RESUMO
AIM: Optimal treatment of cardiovascular disease is essential to decrease mortality among people with diabetes, but information is limited on how actual treatment relates to guidelines. We analysed changes in therapeutic approaches to anti-hypertensive and lipid-lowering medications in people with Type 2 diabetes from 2006 and 2015. METHODS: Summary data from clinical services in seven countries outside North America and Western Europe were collected for 39 684 people. Each site summarized individual-level data from outpatient medical records for 2006 and 2015. Data included: demographic information, blood pressure (BP), total cholesterol levels and percentage of people taking statins, anti-hypertensive medication (angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin II receptor blockers, thiazide diuretics) and antiplatelet drugs. RESULTS: From 2006 to 2015, mean cholesterol levels decreased in six of eight sites (range: -0.5 to -0.2), whereas the proportion with BP levels > 140/90 mmHg increased in seven of eight sites. Decreases in cholesterol paralleled increases in statin use (range: 3.1 to 47.0 percentage points). Overall, utilization of anti-hypertensive medication did not change. However, there was an increase in the use of angiotensin II receptor blockers and a decrease in angiotensin-converting enzyme inhibitors. The percentage of individuals receiving calcium channel blockers and aspirin remained unchanged. CONCLUSIONS: Our findings indicate that control of cholesterol levels improved and coincided with increased use of statins. The percentage of people with BP > 140/90 mmHg was higher in 2015 than in 2006. Hypertension treatment shifted from using angiotensin-converting enzyme inhibitors to angiotensin II receptor blockers. Despite the potentially greater tolerability of angiotensin II receptor blockers, there was no associated improvement in BP levels.
Assuntos
Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão/tratamento farmacológico , Idoso , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/fisiopatologia , Dislipidemias/epidemiologia , Dislipidemias/fisiopatologia , Europa (Continente)/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologiaRESUMO
AIMS: To identify real-world factors affecting adherence to insulin therapy in patients with Type 1 or Type 2 diabetes mellitus. METHODS: A literature search was conducted in PubMed and EMBASE in November 2011 to identify studies reporting factors associated with adherence/non-adherence to insulin therapy in adults with Type 1 or Type 2 diabetes. RESULTS: Seventeen studies were identified; six used self-reported measures and 11 used calculated measures of adherence. Most (13/17) were conducted exclusively in the USA. Four categories of factors associated with non-adherence were identified: predictive factors for non-adherence, patient-perceived barriers to adherence, type of delivery device and cost of medication. For predictive factors and patient-perceived barriers, only age, female sex and travelling were associated with non-adherence in more than one study. Fear of injections and embarrassment of injecting in public were also cited as reasons for non-adherence. Conversely, adherence was improved by initiating therapy with, or switching to, a pen device (in four studies), and by changing to an insurance scheme that lowered the financial burden on patients (in two studies). CONCLUSIONS: Adherence to insulin therapy is generally poor. Few factors or patient-perceived barriers were consistently identified as predictive for non-adherence, although findings collectively suggest that a more flexible regimen may improve adherence. Switching to a pen device and reducing patient co-payments appear to improve adherence. Further real-world studies are warranted, especially in countries other than the USA, to identify factors associated with non-adherence and enable development of strategies to improve adherence to insulin therapy.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Autoeficácia , Percepção Social , Fatores Socioeconômicos , Estados Unidos/epidemiologiaRESUMO
AIM: To evaluate the effect of system interventions (formalized data collection and 100% coverage of medications and supplies) combined with physician and/or patient education on therapeutic indicators and costs in Type 2 diabetes. METHODS: This was a randomized 2 × 2 design in public health, social security or private prepaid primary care clinics in Corrientes, Argentina. Thirty-six general practitioners and 468 adults with Type 2 diabetes participated. Patients of nine participating physicians were selected randomly and assigned to one of four structured group education programmes (117 patients each): control (group 1), physician education (group 2), patient education (group 3), and both physician education and patient education (group 4), with identical system interventions in all four groups. Outcome measures included HbA(1c), BMI, blood pressure, fasting glucose, lipid profile, drug consumption, resource use and patient well-being at baseline and every 6 months up to 42 months. RESULTS: HbA(1c) decreased significantly from 4 mmol/mol to 10 mmol/mol by 42 months (P < 0.05); the largest and more consistent decrease was in the groups where patients and physicians were educated. Blood pressure and triglycerides decreased significantly in all groups; the largest changes were recorded in the combined education group. The World Health Organization-5 Lowe score showed significant improvements, without differences among groups. The lowest treatment cost was seen in the combined education group. CONCLUSIONS: In a primary care setting, educational interventions combined with comprehensive care coverage resulted in long-term improvement in clinical, metabolic and psychological outcomes at the best cost-effectiveness ratio.
