RESUMO
OBJECTIVE: LIN28 control cells reprogramming and pluripotency mainly through miRNA regulation and has been overexpressed in many advanced cancers. In this study, we evaluated the prognostic role of LIN28 and its regulatory miRNAs in a large cohort of adrenocortical tumours (ACTs). PATIENTS AND METHODS: LIN28 protein expression was assessed in 266 adults ACTs (78 adenomas and 188 carcinomas) from Brazil and Germany. LIN28A and LIN28B gene expression was analysed in 59 ACTs (31 adenomas and 28 carcinomas) and copy number variation in 39 ACTs. In addition, we determined the expression of let-7 family, mir-9, mir-30 and mir-125 in 28 carcinomas. RESULTS: LIN28A gene was overexpressed in aggressive ACCs when compared with adenomas and nonaggressive ACCs, but no LIN28A copy number variation was found in ACTs. Unexpectedly, weak LIN28 protein expression was significantly associated with reduced disease-free survival in ACC patients (P = 0·01), but for overall survival only a trend was detectable (P = 0·117). In the multivariate analysis, only Ki67 index ≥10% (HR 4·6, P = 0·000) and weak LIN28 protein expression (HR 2·0, P = 0·03) were independent predictors of recurrence in ACC patients. Interestingly, mir-9 expression, a negative LIN28A/B regulator, was significantly higher in aggressive than in nonaggressive ACCs [2076 (from 36 to 9307) vs 133·4 (from 2·4 to 5193); P = 0·011] and was highly associated with reduced overall (P = 0·01) and disease-free survival (P = 0·01). However, mir-9 prognostic role should be further evaluated in a larger cohort. CONCLUSION: Weak LIN28 protein expression was associated with recurrence in ACCs. Additionally, overexpression of mir-9, a negative LIN28A regulator, was associated with poor outcome.
Assuntos
Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Adenoma/genética , Adenoma/metabolismo , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/metabolismo , Adulto , Brasil , Estudos de Coortes , Variações do Número de Cópias de DNA , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Alemanha , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Resultado do TratamentoAssuntos
Fármacos do Sistema Nervoso Central/uso terapêutico , Agonistas de Dopamina/efeitos adversos , Frutose/análogos & derivados , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/etiologia , Neoplasias Hipofisárias/complicações , Prolactinoma/complicações , Encéfalo/diagnóstico por imagem , Cabergolina , Criança , Agonistas de Dopamina/uso terapêutico , Ergolinas/efeitos adversos , Ergolinas/uso terapêutico , Frutose/uso terapêutico , Humanos , Masculino , Transtornos de Enxaqueca/diagnóstico por imagem , Transtornos de Enxaqueca/metabolismo , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/cirurgia , Prolactinoma/diagnóstico por imagem , Prolactinoma/tratamento farmacológico , Prolactinoma/cirurgia , TopiramatoRESUMO
BACKGROUND Juvenile hemochromatosis is a rare genetic disease that leads to intense iron accumulation. The disease onset usually occurs before the third decade of life and causes severe dysfunction in various organs. The most classical clinical findings are hypogonadotropic hypogonadism, cardiomyopathy, liver fibrosis, glycemic changes, arthropathy and skin pigmentation. However, secondary hypothyroidism is not reported in these patients. Juvenile hemochromatosis has an autosomal recessive inheritance and might be type 2A or type 2B, due to mutation in either the hemojuvelin gene (HJV) or hepcidin antimicrobial peptide (HAMP) gene. CASE REPORT A 26-year-old female patient was admitted with a recent history of diabetic ketoacidosis. Three months after that admission, she presented with arthralgia, diffuse abdominal pain, adynamia, hair loss, darkening of the skin and amenorrhea. Severe iron overload was found and findings in the hepatic biopsy were compatible with hemochromatosis. An upper abdominal magnetic resonance imaging (MRI) showed iron deposition in the liver and pancreas and pituitary MRI exhibited accumulation on the anterior pituitary. After 16 months the patient presented with dyspnea and lower limb edema, and cardiac MRI indicated iron deposition in the myocardium. The patient was diagnosed with juvenile hemochromatosis presenting with hypogonadotropic hypogonadism, cardiomyopathy, insulin-dependent diabetes mellitus, and secondary hypothyroidism. A novel homozygous mutation, c.697delC, in the HJV gene was detected. CONCLUSIONS We describe for the first time a severe and atypical case of juvenile hemochromatosis type 2A presenting classical clinical features, as well as secondary hypothyroidism resulting from a novel mutation in the HJV gene.
