RESUMO
AIMS: A self-management oriented education programme (MEDIAS 2 BSC) for people with Type 2 diabetes who are on a non-intensive insulin treatment regimen was developed. In a randomized, multi-centre trial, the effect of MEDIAS 2 BSC was compared with an established education programme that acted as a control group. METHODS: The primary outcome was the impact of MEDIAS 2 BSC on glycaemic control. Secondary outcomes included the incidence of severe hypoglycaemia, hypoglycaemia unawareness, diabetes-related distress, diabetes knowledge, quality of life and self-care behaviour. RESULTS: In total, 182 participants were randomized to the control group or MEDIAS 2 BSC [median age 64.0 (interquartile range 58.0-68.5) vs. 63.5 (57.0-70.0) years; HbA1c 62.8 ± 12.7 mmol/mol vs. 63.7 ± 14.0 mmol/mol; 7.9% ± 1.2% vs. 8.0% ± 1.3%]. After a 6-month follow-up, there was a mean decrease in HbA1c of 3.5 mmol/mol (0.32%) in the control group and 6.7 mmol/mol (0.61%) in MEDIAS 2 BSC. After adjusting for baseline differences and study centre, the mean difference between the groups was -3.3 mmol/mol [95% confidence interval (CI) -0.54 to -5.90 mmol/mol] [-0.30% (95% CI -0.05 to -0.54)] in favour of MEDIAS 2 BSC (P = 0.018). There were no increases in severe hypoglycaemia or hypoglycaemia unawareness. The education programmes had no significant effects on psychosocial outcome variables. CONCLUSION: MEDIAS 2 BSC was more effective in lowering HbA1c than the control condition. MEDIAS 2 BSC is a safe educational tool that improves glycaemic control without increasing the risk for hypoglycaemia. (Clinical Trials Registry No; NCT 02748239).
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Educação de Pacientes como Assunto , Autogestão/educação , Idoso , Terapia Combinada/efeitos adversos , Efeitos Psicossociais da Doença , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Relação Dose-Resposta a Droga , Seguimentos , Alemanha/epidemiologia , Hemoglobinas Glicadas/análise , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemia/fisiopatologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Incidência , Insulina/administração & dosagem , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Qualidade de Vida , Fatores de Risco , Autorrelato , Índice de Gravidade de DoençaRESUMO
AIMS: To compare the properties of the two most commonly used assessment tools for diabetes distress, the Problem Areas in Diabetes Scale (PAID) and the Diabetes Distress Scale (DDS), in order to discriminate their psychometric capabilities and functions. METHODS: Six hundred and twenty-eight people with diabetes (67% Type 1, 33% Type 2) were cross-sectionally assessed with the PAID, the DDS and further self-report scales regarding coping, quality of life, depressive symptoms and self-care, and medical data were gained. We analysed the PAID and DDS for areas of contentual/psychometric divergence in assessing diabetes distress and compared their associations with criteria of interest. RESULTS: Content analysis: The PAID covers a greater variety of emotional concerns and shows a stronger focus on food-related problems and complications. The DDS is more reflective of physician-related distress and problems concerning diabetes self-management. Psychometric analysis: Exploratory factor analyses revealed four-factor structures of both scales, explaining 60% (PAID) and 67% (DDS) of variance. Confirmatory factor analyses confirmed that single-factor and four-factor models fit the data. Total scales proved high and subscales mostly satisfactory reliability. Associations with criteria of interest: The PAID was significantly more strongly associated with dysfunctional coping styles, quality of life and depressive symptoms. The DDS showed significantly stronger associations with diabetes self-care and metabolic outcomes. CONCLUSION: Our results support both PAID and DDS as good self-report measures of diabetes distress. The observed contentual/psychometric differences suggest that a justified choice with regard to the intended clinical or scientific purpose can improve the acquisition of the required data.
