Body conformation in Great Danes with and without clinical signs of cervical spondylomyelopathy.

It has been suggested that a combination of large head and long neck cause abnormal forces on the cervical vertebral column and are involved in the pathogenesis of cervical spondylomyelopathy (CSM) in Great Danes. The aim of this study was to compare the body conformation of 15 clinically normal and 15 CSM-affected Great Danes. There were no statistically significant differences between clinically normal and CSM-affected Great Danes in any body measurements. There were no significant associations between body conformation and the severity of neurological signs or cervical vertebral body dimensions determined by magnetic resonance imaging in CSM-affected Great Danes. The results of this study do not support the hypothesis that differences in body conformation related to head size, neck length, and body height and length, play a role in the pathogenesis of CSM in Great Danes.

Cervical vertebral trabecular bone mineral density in Great Danes with and without osseous-associated cervical spondylomyelopathy.

BACKGROUND: Great Danes (GDs) with osseous-associated cervical spondylomyelopathy (CSM) have osteoarthritis (OA) of the cervical vertebrae. OA is often associated with increases in bone mineral density (BMD) in people and dogs. HYPOTHESIS/OBJECTIVES: To compare the trabecular BMD of the cervical vertebrae between clinically normal (control) GDs and GDs with osseous-associated CSM by using computed tomography (CT). We hypothesized that the vertebral trabecular BMD of CSM-affected GDs would be higher than that of control GDs. ANIMALS: Client-owned GDs: 12 controls, 10 CSM affected. METHODS: Prospective study. CT of the cervical vertebral column was obtained alongside a calibration phantom. By placing a circular region of interest at the articular process joints, vertebral body, pedicles, and within each rod of the calibration phantom, trabecular BMD was measured in Hounsfield units, which were converted to diphosphate equivalent densities. Trabecular BMD measurements were compared between CSM-affected and control dogs, and between males and females within the control group. RESULTS: Differences between CSM-affected and control dogs were not significant for the articular processes (mean = -39; P = .37; 95% CI: -102 to 24), vertebral bodies (mean = -62; P = .08; 95% CI: -129 to 6), or pedicles (mean = -36; P = .51; 95% CI: -105 to 33). Differences between female and male were not significant. CONCLUSIONS AND CLINICAL IMPORTANCE: This study revealed no difference in BMD between control and CSM-affected GDs. Based on our findings no association was detected between cervical OA and BMD in GDs with CSM.

Cytokine concentrations in the cerebrospinal fluid of great danes with cervical spondylomyelopathy.

BACKGROUND: Chronic inflammation is involved in the pathogenesis of human cervical spondylotic myelopathy and could also play a role in cervical spondylomyelopathy (CSM) in dogs. HYPOTHESIS/OBJECTIVES: That cerebrospinal fluid (CSF) cytokine concentrations would differ between clinically normal (control) and CSM-affected Great Danes (GDs), with affected GDs showing higher levels of inflammatory cytokines, such as interleukin (IL)-6 and monocyte chemoattractant protein-1/chemokine ligand 2 (MCP-1/CCL2). ANIMALS: Client-owned GDs: 15 control, 15 CSM-affected. METHODS: Prospective study. Dogs underwent cervical vertebral column magnetic resonance imaging and collection of CSF from the cerebellomedullary cistern. Cytokine concentrations were measured using a commercially available canine multiplex immunoassay. Cytokine concentrations were compared between groups. Associations with the administration of anti-inflammatory medications, disease duration and severity, severity of spinal cord (SC) compression, and SC signal changes were investigated in affected GDs. RESULTS: Affected GDs had significantly lower MCP-1/CCL2 (mean 138.03 pg/mL, 95% confidence interval [CI] = 114.85-161.20) than control GDs (212.89 pg/mL, 95% CI = 165.68-260.11, P = .028). In affected GDs, MCP-1/CCL2 concentrations correlated inversely with the severity of SC compression. There were no associations with administration of anti-inflammatory medications, disease duration, or disease severity. IL-6 concentrations were significantly higher (2.20 pg/mL, 95% CI = 1.92-2.47, P < .001) in GDs with SC signal changes. CONCLUSIONS AND CLINICAL IMPORTANCE: Lower MCP-1/CCL2 in CSM-affected GDs might compromise clearance of axonal and myelin debris, delay axon regeneration, and affect recovery. Higher IL-6 in CSM-affected GDs with SC signal changes suggests more severe inflammation in this group.

