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The early diagnosis of diabetic neuropathy (DN) is fundamental in order to enact timely therapeutic strategies for limiting disease progression. In this work, we explored the suitability of standing balance task for identifying the presence of DN. Further, we proposed two diagnosis pathways in order to succeed in distinguishing between different stages of the disease. We considered a cohort of non-neuropathic (NN), asymptomatic neuropathic (AN), and symptomatic neuropathic (SN) diabetic patients. From the center of pressure (COP), a series of features belonging to different description domains were extracted. In order to exploit the whole information retrievable from COP, a majority voting ensemble was applied to the output of classifiers trained separately on different COP components. The ensemble of kNN classifiers provided over 86% accuracy for the first diagnosis pathway, made by a 3-class classification task for distinguishing between NN, AN, and SN patients. The second pathway offered higher performances, with over 97% accuracy in identifying patients with symptomatic and asymptomatic neuropathy. Notably, in the last case, no asymptomatic patient went undetected. This work showed that properly leveraging all the information that can be mined from COP trajectory recorded during standing balance is effective for achieving reliable DN identification. This work is a step toward a clinical tool for neuropathy diagnosis, also in the early stages of the disease.
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Algoritmos , Neuropatias Diabéticas , Diagnóstico por Computador , Equilíbrio Postural , Humanos , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/fisiopatologia , Equilíbrio Postural/fisiologia , Masculino , Feminino , Pessoa de Meia-Idade , Diagnóstico por Computador/métodos , Idoso , Reprodutibilidade dos Testes , Posição Ortostática , AdultoRESUMO
Postural control is usually assessed by examining the fluctuations of the center of pressure (COP). Balance maintenance is based on sensory feedback and neural interactions, deployed over multiple temporal scales and producing less complex outputs with aging and disease. This paper aims to investigate postural dynamics and complexity on diabetic patients, since diabetic neuropathy (DN) affects the somatosensory system and impairs postural steadiness. A multiscale fuzzy entropy (MSFEn) analysis, over a wide range of temporal scales, was performed on COP timeseries during unperturbed stance in a group of diabetic individuals without neuropathy and two groups of DN patients, with and without symptoms. A parameterization of the MSFEn curve is also proposed. A significant loss of complexity was recognized for the medial-lateral direction in DN groups with respect to non-neuropathic population. For the anterior-posterior direction, symptomatic DN group showed a lowered sway complexity for longer time scales with respect to non neuropathic and asymptomatic patients. The MSFEn approach and the related parameters highlighted that the loss of complexity might be attributed to different factors depending on sway direction, i.e. related to the presence of neuropathy along the medial-lateral axis and to a symptomatic state on the anterior-posterior direction. Results of this study support the use of the MSFEn for gaining insights into balance control mechanisms for diabetic patients, in particular when comparing non neuropathic with neuropathic asymptomatic patients, whose identification by posturographic analysis would be of great value.
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Objective: Artificial intelligence-based decision support systems (DSS) need to provide decisions that are not inferior to those given by experts in the field. Recommended insulin dose adjustments on the same individual data set were compared among multinational physicians, and with recommendations made by automated Endo.Digital DSS (ED-DSS). Research Design and Methods: This was a noninterventional study surveying 20 physicians from multinational academic centers. The survey included 17 data cases of individuals with type 1 diabetes who are treated with multiple daily insulin injections. Participating physicians were asked to recommend insulin dose adjustments based on glucose and insulin data. Insulin dose adjustments recommendations were compared among physicians and with the automated ED-DSS. The primary endpoints were the percentage of comparison points for which there was agreement on the trend of insulin dose adjustments. Results: The proportion of agreement and disagreement in the direction of insulin dose adjustment among physicians was statistically noninferior to the proportion of agreement and disagreement observed between ED-DSS and physicians for basal rate, carbohydrate-to insulin ratio, and correction factor (P < 0.001 and P ≤ 0.004 for all three parameters for agreement and disagreement, respectively). The ED-DSS magnitude of insulin dose change was consistently lower than that proposed by the physicians. Conclusions: Recommendations for insulin dose adjustments made by automatization did not differ significantly from recommendations given by expert physicians regarding the direction of change. These results highlight the potential utilization of ED-DSS as a useful clinical tool to manage insulin titration and dose adjustments.