Assuntos
Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 2/psicologia , Estresse Psicológico/diagnóstico , Adaptação Psicológica , Adolescente , Adulto , Idoso , Depressão/diagnóstico , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Humanos , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Psicometria , Qualidade de Vida , Autocuidado , Autorrelato , Inquéritos e Questionários , Adulto JovemRESUMO
AIM: To investigate the longitudinal bi-directionality of diabetes-related distress and depressive symptoms. METHODS: A total of 509 patients receiving intensified insulin therapy completed the Centre for Epidemiological Studies Depression scale questionnaire for the assessment of depressive symptoms as well as the Problem Areas in Diabetes questionnaire for the assessment of diabetes-related distress at baseline and at 6-month follow-up. Separate logistic and linear regression analyses for incidence and persistence were performed with demographic (age, gender, BMI) and medical (diabetes type, HbA1c , diabetes duration, late complications) control variables. RESULTS: Diabetes-related distress at baseline increased the risk of the incidence of elevated depressive symptoms by 2.56-fold (odds ratio 2.56; 95% CI 1.15-5.72; P = 0.02) when controlling for demographic and medical variables. In addition, diabetes-related distress at baseline doubled the chance of the persistence of elevated depressive symptoms (odds ratio 2.04, 95% CI 1.04-3.99; P = 0.04) when controlling for demographic and medical variables. The chance of having persistent elevated diabetes-related distress was increased 5.94-fold (odds ratio 5.94, 95% CI 2.60-13.59; P < 0.0001) when elevated depressive symptoms were present at baseline. None of the medical variables had an influence on incidence or persistence. CONCLUSIONS: Diabetes-related distress was identified as a risk factor for the incidence and persistence of depressive symptoms. Reducing diabetes-related distress could help to prevent the development of elevated depressive symptoms. Furthermore, depressive symptoms were identified as an amplifier for diabetes-related distress. Diabetes-related distress and depressive symptoms were independent risk factors for each other and should be monitored in routine care to disentangle their influence.
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Depressão/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/psicologia , Adulto , Idoso , Depressão/complicações , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Escalas de Graduação PsiquiátricaRESUMO
AIMS: To estimate the associations between insufficient diabetes acceptance and relevant diabetes outcomes. METHODS: A total of 320 patients completed questionnaires on diabetes non-acceptance (the Acceptance and Action Diabetes Questionnaire), diabetes distress (the Problem Areas in Diabetes Scale), depressive mood (the Center for Epidemiologic Studies Depression Scale), coping with illness (the Freiburg Questionnaire of Coping with Illness), self-care activities (the Summary of Diabetes Self-Care Activities Measure) and quality of life (the Short Form-36 Health Questionnaire). A six-item version of the Acceptance and Action Diabetes Questionnaire showing good reliability and validity was established, and the associations between insufficient acceptance and clinical outcomes were estimated. RESULTS: Higher diabetes non-acceptance correlated significantly with less active coping (-0.37), reduced self-care (-0.43) and higher HbA1c levels (0.31), higher diabetes distress (0.53) and more depressive symptoms (0.36). Correlations of diabetes non-acceptance with diabetes self-care/glycaemic control were significantly higher than were those of depressive mood or diabetes distress with these criteria. CONCLUSIONS: Low diabetes acceptance is associated with impaired self-care and glycaemic control. Assessment of diabetes acceptance may facilitate the detection of patients at high risk and may present an essential target for treatments to improve diabetes control that is more relevant than elevated depressive mood or diabetes distress.
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Atitude Frente a Saúde , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Cooperação do Paciente , Autocuidado , Adaptação Psicológica , Adulto , Terapia Combinada/psicologia , Depressão/epidemiologia , Depressão/prevenção & controle , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/psicologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Autocuidado/psicologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/prevenção & controle , Inquéritos e QuestionáriosRESUMO
Feed efficiency is an important trait of dairy production. However, assessing feed efficiency is constrained by the associated cost and difficulty in measuring individual feed intake, especially on pastures. The objective of this study was to investigate short-term feed efficiency traits of herbage-fed dairy cows and screening of potential biomarkers (n = 238). Derived feed efficiency traits were ratio-based (i.e., feed conversion ratio (FCR) and N use efficiency (NUE)) or residual-based (i.e., residual feed intake (RFI), residual energy intake (REI), and residual N intake (RNI)). Thirty-eight Holstein and 16 Swiss Fleckvieh dairy cows underwent a 7-d measurement period during mid- and/or late-lactation. The experimental data (n = 100 measurement points) covered different lactational and herbage-fed system situations: mid-lactation grazing (n = 56), late-lactation grazing (n = 28), and late-lactation barn feeding (n = 16). During each measuring period, the individual herbage intake of each cow was estimated using the n-alkane marker technique. For each cow, biomarkers representing milk constituents (n = 109), animal characteristics (n = 13), behaviour, and activity (n = 46), breath emissions (n = 3), blood constituents (n = 35), surface, and rectal temperature (n = 29), hair cortisol (n = 1), and near-infrared (NIR) spectra of faeces and milk (n = 2) were obtained. The relationships between biomarkers and efficiency traits were statistically analysed with univariate linear regression and for NIR spectra using partial least squares regression with feed efficiency traits. The feed efficiency traits were interrelated with each other (r: -0.57 to -0.86 and 0.49-0.81). The biomarkers showed varying R2 values in explaining the variability of feed efficiency traits (FCR: 0.00-0.66, NUE: 0.00-0.74, RFI: 0.00-0.56, REI: 0.00-0.69, RNI: 0.00-0.89). Overall, the feed efficiency traits were best explained by NIR spectral characteristics of milk and faeces (R2: 0.25-0.89). Biomarkers show potential for predicting feed efficiency in herbage-fed dairy cows. NIR spectra data analysis of milk and faeces presents a promising method for estimating individual feed efficiency upon further validation of prediction models. Future applications will depend on the ability to improve the robustness of biomarkers to predict feed efficiency in a greater variety of environments (locations), managing conditions, feeding systems, production intensities, and other aspects.
