RESUMO
AIMS: To evaluate a mobilization campaign, the IMPACT initiative, which included multidisciplinary meetings, provision of information and a systematic prescription of an oral glucose tolerance test to improve the rate of glucose screening in women with gestational diabetes mellitus in the four largest maternity units in our area, starting in March 2011. METHODS: We retrospectively compared the level of self-reported screening during the first 6 months postpartum of women who gave birth after having been diagnosed with gestational diabetes before (January 2009 to December 2010) and after the IMPACT campaign (April 2011 to February 2012). RESULTS: We included 961 women (589 in the period before and 372 in the period after the campaign was initiated) with a mean ± SD age of 33.2 ± 5.3 years and BMI of 27.8 ± 5.3 kg/m². Multivariate analysis, stratified using a propensity score in order to limit bias caused by imbalance between both periods, showed that the postpartum screening rate was higher after the campaign began (48.9 vs 33.3%, odds ratio 1.7, 95% CI 1.1-2.5; P = 0.019) and higher in women who received insulin treatment during pregnancy (odds ratio 2.3, 95% CI 1.5-3.6; P < 0.001), consumed fruit and vegetables daily (odds ratio 1.6, 95% CI 1.1-2.4; P = 0.035) and did not smoke (smoking vs non-smoking: odds ratio 0.3, 95% CI 0.1-0.7; P = 0.01). There was no interaction between the campaign effect and these particular conditions. The proportion of oral glucose tolerance tests performed in women who underwent screening increased from 6.3 to 33.0%. CONCLUSIONS: The IMPACT campaign increased postpartum screening, and the use the oral glucose tolerance test in particular. The effect of this initiative might be reinforced in women who are non-daily consumers of fruit and vegetables, smokers and those who do not receive insulin treatment during pregnancy.
Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Gestacional/fisiopatologia , Cooperação do Paciente , Educação de Pacientes como Assunto , Estado Pré-Diabético/diagnóstico , Adolescente , Adulto , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Gestacional/tratamento farmacológico , Diagnóstico Precoce , Feminino , Seguimentos , França/epidemiologia , Teste de Tolerância a Glucose , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Período Pós-Parto , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/etiologia , Gravidez , Estudos Retrospectivos , Fatores de Risco , Saúde Suburbana , Adulto JovemRESUMO
In chronic diseases such as diabetes, adherence to therapy aims to preserve health, which is a long-term objective, whereas non-adherence tends to present an immediate 'reward'. We propose that non-adherence, like addiction, is at least in part due to the fact that, for physiological, and maybe genetic reasons described in a new field, neuroeconomics, a number of people have a taste for the present rather than the future. Thus, for 'impatient patients' it is natural not to adhere to therapeutic prescriptions that share the characteristic of being future-oriented. This hypothesis may apply to any disease requiring long-term therapy.
Assuntos
Adesão à Medicação/psicologia , Humanos , Adesão à Medicação/estatística & dados numéricos , Fatores de TempoRESUMO
For a message to be conveyed successfully, both the words (translation step) and the meaning (interpretation step) of what is said need to be understood. This holds true even when the patient and healthcare provider speak the same language, in that the message can be lost if the patient is unable to put it into context. Linguistic barriers can pose major problems. Patient education needs to avoid jargon, and when introducing a new concept to the patient, the healthcare provider needs to check that it is understood.
