RESUMO
PURPOSE: To assess the efficacy, safety, and follow-up of 36-month treatment with ranibizumab in patients with diabetic macular edema (DME) in real-life setting. METHODS: This is a prospective phase 4 observational study. Between December 2013 and April 2015, 84 ophthalmologists enrolled a total of 290 adult patients initiating ranibizumab for visual impairment due to DME and treated them according to their routine practice. The primary outcome (mean change in best-corrected visual acuity [BCVA] after 12 months) was previously reported. Here, we present outcomes after 36 months of follow-up for BCVA and change in central subfield thickness (CSFT) and report how participating ophthalmologists treated DME over a 3-year period (number of visits and injections and evolution of treatment strategy). RESULTS: Of the 290 patients enrolled, 187 (64.5%) completed the 36 months of the study (entire cohort). In the entire cohort, 97 patients were treated exclusively with ranibizumab throughout the study, and 90 patients switched to other intravitreal treatments. Mean BCVA was 64.2 (20.1) letters, representing a gain of +4.1 (19.9) letters from baseline to month 36 (M36). CSFT improved over the study, and by M36 had decreased by 127 (138) µm compared to baseline. Over the 36 months of follow-up, patients in the entire cohort paid their ophthalmologists a mean of 30.9 (12.2) visits and had a mean of 7.6 (5.2) any injections. Results for quality of life questionnaires NEI-VFQ25 and HUI-3 remained stable throughout the study. Multivariate analysis on the 145 patients with evaluable BCVA data at M36 found that male gender and milder baseline DME characteristics (BCVA ≥59 and CSFT <500 µm) were predictive factors for achieving a BCVA of ≥70 letters at M36. This study did not find any new safety signals, compared to the known profile of ranibizumab. CONCLUSIONS: Gains in BCVA in this real-life study were lower than those observed in randomized clinical trials with ranibizumab, mainly due to undertreatment. Safety analysis of ranibizumab did not yield any new safety concerns.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Adulto , Inibidores da Angiogênese/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Masculino , Estudos Prospectivos , Qualidade de Vida , Ranibizumab/uso terapêutico , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular , Transtornos da Visão/diagnóstico , Transtornos da Visão/tratamento farmacológico , Transtornos da Visão/etiologia , Acuidade VisualRESUMO
PURPOSE: To report the real-world effectiveness and safety of ranibizumab 0.5 mg in patients with visual impairment due to diabetic macular edema (DME). METHODS: This is a French, 36-month, multicenter, observational cohort study. Between December 2013 and April 2015, ophthalmologists enrolled diabetic patients aged ≥18 years with DME-related visual impairment and for whom ranibizumab 0.5 mg was initiated. Here, we present the 12-month results from this cohort. The primary endpoint was the mean change in best-corrected visual acuity (BCVA); sample size calculations were based on RESTORE trial data (BCVA mean change = 6.8 letters, preci sion = 0.7 letters). Secondary endpoints included the change in central subfield thickness (CSFT), number of visits, number of injections received, and frequency of ocular and nonocular adverse events and serious adverse events. RESULTS: Between December 2013 and April 2015, a total of 290 patients with DME were enrolled by 84 ophthalmologists; 12-month data are available for 242 patients (due to low recruitment rates, precision was recalculated for 242 evaluable patients: the precision was then of 1.0 letters). Mean age (± standard deviation) was 66.1 ± 11.0 years and 56.6% were male. The mean baseline BCVA and CSFT were 59.2 letters (95% confidence interval [CI] 57.3, 61.0) and 457 µm (95% CI: 438, 476), respectively. At month 12, the mean gain in BCVA from baseline was 7.4 letters (95% CI: 5.4, 9.4), with 36.8% of patients with BCVA > 70 letters versus 13.2% at baseline. Mean change in CSFT was -125 µm (95% CI: -146, -103). The mean number of ranibizumab injections was 5.1 ± 2.3 over an average of 10.4 ± 3.0 visits. No new safety findings were identified. CONCLUSIONS: The BOREAL study confirms the effectiveness and safety of ranibizumab for the treatment of DME-related visual impairment in routine clinical practice with fewer injections than reported in clinical trials.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Ranibizumab/uso terapêutico , Transtornos da Visão/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Retinopatia Diabética/fisiopatologia , Feminino , Humanos , Injeções Intravítreas , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Acuidade Visual/fisiologiaRESUMO