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Ração Animal , Biomarcadores , Lactação , Leite , Animais , Bovinos/fisiologia , Feminino , Ração Animal/análise , Biomarcadores/análise , Leite/química , Leite/metabolismo , Indústria de Laticínios/métodos , Dieta/veterinária , Ingestão de Alimentos , Fenômenos Fisiológicos da Nutrição Animal , Ingestão de EnergiaRESUMO
OBJECTIVE: To determine the efficacy and safety of linagliptin in initial combination with metformin in patients with type 2 diabetes. METHODS: This 1-year randomised, double-blind study was an extension of a 6-month randomised controlled trial, in which adults with type 2 diabetes received one of six treatment regimens (linagliptin 2.5 mg plus metformin 500 mg bid, linagliptin 2.5 mg plus metformin mg 1000 bid, metformin 1000 mg bid, metformin 500 mg bid, linagliptin 5 mg qd or placebo). In the extension, patients in the first three treatment groups continued their regimen (non-switched group, n = 333) while the metformin 500 mg bid, linagliptin 5 mg qd and placebo groups were re-randomised to one of the three continuing regimens (switched group, n = 233). RESULTS: All three non-switched groups maintained reductions in glycosylated haemoglobin (HbA1c; mean ± standard deviation reductions across the 1.5-year period: linagliptin 2.5 plus metformin 1000 bid, -1.63 ± 1.05%; linagliptin 2.5 plus metformin 500 bid, -1.32 ± 1.06%; metformin 1000 bid, -1.25 ± 0.91%) while the switched groups showed additional HbA1c reductions. During the extension, there were no clinically meaningful changes in body weight in any group. Adverse event rates were similar between groups, with most events being mild or moderate, and the incidence of investigator-defined hypoglycaemia was low, with no severe events. DISCUSSION: Initial combination of linagliptin and metformin was well tolerated over the 1-year extension period, with low risk of hypoglycaemia, and improved glycaemic control vs. metformin alone. CONCLUSION: The initial combination of linagliptin and metformin appears to provide a useful treatment option in patients whose blood glucose levels are increased to an extent that metformin monotherapy may not achieve treatment targets.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Purinas/administração & dosagem , Quinazolinas/administração & dosagem , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Linagliptina , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Purinas/efeitos adversos , Quinazolinas/efeitos adversos , Resultado do TratamentoRESUMO
After subcutaneous injection, IDeg self-associates to form multihexamer chains that slowly dissociate into monomers. This results in a duration of action of more than 42 hours as well as a smooth level action profile with low intra-individual variability. Pharmacokinetic studies foun IDeg to have a half-life of approximately 25 hours which is considerably longer than that from other current insulin formulations. Based on these properties, IDeg demonstrated low risk for nocturnal hypoglycaemic events in the clinical study program. Concurrently, phase 3 studies have provided evidence for a non-inferior glucose lowering effect when compared to other currently available basal insulin formulations. Moreover, the long duration of action suggests a flexible handling which could be better adapted to patients' needs in daily routine. This article gives an overview of the mechanism of action of IDeg and the latest results from phase 2 and phase 3 studies.
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Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina de Ação Prolongada/uso terapêutico , Disponibilidade Biológica , Glicemia/metabolismo , Ensaios Clínicos Fase III como Assunto , Preparações de Ação Retardada , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Esquema de Medicação , Meia-Vida , Humanos , Injeções Subcutâneas , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/farmacocinéticaRESUMO
Diabetes and periodontitis are chronic diseases with an increasing prevalence in the German population. There is a bi-directional relationship between both diseases. Diabetes promotes the occurrence, the progression and the severity of periodontitis. Periodontitis complicates the glycemic control of diabetes, increases the risk of diabetes-associated complications and possibly even of its onset. In view of the existing evidence, that is still not sufficiently communicated within the medical community, an expert panel consisting of four diabetologists and four periodontists has addressed the following questions: What is the effect of diabetes mellitus on periodontitis and on periodontal therapy? What is the effect of periodontitis on diabetes mellitus? What are the practical consequences, that result for interdisciplinary treatment strategies? The treatment of periodontal infections should become an integral part of the management of diabetes, whereas glycemic control is a prerequisite for successful periodontal therapy.