Assuntos
Diabetes Mellitus/reabilitação , Idioma , Educação de Pacientes como Assunto , Diabetes Mellitus/sangue , Diabetes Mellitus/terapia , Escolaridade , Hemoglobinas Glicadas/metabolismo , Humanos , Relações Médico-PacienteRESUMO
AIM: As the constantly progressing metabolic syndrome is accompanied by an increased risk of type 2 diabetes and cardiovascular complications, it is essential to take appropriate, non-pharmacological, cost-effective measures immediately after the diagnosis has been made. The purpose of our prospective, non-controlled, 6-month study was to determine the impact of lifestyle interventions involving patients' behaviour in collaboration with their general practitioners (GPs). METHODS: We recruited 95 patients (46 men and 49 women, aged 45 to 60 years) who presented with the metabolic syndrome. Each patient received a copy of the national French recommendations (PNNS) leaflet, containing guidelines aimed to balance dietary intake and increase daily physical activity. Socioeconomic status was estimated using the EPICES score. Following a less than 1 hour face-to-face interventional session with each patient to present the lifestyle-modification goals, we contacted each patient's GP by phone to advise on measures to reinforce these lifestyle modifications. RESULTS: The percentage of patients presenting with the metabolic syndrome decreased by 52.4% after 6 months. Hypertension, triglycerides and waist circumference decreased by 30.5, 29.3 and 22.0%, respectively, in the study patients. Rates of compliance to PNNS goals at the last follow-up versus baseline were: for drinks, 63.0% versus 22.2%; for sweet products, 91.4% versus 49.4%; for fat, 91.4% versus 80.3%; and for increased exercise, 26.9% versus 6.4%. CONCLUSION: Short-term, single lifestyle modifications targeting the metabolic syndrome in collaboration with GPs was effective in decreasing most of the parameters of the syndrome. However, no factors predictive of success were identified.
Assuntos
Dieta para Diabéticos , Estilo de Vida , Síndrome Metabólica/psicologia , Médicos de Família , Pressão Sanguínea , Estudos de Coortes , Dieta , Exercício Físico , Medicina de Família e Comunidade , Feminino , França , Humanos , Masculino , Síndrome Metabólica/dietoterapia , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/prevenção & controleRESUMO
AIM: One objective of Ophdiat, a telemedical network using digital non-mydriatic cameras in Ile-de-France, is to develop a comprehensive screening programme that provides access to annual fundus examinations to all diabetic patients. The aim of this study was to evaluate the benefits of this programme in a hospital setting. METHODS: A retrospective analysis of 500 case reports of diabetic patients hospitalized before and after Ophdiat setup was performed in five reference hospital centres. At each centre, 100 case reports (50 before, 50 after) of patients aged greater than 18 years, hospitalized for their annual check-up, with no known diabetic retinopathy (DR) before hospitalization and with the last fundus examination performed greater than 11 months previously, were randomly selected. The primary endpoint was the proportion of patients whose fundus examinations were performed during hospitalization; secondary endpoints were the number of cases of DR found and the time taken by ophthalmologists to make the diagnosis. RESULTS: The mean proportion of patients with fundus examinations was 50.4% and 72.4% before and after, respectively, Ophdiat (P<0.01). The prevalence of DR was 11.1% before and 12.7% after (not significant). The mean time taken by an ophthalmologist per diagnosis of DR was 0.90 half-day before and 0.32 half-day after Ophdiat. CONCLUSION: This evaluation shows that Ophdiat, combined with the availability of modern and effective devices, has improved DR screening in diabetology departments in hospitals. Additional human resources would certainly ensure more effective use of the system.
Assuntos
Telemedicina/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/prevenção & controle , Feminino , França/epidemiologia , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
This narrative review exhibits the construction and validation of a hypothesis to explain how treatment non-adherence in people with chronic disease, a major issue in contemporary medicine, occurs. I propose that non-adherence to long-term therapies is at least in part due to failure to prioritize the future, which is caused by a condition I dub disruption in time projection. This article gives the rationale for this hypothesis, which is largely grounded on philosophical arguments. Then, it demonstrates the plausibility of the hypothesis: on the one hand, it is consistent with certain epidemiological data found in the literature. On the other, it is possible to predict the underlying mechanisms of this lack of prioritization from recent achievements of neuro-economics and neuroscience. Next, it reviews empirical data that provide an experimental verification for this explanatory hypothesis. Finally, a general evolutionary and philosophical meaning for adherence is proposed, considering the advantages of its preconditions, namely, patience and foresight.
Assuntos
Doença Crônica/terapia , Cooperação do Paciente , HumanosRESUMO
The efficient implementation of healthcare is often jeopardized by the lack of patient adherence to medical recommendations and by inadequate healthcare-provider adherence to current guidelines, a phenomenon recently described as "clinical inertia". We propose here a theoretical model, based on concepts developed in the field of analytical philosophy of mind, that describes the mental mechanisms shared by the two phenomena, thus explaining their synergistically deleterious influence on the efficiency of care. We suggest that a failure to give preference to the long-term benefits of treatment intensification may represent a common mechanism underlying both patient non-adherence and physician clinical inertia. We dub such a failure as "clinical myopia". The model is explained in the context of clinical observations made in type 1 and 2 diabetic patients. However, it may also be relevant to other asymptomatic chronic diseases.