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Diabetes Mellitus Tipo 1 , Médicos , Inteligência Artificial , Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Insulina Regular Humana/uso terapêuticoRESUMO
AIMS: To compare insulin dose adjustments made by physicians to those made by an artificial intelligence-based decision support system, the Advisor Pro, in people with type 1 diabetes (T1D) using an insulin pump and self-monitoring blood glucose (SMBG). METHODS: This was a multinational, non-interventional study surveying 17 physicians from 11 countries. Each physician was asked to provide insulin dose adjustments for the settings of the pump including basal rate, carbohydrate-to-insulin ratios (CRs), and correction factors (CFs) for 15 data sets of pumps and SMBG of people with T1D (mean age 18.4 ± 4.8 years; eight females; mean glycated hemoglobin 8.2% ± 1.4% [66 ± 11mmol/mol]). The recommendations were compared among the physicians and between the physicians and the Advisor Pro. The study endpoint was the percentage of comparison points for which there was an agreement on the direction of insulin dose adjustments. RESULTS: The percentage (mean ± SD) of agreement among the physicians on the direction of insulin pump dose adjustments was 51.8% ± 9.2%, 54.2% ± 6.4%, and 49.8% ± 11.6% for the basal, CR, and CF, respectively. The automated recommendations of the Advisor Pro on the direction of insulin dose adjustments were comparable )49.5% ± 6.4%, 55.3% ± 8.7%, and 47.6% ± 14.4% for the basal rate, CR, and CF, respectively( and noninferior to those provided by physicians. The mean absolute difference in magnitude of change between physicians was 17.1% ± 13.1%, 14.6% ± 8.4%, and 23.9% ± 18.6% for the basal, CR, and CF, respectively, and comparable to the Advisor Pro 11.7% ± 9.7%, 10.1% ± 4.5%, and 25.5% ± 19.5%, respectively, significant for basal and CR. CONCLUSIONS: Considerable differences in the recommendations for changes in insulin dosing were observed among physicians. Since automated recommendations by the Advisor Pro were similar to those given by physicians, it could be considered a useful tool to manage T1D.
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Diabetes Mellitus Tipo 1 , Médicos , Adolescente , Adulto , Inteligência Artificial , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes , Insulina , Sistemas de Infusão de Insulina , Masculino , Adulto JovemRESUMO
BACKGROUND: Type 2 diabetes (T2D) is correlated to amnestic mild cognitive impairment (aMCI) and to non-amnestic mild cognitive impairment (naMCI). This study evaluated whether the T2D variable characterizes a peculiar cognitive profile in elderly patients. Moreover, it explores the association between glycated hemoglobin levels (HbA1c), T2D duration, insulin and oral hypoglycemic agent treatment, and cognition in elderly diabetic patients. METHODS: Detailed neuropsychological battery was used to diagnose MCI subtypes. A total of 39 MCI subjects with T2D (T2D-MCI) and 37 MCI subjects without T2D (ND-MCI), matched for age, educational level, and Mini-Mental State Examination score, were included. RESULTS: ND-MCI performed worse in memory and language domains than T2D-MCI. The amnestic subtype is more frequent among ND-MCI and non-amnestic subtype in T2D-MCI. In T2D-MCI, high HbA1c levels correlate with episodic memory (immediate recall) and T2D duration. Some indexes of episodic memory (immediate recall), attention, and visual-spatial ability correlate with insulin treatment. CONCLUSIONS: An association between T2D and non-amnestic MCI is suggested. In the T2D-MCI group, significant associations between insulin treatment and memory (immediate recall), complex figure copy, and attention were found.
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Type 2 diabetes mellitus (T2DM) has a very high impact on quality of life as it is characterized by disabling complications. There is little evidence about taste alterations in diabetes. Since many individual factors are involved in the onset of diabetes, the purpose of our study is to search a possible link between diabetes and individual taste function. Thirty-two participants with T2DM and 32 volunteers without T2DM (healthy controls) were recruited. Four concentrations of each of the four basic tastes (sweet, sour, salty, bitter), and pure rapeseed oil and water, were applied with cotton pads to the protruded tongue, immediately posterior to its first third, either to the left or right side. The results showed significant differences between groups in the ability to recognize sour, bitter, sweet, and water. Taste scores were lower in subjects with T2DM than in healthy controls, and an age-related decline in taste function was found. The taste function reduction associated with T2DM was not related to gender, disease duration, and glycemic control. In conclusion, it can be hypothesized that a general alteration of taste function can lead patients with type 2 diabetes to search for foods richer in sugars, as in a vicious circle, thus decreasing the likelihood of remission of diabetes mellitus.
