HbA(1c) in the prediction of type 2 diabetes compared with fasting and 2-h post-challenge plasma glucose: The Asturias study (1998-2005).

AIM: Fasting plasma glucose (FPG) and the 2-h post-challenge plasma glucose (2hPG) are commonly used to identify those at risk of type 2 diabetes. However, the role of HbA(1c) in this prediction has still not been ascertained. METHODS: The Asturias study is a prospective population-based survey of diabetes and cardiovascular risk factors. Baseline examination, carried out during 1998-1999, involved 1034 individuals, aged 30-75 years, randomly selected to determine the prevalence of type 2 diabetes and prediabetes in the principality of Asturias (northern Spain). In 2004-2005, these same subjects were invited to a follow-up examination, and 700 participated. The present study includes only those who did not have diabetes at baseline. All participants with no known diabetes underwent an OGTT. Baseline HbA(1c) levels were measured by HPLC. RESULTS: Diabetes had developed in 44 participants at the time of follow-up. Quartiles of baseline HbA(1c) values were 3.4-4.8 (Q1), 4.9-5.1 (Q2), 5.2-5.4 (Q3) and 5.5-6.9 (Q4), and the incidence rates of diabetes by quartiles were 1.0 (0.1-7.1), 4.0 (1.5-10.7), 7.9 (4.0-15.9) and 32.6 (22.9-46.4) cases/1000 person-years, respectively. ROC curve analysis comparing HbA(1c), FPG and 2hPG in the prediction of diabetes showed areas under the curve (ROC-AUC) of 0.80 (0.74-0.86), 0.83 (0.77-0.90) and 0.79 (0.72-0.87), respectively. The combination of FPG and HbA(1c) had the best predictive performance with an ROC-AUC of 0.88 (0.82-0.93). CONCLUSION: Our study indicates that HbA(1c) is strongly predictive of new-onset diabetes in this northern Spanish population, and was similar to FPG and 2hPG in predictive capability. Also, the combined measurement of FPG and HbA(1c) improved their individual predictive performance.

Implicaciones clinicoterapéuticas de la deficiencia de yodo en España / Clinical and therapeutic implications of iodine deficiency in Spain

El yodo es un nutriente imprescindible para el organismo humano (esencial para la formación de las hormonas tiroideas), cuya principal fuente de abastecimiento son los pescados de mar y los mariscos; se precisa una ingesta diaria mínima de 100 mg en la primera infancia, 120 hasta la pubertad, 150 en la edad adulta y no menos de 250 durante el embarazo y la lactancia. Hoy día, la Organización Mundial de la Salud estima en más de 2.200 millones de personas en riesgo por habitar en áreas yododeficientes, entre las que se incluye una gran parte de Europa. En España, los estudios realizados confirman también este déficit, que es leve en la población escolar de todas las comunidades autónomas estudiadas, salvo en Asturias, donde el programa de profilaxis con sal yodada iniciado en 1983 ha mostrado tener eficacia. Las gestantes, sin embargo, son el segmento de población más vulnerable, y presentan una marcada deficiencia, que se manifiesta también en los recién nacidos, demostrada por los valores de tirotropina (TSH). Aunque sólo hay 2 estudios en preescolares (Mataró y Asturias), ambos sugieren un estado de nutrición aceptable. Se sabe que la reducción de los trastornos por deficiencia de yodo como grave problema de salud pública ha sido posible con el cambio de los hábitos alimentarios de la población mundial, lo que indica la necesidad de lograr que el consumo de sal yodada en España sea una realidad que alcance al 95% de las familias y, además, que las gestantes y las madres en período de lactancia utilicen suplementos farmacológicos de yodo

