainage of water, while the absorption inherent to imbibed water also shows another type of hysteresis that is quite similar to the sorption isotherms of water. On the basis of the above observations, we show that the transitory white turbidity of nanoporous glasses during changes in humidity can be consistently interpreted and quantitatively analyzed by a simple Rayleigh scattering mechanism.
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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.