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Diabetes Mellitus Tipo 2/fisiopatologia , Paladar , Adolescente , Adulto , Idoso , Envelhecimento/fisiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Dieta para Diabéticos , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The aim of this study was to assess the in vitro effects of Syzygium cumini (L.) (Sc) incubation on platelets from patients with diabetes, in order to test its efficacy as a potential adjuvant therapy. This study was performed on 77 patients with diabetes [29 in good (DMgc) and 48 in poor glycemic control (DMpc)] and 85 controls. In patients, platelets were analyzed at recruitment and after in vitro Sc incubation (final concentration of 200 µg/ml for 3 hours at 37 °C), whereas in controls only basal evaluation was performed. Lipoperoxide and nitric oxide (NO) levels, superoxide dismutase (SOD) and Na(+)/K(+) ATPase activities, total antioxidant capacity (TAC), and membrane fluidity tested by anisotropy of fluorescent probes 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) and 1-6-phenyl-1,3,5-hexatriene (DPH) were determined. Collagen-induced platelet aggregation was also evaluated. In vitro Sc activity counteracts oxidative damage, by improving platelet function through augmented membrane fluidity and Na(+)/K(+) ATPase activity; it also enhances antioxidant system functionality by increasing NO levels, SOD activity, and TAC and by decreasing lipoperoxide levels both in whole samples and in DMgc and DMpc. In addition, a slight tendency towards collagen-induced platelet aggregation decrease after Sc was observed. However, all these parameters, even after improvement, did not reach the levels of control subjects. Our results suggest that Sc may have a preventive and protective effect in oxidative damage progression associated with diabetes mellitus and its complications. If our data will be confirmed, Sc supplementation might become a further tool in the management of this disease, especially in view of its easy availability, safety, low cost, and absence of side effects.
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Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Diabetes Mellitus/metabolismo , Suplementos Nutricionais , Exsudatos de Plantas/farmacologia , Syzygium/química , Adulto , Idoso , Antioxidantes/metabolismo , Biomarcadores , Estudos de Casos e Controles , Colágeno/metabolismo , Colágeno/farmacologia , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Estresse Oxidativo , Agregação Plaquetária , Testes de Função Plaquetária , ATPase Trocadora de Sódio-Potássio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Functional reach (FR) is a clinical measure, defined as the maximum distance one can reach, forward beyond arm's length, able to identify elderly subjects at risk of recurrent falls. Subjects, exhibiting the same FR can perform the motor task in different ways: a kinematic analysis of the FR, task can help to identify the motor strategy adopted. The FR test was applied to 17 diabetic non-neuropathic, (CTRL) and 37 neuropathic (DN) subjects. Motor strategies adopted were defined as: "hip" or "other" strategy; the latter included: "mixed" and "trunk rotation" strategies. Principal Component Analysis and non-parametric statistical tests were used to study the different execution modalities of the FR test. Results show that, in CTRL, the most important parameters are those related to trunk flexion in the sagittal plane. Instead, for DN, the main features are related not only to trunk flexion but also to trunk rotation in the transverse plane. Percentages of subjects who used "hip" or "other" strategies are similar for CTRL and DN subjects. However, within the "other" strategy group, the percentage of DN that used a "trunk rotation" strategy was much higher than for CTRL. Results show that individuals, although exhibiting the same reaching distance, adopt different movement strategies. Consequently it is important to evaluate the kinematic behaviour and not only the clinical measure, because the evaluation of the motor strategy might be useful in the early detection of subjects at risk of postural instability.
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Diabetes Mellitus/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Movimento/fisiologia , Equilíbrio Postural/fisiologia , Acidentes por Quedas , Idoso , Braço/fisiologia , Fenômenos Biomecânicos , Estudos de Casos e Controles , Feminino , Quadril/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Medição de Risco , Tronco/fisiologiaRESUMO
BACKGROUND AND AIM: Type 2 diabetic (T2DM) patients show decreased fibrinolysis, mainly linked to high plasminogen activator inhibitor type 1 (PAI-1) production, together with a reduced bioavailability of nitric oxide and an impairment in Na(+)/K(+)-ATPase activity possibly involved in increased cardiovascular risk. Vitamin E is the major natural lipid-soluble antioxidant in human plasma. The present work was conducted in order to measure PAI-1, ICAM and VCAM-1 plasma levels, platelet nitric oxide production and membrane Na(+)/K(+)-ATPase activity in type 2 diabetic subjects treated with vitamin E (500 IU/day) for 10 weeks and then followed for other 20 weeks. METHODS AND RESULTS: Thirty-seven T2DM patients (24 males and 13 females) were studied. None of them were affected by any other disease or diabetic complications. Significant differences were detected for PAI-1 antigen (p<0.001), PAI-1 activity (p<0.001), nitric oxide (NO) production (p<0.001), and Na(+)/K(+)-ATPase activity (p<0.001) among the 4 phases of the study. A significant decrease both in ICAM and VCAM-1 plasma levels was also found at the 10th week compared with baseline (respectively p<0.001 and p<0.05). CONCLUSION: Our data suggest that vitamin E counteracts endothelial activation in T2DM patients possibly representing a new tool for endothelial protection.