Assuntos
Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Tipo 2/terapia , Educação Médica Continuada , Custos de Cuidados de Saúde , Hiperglicemia/prevenção & controle , Educação de Pacientes como Assunto , Atenção Primária à Saúde , Idoso , Argentina , Custos e Análise de Custo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/economia , Educação Médica Continuada/economia , Feminino , Seguimentos , Clínicos Gerais/educação , Hemoglobinas Glicadas/análise , Promoção da Saúde/economia , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/prevenção & controle , Hipertensão/complicações , Hipertensão/prevenção & controle , Masculino , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Educação de Pacientes como Assunto/economia , Atenção Primária à Saúde/economiaRESUMO
AIMS: To implement a patient registry and collect data related to the care provided to people with type 2 diabetes in six specialized centers of three Latin American countries, measure the quality of such care using a standardized form (QUALIDIAB) that collects information on different quality of care indicators, and analyze the potential of collecting this information for improving quality of care and conducting clinical research. METHODS: We collected data on clinical, metabolic and therapeutic indicators, micro- and macrovascular complications, rate of use of diagnostic and therapeutic elements and hospitalization of patients with type 2 diabetes in six diabetes centers, four in Argentina and one each in Colombia and Peru. RESULTS: We analyzed 1157 records from patients with type 2 diabetes (Argentina, 668; Colombia, 220; Peru, 269); 39 records were discarded because of data entry errors or inconsistencies. The data demonstrated frequency performance deficiencies in several procedures, including foot and ocular fundus examination and various cardiovascular screening tests. In contrast, HbA1c and cardiovascular risk factor assessments were performed with a greater frequency than recommended by international guidelines. Management of insulin therapy was sub-optimal, and deficiencies were also noted among diabetes education indicators. CONCLUSIONS: Patient registry was successfully implemented in these clinics following an interactive educational program. The data obtained provide useful information as to deficiencies in care and may be used to guide quality of care improvement efforts.
Assuntos
Atenção à Saúde/normas , Diabetes Mellitus Tipo 2/terapia , Qualidade da Assistência à Saúde , Argentina , Doença Crônica , Técnicas de Laboratório Clínico/estatística & dados numéricos , Colômbia , Diabetes Mellitus Tipo 2/complicações , Dislipidemias/prevenção & controle , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hiperglicemia/prevenção & controle , Hipertensão/prevenção & controle , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Peru , Sistema de RegistrosRESUMO
AIM: To identify Prediabetes (PreD) as early and serious diabetes step using clinical-biochemical characteristics in the population of the Primary Prevention Diabetes Buenos Aires (PPDBA) study. METHODS: PPDBA Study evaluated benefits of adopting healthy lifestyles to prevent T2D. It recruited people 45-75 years of age with PreD (impaired fasting glycaemia [IFG], impaired glucose tolerance [IGT] or both, American Diabetes Association criteria), using an opportunistic approach. They completed a FINDRISC questionnaire, and those with a score ≥13 points were invited to participate. When they accepted, we performed an oral glucose tolerance test (OGTT) with a complete lipid profile and HbA1c while physicians completed a clinical history. We recruited 367 persons, and depending on OGTT results, the sample was divided into normals (NGT), PreD, or with diabetes (last one was excluded in our analysis). Data were statistically analyzed using parametric and nonparametric tests and logistic regression to identify parameters associated with PreD. RESULTS: From the recruited (n = 367) 47.7% have NGT, 48.5% PreD and 3.8% unknown T2D (excluded). People with PreD were significantly older, with a higher percentage of overweight/obesity, BMI, and larger waist circumference than NGT. They also showed significantly higher fasting and 2 h post glucose load, HbA1c, and triglyceride levels. No significant differences were recorded in the blood pressure, lipid profile though both groups had abnormally high LDL-c values. They also had a larger percentage of TG/HDL-c ratios (insulin resistance indicator) (55% vs. 37.5%). Logistic regression analysis showed that PreD was significant associated with age, waist circumference, and triglyceride above target values. CONCLUSION: Our findings showed that clinical and biochemical parameters were significantly different between people with PreD and those with NGT. This evidence supports the concept that PreD is a serious dysfunction, which should be early diagnosed and treated properly to prevent its transition to T2D and its complications.
