RESUMO
In Spain, according to the Di@bet.es study, 13.8% of the adult population suffers from diabetes and 14.8% from some form of prediabetes (impaired glucose tolerance, impaired fasting glucose or both). Since early detection of prediabetes can facilitate the implementation of therapeutic measures to prevent its progression to diabetes, we believe that preventive strategies in primary care and specialized clinical settings should be agreed. Screening for diabetes and prediabetes using a specific questionnaire (FINDRISC) and/or the measurement of fasting plasma glucose in high risk patients leads to detecting patients at risk of developing diabetes and it is necessary to consider how they should be managed. The intervention in lifestyle can reduce the progression to diabetes and reverse a prediabetic state to normal and is a cost-effective intervention. Some drugs, such as metformin, have also been shown effective in reducing the progression to diabetes but are not superior to non-pharmacological interventions. Finally, an improvement in some cardiovascular risk factors has been observed although there is no strong evidence supporting the effectiveness of screening in terms of morbility and mortality. The Consensus and Clinical Guidelines Working Group of the Spanish Diabetes Society has issued some recommendations that have been agreed by the Sociedad Española de Endocrinología y Nutrición, Sociedad Española de Endocrinología Pediátrica, Sociedad Española de Farmacia Comunitaria, Sociedad Española de Medicina Familiar y Comunitaria, Sociedad Española de Médicos Generales, Sociedad Española de Médicos de Atención Primaria, Sociedad Española de Medicina Interna, Asociación de Enfermería Comunitaria and Red de Grupos de Estudio de la Diabetes en Atención Primaria.
Assuntos
Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/terapia , Algoritmos , Humanos , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND AND AIMS: Mediterranean diet (MedDiet) is causally related to diabetes and is a dietary pattern recommended to individuals with diabetes. We investigated MedDiet adherence in individuals with prediabetes and unknown (PREDM/UKDM) or known diabetes (KDM) compared to those with normal glucose metabolism (NORMAL). METHODS: This was a national, population-based, cross-sectional, cluster-sampling study. MedDiet adherence was scored (MedScore, mean ± SD 24 ± 5) using a qualitative food frequency questionnaire. Logistic regression was used to examine the association between MedScore and PREDM/UKDM or KDM versus control subjects. RESULTS: We evaluated 5,076 individuals. Mean age was 50 years, 57% were female, 826 (582/244) were PREDM/UKDM, 478 were KDM and 3,772 were NORMAL. Mean age increased across MedScore tertiles (46, 51 and 56 years, p < 0.0001). Higher age-adjusted adherence to MedDiet (5-unit increment in the MedScore) was associated with lower and nondifferent odds (OR, 95% CI) of prevalent PREDM/UKDM (0.88, 0.81-0.96, p = 0.001) and KDM (0.97, 0.87-1.07, p = 0.279), respectively, compared to individuals in the NORMAL group. CONCLUSIONS: In a representative sample of the whole Spanish population, MedDiet adherence is independently associated with PREDM/UKDM. Therapeutic intervention may be, in part, responsible for the lack of differences in adherence observed between the KDM and NORMAL groups. However, reverse causation bias cannot be ruled out in cross-sectional studies.
Assuntos
Glicemia/análise , Diabetes Mellitus/epidemiologia , Dieta Mediterrânea , Cooperação do Paciente , Estado Pré-Diabético/epidemiologia , Adulto , Idoso , Análise de Variância , Estudos de Casos e Controles , Estudos Transversais , Inquéritos sobre Dietas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Espanha/epidemiologiaRESUMO
AIMS/HYPOTHESIS: The Di@bet.es Study is the first national study in Spain to examine the prevalence of diabetes and impaired glucose regulation. METHODS: A population-based, cross-sectional, cluster sampling study was carried out, with target population being the entire Spanish population. Five thousand and seventy-two participants in 100 clusters (health centres or the equivalent in each region) were randomly selected with a probability proportional to population size. Participation rate was 55.8%. Study variables were a clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, BMI, waist and hip circumference, blood pressure) and OGTT (75 g). RESULTS: Almost 30% of the study population had some carbohydrate disturbance. The overall prevalence of diabetes mellitus adjusted for age and sex was 13.8% (95% CI 12.8, 14.7%), of which about half had unknown diabetes: 6.0% (95% CI 5.4, 6.7%). The age- and sex-adjusted prevalence rates of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IFG-IGT were 3.4% (95% CI 2.9, 4.0%), 9.2% (95% CI 8.2, 10.2%) and 2.2% (95% CI 1.7, 2.7%), respectively. The prevalence of diabetes and impaired glucose regulation increased significantly with age (p < 0.0001), and was higher in men than in women (p < 0.001). CONCLUSIONS/INTERPRETATION: The Di@bet.es Study shows, for the first time, the prevalence rates of diabetes and impaired glucose regulation in a representative sample of the Spanish population.