Assuntos
Pessoal de Saúde/psicologia , Cooperação do Paciente/psicologia , Diabetes Mellitus/terapia , HumanosRESUMO
BACKGROUND: Day-to-day glucose variability may cause difficulty for patients trying to adjust their insulin dosages and for healthcare providers when they have to make recommendations. The aim of this research was to evaluate the frequency of high variability in a population of diabetic children and adolescents attending summer camp. METHODS AND RESULTS: The mean of the daily differences (MODD) in glucose concentrations was calculated from continuous glucose monitoring (CGM) over five consecutive days in 6 diabetic patients. This index was correlated to the MODD calculated from pre-meal and bedtime blood glucose (BG) measurements (r=0.87). We used the MODD calculated on these four BG measurements for five consecutive days to evaluate day-to-day glucose variability in 100 young diabetic patients treated with glargine and ultrarapid analogue insulin. Only one child had a MODD value lower than 36mg/dl, considered a threshold for high day-to-day variability, and 94 children had a MODD value higher than 45mg/dl. The median value was 78mg/dl. The expected positive correlation between the MODD and its standard deviation (r=0.32, P<0.01) suggested that the greater the day-to-day variability, the more variable the variability across five consecutive days. CONCLUSIONS: The estimation of MODD from four pre-meal BG values correlated to that from CGM, and may represent a simple index of day-to-day glycaemic variability. High day-to-day glucose variability in glucose profile is frequently observed in diabetic children attending summer camp.
Assuntos
Atividades Cotidianas/classificação , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/reabilitação , Adolescente , Acampamento , Criança , HumanosRESUMO
BACKGROUND: The aim of this study was to determine whether adherent and non-adherent patients with type 2 diabetes can be differentiated according to psychosocial characteristics. METHODS: A total of 1214 patients were included in the analysis. Data were derived from a cross-sectional observational study of adults with diabetes of the Access Santé (Access Health) panel of Kantar Health France. Patients completed a questionnaire on adherence to medication, psychological determinants (trust in physicians, constancy of habits, patience, temporal horizon, health locus of control, obedience, psychological reactivity, prevention vs promotion, optimism vs pessimism) and social deprivation. RESULTS: Of these 1214 subjects, 46.2% were considered strictly adherent to antidiabetic medication, as reflected by negative answers to all six questions suggesting a non-adherent behaviours, whereas 48.9% provided 1-2 positive answers and 4.9% provided 3-6 positive answers, and were considered non-adherent. In addition to the effect of younger age (P=0.03), multivariate logistic regression analysis demonstrated the following psychosocial determinants of non-adherence: chance locus of control (P=0.02); lack of trust in physicians (P=0.010); and pessimism (P=0.021). Multiple factor analysis identified adherence and social deprivation as dimensions separating three distinct patient populations: (i) non-adherent; (ii) adherent and socially deprived; and (iii) adherent and non-socially deprived. It also revealed that patience, obedience, cautious behaviour, optimism, trust in physicians and constancy of habits were associated with adherence. CONCLUSION: Of the multiple determinants of adherence, trust in physicians and constancy of habits represent modifiable factors, and constitute targets to prevent non-adherence because they can be reinforced through patient education and improved physician - patient relationship. Also, psychosocial determinants of adherence differ widely between socially deprived and non-deprived patients.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Adesão à Medicação/psicologia , Personalidade , Relações Médico-Paciente , Confiança , Adulto , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 2/psicologia , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
Aldolase B is an enzyme of the glycolytic pathway whose activity and mRNA levels in the liver fluctuate according to dietary status. Both the enzyme activity and the mRNA concentration decline during fasting and increase four- to eightfold upon refeeding of a carbohydrate-rich diet. The mechanism, however, of the mRNA induction remains unknown. To elucidate the mechanisms that regulate this induction responsive to dietary stimuli, we have studied the roles of hormones and glycolytic substrates on aldolase B gene expression in three tissues that synthesize the enzyme. Using a cDNA probe complementary to rat aldolase B mRNA, we determined the amount of cytoplasmic RNAs in the liver, kidney, and small intestine of normal, adrenalectomized, thyroidectomized, diabetic, and glucagon- or cAMP-treated animals refed either a fructose-rich or a maltose-rich diet. The in vivo hormonal control of gene expression was found to be very different in the three organs tested. In the liver, cortisone and thyroid hormones were required for the induction of the specific mRNA by carbohydrates, while in the kidney none of the hormonal modifications tested altered the level of mRNA induction. In the liver, but not in the kidney, diabetes and glucagon administration abolished the induction of aldolase B mRNAs in animals refed the maltose-rich diets. In the small intestine, only diabetes and thyroidectomy affected the gene expression. Finally, no induction occurred when normal fasted rats were given any of the hormones. Thus, the in vivo hormonal control of liver aldolase B gene expression differs significantly from that of kidney and small intestine. In the liver, the mRNA induction requires the presence of dietary carbohydrates, of permissive hormones, and the cessation of glucagon release, while in the kidney, the induction of the mRNAs by fructose occurs regardless of the hormonal status of the animals. The hormonal control of aldolase B mRNA levels in the small intestine is intermediate.