Cervical spondylomyelopathy in Great Danes: a magnetic resonance imaging morphometric study.

Morphometric investigations comparing normal and affected animals increase our understanding of spinal diseases in dogs. The aim of this study was to generate morphometric data for osseous-associated cervical spondylomyelopathy (CSM) in Great Danes (GDs). Magnetic resonance imaging (MRI) morphometric features of the cervical vertebral column of GDs with and without clinical signs of CSM were characterized and compared. Thirty client-owned GDs were prospectively enrolled, including 15 clinically normal and 15 CSM-affected GDs. All dogs underwent MRI of the cervical to thoracic vertebral column (C2-C3 through T1-T2). Areas of the cranial and caudal articular processes, and the height, width and areas of the vertebral canal and spinal cord were determined. Middle foraminal heights were measured. Intervertebral disc width was measured before and after traction. Intraobserver and interobserver agreement were calculated. CSM-affected GDs had larger areas of the caudal articular processes from C2-C3 through T1-T2. In CSM-affected GDs, the vertebral canal and spinal cord areas were significantly smaller at C5-C6 and C6-C7, the vertebral canal width was significantly narrower at C6-C7 and C7-T1, and the spinal cord width was significantly narrower at C5-C6 and C6-C7. Middle foraminal height was smaller in CSM-affected GDs from C3-C4 through C7-T1. Neutral intervertebral disc widths were smaller in CSM-affected GDs. It was concluded that the cervical vertebral canal dimensions are significantly different between normal and CSM-affected GDs. Absolute vertebral canal stenosis and severe foraminal stenosis involving the cervical vertebrae distinguish CSM-affected from clinically normal GDs. These findings are relevant to the pathogenesis of osseous-associated CSM and should be taken into consideration when performing imaging studies and planning surgery.

Transcranial magnetic motor evoked potentials in Great Danes with and without clinical signs of cervical spondylomyelopathy: association with neurological findings and magnetic resonance imaging.

Transcranial magnetic motor evoked potentials (TMMEPs) assess the functional integrity of the descending motor pathways, which are typically compromised in canine cervical spondylomyelopathy (CSM). The objective of this prospective study was to establish the reference ranges of TMMEP latency and amplitude in clinically normal (control) Great Danes (GDs), compare TMMEPs obtained in GDs with and without CSM, and determine whether there is any association between TMMEP data and severity of neurological signs or magnetic resonance imaging (MRI) findings. Twenty-nine client-owned GDs were enrolled (15 controls, 14 CSM-affected). All dogs underwent TMMEPs under sedation, and latencies and amplitudes were recorded from the extensor carpi radialis (ECR) and cranial tibial (CT) muscles. MRI of the cervical vertebral column was performed to evaluate the presence and severity of spinal cord (SC) compression, and the presence of SC signal changes. ECR and CT latencies were significantly longer in CSM-affected than control GDs. No significant differences between groups were found for amplitudes or neuronal path lengths. For the CT TMMEPs, CSM-affected GDs with moderate and severe clinical signs had significantly longer latencies than those with mild clinical signs. Significantly longer CT latencies were found in dogs with moderate and severe SC compression compared with dogs with mild compression. CT TMMEPs could not be recorded in 7/9 CSM-affected GDs with SC signal changes. These results provide a reference range for TMMEPs of clinically normal GDs. The use of TMMEPs is a valid ancillary test to assess the integrity of motor pathways in GDs with CSM.