Assuntos
Diabetes Mellitus/epidemiologia , Intolerância à Glucose/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Diabetes Mellitus/etnologia , Feminino , Intolerância à Glucose/etnologia , Transtornos do Metabolismo de Glucose/epidemiologia , Transtornos do Metabolismo de Glucose/etnologia , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Distribuição por Sexo , Espanha/epidemiologia , Adulto JovemRESUMO
Our aim was to evaluate whether fatty liver index (FLI) is associated with the risk of type 2 diabetes (T2DM) development within the Spanish adult population and according to their prediabetes status; additionally, to examine its incremental predictive value regarding traditional risk factors. A total of 2260 subjects (Prediabetes: 641 subjects, normoglycemia: 1619 subjects) from the Di@bet.es cohort study were studied. Socio-demographic, anthropometric, clinical data and survey on habits were recorded. An oral glucose tolerance test was performed and fasting determinations of glucose, lipids and insulin were made. FLI was calculated and classified into three categories: Low (< 30), intermediate (30-60) and high (> 60). In total, 143 people developed diabetes at follow-up. The presence of a high FLI category was in all cases a significant independent risk factor for the development of diabetes. The inclusion of FLI categories in prediction models based on different conventional T2DM risk factors significantly increase the prediction power of the models when all the population was considered. According to our results, FLI might be considered an early indicator of T2DM development even under normoglycemic condition. The data also suggest that FLI could provide additional information for the prediction of T2DM in models based on conventional risk factors.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Adulto , Biomarcadores/metabolismo , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Our aim was to determine the incidence of type 2 diabetes mellitus in a nation-wide population based cohort from Spain (di@bet.es study). The target was the Spanish population. In total 5072 people older than 18 years,were randomly selected from all over Spain). Socio-demographic and clinical data, survey on habits (physical activity and food consumption) and weight, height, waist, hip and blood pressure were recorder. A fasting blood draw and an oral glucose tolerance test were performed. Determinations of serum glucose were made. In the follow-up the same variables were collected and HbA1c was determined. A total of 2408 subjects participated in the follow-up. In total, 154 people developed diabetes (6.4% cumulative incidence in 7.5 years of follow-up). The incidence of diabetes adjusted for the structure of age and sex of the Spanish population was 11.6 cases/1000 person-years (IC95% = 11.1-12.1). The incidence of known diabetes was 3.7 cases/1000 person-years (IC95% = 2.8-4.6). The main risk factors for developing diabetes were the presence of prediabetes in cross-sectional study, age, male sex, obesity, central obesity, increase in weight, and family history of diabetes. This work provides data about population-based incidence rates of diabetes and associated risk factors in a nation-wide cohort of Spanish population.
Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Obesidade/epidemiologia , Adulto , Idoso , Glicemia , Pressão Sanguínea , Peso Corporal , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/patologia , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Jejum , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/patologia , Fatores de Risco , Espanha/epidemiologiaRESUMO
AIMS: To assess whether patients with Type 2 diabetes mellitus and unrecognized peripheral arterial disease (PAD), detected by the ankle-brachial index (ABI), have poorer cardiovascular risk factor management (CVRFs) and receive fewer medications than patients previously diagnosed with coronary heart disease (CHD) or cerebrovascular disease (CVD). METHODS: In 31 diabetes centres throughout Spain, 1303 patients with Type 2 diabetes mellitus were screened for PAD using the ABI. Patient history of CHD and CVD and treatment and control of CVRFs were recorded. RESULTS: Forty-one patients had an ABI > 1.30 and were excluded, leaving 1262 patients (age 65.3 +/- 7.7 years) for the study. Of those screened, 790 patients had a normal ABI (ABI > 0.9) and no known history of CHD or CVD (no CHD/CVD/PAD group), 194 had unrecognized PAD (ABI < or = 0.9) with no known history of CHD or CVD (undiagnosed PAD group) and 278 had a known history of CHD and/or CVD (CHD/CVD group). The undiagnosed PAD group had higher low-density lipoprotein (LDL) cholesterol (2.9 +/- 0.83 vs. 2.4 +/- 0.84 mmol/l; P < 0.001) and systolic blood pressure (150 +/- 20 vs. 145 +/- 21 mmHg; P < 0.001) compared with the CHD/CVD group. They were less likely to take statins (56.9 vs. 71.6%; P < 0.001), anti-hypertensive agents (75.9 vs. 90.1%, P = 0.001), and anti-platelet agents (aspirin, 28.7 vs. 57.2%; P < 0.001; clopidogrel, 5.6 vs. 20.9%; P < 0.001) and more likely to smoke (21.0 vs. 9.2%; P < 0.001). Higher LDL in the undiagnosed PAD group was associated with the underutilization of statins. CONCLUSIONS: Measurement of ABI detected a significant number of patients with PAD, who did not have CHD or CVD, but whose CVRFs were under treated and poorly controlled compared with subjects with CHD and/or CVD.