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Diabetes Mellitus/epidemiologia , Diabetes Mellitus/fisiopatologia , Periodontite/epidemiologia , Periodontite/fisiopatologia , Comorbidade , Humanos , Medição de Risco , Fatores de RiscoRESUMO
Nine expert drivers operated an instrumented vehicle in tests over a highway at night after being treated with diazepam (5 and 10 milligrams), a placebo, and nothing. They reacted to 10 milligrams of diazepam with increased lateral position variability. Potentially dangerous impairment was inferred from the reactions of some subjects.
Assuntos
Condução de Veículo , Diazepam/farmacologia , Atividade Motora/efeitos dos fármacos , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Lateralidade Funcional , Humanos , Masculino , PlacebosRESUMO
BACKGROUND: This randomized crossover trial examines the effect of continuous glucose monitoring (CGM) with real-time access (RTA) to glucose data versus CGM with a retrospective analysis (RA) of glucose data regarding satisfaction with CGM and other patient-reported outcomes. METHODS: Participants used the CGM device (GlucoDay, Menarini Diagnostics, Florence, Italy) twice. In one study phase, patients were allowed RTA to, and in the other phase RA of, current glucose values. The order of these two conditions was randomized. At baseline and after the first and second trials, subjects completed questionnaires (Continuous Glucose Monitoring Satisfaction Scale) about perceived satisfaction with CGM. They also completed the Problem Areas in Diabetes Questionnaire, a state anxiety scale (State-Trait Anxiety Inventory), and a depression scale (Center of Epidemiological Studies-Depression Scale). RESULTS: Fifty patients with type 1 diabetes (41.7 +/- 12.3 years old, diabetes duration of 14.75 +/- 11.9 years, 48% female, hemoglobin A1c 8.1 +/- 1.5%, years of education 10.3 +/- 2.1 years) participated in this study. At baseline patients perceived CGM as rather advantageous, but after RA and RTA the perceived benefits were reduced (baseline, 101.0 +/- 16.0; RA, 95.7 +/- 20.2; RTA, 93.6 +/- 22.8; P < 0.01). However, there was no significant difference between RA and RTA. Also, there was no significant effect on diabetes-related distress or state anxiety, but a positive effect on depression scores. CONCLUSIONS: There was no specific, significant, negative or positive effect of RA versus RTA on satisfaction with CGM. Exposing patients with type 1 diabetes to their current glucose values does not seem to have a specific negative impact on the appraisal of CGM or more generic patient-reported outcomes.
Assuntos
Glicemia/análise , Diabetes Mellitus/sangue , Diabetes Mellitus/psicologia , Monitorização Ambulatorial/métodos , Satisfação do Paciente , Atividades Cotidianas , Técnicas Biossensoriais , Estudos Cross-Over , Humanos , Microdiálise/métodos , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
A shared-care system should be established to treat diabetic foot wounds. This means including different professions and institutions to optimize the treatment of these patients in respect of medical, psychological and social aspects. This procedure is very well described in the national guidelines of treatment of type 2 diabetes to prevent and treat diabetic foot complications. In the treatment of the diabetic foot syndrome the establishment of such a shared-care system has to recognize the wound classification and the underlying risk of patients. In this article the stage-adjusted approach and the duties of the different levels of responsibility are described.
Assuntos
Pé Diabético/prevenção & controle , Pé Diabético/terapia , Equipe de Assistência ao Paciente/organização & administração , Programas Médicos Regionais/organização & administração , Alemanha , HumanosRESUMO
INTRODUCTION: This study investigates the impacts of experimentally induced hypoglycemia and different insulin infusion rates on feelings of hunger. METHODS: Blood glucose and insulin levels were manipulated by hyperinsulinemic glucose clamp technique. Participants were 16 patients with type 1 diabetes (age 36.2+/-11.7 yrs, diabetes duration 9.0+/-6.3 yrs, HbA1c 8.2+/-2.0%). One group (n=8) received moderate, constant insulin infusion (0.8 microU/kg/min), whereas the insulin infusion was doubled in the other group (1.6 microU/kg/min). Blood glucose was lowered stepwise from euglycemia (5.6 mmol/l) to moderate hypoglycemia (2.5 mmol/l). RESULTS: As expected, there was a significant effect of hypoglycemia on feelings of hunger (F (3, 42)=41.7, p<0.01). But during high insulin infusion, feelings of hunger were significantly less intense than during moderate insulin infusion (F (1, 14)=7.2, p=0.02). CONCLUSION: Peripheral insulin levels seem to be associated with the intensity of feelings of hunger.
Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Fome/efeitos dos fármacos , Hipoglicemia/induzido quimicamente , Insulina/administração & dosagem , Adulto , Glicemia/análise , Glicemia/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sistema Endócrino/fisiopatologia , Feminino , Humanos , Hipoglicemia/fisiopatologia , Insulina/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: In general, stable type B ankle fractures are treated conservatively with cast immobilization or a walking boot during six weeks. Some disadvantages of casting are joint stiffness, muscle wasting and lack of comfort. This study was designed to evaluate whether functional treatment with a removable brace is a safe and more comfortable alternative. MATERIAL AND METHODS: Randomized controlled trial. In the period March 2013 - May 2015, 44 patients visiting the emergency department due to a stable type B ankle fracture were included. During the first week both groups received a splint. After one week the patients were randomized: one group received a cast, the other a removable brace. For outcome Olerud & Molander Ankle Score, Visual Analogue Score for comfort and pain, American Academy of Orthopaedic Surgeons (AAOS) Foot and Ankle score questionnaire, EuroQol-5D and range of motion were used. RESULTS: 44 patients participated (21 cast, 23 brace). There were no differences in baseline characteristics. After 6 weeks, VAS for comfort (cast vs brace; 5.74 vs 7.21; pâ¯=â¯0.02) and total range of motion (40° vs 49°; pâ¯=â¯0.00) showed significant differences in favour of the brace. VAS pain (3.15 vs 2.05; pâ¯=â¯0.16), OMA-score (51.75 vs 61.32; pâ¯=â¯0.22) en EuroQoL-5D (7.26 vs 6.74; pâ¯=â¯0.33) did not show significant differences. Week 52 showed no significant differences at OMA-score (89.29 vs 96.18; pâ¯=â¯0.16), EuroQoL-5D (6.00 vs 5.35; pâ¯=â¯0.15), VAS pain (1.07 vs 0.82; pâ¯=â¯0.69) and AAOS score (91.71 vs 96.06; pâ¯=â¯0.21). No complications occurred in both groups. CONCLUSION: Functional bracing showed significant differences for the VAS comfort score and range of motion at 6 weeks compared to casting. After a year no significant differences were found. Treatment with a brace is a safe and more comfortable option for stable type B ankle fractures.
Assuntos
Fraturas do Tornozelo/reabilitação , Articulação do Tornozelo/fisiopatologia , Braquetes , Moldes Cirúrgicos , Fixação Interna de Fraturas/reabilitação , Amplitude de Movimento Articular/fisiologia , Recuperação de Função Fisiológica/fisiologia , Adolescente , Adulto , Idoso , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/fisiopatologia , Fraturas do Tornozelo/cirurgia , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Cuidados Pós-Operatórios , Radiografia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Diabetic endotheliopathy is the result of hyperglycemia and the production of oxygen-free radicals. In vitro and in vivo data have shown beneficial effects of dexlipotam (DEX), a tromethamine salt of R(+)-alpha-lipoic acid, on oxidative stress in hyperglycemic states, but no data are available on the effects of this agent on endothelial function. The purpose of this pilot study was to evaluate the impact of DEX on endothelial function in patients with type 2 diabetes (DM2) and to estimate the safety and tolerability of DEX. MATERIAL AND METHODS: DEX 960 mg and DEX 1,920 mg were investigated in DM2 patients over a period of 4 weeks using a randomized, placebo- (PLA) controlled, double-blinded study with 3 parallel groups. The marker of arterial function after 4-week therapy with DEX was the maximum percentage change versus baseline in the flow-mediated dilation of the brachial artery (FMD) after reperfusion. RESULTS: A total of 114 diabetic patients were randomized to the three study groups. DEX was safe and well tolerated. Dyspepsia appeared to be the most relevant side effect of DEX treatment. Systolic (p = 0.078) and diastolic blood pressure (p = 0.059) tended to be lower in patients treated with DEX at a dose of 1,920 mg. There were no significant differences in FMD between the placebo- and the DEX-treated groups. In patients with poorer glucose control (HbA1c > 6.5% Hb), FMD increased significantly after 4-week treatment with DEX: PLA -1.51 +/- 2.98%, DEX 960 mg +1.22 +/- 3.22, p = 0.027, DEX 1,920 mg +1.47 +/- 3.78, p= 0.012. The magnitude of the mean change compared to placebo was 2.73% (DEX 920) and 2.98% (DEX 1,920) in patients with HbAlc > 7.5% Hb (DEX 960, p = 0.007, DEX 1,920, p = 0.032). The effects of treatment were usually statistically significant in subgroups with more severe vascular stress (longer duration of disease, pretreatment history, higher LDL-C, higher blood pressure). CONCLUSION: DEX therapy appears to reduce endothelial dysfunction in DM2, especially in men with long history of DM2 and having poor glucose control. These findings will be useful in patient selection in future prospective clinical trials with drugs to treat vascular stress.