Assuntos
Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Resistência à Insulina , Estado Pré-Diabético , Humanos , Estado Pré-Diabético/epidemiologia , Hemoglobinas Glicadas , Glicemia/análise , Triglicerídeos , Diagnóstico Precoce , JejumRESUMO
AIM: To assess diabetes treatment preferences with a focus on patient barriers to insulin treatment. MATERIALS AND METHODS: A questionnaire using indirect and direct methods was administered as part of the International Diabetes Management Practices Study (IDMPS). Discrete choice modelling was used to assess how product attributes influence patients' preferences for diabetes treatment. A multinomial logit model was used to find the odds ratio for each parameter, representing the probability of selecting a chosen alternative given a choice set. This allowed for the derivation of relative attribute importance, an indication of how influential product attributes are in the respondents' choices. RESULTS: The IDMPS questionnaire was administered to 14,033 individuals with diabetes in 18 countries. The majority of respondents were women (53%) and had Type 2 diabetes mellitus (T2DM; 85%). Across subgroups, administration (i.e. oral vs. injection) was a driver of preference. Patient preferences varied according to diabetes type; individuals with T2DM assigned much higher relative importance to administration than those with Type 1 diabetes mellitus (T1DM; 30.86% vs. 4.99%; p<0.0001). Individuals with T2DM treated with insulin placed less importance on administration than insulin-naïve T2DM patients (3.09% vs. 47.48%; p<0.0001). Diabetes education also had a significant effect on the priority given to administration between T2DM patients who received diabetes training and those who did not (28.21% vs. 33.68%, respectively; p<0.0001). CONCLUSION: The insulin barriers perceived by patients with diabetes evolved with their disease experience. While administration was the primary preference driver for insulin-naïve patients, patients were increasingly concerned with more clinically relevant barriers as they gained experience with insulin. This finding suggests that patients using insulin understand the importance of achieving an optimal balance between safety and efficacy.
Assuntos
Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 2/psicologia , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Preferência do Paciente , Adulto , Idoso , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
AIMS: To estimate diabetes-related resource use and investigate its predictors among individuals with type 2 diabetes in 24 countries in Asia, Latin America, the Middle East and Africa. METHODS: Cross-sectional observational data on diabetes-related resource use were collected from 15,016 individuals with type 2 diabetes within the second wave of International Diabetes Management Practices Study. Mean (SD) annual quantities were determined and predictors of diabetes-related hospitalisations, inpatient days, emergency room visits and absenteeism were investigated using negative binomial regression. RESULTS: Patients in Asia (n = 4678), Latin America (n = 6090) and the Middle East and Africa (n = 4248) made a mean (SD) of 3.4 (6.9), 5.4 (6.7) and 2.5 (4.4) General Practitioner visits per year. The mean (SD) number of inpatient days amounted to 3.8 (18.1), 2.2 (13.9) and 2.6 (13.5) per year. Results of the regression analysis showed the major influence of diabetes-related complications and inadequate glycaemic control on resource use. The expected annual rate of hospitalisation of patients with macrovascular complications compared with those without was 4.7 times greater in Asia [incidence rate ratio (IRR) = 4.7, 95% CI: 2.8-7.8, n = 2551], 5.4 times greater in Latin America (IRR = 5.4, 95% CI: 3.0-9.8, n = 3228) and 4.4 times greater in the Middle East and Africa (IRR = 4.4, 95% CI: 2.8-6.9, n = 2630). CONCLUSIONS: Micro- and macrovascular complications and inadequate glycaemic control are significant predictors of resource use in people with type 2 diabetes of developing countries. This knowledge confirms the health economic importance of early diagnosis of diabetes, education of patients and glycaemic control.