Assuntos
Proteínas Ligadas por GPI/genética , Proteína da Hemocromatose/genética , Hemocromatose/congênito , Adulto , Diabetes Mellitus Tipo 1/complicações , Feminino , Hemocromatose/complicações , Hemocromatose/diagnóstico , Hemocromatose/genética , Humanos , Hipogonadismo/etiologia , Hipotireoidismo/etiologia , Sobrecarga de Ferro/sangue , MutaçãoRESUMO
BACKGROUND: Discrimination between benign and malignant tumors is a challenging process in pediatric adrenocortical tumors. New insights in the metabolic profile of pediatric adrenocortical tumors may contribute to this distinction, predict prognosis, as well as identify new molecular targets for therapy. The aim of this work is to characterize the expression of the metabolism-related proteins MCT1, MCT2, MCT4, CD147, CD44, GLUT1 and CAIX in a series of pediatric adrenocortical tumors. METHODS: A total of 50 pediatric patients presenting adrenocortical tumors, including 41 clinically benign and 9 clinically malignant tumors, were included. Protein expression was evaluated using immunohistochemistry in samples arranged in tissue microarrays. RESULTS: The immunohistochemical analysis showed a significant increase in plasma membrane expression of GLUT1 in malignant lesions, when compared to benign lesions (p=0.004), being the expression of this protein associated with shorter overall and disease-free survival (p=0.004 and p=0.001, respectively). Although significant differences were not observed for proteins other than GLUT1, MCT1, MCT4 and CD147 were highly expressed in pediatric adrenocortical neoplasias (around 90%). CONCLUSION: GLUT1 expression was differentially expressed in pediatric adrenocortical tumors, with higher expression in clinically malignant tumors, and associated with shorter survival, suggesting a metabolic remodeling towards a hyperglycolytic phenotype in this malignancy.
RESUMO
Adrenocortical carcinomas (ACCs) are complex neoplasias that may present unexpected clinical behavior, being imperative to identify new biological markers that can predict patient prognosis and provide new therapeutic options. The main aim of the present study was to evaluate the prognostic value of metabolism-related key proteins in adrenocortical carcinoma. The immunohistochemical expression of MCT1, MCT2, MCT4, CD147, CD44, GLUT1 and CAIX was evaluated in a series of 154 adult patients with adrenocortical neoplasia and associated with patients' clinicopathological parameters. A significant increase in was found for membranous expression of MCT4, GLUT1 and CAIX in carcinomas, when compared to adenomas. Importantly MCT1, GLUT1 and CAIX expressions were significantly associated with poor prognostic variables, including high nuclear grade, high mitotic index, advanced tumor staging, presence of metastasis, as well as shorter overall and disease free survival. In opposition, MCT2 membranous expression was associated with favorable prognostic parameters. Importantly, cytoplasmic expression of CD147 was identified as an independent predictor of longer overall survival and cytoplasmic expression of CAIX as an independent predictor of longer disease-free survival. We provide evidence for a metabolic reprogramming in adrenocortical malignant tumors towards the hyperglycolytic and acid-resistant phenotype, which was associated with poor prognosis.
Assuntos
Neoplasias do Córtex Suprarrenal/química , Adenoma Adrenocortical/química , Carcinoma Adrenocortical/química , Biomarcadores Tumorais/análise , Metabolismo Energético , Adolescente , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/terapia , Adenoma Adrenocortical/mortalidade , Adenoma Adrenocortical/patologia , Adenoma Adrenocortical/terapia , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/análise , Basigina/análise , Anidrase Carbônica IX , Anidrases Carbônicas/análise , Intervalo Livre de Doença , Feminino , Transportador de Glucose Tipo 1/análise , Humanos , Receptores de Hialuronatos/análise , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Transportadores de Ácidos Monocarboxílicos/análise , Proteínas Musculares/análise , Gradação de Tumores , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Simportadores/análise , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Low DICER1 expression was associated with poor outcome in several cancers. Recently, hot-spot DICER1 mutations were found in ovarian tumors, and TARBP2 truncating mutations in tumor cell lines with microsatellite instability. In this study, we assessed DICER1 e TRBP protein expression in 154 adult adrenocortical tumors (75 adenomas and 79 carcinomas). Expression of DICER1 and TARBP2 gene was assessed in a subgroup of 61 tumors. Additionally, we investigated mutations in metal biding sites located at the RNase IIIb domain of DICER1 and in the exon 5 of TARBP2 in 61 tumors. A strong DICER1 expression was demonstrated in 32% of adenomas and in 51% of carcinomas (p = 0.028). Similarly, DICER1 gene overexpression was more frequent in carcinomas (60%) than in adenomas (23%, p = 0.006). But, among adrenocortical carcinomas, a weak DICER1 expression was significantly more frequent in metastatic than in non-metastatic adrenocortical carcinomas (66% vs. 31%; p = 0.002). Additionally, a weak DICER1 expression was significantly correlated with a reduced overall (p = 0.004) and disease-free (p = 0.005) survival. In the multivariate analysis, a weak DICER1 expression (p = 0.048) remained as independent predictor of recurrence. Regarding TARBP2 gene, its protein and gene expression did not correlate with histopathological and clinical parameters. No variant was identified in hot spot areas of DICER1 and TARBP2. In conclusion, a weak DICER1 protein expression was associated with reduced disease-free and overall survival and was a predictor of recurrence in adrenocortical carcinomas.
Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma Adrenocortical/metabolismo , RNA Helicases DEAD-box/biossíntese , Ribonuclease III/biossíntese , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Adolescente , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/patologia , Adulto , Idoso , RNA Helicases DEAD-box/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Ligação a RNA/biossíntese , Proteínas de Ligação a RNA/genética , Ribonuclease III/genética , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
The aim of this article is to focus on the fixed-dose combination of phentermine and topiramate, a new antiobesity drug recently approved by the US FDA. The mechanisms of weight loss for each drug in monotherapy is described, followed by the rationale for its use as a combination therapy and a comprehensive review of recently published clinical trials that assessed its efficacy and safety.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Depressores do Apetite/uso terapêutico , Frutose/análogos & derivados , Obesidade/tratamento farmacológico , Fentermina/uso terapêutico , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Frutose/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Topiramato , Resultado do TratamentoRESUMO
Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. The incidence of pediatric adrenocortical tumors (ACT) is remarkably high in Southern Brazil, where it is estimated to be 15 times greater than the world occurrence, due to a high frequency of a germline mutation (p.R337H) of the TP53 gene. Differently from adults, pediatric adrenocortical neoplasms with apparently poor prognosis based on histopathological features have often a good clinical outcome. A high Weiss score is definitely not a good predictor of survival in children, but it is much more discriminative of a poor outcome in adult tumors. Besides important differences in prognosis, adrenocortical tumorigenesis has distinct patterns between children and adults. In this review, we summarize recent data from ours and other Institutions, showing that the prognostic importance of molecular markers is striking different between pediatric and adult ACT. Although the majority of pediatric ACT are associated with p.R337H germline mutation, it is not a predictor of poor outcome in children and adolescents with ACT. On the other side, TP53 somatic mutations define a subgroup of adult ACC with different tumorigenesis and unfavorable prognosis. IGF system has a central role in the malignant phenotype of ACT, but in adult tumors it is mediated by IGF2 over-expression and in pediatric tumors by IGF1R over-expression. Finally, SF1 over-expression is associated with decreased overall survival and recurrence-free survival in adult ACC, but not in the pediatric group. In conclusion, discriminating benign and malignant behavior is more challenging in pediatric ACT than in adult tumors.
Assuntos
Neoplasias do Córtex Suprarrenal , Biomarcadores Tumorais , Transformação Celular Neoplásica , Mutação em Linhagem Germinativa , Adolescente , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias do Córtex Suprarrenal/mortalidade , Adulto , Fatores Etários , Substituição de Aminoácidos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Mutação de Sentido Incorreto , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Recidiva , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: A recent microarray study identified a set of genes whose combined expression patterns were predictive of poor outcome in a cohort of adult adrenocortical tumors (ACTs). The difference between the expression values measured by qRT-PCR of DLGAP5 and PINK1 genes was the best molecular predictor of recurrence and malignancy. Among the adrenocortical carcinomas, the combined expression of BUB1B and PINK1 genes was the most reliable predictor of overall survival. The prognostic and molecular heterogeneity of ACTs raises the need to study the applicability of these molecular markers in other cohorts. OBJECTIVE: To validate the combined expression of BUB1B, DLGAP5, and PINK1 as outcome predictor in ACTs from a Brazilian cohort of adult and pediatric patients. PATIENTS AND METHODS: BUB1B, DLGAP5, and PINK1 expression was assessed by quantitative PCR in 53 ACTs from 52 patients - 24 pediatric and 28 adults (one pediatric patient presented a bilateral asynchronous ACT). RESULTS: DLGAP5-PINK1 and BUB1B-PINK1 were strong predictors of disease-free survival and overall survival, respectively, among adult patients with ACT. In the pediatric cohort, these molecular predictors were only marginally associated with disease-free survival but not with overall survival. CONCLUSION: This study confirms the prognostic value of the combined expression of BUB1B, DLGAP5, and PINK1 genes in a Brazilian group of adult ACTs. Among pediatric ACTs, other molecular predictors of outcome are required.
Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Adolescente , Neoplasias do Córtex Suprarrenal/genética , Biomarcadores Tumorais/metabolismo , Brasil , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas de Neoplasias/genética , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases/genéticaRESUMO
BACKGROUND: A 33-year-old woman presented to an endocrinology clinic with a 5-year history of secondary amenorrhea. 2 years before presentation, she had noticed progressively worsening signs of virilization. INVESTIGATIONS: Measurement of levels of serum free and total testosterone, androstenedione, dehydroepiandrosterone sulfate and gonadotropins; transvaginal ultrasonography, abdominal and pelvic MRI and (18)F-fluorodeoxyglucose PET imaging. DIAGNOSIS: Virilization secondary to an ovarian Leydig cell tumor. MANAGEMENT: The patient underwent a left salpingo-oophorectomy that confirmed the diagnosis of a unilateral Leydig cell tumor. Complete normalization of androgens and gonadotropin levels was achieved after surgery.
Assuntos
Tumor de Células de Leydig/diagnóstico , Neoplasias Ovarianas/diagnóstico , Virilismo/diagnóstico , Adulto , Feminino , Humanos , Tumor de Células de Leydig/sangue , Tumor de Células de Leydig/cirurgia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/cirurgia , Pré-Menopausa/sangue , Virilismo/sangue , Virilismo/cirurgiaRESUMO
Obesity prevalence has risen dramatically over the past decades, which poses a great number of patients at risk of metabolic and cardiovascular complications. Long-term efficacy of lifestyle modification isolated has shown to be modest which, therefore, urges the need of more aggressive interventions such as adjuvant pharmacotherapy or the more radical surgical approach. Bariatric surgery has proven to date to be the most effective treatment, although it may be associated with nutritional and metabolic complications not yet completely recognized. By contrast, there is limited availability of antiobesity agents currently in the market, as well as historical facts involving the suspension of previously existing medications due to safety concerns. This article aims to present recent data on clinical trials of novel weight-loss drugs with short perspective to enter the market, if approved by the regulatory agencies. This review will discuss the efficacy and safety of these compounds, which include lorcaserin (selective serotonin 5-HT2c agonist), tesofensine (triple monoamine reuptake inhibitor), liraglutide (GLP-1 analogue) and cetilistat (gastrointestinal lipase inhibitor), as well as the combination therapies of bupropion/naltrexone, bupropion/zonisamide, phentermine/topiramate and pramlintide/metreleptin.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Obesidade/tratamento farmacológico , Fármacos Antiobesidade/efeitos adversos , Cirurgia Bariátrica , Doenças Cardiovasculares/induzido quimicamente , Quimioterapia Combinada/métodos , Humanos , Obesidade/metabolismo , Obesidade/cirurgia , Fatores de RiscoRESUMO
Obesity is a chronic disease associated with excess morbidity and mortality. Clinical treatment, however, currently offers disappointing results, with very high rates of weight loss failure or weight regain cycles, and only two drugs (orlistat and sibutramine) approved for long-term use. Drugs combinations can be an option for its treatment but, although widely used in clinical practice, very few data are available in literature for its validation. Our review focuses on the rationale for their use, with advantages and disadvantages; on combinations often used, with or without studies; and on new perspectives of combinations being studied mainly by the pharmaceutical industry.
RESUMO
O aumento da prevalência da obesidade, nas últimas décadas, é alarmante, o que implica um grande número de pacientes sob risco de complicações metabólicas e cardiovasculares associadas. A eficácia modesta a longo prazo das modificações de estilo de vida isoladamente exige a necessidade de intervenções mais agressivas, seja por meio do uso adjuvante de medicamentos ou da abordagem mais radical cirúrgica. A cirurgia bariátrica, embora até hoje tenha se mostrado o método mais efetivo de tratamento dessa enfermidade, pode estar associada a complicações nutricionais e metabólicas ainda não totalmente esclarecidas. Contrasta com esse fato a disponibilidade limitada de agentes antiobesidade atualmente no mercado, além de fatos históricos que envolveram a suspensão de alguns fármacos previamente existentes, por questões de segurança. Este artigo tem como objetivo apresentar dados recentes de estudos clínicos de novas drogas propostas para o tratamento da obesidade com perspectivas breves de serem lançadas no mercado, caso passem pela aprovação das agências regulatórias. Nesta revisão serão discutidas a eficácia e a segurança desses fármacos, que incluem a lorcaserina (agonista serotoninérgico seletivo 5-HT2c), tesofensina (inibidor triplo de recaptação de monoaminas), liraglutide (análogo do GLP-1) e cetilistate (inibidor de lipases gastrointestinais), além das combinações de bupropiona/naltrexona, bupropiona/zonisamida, fentermina/topiramato e pramlintide/metreleptina.