Beneficios de la monitorización de la glucemia en pacientes con diabetes mellitus tipo 2 en tratamiento con agentes orales / Benefits of self-monitoring of blood glucose in patients with type 2 diabetes in treatment with oral agents

Los benefi cios de la monitorización de la glucemia en pacientes con diabetesmellitus tipo 2 (DM2) en tratamiento con agentes orales y/o modifi caciones enel estilo de vida han sido cuestionados tras el análisis de los resultados de variosensayos clínicos. La mejora en el control glucémico, que se observa en no pocasocasiones, sólo puede ocurrir si al mismo tiempo que se llevan a cabo los controlesglucémicos tiene lugar un cambio conductual del paciente dirigido por losprofesionales sanitarios. Debemos abogar por el uso de esta herramienta diagnósticade manera sistemática, pero racional, evitando las prácticas derrochadorasque agotan nuestros recursos sanitarios. Para ello, hay que diseñar mejoresprotocolos que exploren las ventajas del autocontrol glucémico cuando se utilizade manera cotidiana en los pacientes con DM2 que no siguen tratamiento coninsulina. Pero de ningún modo se debe negar el acceso al autocontrol glucémicoa estos pacientes, pues ello supondría no tener forma de dirigir la terapiafarmacológica o los cambios en el estilo de vida(AU)

After the analysis of the results of several clinical trials, the benefits of selfmonitoringof blood glucose in type 2 diabetes treated with oral agents and/orlifestyle changes has been questioned. Improvement of glycemic control,which has been often observed, may only be possible if besides glucose monitoringbehaviour modifications guided by health professionals also occurred.We must encourage a systematic but also rational use of this useful diagnostictool, avoiding waste-of-money practices which consume our medical resources.Therefore, better protocols should be designed to demonstrate the advantagesof daily self-monitoring of blood glucose in people with type 2 diabetes treatedwithout insulin. But in any case, self-monitoring of glucose levels should neverbe denied to those patients, because a useful tool to drive pharmacologictherapy or lifestyle changes will be lost(AU)

Hipoglucemias leves y graves en la diabetes mellitus tipo 1 y 2 / Hypoglycemias in type 1 and 2 diabetes

Las hipoglucemias y el temor a presentarlas son factores limitantes,tanto en los pacientes con diabetes mellitus tipo 1 como tipo 2,para alcanzar y mantener un adecuado control glucémico y evitar laaparición/progresión de las complicaciones crónicas. La frecuenciade episodios hipoglucémicos depende del tipo de diabetes, del tratamientoempleado y de factores de riesgo individuales. Los episodiospueden ser leves, asintomáticos, o graves, incluso con pérdidade conciencia. Las hipoglucemias tienen consecuencias clínicasnotables en cuanto al incremento de la morbimortalidad y la reducciónde la calidad de vida. Se trata de una situación muy temida porlos pacientes y sus familiares. Las implicaciones económicas de losepisodios graves son considerables, tanto en los costes hospitalariosdirectos como en los indirectos derivados de la incapacidadpara trabajar. Así pues, la hipoglucemia es el factor limitante básicopara lograr los objetivos glucémicos en los pacientes con diabetesmellitus(AU)

Hypoglycemia and fear to suffer them are limiting factors, both inpatients with type 1 diabetes as well as type 2 diabetes, to achieveand maintain an adequate glycemic control to avoid appearance/progression of chronic complications. Frequency of hypoglycemicepisodes mostly depends on type of diabetes, employed treatmentand individual risk factors. Episodes may be minor, asymptomatic, orsevere even with loss of consciousness. Hypoglycemia may haveimportant clinical outcomes due to an increase in morbidity and mortalityand a reduction in quality of life. This situation is feared eitherby patients or their relatives. Economic implications of severe episodes,both as direct hospital costs as well as indirect costs due toinability to work, are considerable. Therefore, hypoglycemia is thebasic limiting factor to achieve glycemic control goals in patients withdiabetes mellitus(AU)

Obesidad y control glucémico: efecto sobre el peso del recién nacido en la diabetes gestacional / The impact of obesity and glycemic control on birth weight in gestational diabetes