Iodine is an essential nutrient for the human organism (for the formation of thyroid hormones), and its main sources are fish and shellfish, requiring a daily minimal intake of 100 micrograms in early childhood, 120 until puberty, 150 in adulthood and not less than 250 during pregnancy and breastfeeding. The World Health Organization estimates that currently 2,200 million persons are at risk for iodine deficiency as they live in iodine-deficient areas, which include a large part of Europe. Studies performed in Spain confirm this deficiency in our country, which is mild in the school-aged population of all the autonomous communities studied, except in Asturias, where the prophylaxis program with iodized salt initiated in 1983 has been shown to be effective. Pregnant women, however, are the most vulnerable segment of the population and show marked iodine deficiency. This deficiency is also manifested in newborns, demonstrated by thyroid-stimulating hormone levels. Although only two studies have been performed in preschool children (Mataró and Asturias) both suggest acceptable nutritional status. It is known that a reduction in iodine deficiency disorders as a serious public health problem can be achieved with a change in diet in the world population, indicating the need to make iodine intake a reality in Spain. Such an intervention should include 95% of families; moreover, pregnant and breastfeeding women should use iodine supplements

Déficit de yodo en España: situación actual / Iodine deficiency in Spain: current situation

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Comparison of the diagnostic criteria for diabetes mellitus, WHO-1985, ADA-1997 and WHO-1999 in the adult population of Asturias (Spain).

AIMS: To estimate the prevalence of diabetes mellitus with three diagnostic criteria (WHO-1985 and 1999 and ADA-1997), evaluate their concordance and analyse the sensitivity and specificity of the different screening strategies for diabetes. METHODS: A cross-sectional population study with two-step sampling. One thousand and 34 people were selected randomly. A 75-g oral glucose tolerance test (OGTT) was performed and venous blood samples were obtained fasting and at 2 h. RESULTS: The prevalence of known Type 2 diabetes mellitus (DM-2) is 4%[95% confidence interval (CI) 2.8, 5.1]. By WHO-1985 criteria the prevalence of unknown DM-2 is 5.9% (4.5, 7.4); by ADA-1997 criteria 3.5% (2.5, 4.6) and by WHO-1999 criteria 7.3% (5.8, 8.8). Diagnostic overlap and statistical concordance (coefficient K) are WHO-1985/ADA-1997 29.3%, K=0.42; WHO-1985/WHO-1999 80%, K=0.88; ADA-1997/WHO-1999 48%, K=0.63. If only fasting glucose was used (following ADA-1997), 36.3% of those with diabetes (2-h glucose > or =11.1 mmol/l) would be diagnosed. If OGTT was performed (i) in those with a fasting glucose between 6.1 mmol/l and 6.9 mmol/l (9.8% of the population) we would diagnose 66.6%, and (ii) in all those between 5.7 mmol/l and 6.9 mmol/l (18.9% of the population) 81.8% would be diagnosed. CONCLUSIONS: The ADA criteria decrease the prevalence of DM in the adult population of Asturias by 2.4% and concordance with the classical criteria (WHO-1985) was only 29.3%. Using fasting glucose only (ADA-1997) diagnoses 36.3% of those with diabetes. The recent recommendations of the WHO-1999 increases this to 66.6%. To improve the diagnostic strategy for diabetes and detect up to 81.8% of patients, we propose the use of OGTT for all those with a fasting glucose between 5.7 mmol/l and 6.9 mmol/l.

Bocio, función tiroidea y excreción de yodo en gestantes de la zona de El Bierzo / Goiter, thyroid function and iodine excretion in pregnant women from the area of El Bierzo (Spain)

Estudios publicados en el año 1993 demuestran alta incidencia de bocio en escolares de la zona de El Bierzo. Hemos valorado mediante encuesta el consumo de sal yodada, la preencia de bocio mediante palpación y ecografía, la función tiroidea midiendo concentraciones hormonales en plasma y la excreción de yodo en orina y leche mediante el método de Benotti, en un grupo de mujeres embarazadas de la zona, en los tres trimestres de la gestación y en el posparto. Nuestros resultados demuestran escaso consumo de sal yodada, endemia bociosa grave, hipotiroxinemia materna, pobre excreción de yodo en orina en las gestantes y escasa presencia de yodo en la leche materna. Todo ello indica la necesidad de campañas institucionales para remediar la situación (AU)

[Prevalence of diabetes mellitus and glucose intolerance in the population aged 30 to 75 years in Asturias, Spain]. / Prevalencia de diabetes mellitus e intolerancia a la glucosa en población entre 30 y 75 años en Asturias, España.

