Is HLA the cause of the high incidence of type 1 diabetes in the Canary Islands? Results from the Type 1 Diabetes Genetics Consortium (T1DGC).

INTRODUCTION: Incidence of childhood-onset type 1 diabetes mellitus in the Canary Islands is the highest reported so far in Spain, and among the highest worldwide. The HLA region accounts for approximately half the genetic risk of type 1 diabetes. Our aim was to assess distribution of high-risk and protective HLA haplotypes in the Canarian families included in the T1DGC, as compared to the rest of Spain. METHODS: The T1DGC study, an international project to study the genetics and pathogenesis of type 1 diabetes, enrolled more than 3000 families with type 1 diabetes worldwide. Spain provided 149 of these families, of whom 42 were from Tenerife and Gran Canaria. HLA was genotyped centrally using a PCR-based, sequence-specific oligonucleotide probe system. Haplotypes were reconstructed using the deterministic algorithm alleHap in the R programming environment. Based on prior T1DGC results in Caucasian population, haplotypes DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0401-DQA1*0301-DQB1*0302, DRB1*0301-DQA1*0501-DQB1*0201, DRB1*0402-DQA1*0301-DQB1*0302 and DRB1*0404-DQA1*0301-DQB1*0302 were considered high-risk. DRB1*0701-DQA1*0201-DQB1*0303, DRB1*1401-DQA1*0101-DQB1*0503, DRB1*1501-DQA1*0102-DQB1*0602, DRB1*1101-DQA1*0501-DQB1*0301, DRB1*1104-DQA1*0501-DQB1*0301, DRB1*1303-DQA1*0501-DQB1*0301, DRB1*1301-DQA1*0103-DQB1*0603 and DRB1*0403-DQA1*0301-DQB1*0302 were considered protective. The distribution of protective, high-risk, and other haplotypes in the (first two) affected siblings and unaffected parents from Canarian and non-Canarian Spanish families was compared (Chi-square test). RESULTS: No significant differences were found between the regions in distribution of the HLA haplotypes in the affected siblings or in the non-affected parents. CONCLUSIONS: The high incidence of childhood-onset type 1 diabetes in the Canarian population does not appear to be explained by a greater prevalence of high-risk class II HLA haplotypes in families with the disease. However, sample size limits the differences that can be detected in this study.

Is HLA the cause of the high incidence of type 1 diabetes in the Canary Islands? Results from the Type 1 Diabetes Genetics Consortium (T1DGC) / ¿Es el HLA la causa de la alta incidencia de diabetes tipo 1 en las Islas Canarias? Resultados del Consorcio de Genética de la Diabetes tipo 1 (T1DGC)

Introduction: Incidence of childhood-onset type 1 diabetes mellitus in the Canary Islands is the highest reported so far in Spain, and among the highest worldwide. The HLA region accounts for approximately half the genetic risk of type 1 diabetes. Our aim was to assess distribution of high-risk and protective HLA haplotypes in the Canarian families included in the T1DGC, as compared to the rest of Spain. Methods: The T1DGC study, an international project to study the genetics and pathogenesis of type 1 diabetes, enrolled more than 3000 families with type 1 diabetes worldwide. Spain provided 149 of these families, of whom 42 were from Tenerife and Gran Canaria. HLA was genotyped centrally using a PCR-based, sequence-specific oligonucleotide probe system. Haplotypes were reconstructed using the deterministic algorithm alleHap in the R programming environment. Based on prior T1DGC results in Caucasian population, haplotypes DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0401-DQA1*0301-DQB1*0302, DRB1*0301-DQA1*0501-DQB1*0201, DRB1*0402-DQA1*0301-DQB1*0302 and DRB1*0404-DQA1*0301-DQB1*0302 were considered high-risk. DRB1*0701-DQA1*0201-DQB1*0303, DRB1*1401-DQA1*0101-DQB1*0503, DRB1*1501-DQA1*0102-DQB1*0602, DRB1*1101-DQA1*0501-DQB1*0301, DRB1*1104-DQA1*0501-DQB1*0301, DRB1*1303-DQA1*0501-DQB1*0301, DRB1*1301-DQA1*0103-DQB1*0603 and DRB1*0403-DQA1*0301-DQB1*0302 were considered protective. The distribution of protective, high-risk, and other haplotypes in the (first two) affected siblings and unaffected parents from Canarian and non-Canarian Spanish families was compared (Chi-square test). Results: No significant differences were found between the regions in distribution of the HLA haplotypes in the affected siblings or in the non-affected parents. Conclusions: The high incidence of childhood-onset type 1 diabetes in the Canarian population does not appear to be explained by a greater prevalence of high-risk class II HLA haplotypes in families with the disease. However, sample size limits the differences that can be detected in this study (AU)