Assuntos
Diabetes Mellitus Tipo 2/terapia , Recursos em Saúde/estatística & dados numéricos , África/epidemiologia , Ásia/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/terapia , Escolaridade , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Incidência , América Latina/epidemiologia , Masculino , Pessoa de Meia-Idade , Oriente Médio/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricosRESUMO
BACKGROUND: Pharmacology has provided efficient tools to improve insulin effect/secretion but the decrease in ß-cell mass remains elusive. INGAP-PP could provide a therapeutic alternative to meet that challenge. AIM: To further understand the mechanism that links INGAP-PP effects upon ß-cell mass and function with islet angiogenesis. METHODOLOGY: Normal male Wistar rats were divided into 2 groups and injected with a single dose of 100 mg/Kg suramin or saline. Both groups were divided into 2 subgroups that received daily doses of 2 mg/kg INGAP-PP or saline for ten days. Plasma glucose, triacylglycerol, TBARS, and insulin levels were measured. Pancreas immunomorphometric analyses were also performed. Pancreatic islets were isolated to measure glucose-stimulated insulin secretion (GSIS). Specific islet mRNA levels were studied by qRT-PCR. Statistical analysis was done using ANOVA. RESULTS: No differences were recorded in body weight, food intake, or any other plasma parameter measured in all groups. Islets from INGAP-PP-treated rats significantly increased GSIS, ß-cell mass, and mRNA levels of Bcl-2, Ngn-3, VEGF-A, VEGF-R2, CD31, Ang1 and Ang2, Laminin ß-1, and Integrin ß-1, and decreased mRNA levels of Caspase-8, Bad, and Bax. Islets from suramin-treated rats showed significant opposite effects, but INGAPP-PP administration rescued most of the suramin effects in animals treated with both compounds. CONCLUSION: Our results reinforce the concept that INGAP-PP enhances insulin secretion and ß-cell mass, acting through PI3K/Akt/mTOR pathways and simultaneously activating angiogenesis through HIF-1α-mediated VEGF-A secretion. Therefore, INGAP-PP might be a suitable antidiabetic agent able to overcome two major alterations present in T2D.
Assuntos
Citocinas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Células Secretoras de Insulina/metabolismo , Fragmentos de Peptídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/biossíntese , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Células Secretoras de Insulina/patologia , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Serina-Treonina Quinases TOR/metabolismoRESUMO
OBJECTIVE: To implement a controlled clinical trial (PRODIACOR) in a primary care setting designed 1) to improve type 2 diabetes care and 2) to collect cost data in order to be able to measure cost-effectiveness of three system interventions (checkbook of indicated procedures, patient/provider feedback and complete coverage of medications and supplies) and physician and/or patient education to improve psychological, clinical, metabolic and therapeutic indicators. All three Argentinean health subsectors (public health, social security and the private, prepaid system) are participants in the study. Patients of participating physicians were randomly selected and assigned to one of four groups: control, provider education, patient education, and provider/patient education; the system interventions were provided to all four groups. BASELINE RESULTS: Mean BMI was 29.8 kg/m(2); most subjects had blood pressure, fasting glucose and total cholesterol above targets recommended by international standards. Only 1% had had microalbuminuria measured, 57% performed glucose self-monitoring, 37% had had an eye examination and 31% a foot examination in the preceding year. Ten percent, 26% and 73% of people with hyperglycemia, hypertension and dyslipidemia, respectively, were not on medications. Most patients treated with either insulin or oral antidiabetic agents were on monotherapy as were those treated for hypertension and dyslipidemia. WHO-5 questionnaire scores indicated that 13% of the subjects needed psychological intervention. CONCLUSIONS: Baseline data show multiple deficiencies in the process and outcomes of care that could be targeted and improved by PRODIACOR intervention.