OBJECTIVE: To know the prevalence of type 2 diabetes mellitus (DM2) and glucose intolerance (GIT) in the adult population in Asturias. METHODS: Population based, cross-sectional study. A total of 1,034 individuals (54,1%, women) aged 30-75 years were randomly selected. Individuals responded to a questionnaire, underwent physical examination, and an oral glucose overload test; vein blood was extracted to determine both basal and 2-hour glucose levels. The diagnostic criteria set up by the World Health Organization in 1985 were used. RESULTS: The overall DM2 prevalence was 9.9% (8.2% to 11.7%), known DM 4% (2.8% to 5.1%), unknown DM 5.9% (4.5% to 7.4%). The unknown diabetes/hnown diabetes ratio was 1.5/1. The prevalence of GIT was 13.3 % (11.3% to 15.2%). The prevalence of DM for the Segi population (30-64 years) was 8.2% among men and 5.2% among women. Factors independently associated with DM included age, increased blood pressure, family history of diabetes, obesity, and hypertriglyceridemia. CONCLUSION: The prevalence of DM2 in the adult population of Asturias (9.9%) is moderately high and similar to that observed in our country and other white populations in the world. More than half of patients with DM are unaware of their condition; thus, planning strategies for and early diagnosis would be helpful for the high risk populations.

Prevalencia de diabetes mellitus e intolerancia a la glucosa en población entre 30 y 75 años en Asturias, España / Prevalence of diabetes mellitus and glucose intolerance in the population aged 30 to 75 years in Asturias, Spain

Fundamento. Conocer la prevalencia de diabetes mellitus tipo 2 (DM2) e intolerancia a la glucosa (ITG) en la población adulta de Asturias. Métodos. Estudio poblacional transversal. Mil treinta y cuatro personas (54,1 por ciento mujeres) entre 30 y 75 años que fueron seleccionadas aleatoriamente. Se realizó cuestionario, exploración y sobrecarga oral de glucosa con extracción venosa basal y dos horas. Se utilizaron los criterios diagnósticos establecidos por la Organización Mundial de la Salud en 1985.Resultados. Prevalencia de DM2 global 9,9 por ciento (8,2 por ciento-11,7 por ciento), DM conocida 4 por ciento (2,8 por ciento-5,1 por ciento), DM ignorada 5,9 por ciento (4,5 por ciento-7,4 por ciento)- Ratio diabetes ignorada/conocida: 1,5/1. Prevalencia de ITG 13,3 por ciento (11,3 por ciento-15,2 por ciento). Prevalencia de DM para la población de Segi (30-64 años), 8,2 por ciento en varones y 5,2 por ciento en mujeres. Los factores que se asocian a DM de manera independiente son la edad, la hipertensión arterial, tener antecedentes familiares de diabetes, la obesidad y la hipertrigliceridemia. Conclusión. La prevalencia de DM2 en la población adulta de Asturias (9,9 por ciento) es moderadamente elevada y similar a la observada en nuestro país y en otras poblaciones blancas en el mundo. Más de la mitad de las personas con DM desconocen su condición, por lo que podría ser útil plantear estrategias de diagnóstico precoz en los grupos de población de alto riesgo (AU)

Epidemiología de la diabetes tipo 2 en España / Epidemiology of type 2 diabetes in spain

La diabetes mellitus es una de las enfermedades con mayor impacto sociosanitario, no sólo por su alta prevalencia, sino también por sus complicaciones crónicas y su elevada tasa de mortalidad. La forma más exacta de estimar la prevalencia de DM es la práctica de un test de tolerancia oral a la glucosa. En España, la prevalencia de DM se estima en un 6,2 por ciento para grupos de edad 30-65 años, y en un 10 por ciento para 30-89 años. La proporción de DM conocida frente a la ignorada oscila entre 1/3 y 2/3 del total. Los factores de riesgo de DM más importantes son la edad, la obesidad y la historia familiar de DM. La incidencia de DM2 se estima en 8/1.000 habitantes año. La prevalencia de las distintas complicaciones crónicas varía en función del tipo de DM, tiempo de evolución y grado de control metabólico, estimándose globalmente en la siguiente: neuropatía 25 por ciento, retinopatía 32 por ciento y nefropatía 23 por ciento. La DM es una de las principales causas de mortalidad en España, ocupando el tercer lugar en mujeres y el séptimo en varones (AU)