Assuntos
Carboidratos da Dieta/farmacologia , Frutose-Bifosfato Aldolase/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônios/farmacologia , Adrenalectomia , Animais , Arginina/farmacologia , AMP Cíclico/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Glucagon/farmacologia , Intestino Delgado/enzimologia , Rim/enzimologia , Fígado/enzimologia , Masculino , Glândulas Paratireoides/fisiologia , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Ratos , Ratos Endogâmicos , TireoidectomiaRESUMO
OBJECTIVE: To evaluate, using fundus photography, the prevalence of diabetic retinopathy (DR) in young diabetic subjects attending summer camps run by the Aide aux Jeunes Diabétiques Association (Aid to Young Diabetics). RESEARCH DESIGN AND METHODS: Five hundred and four children and adolescents (250 boys and 254 girls), with type 1 diabetes mellitus, aged 10-18 years (mean:13+/-2), were screened for DR using non mydriatic photography, during their stay in a holiday camp. Demographic and clinical data recorded on subjects' arrival in the camp included date of birth, height, weight, treatment, blood pressure, and duration of diabetes. HbA(1c) was determined with a DCA 2000 kit. RESULTS: Mean diabetes duration was 4.8+/-3.4 years and mean HbA(1c) was 8.5+/-1.3%. Mild non proliferative DR was diagnosed in 23 children (4.6%). Compared to subjects without DR, those with DR were significantly older (P<10(-3)), had a longer duration of diabetes (P=0.001), higher systolic blood pressure (P=0.04), and had higher (but not significantly so) HbA(1c) (P=0.15). After adjustment for age, only longer duration remained significantly associated with DR (P=0.01). CONCLUSION: The prevalence of DR in these young patients was low compared to that reported in previous studies. The decrease may be due to modern diabetes care with multiple insulin injections. However, early detection of DR in adolescents, especially in their late teens, remains important, because it allows the identification of patients at high risk of progression towards severe stages of DR.
Assuntos
Retinopatia Diabética/epidemiologia , Estado Pré-Diabético/complicações , Estado Pré-Diabético/epidemiologia , Adolescente , Acampamento , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Retinopatia Diabética/diagnóstico , Feminino , Angiofluoresceinografia , França/epidemiologia , Hemoglobinas Glicadas/análise , Humanos , Masculino , PrevalênciaRESUMO
Many people with type 2 diabetes mellitus (T2DM) fail to achieve glycaemic control promptly after diagnosis and do not receive timely treatment intensification. This may be in part due to 'clinical inertia', defined as the failure of healthcare providers to initiate or intensify therapy when indicated. Physician-, patient- and healthcare-system-related factors all contribute to clinical inertia. However, decisions that appear to be clinical inertia may, in fact, be only 'apparent' clinical inertia and may reflect good clinical practice on behalf of the physician for a specific patient. Delay in treatment intensification can happen at all stages of treatment for people with T2DM, including prescription of lifestyle changes after diagnosis, introduction of pharmacological therapy, use of combination therapy where needed and initiation of insulin. Clinical inertia may contribute to people with T2DM living with suboptimal glycaemic control for many years, with dramatic consequences for the patient in terms of quality of life, morbidity and mortality, and for public health because of the huge costs associated with uncontrolled T2DM. Because multiple factors can lead to clinical inertia, potential solutions most likely require a combination of approaches involving fundamental changes in medical care. These could include the adoption of a person-centred model of care to account for the complex considerations influencing treatment decisions by patients and physicians. Better patient education about the progressive nature of T2DM and the risks inherent in long-term poor glycaemic control may also reinforce the need for regular treatment reviews, with intensification when required.