Assuntos
Doenças Cardiovasculares/terapia , Diabetes Mellitus Tipo 2/terapia , Assistência Centrada no Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Idoso , Argentina , Índice de Massa Corporal , Coleta de Dados/estatística & dados numéricos , Feminino , Indicadores Básicos de Saúde , Humanos , Capacitação em Serviço , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Satisfação do Paciente , Atenção Primária à Saúde , Garantia da Qualidade dos Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Sistemas de Alerta , Projetos de Pesquisa , Fatores de Risco , Tamanho da AmostraRESUMO
Administration of a sucrose-rich diet (SRD) to normal hamsters induces an insulin-resistant state and a significant increase of insulin secretion and beta-cell mass. Islets isolated from these animals had a marked increase in glucose metabolism and glucose-induced insulin secretion, at both low and high glucose concentrations. They also presented increased hexokinase (HK) activity, without measurable changes in glucokinase (GK) activity. In this study we measured HK and GK activity in homogenates of islets isolated from normal control and SRD-fed hamsters, as well as in their particulate and cytosolic fractions. We also measured transcription rate (mRNA by reverse transcriptase PCR) and expression levels (Western blotting) of both enzymes in these islets. We found an increase in HK activity and expression levels, without measurable changes in HK mRNA level in SRD-fed animals. Whereas a similar GK activity was measured in homogenates of islets isolated from both groups, such activity was significantly higher in the cytosolic fraction of SRD islets. On the other hand, GK transcription rate and expression level were similar in both experimental groups. Our results suggest that the increased beta-cell secretory response to low glucose can be partly ascribed to an increased activity of islet HK consecutive to an enhanced expression of the enzyme, while the enhanced response to high glucose could be due to changes in GK compartmentalization.
Assuntos
Glucoquinase/metabolismo , Hexoquinase/metabolismo , Ilhotas Pancreáticas/metabolismo , Sacarose/administração & dosagem , Animais , Glicemia/análise , Western Blotting/métodos , Peso Corporal/fisiologia , Cricetinae , Citosol/metabolismo , Dieta , Ingestão de Líquidos/fisiologia , Expressão Gênica/genética , Glucoquinase/análise , Glucoquinase/genética , Hexoquinase/análise , Hexoquinase/genética , Insulina/sangue , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Masculino , Mesocricetus , Fosforilação , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transcrição Gênica/genéticaRESUMO
The aim of this study was to quantify the glucose modulation of the plasma membrane calcium pump (PMCA) function in rat pancreatic islets. Ca2+-ATPase activity and levels of phosphorylated PMCA intermediates both transiently declined to a minimum in response to stimulation by glucose. Strictly dependent on Ca2+ concentration, this inhibitory effect was fully expressed at physiological concentrations of the cation (less than 0.5 muM), then progressively diminished at higher concentrations. These results, together with those previously reported on the effects of insulin secretagogues and blockers on the activity, expression and cellular distribution of the PMCA, support the concept that the PMCA plays a key role in the regulation of Ca2+ signaling and insulin secretion in pancreatic islets.
Assuntos
Cálcio/fisiologia , Membrana Celular/enzimologia , Ilhotas Pancreáticas/enzimologia , ATPases Transportadoras de Cálcio da Membrana Plasmática/fisiologia , Animais , Membrana Celular/efeitos dos fármacos , Glucose/farmacologia , Técnicas In Vitro , Ativação do Canal Iônico , Ilhotas Pancreáticas/efeitos dos fármacos , Isoenzimas/fisiologia , Masculino , Fosforilação , Ratos , Ratos WistarRESUMO
OBJECTIVE: In PROPAT we implemented an integrated approach to diabetes care designed to improve the quality and reduce the cost of care. STUDY DESIGN AND METHODS: PROPAT was a case-control study matching patients by age and gender (diabetes:control ratio 1:2) within IOMA, a public employment-based health maintenance organization (HMO) of the Province of Buenos Aires, Argentina. Costs were evaluated using prevalence data from an HMO perspective. We currently report clinical and biochemical data and costs from the first 297 patients enrolled who completed 1 year in PROPAT, and compare them with those derived from control patients. RESULTS: All recommended practices recorded as care provided at baseline increased significantly 1 year after implementing PROPAT, with a parallel significant improvement in several clinical and biochemical parameters, and markedly lower total annual per capita costs. CONCLUSIONS: These results demonstrate that the implementation of a comprehensive diabetes care program can simultaneously improve quality while reducing costs.