Assuntos
Antioxidantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ácido Tióctico/uso terapêutico , Trometamina/uso terapêutico , Vasodilatação/efeitos dos fármacos , Adulto , Idoso , Antioxidantes/efeitos adversos , Velocidade do Fluxo Sanguíneo , Artéria Braquial/efeitos dos fármacos , Artéria Braquial/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Método Duplo-Cego , Combinação de Medicamentos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Tióctico/efeitos adversos , Trometamina/efeitos adversosRESUMO
BACKGROUND: This study was designed to assess clinical performance and patients' acceptance of the minimally invasive microdialysis-based continuous glucose monitoring system Gluco- Day() (Menarini Diagnostics, Florence, Italy) with a targeted monitoring time of 48 h. METHODS: An inpatient sample of 28 patients with diabetes was studied. The analysis of clinical performance was performed using mean absolute differences (MAD) (in percent), Pearson correlations, the Bland-Altman analysis, and Clarke Error Grid Analysis (EGA). GlucoDay glucose values were compared with laboratory standard blood glucose measurements (glucohexokinase assay). The patients' acceptance of the monitoring device was assessed via two self-report scales (pain during application and discomfort while wearing device). RESULTS: A mean (+/- SD) monitoring time of 45.7 +/- 3.3 h with a total of 484 paired readings could be achieved. A correlation of r (average) = 0.91 and a MAD of 19.9% indicated satisfactory to good clinical performance. Of the paired readings, 95.5% fell into the acceptable A and B zones of the EGA. Rather wide 95% limits of agreement were revealed in the Bland-Altman analysis. Whereas virtually no pain was experienced during sensor application, discomfort associated with wearing the device was rather high. All of the participants, however, stated that they would wear the device again. CONCLUSIONS: Satisfactory to good performance of the GlucoDay monitor was observed, indicating the device to be suitable for routine clinical use. In particular, however, the discomfort experienced during wearing requires further improvements in its usability.
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Técnicas Biossensoriais/instrumentação , Automonitorização da Glicemia/instrumentação , Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Microdiálise/instrumentação , Satisfação do Paciente , Adulto , Automonitorização da Glicemia/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
INTRODUCTION: There is an established role of clinical risk factors such as arterial hypertension and smoking in causing cardiovascular morbidity and diabetic nephropathy (DNP). Genetic factors increase the risk for DNP. To examine the genetic risk, we initiated a case-control study with predefined follow-up examinations. We describe the study design and baseline characteristics under special consideration of comedication, and give preliminary results of the 4-year follow-up. METHODS: We enrolled all 477 patients with DNP receiving maintenance hemodialysis in 30 centers in Southern Germany between August 1999 and January 2000. As controls, we enrolled all 482 diabetes mellitus type 2 patients without urinary microalbuminuria in two examinations on consecutive days and without other signs of renal disease in a large diabetes clinic from September 2000 to September 2001. Follow-up examinations are performed 4 and 6 years after inclusion by questionnaire and telephone interview to determine mortality and new morbidity. Controls progressing to novel DNP at follow-up, as defined by semiquantitative dipstick urinary albumin/creatinine ratio > 30 mg/g, are defined as cases in the study's nested case control component. RESULTS: At study inclusion in cases and controls, respectively, mean age was 67.3 +/- 8.2 and 58.1 +/- 11.2 years and duration of diabetes mellitus was 15.6 +/- 9.6 (at dialysis initiation) and 11.0 +/- 8.6 years. 328 controls (of which 25 had died and 14 did not perform urinalysis) were subjected to follow-up at 4 years, at a mean of 3.5 +/- 0.8 years after inclusion. 51.2% (n = 148) of living controls remained normalbuminuric, 33.9% (n = 98) had microor macroalbuminuria, and in 14.9% (n = 43) the dipstick test was inconclusive. There was no significant difference in progression to micro- or macroalbuminuria between controls treated with ACE or AT-2 inhibitors at baseline or not. Renal function as estimated by the abbreviated MDRD formula declined from 86.8 +/- 21.0 to 82.5 +/- 22.3 ml/min/1.73 m2 (p < 0.001). The decline was significant in patients on ACE or AT-2 inhibitors at baseline and not in patients without such medication at baseline. DISCUSSION: GENDIAN is a large case-control study designed to evaluate clinical and genetic determinants of DNP and other complications of long-standing diabetes mellitus type 2. We observed an association of ACE or AT-2 inhibitor therapy with cardiovascular comorbidity and a significant decline in renal function after a 4-year follow-up.