Valoración de los efectos de un programa de educación nutricional sobre los datos antropométricos y bioquímicos de los niños de los centros de acogida del principado de asturias / Evaluation of the effects of an educational programme on anthropometric and biochemical data in the children of asturias´ community centres

Introducción. Entre los problemas más frecuentes en la población infantil se encuentran la elevada prevalencia del exceso de peso y las concentraciones inadecuadas de lípidos. En este estudio se valoran los efectos de un programa de educación nutricional sobre dichos parámetros. Material y método. Se estudian los menús de 11 centros de acogida, así como los datos antropométricos y los valores de lípidos de los 319 niños allí residentes. Se realiza un programa de educación nutricional y se valoran sus efectos al año de la intervención. Resultados. Los niños presentaban inicialmente valores de talla, peso e índice de masa corporal (IMC) similares a los utilizados como referencia, con medidas de pliegue tricipital (PT) inferiores y subescapular (PS) y circunferencia muscular del brazo (CMB) superiores. Las concentraciones de colesterol (CT) y colesterol unido a lipoproteínas de alta densidad (cHDL) eran menores que en la mayoría de los estudios realizados en España. Tras la intervención, se mejoraron las dietas, disminuyendo la frecuencia de alimentos ricos en grasa saturada y colesterol. Se incrementaron la talla, el peso, IMC y la CMB, con disminución del PT y PS. Los valores de CT aumentaron y los de cHDL no se modificaron. Conclusiones. El programa de educación nutricional fue efectivo para modificar las dietas, pero no para corregir los datos antropométricos o las concentraciones de lípidos que se podían considerar inadecuados (AU)

Síndrome de cushing por hiperplasia adrenal macronodular bilateral ACTH-independiente / Cushing's syndrome due to ACTH-independent bilateral macronodular adrenal hyperplasia

La hiperplasia suprarrenal macronodular bilateral ACTH-independiente (HAMAI) se considera hoy día una entidad diferente y separada del resto de causas de síndrome de Cushing. Su etiología es incierta aunque en los últimos años se ha demostrado la existencia de respuesta anormal de glándulas suprarrenales a distintas hormonas que estimulan la secreción de cortisol. En este artículo presentamos un caso de hipercortisolismo no suprimible con dexametasona, cifras de ACTH indetectables, hiperplasia suprarrenal bilateral de aspecto nodular y resonancia magnética nuclear hipofisaria normal. Se realizó suprarrenalectomía bilateral, objetivando cifras detectables de ACTH a los 3 meses (AU)

[Recurrence and prognostic factors after treatment with antithyroid agents in Graves-Basedow disease. Multicenter study in Northern Spain]. / Recidiva y factores pronósticos tras tratamiento con antitiroideos en la enfermedad de Graves-Basedow. Estudio multicéntrico en el norte de España.

Therapy with anti-thyroid drugs is the initial option mostly used in our country for the treatment of hyperthyroidism due to Graves-Basedow disease. To evaluate the long term results of this kind of therapy, a total of 773 patients were studied who were diagnosed from 1975 to 1994 in three hospitals in Northern Spain (Hospital Central de Asturias, Hospital de Cruces and Hospital de Navarra) after a mean follow-up time after anti-thyroid drug withdrawal of 46 +/- 33.1 months. The results showed a likelihood of hyperthyroidism relapse of 42.9%, 59.8%, 67.9% and 78.9% at one, three, five and ten years, respectively. Goitre size was correlated very significantly with the likelihood of relapse (p < 0.0001). In contrast, only TBII positivity at the end of therapy among the remaining parameters (age, sex, goitre size, length of therapy, positivity of anti-thyroid antibodies and TBII) influenced significantly on the relapse likelihood (p < 0.05). In conclusion, after a long term follow-up after anti-thyroid therapy, a high relapse rate of hyperthyroidism in Graves-Basedow disease, which amounts up to 79% at ten years, was observed. Goitre size was the main predictive factor for this relapse.