En el presente artículo se valora el efecto relativo del control glucémicoy la obesidad sobre parámetros ponderales del recién nacido en 1.960mujeres con diabetes gestacional (DG). Se consideró la existencia demacrosomía, peso elevado para la edad gestacional (LGA) e índice ponderalfetal (IPF). El IPF fue mayor en las gestantes con obesidad y en lasque presentaban un mal control metabólico. La frecuencia de recién nacidoscon LGA fue mayor en las mujeres obesas respecto a las no obesas(odds ratio [OR]= 2,16; intervalo de confi anza [IC] del 95%: 1,44-3,25) y en las gestantes que presentaban un mal control metabólicofrente a las que tenían un buen control (OR= 1,88; IC del 95%: 1,35-2,63). En éstas se constató un incremento del IPF y de la frecuencia deLGA si eran obesas. Los riesgos de LGA atribuibles a la obesidad y elmal control metabólico fueron del 53,7 y el 46,8%, respectivamente. Enresumen, la obesidad y el mal control de la DG provocan en los reciénnacidos un incremento del IPF y una mayor frecuencia de LGA. El IPFaumenta con independencia del control glucémico si la madre es obesa,y el excedente de LGA en gestantes con buen control puede explicarsepor la presencia de obesidad(AU)

The aim was to evaluate the effect of glycemic control and obesityon birth weight in 1960 women with gestational diabetes. Differentbirth weight parameters were considered: macrosomia, large-forgestational-age (LGA) and foetal ponderal index. Foetal ponderal indexwas higher in obese and poor-glycemic-control groups. The LGArate was higher in obese women compared to non-obese (OR=2.16; IC95%: 1.44-3.25%) and in patients with poor glycemic controlcompared to good-glycemic-control group (OR= 1.88; IC95%:1.35-2.63). In the latter, an increase in foetal ponderal index andLGA rate was observed in obese women. The LGA attributable riskpercentage was 53.7% for obesity and 46.8% for bad-glycemiccontrol.In conclusion, obesity and poor glycemic control are associatedwith a higher foetal ponderal index and a higher risk of LGAnewborn in gestational diabetic women. There is an increase in thefoetal ponderal index of the obese subgroup independently of glycemiccontrol. And obesity could explain the excess of LGA newbornsdespite mother’s good glycemic control during pregnancy(AU)

Mastopatía diabética en una mujer joven / Diabetic mastopathy in a young woman

No disponible

Nuevo método de referencia para la estandarización de la HbA1c: repercusiones clínicas / A new method for the standardization of the HbA1c: clinical impact

No disponible

Implantación de los sistemas de infusión subcutánea continua de insulina (ISCI) en la Comunidad de Madrid / Continuous subcutaneous insulin infusion (CSII) implementation in Madrid Autonomous Community

Objetivo: Conocer la implantación de los sistemas de infusión subcutánea continua de insulina (ISCI) en la Comunidad de Madrid (CM) y observar la evolución desde que dichos sistemas son cubiertos por los Servicios Públicos de Salud (SPS). Método: Estudio transversal descriptivo mediante encuesta enviada por correo electrónico a los médicos responsables de la utilización de los sistemas ISCI de los Servicios de Endocrinologíao Pediatría en cada Área Sanitaria (AS) de la CM entre 2004-2005. Resultados: Todos los representantes de las AS madrileñas remitieron el cuestionario contestado: 11 Áreas de Salud con su hospital de referencia y 2 centros hospitalarios que no tienen AS propia. En una de las Áreas, se han considerado por separado las respuestas de pediatría y de adultos, por lo que en total fueron 14 los encuestados. En el año 2004 había 109 dispositivos ISCI seguidos en nuestra Comunidad, y 213 en el 2005. Actualmente esla gerencia de cada Centro Hospitalario (CH) quien soporta el 72% del gasto subyacente a los sistemas ISCI. En 5 CH se abona la bomba de insulina y el fungible a pacientes diabéticos de otras AS de la Comunidad, pero no es así si los pacientes pertenecen a otra Comunidad Autónoma. El número de médicos involucrados en el año 2005 ascendía a 24 (20 endocrinólogos y 4 pediatras). Sólo en una de las AS se ha logrado un nuevo endocrinólogo en la plantilla y no ha habido aumentos en el personal de enfermería. En 10 de los 13 CH el fungible de los sistemas ISCI es dispensado por el propio Servicio de Endocrinología. Sólo 1 de ellos está dotado de hospital de día, teléfono de 24 horas, personal de enfermería educador, lugar específico y remuneración por ese concepto, mientrasque 2 CH no disponen de ninguno de estos requisitos. Siete de los 14 encuestados creen que debería existir un "Comité de Endocrinólogos" que marcase las pautas a seguir en materia de sistemas ISCI. Sin embargo, sólo 3 creen que "ese Comité" debería tener capacidad ejecutiva para acreditar o no a los distintos centros en materia de bombas de infusión. En 4 de los 13 CH no existe aún un protocolo de aplicación y seguimiento de ISCI. Conclusión: La dispensación de sistemas ISCI es poco homogénea entre las diferentes AS de la CM. Este hecho probablemente sea debido a diferencias en las infraestructuras de los CH, y en la capacitación y motivación de los profesionales involucrados