Introducción: La incidencia de diabetes tipo 1 infantil en Canarias es la más alta descrita hasta el momento en España y una de las mayores a nivel mundial. La región HLA explica aproximadamente el 50% del riesgo genético de la diabetes tipo 1. Nuestro objetivo fue comparar la frecuencia de haplotipos de HLA de riesgo y protectores en familias españolas canarias y peninsulares incluidas en el T1DGC. Métodos: El T1DGC es un proyecto internacional que estudia la genética y patogenia de la diabetes tipo 1, para el que fueron inluidas más de 3000 familias con la enfermedad. Un total de 149 familias provenían de España, y 42 de ellas, de Tenerife y Gran Canaria. El HLA fue genotipado en un laboratorio central, utilizando un método basado en PCR y sondas específicas de secuencia. Los haplotipos fueron reconstruidos utilizando el algoritmo determinista alleHap en el entorno de programación R. En base a los resultados previos del T1DGC en población caucásica, los haplotipos DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0401-DQA1*0301-DQB1*0302, DRB1*0301-DQA1*0501-DQB1*0201, DRB1*0402-DQA1*0301-DQB1*0302 y DRB1*0404-DQA1*0301-DQB1*0302 fueron definidos como de alto riesgo. DRB1*0701-DQA1*0201-DQB1*0303, DRB1*1401-DQA1*0101-DQB1*0503, DRB1*1501-DQA1*0102-DQB1*0602, DRB1*1101-DQA1*0501-DQB1*0301, DRB1*1104-DQA1*0501-DQB1*0301, DRB1*1303-DQA1*0501-DQB1*0301, DRB1*1301-DQA1*0103-DQB1*0603 y DRB1*0403-DQA1*0301-DQB1*0302 fueron considerados protectores. La distribución de haplotipos de riesgo, protectores y otros en los (dos primeros) hermanos afectos y en los padres no afectos fue comparada entre las familias canarias y no canarias (chi cuadrado). Resultados: No se encontraron diferencias significativas en la distribución de haplotipos HLA entre las regiones estudiadas, ni en los hermanos afectos ni en los padres no afectos. Conclusiones: La alta incidencia de la enfermedad en la población canaria no parece ser explicada por una mayor prevalencia de haplotipos de HLA de clase II de riesgo en los casos con agregación familiar, aunque el tamaño de la muestra limita las diferencias detectables en este estudio (AU)

Uromastyx acanthinura as a natural treatment in a mouse model of type 2 diabetes / Uromastyx acanthinura como tratamiento natural en un modelo murino de diabetes tipo 2

Aims: Oral testimonies from North Africa attribute anti-diabetic effects to medicinal preparations of the lizard Uromastyx acanthinura (UA). No scientific evidence of such effects is currently available. The acute effects of oral administration of UA to C57Bl/6J mice with diet-induced diabetes were tested and, if effectiveness was shown, the effect of subchronic UA administration was assessed in the same model. Methods: Mice were fed a diet containing 60% fat for at least 12 weeks. To assess acute effects, different doses of UA or saline were orally administered with 2 g of glucose/kg during an oral glucose tolerance test (OGTT) on different days in a randomised crossover design. The most effective dose was then fed together with the high-fat diet for 90 days and compared to high-fat diet alone in a parallel design. Body weight (BW), food consumption, welfare, and external appearance were assessed weekly. HbA1c, OGTT, and intraperitoneal insulin tolerance tests (IPITT) were performed at baseline and after treatment. Severity of neuropathy was evaluated by cold allodynia response in the acetone test. Results: UA significantly decreased glucose levels as compared to saline 15 min after administration. After 90 days of treatment, no differences were seen in OGTT or HbA1c between the groups, while IPITT showed higher glucose levels in UA-treated animals. Although weight increase was similar in both groups, weight tended to be higher in the treated group, which had a significantly higher daily food consumption. Cold allodynia response improved in frequency and intensity in the UA group. Conclusions: Orally administered UA acutely decreased blood glucose in diabetic mice. Paradoxically, long-term administration of UA increased food consumption, weight, and insulin resistance. Improved nociceptive response suggested an effect on pain and/or neuropathy. Although additional studies are needed to elucidate the properties and potential applications of UA, our results highlight the value of ethnomedical approaches to African traditional medicine as starting point to evaluate new bioactive components (AU)