BACKGROUND: Centenarians have been proposed as a model of successful aging but recent studies suggest a high prevalence of cardiovascular diseases. Some findings on their electrocardiograms (ECGs) are simply age-related and others mirror underlying diseases. We aimed to identify ECG features truly associated with extreme age. METHODS: Retrospective analysis of 55 centenarians hospitalized between January 2000 and June 2010. Each centenarian was matched with three octogenarians according to gender, presence of hypertension, aortic stenosis, heart failure, and ischemic heart disease. RESULTS: A history of hypertension was present in 32 (58%) centenarians, aortic stenosis in 6 (11%), heart failure in 8 (15%), and ischemic heart disease in 6 (11%). Centenarians had a higher heart rate than octogenarians (81 ± 15 bpm vs. 72 ± 15 bpm, respectively, P < 0.001) but were less frequently on beta-blockers (7% vs. 36%, respectively, P < 0.001). Centenarians displayed more frequently atrial premature beats than octogenarians (18% vs. 3%, respectively, P < 0.001) but tended to have less atrial fibrillation (15% vs. 22% respectively, P = 0.21). Centenarians had more frequently left QRS axis deviation (48% vs. 28%, P = 0.009) and Q waves (14% vs. 1%, P = 0.02). QT interval was more prolonged in centenarians (446 ± 42 ms vs. 429 ± 39 ms, P = 0.008). Two centenarians (4%) and 24 (15%) octogenarians had a strictly normal ECG (P = 0.02). CONCLUSIONS: Abnormal ECG is a common finding in centenarians, with different characteristics than in younger elderly individuals. These differences are unrelated to the presence of cardiac diseases.
Assuntos
Eletrocardiografia/estatística & dados numéricos , Avaliação Geriátrica/métodos , Avaliação Geriátrica/estatística & dados numéricos , Cardiopatias/epidemiologia , Cardiopatias/fisiopatologia , Frequência Cardíaca , Fatores Etários , Idoso de 80 Anos ou mais , Arritmias Cardíacas , Eletrocardiografia/métodos , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Paris/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Liver adenomatosis (LA) is a rare disease resulting from biallelic inactivation of the hepatocyte nuclear factor-1 alpha (HNF1A) gene, which induces the proliferation of adenoma cells in liver parenchyma. Liver adenomatosis has only been documented in case reports from patients carrying a HNF1A germline mutation. We have evaluated the frequency of LA among a large cohort of patients with HNF1A-maturity onset diabetes of the young (MODY), previously termed "MODY3," and herein describe its clinical, radiological, and pathological characteristics. METHODS: In all, 137 HNF1A-MODY subjects from 74 families were screened by liver ultrasonography in 13 centers, and 15 additional cases of LA were later included in the series. Liver adenomatosis was confirmed by liver computed tomography, magnetic resonance imaging (MRI), and/or histopathology. RESULTS: Among 137 carriers of an HNF1A mutation, 9 patients (6.5%) from seven families were diagnosed with LA. Diabetes mellitus was present in 87.5% of patients with LA. In 25% of patients, LA was diagnosed due to intra-abdominal or intratumoral bleeding. Liver biochemistry was near normal in all patients. Liver imaging showed adenomas of various sizes and numbers. On MRI, most nodules had the radiological characteristics of steatotic adenomas. Histopathological confirmation of LA was available in 13 cases, and these adenomas were mostly steatotic. Surgery was initially performed in 37.5% of patients, and liver disease progression was observed in 30%. No disease progression was observed in 14 pregnancies. CONCLUSIONS: The frequency of LA in a cohort of screened HNF1A-MODY patients and the high incidence of LA progression and/or hemorrhage warrants systematic screening for liver adenomatosis in HNF1A-MODY families.