Recidiva y factores pronósticos tras tratamiento con antitiroideos en la enfermedad de Graves-Basedow. Estudio multicéntrico en el norte de España / Relapse and prognostic factors after anti-thyroid therapy for Graves-Basedow disease. Multicentric study in Northern Spain

Recidiva y factores pronósticos tras tratamiento con antitiroideos en la enfermedad de Graves-Basedow. Estudio multicéntrico en el norte de España El tratamiento con fármacos antitiroideos es la opción inicial más utilizada en nuestro país para el tratamiento del hipertiroidismo por enfermedad de Graves-Basedow. Para evaluar el resultado a largo plazo de este tipo de tratamiento hemos estudiado 773 pacientes diagnosticados entre 1975 y 1994 en tres hospitales del norte de España (Hospital Central de Asturias, Hospital de Cruces y Hospital de Navarra) después de un tiempo medio de seguimiento tras la retirada de los antitiroideos de 46 ñ 33,1 meses. Los resultados mostraron una probabilidad de recidiva del hipertiroidismo del 42,9 por ciento al año, del 59,8 por ciento a los 3 años, del 67,9 por ciento a los 5 años y del 78,9 por ciento a los 10 años. El tamaño del bocio se correlacionó muy significativamente con la probabilidad de recidiva (p < 0,0001), mientras que del resto de las variables estudiadas (edad, sexo, tamaño del bocio, duración del tratamiento, positividad de los anticuerpos antitiroideos y de los TBII) sólo la positividad de los TBII al final del tratamiento influyó de forma muy significativa (p < 0,05). En conclusión, tras un seguimiento a largo plazo después del tratamiento con antitiroideos se observa una alta tasa de recidiva del hipertiroidismo en la enfermedad de Graves-Basedow, que llega a ser del 79 por ciento a los 10 años, siendo el tamaño del bocio el factor fundamental a la hora de predecir esta recidiva (AU)

Multiple endocrine neoplasia type 1 (MEN1): clinical heterogeneity in a large family with a nonsense mutation in the MEN1 gene (Trp471Stop).

OBJECTIVE: Familial multiple endocrine neoplasia type 1 (MEN1) is an hereditary dominant trait characterized by tumours of the parathyroids, anterior pituitary and endocrine pancreatic glands, among others. The MEN1 gene has recently been cloned, and MEN1-mutations have been identified in several families as well as in a number of sporadic cases. The aim of this study was to search for mutations in a large MEN1-family in order to define the clinical heterogeneity among mutation-carriers. We also analysed DNA from several tumour tissues in order to test the 'two hit' model for inactivation of the MEN1 gene. PATIENTS AND METHODS: We searched for mutations in the MEN1-gene in members of a large MEN1-family. A total of 11 affected and 4 healthy at risk individuals were analysed. DNA was obtained and exons 1 to 10 of the MEN1-gene were PCR-amplified and subjected to automated-direct sequencing. In addition, we isolated DNA from parathyroid tumours of two family members, and compared this DNA with that of the normal tissue counterpart to define if the normal copy of the MEN1-gene was deleted. RESULTS: G to A change at nucleotide 7640 (exon 10) that would convert Trp to Stop at codon 471 was found. This mutation was identified in eleven affected individuals, as well as in four healthy (asymptomatic) family members. These patients showed a wide spectrum of clinical symptoms and ages of presentation. Comparison of normal and tumour DNAs showed the loss of the normal (non-mutated) copy of MEN1 gene in the tumour tissue. CONCLUSION: The different ages of disease presentation and the heterogeneity of symptoms among carriers of the Trp471Stop mutation, which would lead to the synthesis of a truncated non-functional protein, suggest that clinical heterogeneity is a characteristic of MEN1 independent of the type of mutation. Finally, the lack of amplification of the normal MEN1-allele on DNA from parathyroid tumours of two family members indicates that MEN1 is a tumour suppressor gene, the second hit that inactivates the normal copy in mutation carriers being a deletion.