Objective: To assess the implementation of continuous subcutaneous insulin infusion (ISCI) in the Madrid Autonomous Community (MAC) and to evaluate the evolution since the coverage by the Public Health System. Methods: Descriptive cross-sectional study using questionnaires sending by e-mail to the physicians responsible for CSII therapy in Departments of Endocrinology or Pediatrics in each Heath Area of MAC between 2004-2005. Results: All the contacted physicians sent back the questionnaires: 11 health areas with a reference hospital, 2 centers without a self health area and two centers of pediatrics or endocrinology from the same area, making a total of 14 centers to be evaluated. During 2004, 109 devices were followed in MAC, increasing to 213 in 2005. Nowadays, each management center sustained at least 72% of the expenses related to CSII therapy. In 5 centers, pump and fungible material were covered for diabetic patients coming from other health areas but no from other autonomous communities. In 2005, 24 health personnel (20 endocrinologists and 4 pediatricians) were involved in the therapy. Only one center incorporated a new staff physician but no changes occurred in the number of diabetic educators. In 10 centers, fungible material are dispensed by the endocrinology department. Finally, only one center had a day-care clinic, 24 h assistance phone, diabetes educator, an appropriate area for therapy and a budget for CSII therapy. Two centers didn’t have any of the above requirements. Seven of 14 interviewed physicians suggest that a committee of endocrinologists will be necessary to establish the rules for CSII. However, only 3 were in accordance to give executive faculties to the committee to give accreditation for CSII therapy. Finally, in 4 out of 13 centers there are still no pump therapy protocols and followup. Conclusions: The implementation of CSII therapy is no homogeneous between different health areas of MAC. This fact is probably due to differences in the resources and personal motivated enough with pump therapy

Adaptación de la tasa basal frente a dosis elevadas de corticoides en mujer con diabetes pregestacional, embarazo gemelar y tratamiento con infusión subcutánea continua de insulina (ISCI) / Adaptation of the basal rate against elevated glucocorticoid doses in a woman suffering pregestational diabetes, twin pregnancy and therapy with continuous subcutaneous insulin infusion

El tratamiento con corticoides puede alterar el control metabólico de las mujeres gestantes con diabetes. El caso que se presenta corresponde al de una mujer con diabetes pregestacional en tratamiento con ISCI que, tras la inyección de 2 dosis de 12 mg betametasona vía im (cada 12 h) para maduración del pulmón fetal, necesitó una adaptación de la tasa basal de insulina de la bomba de infusión. La tasa basal de insulina fue modificada en todos los periodos previamente programados, triplicando las tasas después de aplicada la primera dosis de corticoides durante las 24 h siguientes, duplicándolas el segundo día y aumentando 0,1 UI/hora el tercer y cuarto días. El incremento de insulina que supuso la nueva pauta fue de 39,5 UI/24 h el primer día, 19,75 UI/24 h el segundo, y 2,4 UI/24 h el tercer y cuarto días. Los valores de glucemia media logrados en los 4 días siguientes de las inyecciones de corticoides fueron 152, 99, 108, y 116 mg/dl (65-206), encontrándose más del 75% de las mediciones en un rango aceptable de entre 60 a 140 mg/dl. Falta saber si los buenos resultados obtenidos son reproducibles en el resto de gestantes con diabetes tipo 1 que sigan terapia con ISCI