Assuntos
Diabetes Mellitus/economia , Desenvolvimento de Programas , Qualidade da Assistência à Saúde , Adulto , Idoso , Argentina/epidemiologia , Automonitorização da Glicemia/estatística & dados numéricos , Índice de Massa Corporal , Estudos de Casos e Controles , Controle de Custos/métodos , Efeitos Psicossociais da Doença , Custos e Análise de Custo/estatística & dados numéricos , Atenção à Saúde/economia , Atenção à Saúde/organização & administração , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Feminino , Hemoglobinas Glicadas/análise , Custos de Cuidados de Saúde/estatística & dados numéricos , Sistemas Pré-Pagos de Saúde/economia , Sistemas Pré-Pagos de Saúde/organização & administração , Sistemas Pré-Pagos de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Serviços Preventivos de Saúde/economia , Serviços Preventivos de Saúde/organização & administração , Atenção Primária à Saúde/estatística & dados numéricos , Desenvolvimento de Programas/estatística & dados numéricos , Qualidade da Assistência à Saúde/estatística & dados numéricosRESUMO
Plasma membrane Ca2+-ATPase activity was measured in rat islet homogenates. The enzyme was inhibited, in a dose-dependent manner, when the islets were preincubated for 5 min with different concentrations of glucose (2 to 16 mM). This inhibition disappeared almost entirely after 15 min incubation, regardless of the glucose concentration in the medium. Simultaneous measurement of insulin in the medium revealed a stimulatory effect of glucose upon insulin secretion. The Ca2+-ATPase activity was also inhibited when the islets were preincubated for 3 min with other stimulators of insulin secretion such as gliclazide (76 microM), tolbutamide (1.5 mM), glucagon (1.4 microM) + theophylline (10 mM) and ketoisocaproic acid (15 mM). Conversely, the activity of the enzyme was significantly enhanced when the islets were preincubated briefly with the insulin secretion blocker, somatostatin (1.4 microM). Neither glucose nor any of the other substances tested when added directly to the enzyme assay medium modified significantly the Ca2+-ATPase activity measured in the islet homogenates. These results would suggest that the activity of the islet plasma membrane is modulated by one or more of the intracellular metabolites produced when the islets are challenged by the insulin stimulator or blocking agents.
Assuntos
ATPases Transportadoras de Cálcio/metabolismo , Insulina/metabolismo , Ilhotas Pancreáticas/enzimologia , Animais , Caproatos/farmacologia , Membrana Celular/enzimologia , Gliclazida/farmacologia , Glucagon/farmacologia , Glucose/farmacologia , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Cetoácidos/farmacologia , Cinética , Masculino , Ratos , Somatostatina/farmacologia , Teofilina/farmacologia , Tolbutamida/farmacologiaRESUMO
Multilamellar liposomes of dimyristoylphosphatidylcholine are susceptible to lytic action of lysophosphatidylcholine at the gel state, an effect which is not observed when liposomes are in the liquid crystalline state. The lytic action has been found to be enhanced when liposomes are dispersed in hypertonic solutions. On the contrary, hypotonic solutions decreased the effectiveness of the lysolipid. Shrunken liposomes present surface changes as detected by merocyanine 540 and 1-anilinonaphthalene-8-sulfonic acid which can be ascribed to the spontaneous curvature promoted by shrinkage.
Assuntos
Lipossomos , Lisofosfatidilcolinas/farmacologia , Dimiristoilfosfatidilcolina , Géis , Soluções Hipertônicas , Soluções Hipotônicas , Lipossomos/metabolismo , Micelas , NAD/metabolismo , Osmose , Espectrometria de Fluorescência , EspectrofotometriaRESUMO
Ca2+-ATPase activity was measured in rat islet homogenates, in a medium of low ionic strength containing a low concentration of Ca2+ and Mg2+ and devoid of K+. The enzyme activity was highly sensitive to inhibition by compound 48/80 (a calmodulin inhibitor), stimulated by 120 nM calmodulin and slightly affected by 10 mM NaN3. The addition of Mg2+ to the assay medium promotes the disappearance of apparent Ca2+-ATPase activity. Ouabain (0.1 mM) did not modify this ATPase activity. The enzyme showed two kinetic components for Ca2+ as well as for ATP: one with high apparent affinity and low maximum velocity and the other with low apparent affinity and high maximum velocity. Incubation of islet homogenates in this assay medium with [gamma-32P]ATP in the presence of proteolytic inhibitors, results in the appearance of a single labelled band of 130 kDa, identified by gel electrophoresis. The incorporation of 32P into this band was similar in the presence of either 2.8 or 50 microM Ca2+ and susceptible to hydroxylamine attack. The results indicate that, under the conditions described above, the Ca2+-ATPase activity evidenced in the islet homogenates had characteristics resembling those of the enzyme which catalyzes the outward Ca2+ transport. On the other hand, the method could provide a useful tool to test the effect of different agents which affect insulin secretion upon the islet plasma membrane Ca2+-ATPase activity.