Assuntos
Adenoma/genética , Diabetes Mellitus Tipo 2/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Neoplasias Hepáticas/genética , Mutação , Adenoma/diagnóstico por imagem , Adenoma/patologia , Adolescente , Adulto , Criança , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/patologia , Diagnóstico por Imagem/métodos , Saúde da Família , Feminino , França , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
In the context of implementing hospital reforms, the objective of this work was to compare practice in relation to evidence-based guidelines and recommendations for good practice in diabetes screening and management. Laboratory test consumption was determined for patients hospitalized for diabetes in 2005 in three public hospitals (one civilian, two military) taking care of diabetic patients and performing related biological tests. For the 395 admissions in these three hospitals during 2005 [Diagnosis-related group (DRG) 10M02V "Diabetes, age 36 to 69 years without co-morbidity"], the average length of stay and the number of biological acts ["B"] performed were lower than those given by the French national health cost study scale and by the Montpellier University Hospital database. In terms of qualitative coherence between the guidelines for treatment and the recommendations, the total number of biological acts ["B"] is higher than if one were to strictly apply the good practice suggested by the French Health Authority. These three hospitals have and apply different guidelines for practice in the area of diabetes management. The implementation of reforms such as DRG-based payment scales may be an additional leverage to ensure that the recommendations of best practices are effective. Improved methods and tools for data collection and monitoring are essential, especially for estimating revenue and expenditure.
Assuntos
Diabetes Mellitus/diagnóstico , Diabetes Mellitus/terapia , Economia Hospitalar , Reforma dos Serviços de Saúde , Administração Hospitalar/normas , Hospitais/normas , Prática Institucional/normas , Saúde Pública , Adulto , Idoso , Distribuição de Qui-Quadrado , Diabetes Mellitus/sangue , Grupos Diagnósticos Relacionados/economia , França , Hemoglobinas Glicadas/análise , Reforma dos Serviços de Saúde/economia , Hospitais Militares/normas , Humanos , Prática Institucional/economia , Tempo de Internação , Pessoa de Meia-Idade , Regionalização da Saúde , Fatores de TempoRESUMO
The aim of the observational pharmaco-epidemiological study Optimax II was to seek whether the pre-existence of a metabolic syndrome (MS) defined by the NCEP-ATP III criteria impacts blood pressure (BP) control in hypertensive patients receiving a fixed perindopril/indapamide combination therapy. The primary objective of the study was to compare in patients with and without MS the rate of BP control defined as a systolic BP < or = 140 mmHg and a diastolic BP < or = 90 mmHg. Patients were prospectively included and the follow-up lasted 6 months. The study population consisted of 24,069 hypertensive patients (56% men; mean age 62 +/- 11 years; 18% diabetics; mean BP at inclusion 162 +/- 13/93 +/- 9 mmHg). MS was found in 30.4% of the patients (n = 7322): 35.2% women and 20.1% men. Three therapeutic subgroups were constituted: Group A, previously untreated, received the combination therapy as initial treatment; Group B, previously treated but with unsatisfactory results and/or treatment intolerance, had its previous treatment switched to perindopril/indapamide; and Group C, previously treated, with good treatment tolerance but uncontrolled BP, received the study treatment in adjunction to the previous one. The normalization rate was 70.3% in group A, 68.4% in Group B, and 64.1% in Group C (p < 0.0001). The pre-existence of MS did not show any significant influence on these rates since BP lowering was -22.7 +/- 13.7 (SBP) and -12.0 +/- 10.0 mmHg (DBP) in patients without MS and 22.6 +/- 13.3 (SBP) and -12.1 +/- 9.7 (DBP) in those with MS. The results of this study show a significant effect of perindopril/indapamide treatment on systolic BP lowering, whatever the treatment status: initiation, switch, or adjunctive therapy, and independently from the presence or not of MS. This effect may be related to the specific vascular effect of the perindopril/indapamide combination, which has recently demonstrated in the ADVANCE trial its ability to reduce mortality, and cardiovascular and renal complications in diabetic patients.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Diuréticos/uso terapêutico , Hipertensão/tratamento farmacológico , Indapamida/uso terapêutico , Síndrome Metabólica/complicações , Perindopril/uso terapêutico , Idoso , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Diuréticos/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Indapamida/efeitos adversos , Masculino , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Perindopril/efeitos adversos , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Hypophosphatemia, a common metabolic disorder, is usually silent and diagnosed by blood tests. However, misdiagnosis may result in delayed phosphate repletion, responsible for significant morbidity and potential mortality. We report an exceptional case of hypophosphatemia-related, life-threatening encephalopathy. A 49-year-old type-1 diabetic woman was admitted to our intensive care unit with coma and severe ketoacidosis. Initial neurologic impairment worsened despite improvement in acid-base disturbances and glucose levels. The electroencephalogram showed bilateral spikes with a background theta wave rhythm. Profound hypophosphatemia <0.20 mmol/L (<0.6 mg/dL) was diagnosed. No other cause of encephalopathy was found. Prompt phosphate repletion resulted in progressive and complete recovery. This observation allowed us to study the relations between the coma depth, the electroencephalographic findings, and the serum phosphate concentrations. Our data strongly suggest that phosphate depletion-induced encephalopathy probably originates from direct impairment of cerebral electrophysiological activity rather than from cardiac flow alteration.