Assuntos
Sistemas de Apoio a Decisões Clínicas , Diabetes Mellitus Tipo 2 , Relações Médico-Paciente , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Humanos , Medicina , Morbidade , Médicos de Atenção Primária , Padrões de Prática Médica , Qualidade de Vida , Especialização , Resultado do TratamentoRESUMO
AIM: To explore the influence of migration and this parameters on the control of diabetes. METHODS: A cohort of migrant patients with type 2 diabetes was recruited in a center affiliated to the French national insurance system situated in a department with important migratory phenomenon. Patients fulfilled a questionnaire about diabetes, their migration history, and the EPICES score (deprivation score). We have explored by univariate and multivariate analysis if any of the characteristics of migration could be related to the control of diabetes. This cohort was compared to a non-migrant control group of age and sex-matched patients. RESULTS: We included 72 patients, 36 women and 36 men from 20 different countries. The mean age was 57.7 ± 9.6 years. A migration for family reunification was associated with better diabetes equilibrium (Risk of having an HbA1c ⩾8% (63.9 mmol/mol): OR 0.07 (95% IC [0.005-0.86], p = 0.04). The migrant patients who wished to share their time between France and country of origin during their retirement had a better glycaemic control than the migrant patients who would like to go alone into their country (OR 0.08 [0.01-0.78], p = 0.03). Compared to the non migrant group, the EPICES score was higher in the migrant group (52.8 vs. 28.3, p < 0.05), HbA1c was also higher in the migrant group (8.4 vs. 6.7% (68 vs. 50 mmol/mol)). CONCLUSIONS: We may fear that migrants share an increased risk of uncontrolled diabetes. Individual migration could be a risk factor of uncontrolled diabetes. Knowing the migration history of migrant patients is fundamental to understand some barriers of care.
RESUMO
The purpose of this text is to try to understand why certain innovations are not permitted, although they are possible. Our guiding thread will be the four principles of biomedical ethics defined by Beauchamp and Childress: beneficence, non-maleficence, justice and autonomy. We shall show how they can guide the ethical inquiry in the field of pancreas or islet transplantation, leading to an analysis of the risks and benefits of the innovations epistemologically taking into account their historical context.
Assuntos
Diabetes Mellitus/terapia , Ética Médica , Humanos , Modelos BiológicosRESUMO
The lag in insulin release in response to glucose is an obstacle to the development of hybrid pancreatic devices, in which an artificial membrane protects transplanted islets against immune rejection. We designed a U-shaped bioartificial pancreas, in which the blood channel surrounds the islet chamber consisting of two flat membranes; blood circulates successively above the first membrane and then in the reverse direction, below the second membrane. Isolated rat islets were introduced into the chamber, which was perfused with Krebs buffer, and the kinetics of insulin release in response to glucose was determined. During a 20-min, 2.8-20-mM, square-wave glucose stimulation, insulin release in the effluent of the device rose from 0.7 +/- 0.2 to 3.2 +/- 1.0 ng/100 islets/min (P less than 0.05) within 3 min, and reached a maximal level of 12.8 +/- 3.3 ng/100 islets/min at 10 min; 5 min after the return of the glucose concentration to substimulatory level, insulin release dropped from 11.3 +/- 1.5 to 8.0 +/- 1.7 ng/100 islets/min (P less than 0.05), and reached basal value (1.0 +/- 0.2 ng/100 islets/min) 40 min after the end of the stimulation. A 0.1-mM/L/min ramp increase in glucose concentration triggered a significant rise in insulin release (P less than 0.02) when the glucose concentration reached 5.3 +/- 0.2 mM; islets concomitantly perifused within a chamber set up without membrane responded to the same glucose stimulation 5 min earlier. For up to 1000 islets, insulin release in response to glucose was linearly correlated to the number of islets (N = 12, P less than 0.01), indicating that insulin did not significantly inhibit its own secretion in this system. Finally, during glucose stimulation, the insulin concentration in the effluent from the chamber was found to be four times the concentration present at the turning point of the blood channel, suggesting that insulin was transferred into the perfusing medium in part by a countercurrent flux of ultrafiltrate crossing the membranes. We present herein the kinetic modelling of glucose and insulin transfer in this "ultrafiltration chamber," whose functional characteristics are compatible with closed-loop insulin delivery.