Assuntos
ATPases Transportadoras de Cálcio/metabolismo , Ilhotas Pancreáticas/enzimologia , Trifosfato de Adenosina/farmacologia , Animais , Cálcio/farmacologia , ATPases Transportadoras de Cálcio/antagonistas & inibidores , Cinética , Magnésio/farmacologia , Masculino , Concentração Osmolar , Fosforilação , Ratos , Ratos Endogâmicos , p-Metoxi-N-metilfenetilamina/farmacologiaRESUMO
The aim of this work was the identification of the calmodulin-stimulated protein phosphatase, calcineurin, in rat pancreatic islets. For this purpose, a high-affinity calcineurin antibody and the Western blotting technique were used to detect the presence of calcineurin in freshly collagenase-isolated islets. The calcineurin content detected by this method was about 0.30 ng islet (approx. 0.07% of the total islet protein). The subunit composition and Mr of islet calcineurin were similar to those of bovine brain calcineurin. Incubation of nitrocellulose membranes of the Western blotting, containing the islet protein fractions, with 125I-labeled calmodulin and 45Ca2+ demonstrated that the A subunit bound calmodulin, while the B subunit bound Ca2+. The presence of calcineurin in the islets of Langerhans would suggest its possible participation, as a counterpart of the kinases effect, in the regulatory mechanism of insulin secretion.
Assuntos
Proteínas de Ligação a Calmodulina/análise , Ilhotas Pancreáticas/enzimologia , Fosfoproteínas Fosfatases/análise , Animais , Western Blotting , Calcineurina , Cálcio/metabolismo , Calmodulina/metabolismo , Proteínas de Ligação a Calmodulina/isolamento & purificação , Proteínas de Ligação a Calmodulina/metabolismo , Substâncias Macromoleculares , Masculino , Peso Molecular , Fosfoproteínas Fosfatases/isolamento & purificação , Fosfoproteínas Fosfatases/metabolismo , Ligação Proteica , Ratos , Ratos EndogâmicosRESUMO
The effect of insulin on the bilayer properties of dimyristoylphosphatidylcholine liposomes at the gel and the liquid crystalline state was measured by differential scanning calorimetry and absorbance at 450 nm. It is found that insulin promotes a decrease in the enthalpy of the gel-liquid crystalline transition without displacing the transition temperature. Under these conditions the lytic action of monomyristoylphospatidylcholine is enhanced, decreasing the critical lytic concentrations to values comparable to the bilayer at the gel state. The effect of the lysoderivate on liposomes in contact with increasing concentrations of insulin promotes a reorganization of the lipids into smaller particles as inferred from fluorescence dequenching, turbidity and exclusion chromatography assay. It is concluded that the action of lysoderivates can be enhanced, at temperatures above the transition temperature, by proteins that without spanning the lipid bilayers can perturb the bilayer interface.
Assuntos
Insulina/farmacologia , Bicamadas Lipídicas/química , Lipossomos/química , Lisofosfatidilcolinas/farmacologia , Varredura Diferencial de Calorimetria , Fenômenos Químicos , Físico-Química , Dimiristoilfosfatidilcolina/química , TemperaturaRESUMO
Erythrocyte membranes drawn from diabetic patients with poor metabolic control have increased protein glycosylation and decreased Ca2(+)-ATPase activity. A significant relationship was found between these two parameters. Similar results were obtained when protein glycosylation and Ca2(+)-ATPase activity were measured in membranes from normal erythrocytes preincubated with glucose. In this condition, both parameters showed a clear time and dose dependence. Incubation of erythrocyte membranes instead of intact erythrocytes with glucose and glucose-6-phosphate strongly suggests that only the glycosylation of the membrane inner-surface proteins can affect Ca2(+)-ATPase activity. The simultaneous presence of 10 mM glucose and 5 mM ATP in the incubation medium did not affect the degree of erythrocyte membrane protein glycosylation but significantly blocked the inhibitory effect of glucose on Ca2(+)-ATPase activity. However, 5 mM ATP only partially blocked the inhibitory effect of 100 mM glucose, suggesting a competitive mechanism of glucose and ATP for the enzyme active site. Our results show that glycosylation of erythrocyte membrane proteins significantly inhibits Ca2(+)-ATPase activity. This effect could contribute to the development of the capillary closure process observed in diabetic patients. Furthermore, it could represent an index of a general impairment of enzyme function arising in cells chronically exposed to high glucose levels.