Assuntos
Encefalopatias Metabólicas , Cetoacidose Diabética/complicações , Hipofosfatemia , Encefalopatias Metabólicas/etiologia , Encefalopatias Metabólicas/fisiopatologia , Encefalopatias Metabólicas/terapia , Diabetes Mellitus Tipo 1 , Cetoacidose Diabética/diagnóstico , Cetoacidose Diabética/terapia , Eletroencefalografia , Feminino , Humanos , Hipofosfatemia/complicações , Hipofosfatemia/diagnóstico , Hipofosfatemia/terapia , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Drug treatment of 2 diabetes is intended to normalize glycosylated hemoglobin levels (HbA(1c)<6.5%) and thereby prevent the development of micro- and macrovascular complications. Oral antidiabetic agents target the metabolic abnormalities that cause diabetes. The two principal families of oral antidiabetic agents - insulin sensitizers and insulin secretagogues - can be taken together. Thiazolidinediones or glitazones (insulin sensitizers) improve peripheral tissue sensitivity to insulin. Metformin (an insulin sensitizer) reduces hepatic glucose production. Sulfonylureas and meglitinides (insulin secretagogues) stimulate insulin secretion and can cause hypoglycemia. GLP-1 (Glucagon-Like Peptide-1) analogs and DPP-IV (dipeptidyl-peptidase-IV) inhibitors are new drug classes currently under development.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Metformina/farmacologia , Metformina/uso terapêutico , Compostos de Sulfonilureia/farmacologia , Compostos de Sulfonilureia/uso terapêutico , Tiazolidinedionas/farmacologia , Tiazolidinedionas/uso terapêuticoRESUMO
Insulin secretagogues and insulin sensitizers can be combined with one another as well as with other treatments (described below). Alpha-glucosidase inhibitors delay intestinal absorption of carbohydrates and reduce postprandial glycemia. Orlistat and sibutramine improve insulin sensitivity by helping patients lose weight. Orlistat inhibits hydrolysis of dietary triglycerides. Sibutramine, a noradrenaline and serotonin reuptake inhibitor, reinforces feelings of satiety and increases energy expenditure. After approximately 10 years, insulin therapy is usually required together with oral antidiabetic agents (except glitazones) or alone if HbA(1c) (glycosylated hemoglobin) is>6.5%. New guidelines for management of type 2 diabetes were published in 2006.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Fármacos Antiobesidade/uso terapêutico , Inibidores de Glicosídeo Hidrolases , Humanos , Insulina/uso terapêuticoRESUMO
Advanced glycation end products (AGE) resulted from a reaction between free amino group of proteins and carbohydrates. This reaction is followed by oxidation and molecular rearrangement. Alternatively AGEs can be produced by glycolysis and oxidation. AGEs bind to a cellular receptor RAGE. RAGE engagement by ligands AGE, ß-amyloid peptide, and S100 calgranulin induces a stimulation of NADPH oxidase, reactive oxygen intermediate formation, NFκB activation and gene transcription. This cascade of reaction leads to an inflammatory reaction responsible for alteration of microvessels in the retina and the kidney. Blockade of RAGE by antibodies anti-RAGE, TTP488 (azeliragon), or rRAGE prevents or limits the deleterious effect of AGEs.