Corticoid treatment can alter the metabolic control of pregnant women with diabetes. The reported case describes a woman with pregestational diabetes under CSII therapy, who needed an adaptation of basal rate of the insulin pump after the i.m. injection of two doses of 12 mg beclametasone (t.i.d) administered to accelerate fetal lung maturation. The basal rate was modified in each of the previously programmed periods, increasing all of them three times during the first 24 h, twice during the second day, and 0.1 IU./h the third and the forth following days. The insulin increment was the first day 39.5 IU./24 h, the second day 19.75 IU./24 h, and 2.4 IU./24 h the ensuing third and forth days. Mean blood glucose values were achieved these days were 152, 99, 108 and 116mg/dl (range 65-206), being more than 75% of determinations in an acceptable range between 60-140 mg/dl. Our recommendation needs also to be confirmed in other type 1 diabetic women treated with CSII who receive corticoids during pregnancy

Infusión subcutánea continua de insulina (ISCI) en gestantes con diabetes pregestacional / CSII in pregnancy with pregestational diabetes

El embarazo de una mujer con diabetes tipo 1 requiere extremar el control glucémico para llevarlo tan cerca de la normalidad como sea posible. Los dispositivos de infusión subcutánea continua de insulina (ISCI) nos permiten lograr un buen control metabólico minimizando las hipoglucemias graves que la “casi” normalidad glucémica acarrea con mayor facilidad que con las pautas de múltiples dosis de insulina (MDI). En los “años 80” se publicaron varios trabajos clínicos de gestantes con diabetes pregestacional y sistemas de infusión subcutánea continua de insulina en los que apenas se apreciaban diferencias de control metabólico ni de resultados perinatales empleando los sistemas de infusión, con el “fantasma de fondo” de un mayor número de cetoacidosis; situación nada deseable durante el embarazo. Quizás por ello los “años 90” dejaron un vacío claro de publicaciones médicas, y ha tenido que venir la “década del 2000” a recuperar los sistemas ISCI para una situación de “primicia metabólica” como es el embarazo. Ahora bien, siguen siendo pocos los estudios realizados en gestantes con diabetes pregestacional y dispositivos de infusión de insulina y se echa en falta un gran estudio prospectivo y aleatorio que compare, en igualdad de condiciones, resultados perinatales y maternos entre ambas formas de terapia: inyecciones múltiples de insulina y sistemas de infusión continua

Pregnancy in women with type 1 diabetes need to led blood glucose control as normal as possible. Continuous subcutaneous insulin infusion (CSII) may be useful to achieve this objective avoiding severe hypoglucemia episodes, which frequently are associated to near-normoglycemia when multiple daily injections (MDI) are used. In the 80’several articles were published on the field. They didn’t show any advantages of CSII therapy on pregnant diabetic women as compared with MDI therapy on metabolic control or perinatal outcomes, although at this time it was not clear if CSII was associated with an increased risk of ketoacidosis, a situation which will be extremely dangerous in pregnancy. During the 90’s no other articles were published, but new data on the usefulness of CSII in pregnancy appeared in the past 5 years. Taken all the studies into account, we are still waiting for a prospective, randomised study which compares CSII and MDI therapy in pregnant women with prepregnancy diabetes, either type 1 or type 2 diabetes

Liver transplantation for type Ib glycogenosis with reversal of cyclic neutropenia.

We describe a case of glycogen storage disease type Ib in 32-year old male patient with poor metabolic control in spite of medical and nutritional management and the use of recombinant granulocyte stimulating factor. Because of this, liver transplantation was considered as a definitive treatment. We comment on the metabolic results of liver transplantation performed, with reversal of hypoglycemia, hyperuricemia, hypertriglyceridemia and cyclic neutropenia, all of which persist 4 years post-transplant. In view of this case, we believe that liver transplantation is a feasible option to consider in patients with type Ib glycogenosis as a definitive therapeutic procedure.