Assuntos
Albuminúria/prevenção & controle , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/terapia , Fatores Etários , Idoso , Albuminúria/epidemiologia , Albuminúria/mortalidade , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Estudos de Casos e Controles , Comorbidade , Creatinina/urina , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/genética , Progressão da Doença , Quimioterapia Combinada , Feminino , Seguimentos , Predisposição Genética para Doença/genética , Alemanha/epidemiologia , Humanos , Masculino , Diálise Renal , Fatores Sexuais , Inquéritos e Questionários , Taxa de SobrevidaRESUMO
BACKGROUND: Angiotensin II has been shown to induce the synthesis of endothelium-derived relaxing factor nitric oxide (NO) and endothelin in vitro. In human beings, to our knowledge, no data on NO release in response to angiotensin II and on the influence of angiotensin II type 1 receptor blockade have been published. METHODS: In a placebo-controlled study in nine healthy volunteers, angiotensin II was administered intravenously for 6 hours with and without pretreatment with valsartan, a specific angiotensin II type 1 receptor antagonist. NO (NO2 + NO3) and endothelin plasma concentrations, clearance values for inulin and paraaminohippuric acid and NO (NO2 + NO3) excretion in urine were determined. RESULTS: During angiotensin II infusion NO plasma concentrations remained unaltered compared with placebo after 3 hours: 6.66 +/- 5.49 versus 5.56 +/- 3.09 micromol/L (P = ns) but increased after 6 hours: 18.36 +/- 20.02 versus 7.13 +/- 3.87 micromol/L (P < .04). The same was noted after pretreatment with valsartan: 7.61 +/- 5.69 versus 5.56 +/- 3.09 micromol/L (P= ns) after 3 hours, and 21.70 +/- 11.51 versus 7.13 +/- 3.87 micromol/L (P = .02) after 6 hours. In urine fractional NO excretion decreased after angiotensin II infusion: 0.87 +/- 0.72 versus 0.95 +/- 0.71 (P = .5) during the first 3 hours, and 0.44 +/- 0.39 versus 0.78 +/- 0.43 (P = .01) during the following 3 hours. After valsartan pretreatment the decrease in fractional urinary NO excretion began earlier: 0.40 +/- 0.15 versus 0.95 +/- 0.71 (P = .04) during the first 3 hours, and 0.17 +/- 0.11 versus 0.78 +/- 0.43 (P = .01) during the following 3 hours. Endothelin plasma concentrations showed no difference after angiotensin II infusion with or without valsartan. CONCLUSIONS: Our observations demonstrate for the first time that angiotensin II increases NO plasma concentrations in human beings and that this response is not mediated by angiotensin II type 1 receptor. In spite of increased NO plasma levels, urinary NO excretion decreased. Endothelin plasma levels remained unchanged during angiotensin II infusion.
Assuntos
Angiotensina II/farmacologia , Antagonistas de Receptores de Angiotensina , Anti-Hipertensivos/farmacologia , Endotelinas/sangue , Óxido Nítrico/metabolismo , Tetrazóis/farmacologia , Valina/análogos & derivados , Adulto , Angiotensina II/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Humanos , Infusões Intravenosas , Masculino , Óxido Nítrico/sangue , Óxido Nítrico/urina , Receptor Tipo 1 de Angiotensina , Receptor Tipo 2 de Angiotensina , Valina/farmacologia , ValsartanaRESUMO
The purpose of this study was to investigate the effect of fluvastatin on the microcirculation of patients with hyperlipidaemia (low-density lipoprotein cholesterol > 160 mg/dL, triglycerides < 350 mg/dl) inadequately controlled by diet. After a dietary run-in of 4 weeks, patients were randomised in a double-blind study to receive fluvastatin 40 mg twice daily (n = 24) or placebo (n = 24) for 12 weeks. The effect on microcirculation was assessed using capillary microscopy and laser Doppler fluxmetry at the nailfold at baseline and at 6 and 12 weeks after initiation of therapy. Capillaroscopy showed that fluvastatin improved microcirculation, i.e. time to peak flow during postocclusive reactive hyperaemia dropped from 19.7 +/- 7.2 s at baseline to 12.3 +/- 9.5 s at week 6 (P < 0.01) and 10.6 +/- 6.5 s at week 12 (P < 0.0001). These results were confirmed using laser Doppler fluxmetry to study microcirculation in thermoregulatory capillaries at the same site. A significant decrease in total and LDL-cholesterol was achieved during fluvastatin therapy. In conclusion, fluvastatin therapy improves microcirculation in nutritive as well as thermoregulatory capillaries in hypercholesterolaemic patients within 6 weeks.