Assuntos
Produtos Finais de Glicação Avançada/efeitos adversos , Produtos Finais de Glicação Avançada/metabolismo , Saúde , Receptor para Produtos Finais de Glicação Avançada/agonistas , Animais , Humanos , Inflamação/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de SinaisRESUMO
Primary Sjögren syndrome (pSS) is a chronic systemic autoimmune disease characterized by xerophthalmia, xerostomia, and potential peripheral or central neurological involvement. In pSS, the prevalence of cognitive disorders is generally sparse across literature and the impact of pain on cognitive profile is unclear. The aim of this study was to determine the relation between pain, cognitive complaint, and impairment in a very homogenous population of 10 pSS patients with painful small fiber neuropathy (PSFN) and spontaneous cognitive complaint. Neurological exam, neuropsychological assessment, clinical evaluation measuring pain level, fatigue, anxiety, depression, and cognitive complaint were performed. Our results showed that 100% of patients had cognitive dysfunction especially in executive domain (80%). The most sensitive test was the Wisconsin Card Sorting Test (WCST), abnormal in 70% of our population. Moreover, we found clear cut significant correlations between pain levels and 3 measures of WCST: the number of errors (Râ=â-0.768, Pâ=â.0062), perseverations (Râ=â0.831, Pâ=â.0042), and categories (Râ=â0.705, Pâ=â.02). In the literature review, the impact of pain is underexplored and results could be discordant. In a homogeneous cohort of pSS patients with PSFN, a cognitive complaint seems to be a valid reflection of cognitive dysfunction marked by a specific executive profile found with the WCST. In this preliminary study, this profile is linked to the level of pain and highlights that an appropriate management of pain control and a cognitive readaptation in patients could improve the quality of life.
Assuntos
Cognição , Dor/psicologia , Síndrome de Sjogren/psicologia , Neuropatia de Pequenas Fibras/psicologia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Dor/complicações , Dor/fisiopatologia , Projetos Piloto , Síndrome de Sjogren/complicações , Síndrome de Sjogren/fisiopatologia , Neuropatia de Pequenas Fibras/complicações , Neuropatia de Pequenas Fibras/fisiopatologiaRESUMO
Nonautoimmune ketosis-prone diabetic syndromes are increasingly frequent in nonwhite populations. We have characterized a cohort of patients of sub-Saharan African origin who had ketosis-prone type 2 diabetes (n = 111), type 1 diabetes (n = 21), and type 2 diabetes (n = 88) and were admitted to a hospital for management of uncontrolled diabetes. We compared epidemiological, clinical, and metabolic features at diabetes onset and measured insulin secretion (glucagon-stimulated C-peptide) and insulin action (short intravenous insulin tolerance test) during a 10-year follow-up. Ketosis-prone type 2 diabetes shows a strong male predominance, stronger family history, higher age and BMI, and more severe metabolic decompensation than type 1 diabetes. In ketosis-prone type 2 diabetes, discontinuation of insulin therapy with development of remission of insulin dependence is achieved in 76% of patients (non-insulin dependent), whereas only 24% of patients remain insulin dependent. During evolution, ketosis-prone type 2 diabetes exhibit specific beta-cell dysfunction features that distinguish it from type 1 and type 2 diabetes. The clinical course of non-insulin-dependent ketosis-prone type 2 diabetes is characterized by ketotic relapses followed or not by a new remission. Progressive hyperglycemia precedes and is a strong risk factor for ketotic relapses (hazard ratio 38). The probability for non-insulin-dependent ketosis-prone type 2 diabetes to relapse is 90% within 10 years, of whom approximately 50% will become definitively insulin dependent. Insulin sensitivity is decreased in equal proportion in both ketosis-prone type 2 diabetes and type 2 diabetes, but improves significantly in non-insulin-dependent ketosis-prone type 2 diabetes, only after correction of hyperglycemia. In conclusion, ketosis-prone type 2 diabetes can be distinguished from type 1 diabetes and classical type 2 diabetes by specific features of clinical pathophysiology and also by the natural history of beta-cell dysfunction and insulin resistance reflecting a propensity to glucose toxicity.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Resistência à Insulina/fisiologia , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Adulto , África Subsaariana , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/classificação , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/classificação , Humanos , Insulina/sangue , Anticorpos Anti-Insulina/sangue , Secreção de Insulina , Ilhotas Pancreáticas/fisiopatologia , ObesidadeAssuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Hiperglicemia/prevenção & controle , Projetos de Pesquisa , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Interpretação Estatística de Dados , Diabetes Mellitus Tipo 2/complicações , Hemoglobinas Glicadas/metabolismo , Humanos , Hiperglicemia/complicações , Comportamento de Redução do Risco , Resultado do TratamentoRESUMO