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Antioxidantes/uso terapêutico , Plaquetas/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Óxido Nítrico/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Vitamina E/uso terapêutico , Idoso , Antioxidantes/farmacologia , Plaquetas/enzimologia , Plaquetas/metabolismo , Diabetes Mellitus Tipo 2/sangue , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Feminino , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Pessoa de Meia-Idade , ATPase Trocadora de Sódio-Potássio/sangue , Fatores de Tempo , Resultado do Tratamento , Molécula 1 de Adesão de Célula Vascular/sangue , Vitamina E/farmacologiaRESUMO
BACKGROUND AND AIM: Three NOS isoforms are responsible for nitric oxide production in various tissues. Endothelial constitutive NOS is expressed in vascular endothelium and in platelets, contributing to vascular tone regulation and platelet aggregation. The aim of the present work was to examine eNOS polymorphism, to find a correlation with platelet NO production and degree of insulin resistance (IR) in non-diabetic subjects and in patients affected by type 2 diabetes. METHODS AND RESULTS: Seventy-one non-diabetic subjects and 37 patients affected by Type 2 diabetes were recruited. The subjects were subdivided into 3 groups as cut-off for the definition of an insulin resistant state: IR non-diabetic subjects, insulin sensitive subjects, and insulin-resistant patients affected by Type 2 diabetes. Plasma glyco-metabolic parameters, platelet nitric oxide production, endothelial nitric oxide synthase (eNOS) gene polymorphism were measured in all subjects enrolled. Significant differences between groups were found in BMI, fasting glycaemia, fructosamine and HbA(1c), triglycerides and HDL cholesterol levels. Evaluating all the subjects, platelet NO production was significantly related with BMI, waist circumference, and triglycerides concentrations, thus suggesting an association between increased platelet NO production, obesity and hypertriglyceridemia, independent of the degree of insulin-resistance. CONCLUSION: The modified platelet NO synthesis does not seem to be due to eNOS Glu298Asp polymorphism, while it can be hypothesized that it is caused by an iNOS induction, present in obesity, hypertriglyceridemia and in type 2 diabetes.
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Plaquetas/fisiologia , Hipertrigliceridemia/sangue , Resistência à Insulina/genética , Óxido Nítrico/sangue , Obesidade/sangue , Adulto , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/genética , Teste de Tolerância a Glucose , Humanos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/enzimologia , Hipertrigliceridemia/genética , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/genética , Obesidade/complicações , Obesidade/enzimologia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Valores de ReferênciaRESUMO
The aim of the present study was to investigate if aging is associated with platelet membrane modifications possibly related with cellular activation and hyperaggregability and if platelets from centenarians show different properties which might play a role in successful aging and longevity. Platelet plasma membranes were obtained from 60 healthy subjects, divided into four groups according to the age range: (1) 21-39 years; (2) 40-59 years; (3) 60-79 years; (4) centenarians (>/=100 years). Both centenarians and control subjects were submitted to the following inclusion criteria: liver, kidney, and thyroid function tests within the normal range; absence of history of diabetes, hypertension or coronary heart disease; no signs of edema or dehydration; no drug or vitamin supplement in the 4 weeks before the study; absence of Alzheimer's disease or secondary dementia. The following determinations were performed: lipid peroxide levels (Lp) evaluated by the measurement of thiobarbituric acid (TBA) reactivity, fluidity studied by the fluorescence anisotropy of the probe 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), Na(+)/K(+)-ATPase activity measured by the method of Kitao and Hattori, and sialic acid (SA) content evaluated by the periodate-thiobarbituric acid method. Centenarians showed: (i) Lp concentrations lower than elderly subjects; (ii) increased Na(+)/K(+)-ATPase activity compared with adult and elderly subjects; (iii) higher TMA-DPH anisotropy than elderly subjects; (iv) SA content similar to the young and adult groups.The present work found deep platelet membrane modifications in centenarians compared with elderly subjects. These changes are likely associated with a decreased platelet activation and therefore might exert a protective role against cardiovascular accidents, as platelet activation is a key event in the initiation and progression of arteriosclerosis.