Assuntos
ATPases Transportadoras de Cálcio/sangue , Membrana Eritrocítica/metabolismo , Adolescente , Adulto , Proteínas Sanguíneas/metabolismo , Meios de Cultura , Diabetes Mellitus Tipo 1/sangue , Relação Dose-Resposta a Droga , Feminino , Glucose/farmacologia , Glucose-6-Fosfato , Glucofosfatos/farmacologia , Glicosilação , Humanos , Concentração de Íons de Hidrogênio , Hiperglicemia/sangue , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
OBJECTIVE: To implement an educational program in 10 Latin American countries and to evaluate its effect on the clinical, biochemical, and therapeutic aspects as well as the economic cost of diabetes. RESEARCH DESIGN AND METHODS: Educators from each participating country were previously trained to implement the educational model. The patient population included 446 individuals with type 2 diabetes; all patients were <65 years of age, did not require insulin for metabolic control, did not have severe complications of diabetes or life-limiting illnesses, and had not previously participated in diabetes education courses. Clinical and therapeutic data and the cost of their pharmacological treatment were collected 6 months before participation in the educational program (-6 months), on entry into the program (time 0), and at 4, 8, and 12 months after initiation of the program. RESULTS: All parameters measured had improved significantly (P < 0.001) by 1 year: fasting blood glucose (mean +/- SD) 10.6 +/- 3.5 vs. 8.7 +/- 3.0 mmol/l; HbA(1c) 9.0 +/- 2.0 vs. 7.8 +/- 1.6%; body weight 84.6 +/- 14.7 vs. 81.2 +/- 15.2 kg; systolic blood pressure 149.6 +/- 33.6 vs. 142.9 +/- 18.8 mmHg; total cholesterol 6.1 +/- 1.1 vs. 5.4 +/- 1.0 mmol/l; and triglycerides 2.7 +/- 1.8 vs. 2.1 +/- 1.2 mmol/l. At 12 months, the decrease in pharmacotherapy required for control of diabetes, hypertension, and hyperlipidemia represented a 62% decrease in the annual cost of treatment ($107,939.99 vs. $41,106.30 [U.S.]). After deducting the additional cost of glucosuria monitoring ($30,604), there was still a 34% annual savings. CONCLUSIONS: The beneficial results of this educational model, implemented in 10 Latin American countries, reinforce the value of patient education as an essential part of diabetes care. They also suggest that an educational approach promoting healthy lifestyle habits and patient empowerment is an effective strategy with the potential to decrease the development of complications related to diabetes as well as the socioeconomic costs of the disease.
Assuntos
Diabetes Mellitus Tipo 2/reabilitação , Modelos Educacionais , Educação de Pacientes como Assunto , Adulto , Anticolesterolemiantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Glicemia/análise , Pressão Sanguínea , Colesterol/sangue , Currículo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Avaliação Educacional , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , América Latina , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Seleção de Pacientes , Fatores de Tempo , Triglicerídeos/sangueRESUMO
OBJECTIVE: To evaluate the indirect costs of diabetes and show their relationship to the chronic complications of diabetes. RESEARCH DESIGN AND METHODS: The cost of temporary and permanent disability for diabetic patients was studied in a group of La Plata University employees and in a second group at the government institutions of the Buenos Aires Province during 3 consecutive yr (1984-1986). RESULTS: Absences due to temporary disability were similar for the diabetic group without chronic complications and an age- and sex-matched nondiabetic control group. Conversely, diabetic patients with chronic complications had major increases in absences compared with the control subjects. Diabetes mellitus was the third leading cause of permanent disability mainly due to macrovascular and retinal lesions. This disability resulted in an average of 11 yr of work production loss per patient. CONCLUSIONS: These results suggest that diabetic individuals without complications incur few additional costs compared with nondiabetic individuals. However, once complications appear, the indirect costs are very high, suggesting that secondary preventions of the diabetic complications might be an optimal approach for reducing the health-care burden of diabetes.