Obesity prevalence has risen dramatically over the past decades, which poses a great number of patients at risk of metabolic and cardiovascular complications. Long-term efficacy of lifestyle modification isolated has shown to be modest which, therefore, urges the need of more aggressive interventions such as adjuvant pharmacotherapy or the more radical surgical approach. Bariatric surgery has proven to date to be the most effective treatment, although it may be associated with nutritional and metabolic complications not yet completely recognized. By contrast, there is limited availability of antiobesity agents currently in the market, as well as historical facts involving the suspension of previously existing medications due to safety concerns. This article aims to present recent data on clinical trials of novel weight-loss drugs with short perspective to enter the market, if approved by the regulatory agencies. This review will discuss the efficacy and safety of these compounds, which include lorcaserin (selective serotonin 5-HT2c agonist), tesofensine (triple monoamine reuptake inhibitor), liraglutide (GLP-1 analogue) and cetilistat (gastrointestinal lipase inhibitor), as well as the combination therapies of bupropion/naltrexone, bupropion/zonisamide, phentermine/topiramate and pramlintide/metreleptin.
Assuntos
Humanos , Fármacos Antiobesidade/uso terapêutico , Obesidade/tratamento farmacológico , Fármacos Antiobesidade/efeitos adversos , Cirurgia Bariátrica , Doenças Cardiovasculares/induzido quimicamente , Quimioterapia Combinada/métodos , Obesidade/metabolismo , Obesidade/cirurgia , Fatores de RiscoRESUMO
OBJETIVO: Avaliar a variabilidade do controle glicêmico em pacientes com diabetes tipo1 (DM1) em acompanhamento ambulatorial. PACIENTES E MÉTODOS: Foram estudados 100 pacientes com DM1 (55 do sexo feminino), com idade de 18,6±9 anos, idade de diagnóstico de 12 anos (1-35) e duraçäo do diabetes de 5 anos (0,09-40), com tempo de seguimento de 4,3 anos (2-8,5). A HbA1c foi determinada por cromatografia de troca iônica (valor de referência: 2,4-6,2 por cento). RESULTADOS: Foram analisados os dados de 94 pacientes. A HbA1c inicial e final foi de 7,6±1,8 por cento e 8,7±2,1, com aumento absoluto de 1,1 por cento (-7; 7,2) e anual de 0,22 por cento (-3,5; 3,6). A HbA1c permaneceu inalterada em 2 pacientes (2,1 por cento), aumentou em 64 (68,1 por cento) e diminuiu em 28 (29,8 por cento). Do grupo geral, 48 pacientes (51,1 por cento) tiveram deterioraçäo, 12 (12,8 por cento) melhora, 21 (22,3 por cento) permaneceram com controle bom ou excelente e 13 (13,8 por cento) com controle glicêmico regular ou péssimo. O número de HbA1c realizadas no acompanhamento foi de 6 (3-10) por paciente. Houve diferença significativa quanto ao número de HbA1c realizadas entre o grupo que apresentou piora no controle glicêmico (7,2±2,1) e o que manteve controle regular ou péssimo (4,7±1) (p=0,003). A diferença intra-individual entre a maior e a menor HbA1c foi de 3,1 por cento (0,3-9,5). O coeficiente de variaçäo e o desvio padräo da HbA1c foi de 15,5±8,1 e 1,2±0,7 por cento, respectivamente, sendo menor nos pacientes que mantiveram controle excelente ou bom. A correlaçäo entre a HbA1c final e a inicial foi de r= 0,37 (p=0,000) e entre a HbA1c média durante o estudo e a inicial foi r= 0,71 (p=0,000). CONCLUSÄO: A maioria dos pacientes desta amostra apresentou piora do controle glicêmico durante acompanhamento ambulatorial de rotina havendo também grande variabilidade intra-individual do controle glicêmico. A HbA1c inicial do paciente mostrou-se um importante preditor do controle glicêmico