[The nerve endings in contact with the parafollicular cells of the thyroid]. / Etude des terminaisons nerveuses au contact des cellules parafolliculaires de la thyroïde.

We studied nerve endings in the parafollicular cells of thyroid glands in necropsy examinations of 50 young males with no know thyroid disorder. The Jabonero and Maillet techniques. ultrastructural and morphology study were performed together with a statistical analysis of nerve endings. Optic microscope visualized preterminal and exceptionally terminal nerve endings located near parafollicular cells. Swellings of the axons without Schwann's cell sheath were identified close to the par follicular cells with electronic microscopy, these swellings had an ellipsoidal or spherical shape and laid close to the cellular membrane (30 nm). Three types of synaptic-like vesicles were found in these nerve endings. a) Abundant clear vesicles, generally spherical in shape (average diameter 50.40 +/- 5.91 nm); b) A few large granural vesicles with an electron-dense core (average diameter 105.49 +/- 9.98 nm); and c) Several small granular vesicles with an electron-dens core (average diameter 55.09 +/- 6.56 nm). Emphasis should be given to the finding of nerve endings (cholinergic-like, adrenergic-like and peptidergic-like nerve endings) in the parafollicular cells. We discuss their possible function.

Multiple endocrine neoplasia type 1 (MEN1): LOH studies in a affected family and in sporadic cases.

Multiple endocrine neoplasia (Menl) is an autosomai dominant hereditary trait characterized by tumors of endocrine tissues. The MEN1 gene maps to chromosome llql3, has been recently isolated, and encodes a protein termed menin that is ubiquitously expressed. This gene is likely to be a tumor suppressor gene, with tumors developing after the inactivation of both copies of the gene in a single cell. In agreement with this, 11q-deletions (loss of heterozygosity) are frequently found in neoplasms from MEN1 patients. In this study, DNA from family-members was extracted and analysed for 10 microsatellites flanking the MEN1-gene on chromosome 11q. SSCP was used to determine the presence of MEN1-mutations in several patients. DNA was extracted from paraffin blocks containing tissue from 10 parathyroid tumors (4 familial and 6 sporadic) and 2 gastrinomas (both from patients of the Men1-family). LOH was determined by comparing the autoradiographic patterns of several markers between the normal tissue and the malignant tissue counterpart. All the affected individuals in the MEN1-family shared one haplotype, not present in the healthy individuals. We searched for mutations at the MEN1 gene (SSCP-analysis) in several affected members. An SSCP-mobility shift was found at exon 9, and direct sequencing showed that this corresponded to a common polymorphism at codon 418 (GAC/GAT), LOH, a genetic alteration characteristic of genomic regions containing tumor suppressor genes, was found in all the parathyroid tumors, but not in two gastrinomas. SSCP-analysis of the MEN1-exon 9 polymorphism showed that LOH included the MEN1-gene in the informative parathyroid tumors. In conclusion, LOH at 11q is frequent in Menl-parathyroid tumors, either sporadic or familial, and the deletion involves the MEN1-gene. In contrast, the two gastrinomas did not show LOH, indicating the existence of a second mutation other than the MEN1-deletion in these tumors. Our data suggest that the mechanism that drives tumorigenesis in Menl either familial or sporadic, is influenced by the tissue context.

[Follicular thyroid cancer: the prognostic factors]. / Cáncer folicular de tiroides: factores pronósticos.

30 patients affected by follicular carcinoma of the thyroid gland (well differentiated, poorly differentiated and Hürthle's cell) are studied. We analyse the factors which affect the mortality; the percentage was of 63% during 3 years follow-up of metastatic patients and was null in non-metastatic patients (P < 0.0001); without significant differences between sex, age and histological type. Patients without metastasis at diagnosis had increased TG in 60% of the Hürthle's cell carcinomas and in 30%. Of the follicular carcinomas; poorly differentiated and not detected in 100% of the well differentiated follicular carcinoma, after a median follow-up of 7 years. This suggests that prognosis might be different depending of histological type.