Assuntos
Glucose/farmacologia , Sistemas de Infusão de Insulina , Insulina/metabolismo , Transplante das Ilhotas Pancreáticas , Animais , Desenho de Equipamento , Humanos , Técnicas In Vitro , Insulina/sangue , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Cinética , Modelos Biológicos , Perfusão , Ratos , UltrafiltraçãoRESUMO
Enzymatic glucose sensors are based on the amperometric detection of an oxidable species generated during the oxidation of glucose by glucose oxidase. This measurement usually requires a working electrode (anode), an auxiliary electrode (cathode), and a reference electrode, the function of the latter being to keep constant the working potential of the anode, which is responsible for current generation. However, in the needle-type glucose sensors proposed so far, the reference electrode is missing, and its function is performed by the auxiliary electrode. We investigated, in vitro and in vivo in rats, the ability of several cathode-needle materials to behave as a reference electrode in two-electrode glucose sensors, i.e., to present a stable auxiliary electrode potential. In vitro, when glucose concentration was raised from 0 to 30 mM, the auxiliary potential of both gold- and silver-coated sensors presented a cathodic drift, whereas that of silver/silver chloride-coated sensors remained stable. In vivo, during insulin-induced hypoglycemia (5.9-2.4 mM), the auxiliary potentials of all sensors remained stable, whereas during glucose infusion (mean blood glucose concentration 11.2 mM), the auxiliary potentials of both gold- and silver-coated sensors presented an anodic drift, whereas those of silver/silver chloride-coated sensors remained stable. We also indirectly quantified the changes in sensor response induced by variations in the working potential in vitro and in vivo, simulating those that might be produced by a drift in the auxiliary potential. Such changes in the working potential could bring about a 30% unspecific variation in sensor response. We conclude that improvements in sensor analytical characteristics should be obtained with silver/silver-chloride-coated cathodes.
Assuntos
Técnicas Biossensoriais , Glicemia/análise , Animais , Técnica Clamp de Glucose , Glucose Oxidase , Insulina/farmacologia , Masculino , Ratos , Ratos EndogâmicosRESUMO
Four patients, treated with pentamidine because of Pneumocystis carinii pneumonitis, displayed severe fasting hypoglycemia during this treatment. Diabetes mellitus appeared later, requiring insulin therapy in the three of them who survived more than a few weeks. The metabolic study, performed in two cases during the hypoglycemic period, demonstrated inappropriately high insulin levels in the postabsorptive state. 28 +/- 1 microunits/ml (blood glucose 41 +/- 4 mg/dl) and 86 +/- 5 microunits/ml (blood glucose 15 +/- 5 mg/dl) vs. 15 +/- 3 microunits/ml in 10 control subjects and 55 +/- 3 microunits/ml in 6 patients with a verified B-cell tumor, respectively. Poor B-cell secretory responses followed the stimulations by oral glucose (maximal increment over basal: +5 microunits/ml vs. + 40 microunits/ml in control group and +77 microunits/ml in the insulinoma group), by i.v. arginine (maximal increment + 10 and +28 microunits/ml, respectively, vs. +55 in the controls and +90 microunits/ml in the insulinoma group) and by i.v. glucagon (+10 and +23 microunits/ml, respectively) vs. +40 microunits/ml in both the control and the insulinoma groups). Plasma cortisol and glucagon, and the A-cell response to arginine were higher than normal. These high, nonsuppressible, nonstimulable insulin levels and the sequence of hypoglycemia followed by insulin-dependent diabetes mellitus is consistent with the hypothesis of a selective toxicity turned towards the B-cells. In vitro incubation of islets with pentamidine 10(-10) M produced a passive release of insulin, followed by a significant decrease in B-cell response to glucose + theophylline. It is suggested that pentamidine can induce hypoglycemia because of an early cytolytic release of insulin, and then diabetes mellitus because of B-cell destruction and insulin deficiency.