Objetivos: Testimonios orales Norteafricanos atribuyen efectos hipoglucemiantes a preparados medicinales del lagarto Uromastyx acanthinura (UA), para los que no existen evidencias científicas actualmente. El objetivo de este trabajo fue el de investigar los efectos agudos de UA administrado oralmente en ratones diabéticos C57Bl/6J inducidos por dieta grasa, y si se demostrase su efectividad evaluar el efecto de su administración subcrónica en el mismo modelo animal. Métodos: Fue administrada una dieta a los animales con un contenido graso del 60% durante al menos 12 semanas. Para evaluar los efectos agudos diferentes dosis de UA o suero salino fueron administrados conjuntamente con 2 g/kg de glucosa durante sobrecargas orales de glucosa (SOG), en diferentes días, siguiendo un diseño cruzado aleatorizado. La dosis más efectiva en esta fase fue entonces administrada mezclada en la dieta durante 90 días y comparada con dieta solo en un diseño paralelo. El peso corporal y el consumo de alimento fueron evaluados semanalmente. HbA1c, SOG, y test de tolerancia intraperitoneal a la insulina (TTIPI) fueron realizados al inicio y tras el tratamiento. La gravedad de la neuropatía fue determinada mediante la evaluación de la alodinia al frío. Resultados: El UA redujo significativamente las concentraciones de glucosa de manera aguda en comparación con el control a los 15 min tras su administración. Tras 90 días de tratamiento no se observaron diferencias en las SOG o HbA1c entre grupos, mientras que para los test de tolerancia intraperitoneal a la isulina valores más altos de glucosa fueron determinados en los animales tratados con UA. Aunque ambos grupos aumentaron su peso, este tendió a ser mayor en los tratados, que a su vez consumieron significativamente más comida por día. La respuesta a la alodinia al frío mejoró en frecuencia e intensidad en los tratados con UA. Conclusiones: El UA administrado oralmente redujo de manera aguda la glucosa en sangre en ratones con diabetes. Paradójicamente, su administración crónica aumentó el consumo de alimento, el peso y la resistencia a la insulina. La mejora en la respuesta nociceptiva sugiere un efecto en el dolor y/o la neuropatía. Aunque son necesarios más estudios para aclarar las propiedades y posibles aplicaciones de este producto, nuestros resultados subrayan el valor de los enfoques etnomédicos hacia la medicina tradicional africana como origen para la evaluación de nuevos compuestos bioactivos (AU)

Uromastyx acanthinura as a natural treatment in a mouse model of type 2 diabetes.

AIMS: Oral testimonies from North Africa attribute anti-diabetic effects to medicinal preparations of the lizard Uromastyx acanthinura (UA). No scientific evidence of such effects is currently available. The acute effects of oral administration of UA to C57Bl/6J mice with diet-induced diabetes were tested and, if effectiveness was shown, the effect of subchronic UA administration was assessed in the same model. METHODS: Mice were fed a diet containing 60% fat for at least 12 weeks. To assess acute effects, different doses of UA or saline were orally administered with 2g of glucose/kg during an oral glucose tolerance test (OGTT) on different days in a randomised crossover design. The most effective dose was then fed together with the high-fat diet for 90 days and compared to high-fat diet alone in a parallel design. Body weight (BW), food consumption, welfare, and external appearance were assessed weekly. HbA1c, OGTT, and intraperitoneal insulin tolerance tests (IPITT) were performed at baseline and after treatment. Severity of neuropathy was evaluated by cold allodynia response in the acetone test. RESULTS: UA significantly decreased glucose levels as compared to saline 15min after administration. After 90 days of treatment, no differences were seen in OGTT or HbA1c between the groups, while IPITT showed higher glucose levels in UA-treated animals. Although weight increase was similar in both groups, weight tended to be higher in the treated group, which had a significantly higher daily food consumption. Cold allodynia response improved in frequency and intensity in the UA group. CONCLUSIONS: Orally administered UA acutely decreased blood glucose in diabetic mice. Paradoxically, long-term administration of UA increased food consumption, weight, and insulin resistance. Improved nociceptive response suggested an effect on pain and/or neuropathy. Although additional studies are needed to elucidate the properties and potential applications of UA, our results highlight the value of ethnomedical approaches to African traditional medicine as starting point to evaluate new bioactive components.

Anti-albuminuric effects of the angiotensin AT1 receptor blocker telmisartan in hypertensive patients.

We evaluated the anti-hypertensive and anti-albuminuric effect of the angiotensin receptor blocker telmisartan alone and in combination with torasemide and amlodipine. Patients were hypertensive, both diabetics and non-diabetics with persistent microalbuminuria. Our primary endpoint was a change in microalbuminuria levels, while the secondary endpoints were changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), serum creatinine levels, and glomerular filtration rate.After the 16-week treatment period, the patients significantly reduced microalbuminuria levels (76.4 ± 52.4 µg/min; p < 0.001), SBP (16.4 ± 8.7 mmHg; p < 0.001) and DBP (17.7 ± 5.9 mmHg; p < 0.001). Both diabetics and non-diabetics showed an identical pattern of significance with respect to the whole population. Systolic blood pressure, DBP, and microalbuminuria were significantly reduced as a consequence of therapy, both in diabetics and non-diabetics.