Assuntos
Transtornos Cerebrovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Angiopatias Diabéticas/prevenção & controle , Acessibilidade aos Serviços de Saúde/normas , Doenças Vasculares Periféricas/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Tornozelo/irrigação sanguínea , Anti-Hipertensivos/uso terapêutico , Artéria Braquial/fisiologia , Angiopatias Diabéticas/diagnóstico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão/tratamento farmacológico , Masculino , Doenças Vasculares Periféricas/diagnóstico , Atenção Primária à Saúde/normas , Qualidade da Assistência à Saúde , EspanhaRESUMO
In Spain, according to the Di@bet.es study, 13.8% of the adult population suffers from diabetes and 14.8% from some form of prediabetes (impaired glucose tolerance, impaired fasting glucose or both). Since early detection of prediabetes can facilitate the implementation of therapeutic measures to prevent its progression to diabetes, we believe that preventive strategies in primary care and specialized clinical settings should be agreed. Screening for diabetes and prediabetes using a specific questionnaire (FINDRISC) and/or the measurement of fasting plasma glucose in high risk patients leads to detecting patients at risk of developing diabetes and it is necessary to consider how they should be managed. The intervention in lifestyle can reduce the progression to diabetes and reverse a prediabetic state to normal and is a cost-effective intervention. Some drugs, such as metformin, have also been shown effective in reducing the progression to diabetes but are not superior to non-pharmacological interventions. Finally, an improvement in some cardiovascular risk factors has been observed although there is no strong evidence supporting the effectiveness of screening in terms of morbility and mortality. The Consensus and Clinical Guidelines Working Group of the Spanish Diabetes Society has issued some recommendations that have been agreed by the Sociedad Española de Endocrinología y Nutrición, Sociedad Española de Endocrinología Pediátrica, Sociedad Española de Farmacia Comunitaria, Sociedad Española de Medicina Familiar y Comunitaria, Sociedad Española de Médicos Generales, Sociedad Española de Médicos de Atención Primaria, Sociedad Española de Medicina Interna, Asociación de Enfermería Comunitaria and Red de Grupos de Estudio de la Diabetes en Atención Primaria.
Assuntos
Diabetes Mellitus/prevenção & controle , Programas de Rastreamento/métodos , Estado Pré-Diabético/terapia , Adulto , Progressão da Doença , Humanos , Estado Pré-Diabético/diagnóstico , Atenção Primária à Saúde/métodos , EspanhaRESUMO
In Spain, according to the Di@bet.es study, 13.8% of the adult population suffers from diabetes and 14.8% from some form of prediabetes (impaired glucose tolerance, impaired fasting glucose or both). Since early detection of prediabetes can facilitate the implementation of therapeutic measures to prevent its progression to diabetes, we believe that preventive strategies in primary care and specialized clinical settings should be agreed. Screening for diabetes and prediabetes using a specific questionnaire (FINDRISC) and/or the measurement of fasting plasma glucose in high risk patients leads to detecting patients at risk of developing diabetes and it is necessary to consider how they should be managed. The intervention in lifestyle can reduce the progression to diabetes and reverse a prediabetic state to normal and is a cost-effective intervention. Some drugs, such as metformin, have also been shown effective in reducing the progression to diabetes but are not superior to non-pharmacological interventions. Finally, an improvement in some cardiovascular risk factors has been observed although there is no strong evidence supporting the effectiveness of screening in terms of morbility and mortality. The Consensus and Clinical Guidelines Working Group of the Spanish Diabetes Society has issued some recommendations that have been agreed by the Sociedad Española de Endocrinología y Nutrición, Sociedad Española de Endocrinología Pediátrica, Sociedad Española de Farmacia Comunitaria, Sociedad Española de Medicina Familiar y Comunitaria, Sociedad Española de Médicos Generales, Sociedad Española de Médicos de Atención Primaria, Sociedad Española de Medicina Interna, Asociación de Enfermería Comunitaria and Red de Grupos de Estudio de la Diabetes en Atención Primaria.