Assuntos
Amidinas/efeitos adversos , Diabetes Mellitus/etiologia , Hipoglicemia/induzido quimicamente , Pentamidina/efeitos adversos , Adulto , Idoso , Glicemia/análise , Humanos , Hipoglicemia/complicações , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/tratamento farmacológicoRESUMO
Peroxisome proliferator-activated receptor (PPAR)-alpha controls the expression of genes involved in lipid metabolism. PPAR-alpha furthermore participates to maintain blood glucose during acute metabolic stress, as shown in PPAR-alpha-null mice, which develop severe hypoglycemia when fasted. Here, we assessed a potential role for PPAR-alpha in glucose homeostasis in response to long-term high-fat feeding. When subjected to this nutritional challenge, PPAR-alpha-null mice remained normoglycemic and normoinsulinemic, whereas wild-type mice became hyperinsulinemic (190%; P < 0.05) and slightly hyperglycemic (120%; NS). Insulin tolerance tests (ITTs) and glucose tolerance tests (GTTs) were performed to evaluate insulin resistance (IR). Under standard diet, the response to both tests was similar in wild-type and PPAR-alpha-null mice. Under high-fat diet, however, the efficiency of insulin in ITT was reduced and the amount of hyperglycemia in GTT was increased only in wild-type and not in PPAR-alpha-null mice. The IR index, calculated as the product of the areas under glucose and insulin curves in GTT, increased fourfold in high-fat-fed wild-type mice, whereas it remained unchanged in PPAR-alpha-null mice. In contrast, PPAR-alpha deficiency allowed the twofold rise in adiposity and blood leptin levels elicited by the diet. Thus, the absence of PPAR-alpha dissociates IR from high-fat diet-induced increase in adiposity. The effects of PPAR-alpha deficiency on glucose homeostasis seem not to occur via the pancreas, because glucose-stimulated insulin secretion of islets was not influenced by the PPAR-alpha genotype. These data suggest that PPAR-alpha plays a role for the development of IR in response to a Western-type high-fat diet.
Assuntos
Gorduras na Dieta/administração & dosagem , Resistência à Insulina , Receptores Citoplasmáticos e Nucleares/deficiência , Fatores de Transcrição/deficiência , 1-Metil-3-Isobutilxantina/farmacologia , Animais , Glicemia/metabolismo , Carbacol/farmacologia , Sinergismo Farmacológico , Jejum , Glucose/farmacologia , Teste de Tolerância a Glucose , Homeostase , Hiperinsulinismo/etiologia , Hiperinsulinismo/prevenção & controle , Hipoglicemia/genética , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ácido Palmítico/farmacologia , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologiaRESUMO
OBJECTIVES: The aim of this study was (1) to measure adherence in males and females with uncontrolled hypertension, and (2) to identify factors associated with non-adherence to antihypertensive medication. PATIENTS AND METHODS: Each general practitioner (GP) should include the first two male and the first two female patients with uncontrolled treated hypertension. Adherence to antihypertensive treatment was estimated by the GP and using the French League Against High blood pressure (FLAH) self-administered questionnaire. A stepwise logistic regression analysis was used to identify factors associated with non-adherence on the FLAH scale, independently in males and in females. RESULTS: A total of 1630 males and 1612 females were included in the analysis. Adherence to treatment was significantly better in females or when estimated by the GP. Lack of motivation was the first factor associated with poor adherence in both sexes. Considering hypertension as a simple anomaly and not a disease that can lead to cardiac or cerebral disorders was the second common parameter in both sexes. Other common factors were: having monthly periods of financial difficulties in facing his/her needs and absence of regular screening for colon cancer. CONCLUSION: Adherence to treatment is better in uncontrolled hypertensive females. Poor adherence is mainly associated with non-clinical factors. The lack of motivation is the most important element.