Compliance with treatment is crucial to the optimal management of any chronic disease. Non-compliance with antihyperglycemic treatment is clearly a significant issue for patients with type 2 diabetes mellitus as it decreases the efficacy of the treatment and increases the risk of developing microvascular and macrovascular complications, therefore increasing the human and economic costs of this disease. The effect of low compliance on metabolic control has been shown to represent an increase of up to 1.4% in glycosylated hemoglobin. Achieving optimal compliance is therefore a therapeutic objective of prime importance. Many factors have been cited as contributing to poor compliance. Some of these, such as age, severe complications and disabilities, and social, educational, and financial difficulties, affect compliance with treatment in quite a significant manner, but are not modifiable by the healthcare provider. Other factors, such as the number of tablets per dose and polymedication, are modifiable but do not appear to be of major importance, whereas the frequency of administration is both an important and a modifiable factor affecting compliance with treatment. One strategy for optimization of compliance involves treatment of type 2 diabetes using oral antihyperglycemic agents with once-daily formulations. Recent data indicate that reducing the daily administration frequency of oral antihyperglycemic agents improves compliance with treatment and consequently metabolic control. Therefore, optimization of treatment through a reduction in the frequency of antihyperglycemic administration could be a valuable weapon in the battle to improve health outcomes and reduce the burden of type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Cooperação do Paciente , Resultado do Tratamento , Administração Oral , Diabetes Mellitus Tipo 2/terapia , Hemoglobinas Glicadas/análise , Custos de Cuidados de Saúde , Humanos , Estilo de VidaRESUMO
In vitro experiments and animal models indicate that advanced glycation end products (AGEs) may play a crucial role in the vascular dysfunctions observed in patients with diabetes mellitus. These results prompted us to study subrogate markers of inflammation or vascular dysfunction in type II diabetic patients. Monocyte count and activation are dependent upon macrophage colony stimulating factors (M-CSF). Soluble vascular cell adhesion molecule (sVCAM-1) blood levels have been proposed as a marker for endothelium activation. To explore a possible relationship between these factors in diabetic patients, we measured a chemically defined AGE, N(carboxymethyl)lysine-protein (CML-protein) in a group of normal subjects (n = 55) and of diabetic patients (n = 40) using ELISA. Simultaneously, we determined M-CSF and sVCAM-1 blood levels. We found that CML-protein blood levels were significantly higher in patients with diabetes compared to non-diabetic subjects (40.2 +/- 4.7 and 7.9 +/- 0.7 pmol/mg protein respectively, p < 0.0001). M-CSF was increased while sVCAM-1 blood levels were normal in the group of diabetics. M-CSF blood level was correlated to CML-protein blood level (p < 0.05). In addition CML-protein, M-CSF and sVCAM-1 were increased in patients with micro-angiopathy. These results suggest that AGE may contribute to vascular dysfunction including microangiopathy.
Assuntos
Angiopatias Diabéticas/sangue , Produtos Finais de Glicação Avançada/sangue , Lisina/análogos & derivados , Fator Estimulador de Colônias de Macrófagos/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Técnicas de Cocultura , Angiopatias Diabéticas/etiologia , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Ensaio de Imunoadsorção Enzimática , Eritrócitos/patologia , Feminino , Humanos , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Veias Umbilicais/citologia , Regulação para CimaRESUMO
OBJECTIVE: To evaluate the impact of optimization of treatment and improvement in observance awareness in patients with type 2 diabetes on compliance with oral antidiabetic drug therapy and long-term glycemic control. Method Evaluation of compliance with oral antidiabetic therapy and of HbA1c levels in a cohort of 4 802 patients with type 2 diabetes followed by their general practitioner, before and after 6 Months on optimized treatment: reduction in percentage of combination treatments from 69.5 to 56.8%, and increase in percentage of once-daily dosing regimen from 12 to 58.4%. RESULTS: Optimization of treatment led to an increase in the percentage of patients achieving optimal compliance with oral antidiabetic drug therapy from 44 to 69.5% after 6 Months (p<0.001). Metabolic control also improved, as evidenced by a decrease in HbA1c levels observed both in the whole cohort (7.5+/-1.6% to 6.9+/-1.2%; p<0.0005), as well as in individual therapeutic subgroups of patients (having switched from multiple-daily dosing to once-daily-dosing schedules and from gliclazide 80 to gliclazide 30 MR once-daily formulation). CONCLUSION: These findings suggest that optimization of oral antidiabetic therapy favoring the use of oral antidiabetic agents with once-daily dosing administration modalities may improve metabolic control in patients with type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Gliclazida/administração & dosagem , Hipoglicemiantes/administração & dosagem , Cooperação do Paciente , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Distribuição de Qui-Quadrado , Estudos de Coortes , Coleta de Dados , Interpretação Estatística de Dados , Diabetes Mellitus Tipo 2/sangue , Medicina de Família e Comunidade , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Inquéritos e Questionários , Fatores de TempoRESUMO
The prevalence of urinary tract infection (UTI) is high in patients with diabetes mellitus. They run a distinctly greater risk of complications than non-diabetics. Systematic antibiotic treatment is mandatory. Screening of UTI must be carried out in diabetics at least annually, and be considered when the metabolic control of diabetes becomes increasingly difficult without another clear explanation. Complicated forms are common. They comprise severe pyelonephritis and renal abscesses, emphysematous pyellitis and pyelonephritis, renal papillary necrosis and sepsis. Nosocomial UTI is frequent in such patients. Meticulous preventive measures are the best means of reducing the prevalence of UTI in diabetics.