Assuntos
Anticolesterolemiantes/uso terapêutico , Ácidos Graxos Monoinsaturados/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Indóis/uso terapêutico , Microcirculação/efeitos dos fármacos , Anticolesterolemiantes/farmacologia , Arteriosclerose/epidemiologia , Arteriosclerose/prevenção & controle , Proteínas Sanguíneas/análise , Capilares/ultraestrutura , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Método Duplo-Cego , Ácidos Graxos Monoinsaturados/farmacologia , Fluvastatina , Hemostasia/efeitos dos fármacos , Homocisteína/sangue , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hiperemia/fisiopatologia , Hiperlipidemias/sangue , Hiperlipidemias/fisiopatologia , Indóis/farmacologia , Fluxometria por Laser-Doppler , Microscopia de Vídeo , Fatores de Risco , Fatores de Tempo , Triglicerídeos/sangueRESUMO
In order to gain insight into the potential role of endothelin, a 21 amino acid peptide produced by endothelial cells, in the development of complications of diabetes mellitus, basal plasma endothelin levels were measured in 152 patients with diabetes mellitus (83 patients with type 1 diabetes mellitus, 69 patients with type 2 diabetes mellitus) and compared to those in 50 healthy controls. Blood was drawn at 8:00 AM under resting conditions and endothelin was measured after prior extraction by a sensitive radioimmunoassay specific for both endothelin 1 and 2. Endothelin levels were increased in patients with diabetes mellitus in comparison to controls. In type 1 diabetes mellitus a positive correlation between endothelin levels and age was found. We found that 60% of patients with type 1 diabetes mellitus and elevated endothelin levels higher than 2.5 pg/mL (highest value in a control person) had had diabetes for more than 20 years (P less than .05 v patients with normal endothelin levels). In type 2 diabetes mellitus the relation between elevated endothelin levels and diabetes duration was reversed. Glycosylated hemoglobin (HbA1) concentrations above 10% of total hemoglobin were measured in 62% of the patients. Arterial hypertension was present in 60% of the patients with type 1 diabetes mellitus and increased endothelin levels greater than 2.5 pg/mL (both P less than .05 v patients with normal endothelin levels).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Endotelinas/sangue , Hipertensão/sangue , Adulto , Idoso , Glicemia/análise , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/sangue , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , RadioimunoensaioRESUMO
The effect of short-term nicotine consumption on endothelin-1 (ET-1) levels was studied in 10 male healthy smokers. Volunteers smoked in random order on 3 separate days a low-tar cigarette or a high-tar cigarette, or were studied without having smoked (no-cigarette experiment). ET-1, corticotropin, and cortisol levels, heart rate, and blood pressure were determined before and 1, 3, 5, 10, 20, and 30 minutes after smoking. In contrast to results obtained after smoking a low-tar cigarette or not smoking, smoking a high-tar cigarette resulted in a significant increase in ET-1 levels within 10 minutes, followed by an increase in corticotropin levels within 20 minutes after smoking. Thirty minutes after smoking, cortisol levels were higher after a high-tar cigarette compared with a low-tar cigarette or no smoking. Increases in heart rate and systolic blood pressure were likewise higher after smoking a high-tar cigarette than after smoking a low-tar cigarette. In conclusion, it is tempting to speculate that ET-1 may indeed act as the long-searched-for link between vasopressin and corticotropin-releasing hormone (CRH) and thus play an essential role in the stimulation of the hypothalamic-pituitary-adrenal axis. In addition, these results suggest that the increase in the level of ET-1, a powerful vasoconstrictor and mitogen, may play an important part in the disease mechanisms of atherosclerosis arising from smoking.