Assuntos
Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/terapia , Algoritmos , HumanosRESUMO
In Spain, according to the Di@bet.es study, 13.8% of the adult population suffers from diabetes and 14.8% from some form of prediabetes (impaired glucose tolerance, impaired fasting glucose or both). Since early detection of prediabetes can facilitate the implementation of therapeutic measures to prevent its progression to diabetes, we believe that preventive strategies in primary care and specialized clinical settings should be agreed. Screening for diabetes and prediabetes using a specific questionnaire (FINDRISC) and/or the measurement of fasting plasma glucose in high risk patients leads to detecting patients at risk of developing diabetes and it is necessary to consider how they should be managed. The intervention in lifestyle can reduce the progression to diabetes and reverse a prediabetic state to normal and is a cost-effective intervention. Some drugs, such as metformin, have also been shown effective in reducing the progression to diabetes but are not superior to non-pharmacological interventions. Finally, an improvement in some cardiovascular risk factors has been observed although there is no strong evidence supporting the effectiveness of screening in terms of morbility and mortality. The Consensus and Clinical Guidelines Working Group of the Spanish Diabetes Society has issued some recommendations that have been agreed by the Sociedad Española de Endocrinología y Nutrición, Sociedad Española de Endocrinología Pediátrica, Sociedad Española de Farmacia Comunitaria, Sociedad Española de Medicina Familiar y Comunitaria, Sociedad Española de Médicos Generales, Sociedad Española de Médicos de Atención Primaria, Sociedad Española de Medicina Interna, Asociación de Enfermería Comunitaria and Red de Grupos de Estudio de la Diabetes en Atención Primaria.
RESUMO
In about 25% of cases medullary thyroid carcinoma (MTC) is hereditary. In this group is possible to detect germline point mutations of the RET proto-oncogene in about 95% of the studied cases. The purpose of the present paper is to confirm the value of the RET in the screening of the hereditary MTC. We studied 43 subjects at risk for a Multiple Endocrine Neoplasia Type 2A Syndrome. RET analysis was positive for MEN 2A in 22 subjects. Fifteen of the 22 have undergone a total thyroidectomy at our facility. Histopathological study of the surgical specimens confirmed the presence of a MTC in all the cases. According with our experience. RET analysis is a 100% sensitive and specific method of hereditary MTC screening, and we think it has obvious advantages over the calcitonin tests in technical, economic and ethic aspects.
Assuntos
Carcinoma Medular/diagnóstico , Carcinoma Medular/genética , Proteínas de Drosophila , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Carcinoma Medular/cirurgia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-ret , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
BACKGROUND: Despite the marked increase in cardiovascular risk factors in Spain in recent years, the prevalence and incidence of cardiovascular diseases have not risen as expected. Our objective is to examine the association between consumption of olive oil and the presence of cardiometabolic risk factors in the context of a large study representative of the Spanish population. SUBJECTS AND METHODS: A population-based, cross-sectional, cluster sampling study was conducted. The target population was the whole Spanish population. A total of 4572 individuals aged ≥ 18 years in 100 clusters (health centers) were randomly selected with a probability proportional to population size. The main outcome measures were clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, body mass index, waist, hip and blood pressure) and oral glucose tolerance test (OGTT) (75 g). RESULTS: Around 90% of the Spanish population use olive oil, at least for dressing, and slightly fewer for cooking or frying. The preference for olive oil is related to age, educational level, alcohol intake, body mass index and serum glucose, insulin and lipids. People who consume olive oil (vs sunflower oil) had a lower risk of obesity (odds ratio (OR)=0.62 (95% confidence interval (CI)=0.41-0.93, P=0.02)), impaired glucose regulation (OR=0.49 (95% CI=0.28-0.86, P=0.04)), hypertriglyceridemia (OR=0.53 (95% CI=0.33-0.84, P=0.03)) and low HDL cholesterol levels (OR=0.40 (95% CI=0.26-0.59, P=0.0001)). CONCLUSIONS: The results show that consumption of olive oil has a beneficial effect on different cardiovascular risk factors, particularly in the presence of obesity, impaired glucose tolerance or a sedentary lifestyle.
Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Intolerância à Glucose/sangue , Intolerância à Glucose/dietoterapia , Óleos de Plantas/administração & dosagem , Adulto , Idoso , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Peso Corporal , Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Análise por Conglomerados , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/prevenção & controle , Insulina/sangue , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/prevenção & controle , Razão de Chances , Azeite de Oliva , Prevalência , Fatores de Risco , Comportamento Sedentário , Espanha/epidemiologia , Óleo de Girassol , Triglicerídeos/sangueRESUMO
BACKGROUND & AIMS: To date no nation-wide study has yet been undertaken in Spain to estimate the iodine deficiency. The aim was to evaluate iodine intake and its conditioning factors in a representative sample of the whole adult population. METHODS: The Di@bet.es Study is a national, cross-sectional, population-based survey conducted in 2009-2010 in Spain. RESULTS: The median urinary iodine (UI) was 117.2 µg/L. Iodized salt (IS) was consumed by 43.9% of the population. The median UI in those who consumed IS and in those who did not consume IS was 131.1 and 110.8 µg/L respectively (p<0.0001). The likelihood of having UI levels above 100 µg/L was significantly associated with the intake of IS (OR=1.47) and milk at least once a day (OR=1.22). Within each individual autonomous communities, the median UI levels in those who consumed IS correlated significantly with the median levels of those who did not consume IS (r=0.76, p=0.001). CONCLUSIONS: Though strictly speaking, Spain should be considered within the category of a country having an adequate iodine intake, the current value is too close to the cut point and does not guarantee that those groups with a greater need for iodine will have the required intake of iodine.
Assuntos
Iodo/administração & dosagem , Iodo/deficiência , Iodo/urina , Desnutrição/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Cloreto de Sódio na Dieta/administração & dosagem , Espanha/epidemiologia , Adulto JovemRESUMO
Objective. To evaluate the association between diabetes mellitus and health-related quality of life (HRQOL) controlled for several sociodemographic and anthropometric variables, in a representative sample of the Spanish population. Methods. A population-based, cross-sectional, and cluster sampling study, with the entire Spanish population as the target population. Five thousand and forty-seven participants (2162/2885 men/women) answered the HRQOL short form 12-questionnaire (SF-12). The physical (PCS-12) and the mental component summary (MCS-12) scores were assessed. Subjects were divided into four groups according to carbohydrate metabolism status: normal, prediabetes, unknown diabetes (UNKDM), and known diabetes (KDM). Logistic regression analyses were conducted. Results. Mean PCS-12/MCS-12 values were 50.9 ± 8.5/ 47.6 ± 10.2, respectively. Men had higher scores than women in both PCS-12 (51.8 ± 7.2 versus 50.3 ± 9.2; P < 0.001) and MCS-12 (50.2 ± 8.5 versus 45.5 ± 10.8; P < 0.001). Increasing age and obesity were associated with a poorer PCS-12 score. In women lower PCS-12 and MCS-12 scores were associated with a higher level of glucose metabolism abnormality (prediabetes and diabetes), (P < 0.0001 for trend), but only the PCS-12 score was associated with altered glucose levels in men (P < 0.001 for trend). The Odds Ratio adjusted for age, body mass index (BMI) and educational level, for a PCS-12 score below the median was 1.62 (CI 95%: 1.2-2.19; P < 0.002) for men with KDM and 1.75 for women with KDM (CI 95%: 1.26-2.43; P < 0.001), respectively. Conclusion. Current study indicates that increasing levels of altered carbohydrate metabolism are accompanied by a trend towards decreasing quality of life, mainly in women, in a representative sample of Spanish population.
RESUMO
Increased blood ammonia was induced in fasting mice by ip administration of 200 mg/kg Na-valproate followed 1 h later by 13 and 4 mmol/kg alanine and ornithine, respectively. When valproate was not used blood or liver ammonia was not increased, but increases were observed in liver glutamate (5-fold), glutamine (2-fold), aspartate (5-fold), acetylglutamate (15-fold), citrulline (35-fold), argininosuccinate (11-fold), arginine (11-fold), and urea (3-fold). The level of carbamoyl phosphate (less than 2 nmol/g) was, by far, the lowest of all urea cycle intermediates. The large increase in citrulline indicates that argininosuccinate synthesis was limiting, and that the increase in acetylglutamate induced a considerable activation of carbamoyl phosphate synthetase, which agrees with theoretical expectations, irrespective of the actual KD value for acetylglutamate. Pretreatment with valproate resulted in lower hepatic levels of glutamate, glutamine, aspartate, acetyl-CoA, and acetylglutamate. At the level found of acetylglutamate the activation of carbamoyl phosphate synthetase would be expected to be similar to that without valproate. Indeed, the levels of citrulline were similar with or without valproate. Argininosuccinate, arginine, and urea levels exhibited little if any change. Although the model used may not replicate exactly the situation in patients, from our results it appears that changes in citrullinogenesis or in other steps of the urea cycle do not account for the increase in blood ammonia induced by valproate, and it is proposed that valproate may alter glutamine metabolism.