[Effect of preconceptional metabolic control in the course of pregnancy in diabetic patients]. / Influencia del control metabólico preconcepcional en la evolución de la gestación de la paciente diabética.

BACKGROUND: We analysed the relationship between metabolic control parameters during the preconception stage and pregnancy outcome in diabetic patients. PATIENTS AND METHOD: We examined 69 diabetic patients who underwent a preconception control at the Diabetes and Pregnancy Unit between 1992-1998. At the end of the preconception care period, 50 women (72.6%) became pregnant. Eight out of them (16%) had an abortion. RESULTS: Women who had an abortion did not differ from those who had not an abortion with regard to HbA1c levels at the end of the preconception period, age, duration of diabetes, age at diagnosis,anti-thyroid antibodies or microvascular disease. Among 41 single age stations, fetal macrosomia was observed in 36.6% cases, neonatal hypoglycemia in 19.5% and major congenital malformations in one case. Average level of HbA1c was 7.6 +/- 1.3%and 6.5 +/- 0.7 at the beginning and at the end of the preconception period, respectively (p < 0.001). In the group with macrosomia,average HbA1c at the end of the preconception period was 6.8 +/- 0.66% as opposed to 6.3 +/- 0.7% for the non-macrosomic group (p < 0.05). A linear correlation was seen between HbA1c levels at the end of the preconception period and infant weight (r = 0,432; p = 0,014), birth weight ratio (r = 0,450; p = 0,009), and a morbidity score (r = 0,458;p = 0,007). CONCLUSIONS: A better metabolic control during the preconception period may contribute to lessen the risk of fetal macrosomia and neonatal morbidity.

Molecular scanning for mutations in the insulin receptor substrate-1 (IRS-1) gene in Mexican Americans with Type 2 diabetes mellitus.

BACKGROUND: Insulin receptor substrate-1 (IRS-1) is an endogenous substrate for the insulin receptor tyrosine kinase, which plays an important role in insulin signaling. Mutations in the IRS-1 gene are associated in some populations with obesity and Type 2 diabetes. METHODS: To determine whether variation in the IRS-1 gene contributes to genetic susceptibility to insulin resistance and Type 2 diabetes in Mexican Americans, the entire coding region of the IRS-1 gene was screened for variation in 31 unrelated subjects with Type 2 diabetes using single-stranded conformational polymorphism analysis (SSCP) and dideoxy sequence analysis. Variants encoding amino acid substitutions were genotyped in 27 unrelated nondiabetic Mexican Americans and in all family members of subjects containing these variants, and association analyses were performed. To trace the ancestral origins of the variants, Iberian Caucasians and Pima Indians were also genotyped. RESULTS: Eight single base changes were found: four silent polymorphisms and four missense mutations (Ala94Thr, Ala512Pro, Ser892Gly and Gly971Arg). Allele frequencies were 0.009, 0.017, 0.017 and 0.043, respectively. There were no significant associations of any of these variants with diabetes, glucose or insulin levels during an oral glucose tolerance test, or with body mass index (BMI) in Mexican American families except for a modest association between the Ala94Thr variant and decreased BMI (30.4 kg/m(2) vs 24.0 kg/m(2); p=0.035). None of these four missense mutations were detected in Pima Indians. In Iberian Caucasians, neither Ala94Thr nor Ser892Gly were detected, and Ala512Pro was detected in only 0/60 diabetic patients and 1/60 nondiabetic controls. Gly971Arg was relatively more common in Iberian Caucasians with 12/58 diabetic patients and 7/60 nondiabetic controls being heterozygous for this variant (p=0.21 for comparison between diabetic and nondiabetic subjects). CONCLUSIONS: Ala94Thr, Ala512Pro and Ser892Gly mutation are rare in the populations studied. Gly971Arg, is more common in Mexican Americans and Caucasians, but is not a major contributor to genetic susceptibility to Type 2 diabetes.