Assuntos
Complicações do Diabetes , Infecções Urinárias/etiologia , Doença Aguda , Bacteriúria/tratamento farmacológico , Bacteriúria/etiologia , Cistite/tratamento farmacológico , Cistite/microbiologia , Humanos , Pielonefrite/complicações , Pielonefrite/epidemiologia , Pielonefrite/microbiologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologiaRESUMO
PURPOSE: To study spontaneous variations of central macular thickness (CMT) and its relation to blood pressure (BP) in patients with diabetic macular oedema (DME). METHODS: 23 diabetic patients presenting with DME with a CMT ≥ 260 µm on optical coherence tomography (OCT-3, Carl Zeiss Meditec, CA) were followed every 2 weeks for 3 months. At baseline, ambulatory 24H-BP monitoring (ABPM) was performed, as well as five CMT measurements (9 am, 12 am, 3 pm, 6 pm and 9 am the day after). During follow-up, BP and CMT were simultaneously measured at 9 am. RESULTS: Significant spontaneous variations in CMT (at least one change in CMT greater than 11% compared to the median CMT value) were observed over 3 months in 48% of patients. Mean CMT decreased over the day and increased during the night, but not significantly (p = 0.1). During the 6 visits, the CMT at 9 am positively correlated with the pulse pressure (PP) measured at the same time (r = 0.29, p = 0.0008). In addition, the mean 24H-CMT was positively correlated with the mean 24H- PP (r = 0.48, p = 0.02). CONCLUSION: Significant spontaneous changes in CMT of patients with DME were observed in nearly half of cases over 3 months. Retinal thickness was correlated to PP levels (patients with higher CMT had higher PP levels). This high variability of macular oedema, and the influence of BP on retinal thickness, should be taken into consideration by practitioners when evaluating the benefit of a therapy in DME.
Assuntos
Pressão Sanguínea/fisiologia , Retinopatia Diabética/fisiopatologia , Macula Lutea/patologia , Edema Macular/fisiopatologia , Idoso , Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Tomografia de Coerência Óptica , Acuidade VisualRESUMO
Insulin-dependent juvenile-onset diabetes may occur in the context of rare syndromic presentations suggesting monogenic inheritance rather than common multifactorial autoimmune type 1 diabetes. Here, we report the case of a Lebanese patient diagnosed with juvenile-onset insulin-dependent diabetes presenting ketoacidosis, early-onset retinopathy with optic atrophy, hearing loss, diabetes insipidus, epilepsy, and normal weight and stature, who later developed insulin resistance. Despite similarities with Wolfram syndrome, we excluded the WFS1 gene as responsible for this disease. Using combined linkage and candidate gene study, we selected ALMS1, responsible for Alström syndrome, as a candidate gene. We identified a novel splice mutation in intron 18 located 3 bp before the intron-exon junction (IVS18-3T>G), resulting in exon 19 skipping and consequent frameshift generating a truncated protein (V3958fs3964X). The clinical presentation of the patient significantly differed from typical Alström syndrome by the absence of truncal obesity and short stature, and by the presence of ketoacidotic insulin-dependent diabetes, optic atrophy and diabetes insipidus. Our observation broadens the clinical spectrum of Alström syndrome and suggests that ALMS1 mutations may be considered in patients who initially present with an acute onset of insulin-dependent diabetes.