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Evidence of association between type 1 diabetes and exposure to enterovirus in Cuban children and adolescents
Luis Sarmiento,Ileana Cubas-Due?as,Eduardo Cabrera-Rode
MEDICC Review , 2013,
Abstract: A possible etiologic role of enteroviruses for type 1 diabetes has been researched for 40 years, but evidence to date is inconclusive. This article summarizes new evidence from Cuban research supporting a role for enteroviruses, both in preclinical stages of autoimmune reactions against pancreatic β cells and at clinical onset, in a population with low type 1 diabetes incidence. Possible pathogenetic mechanisms are also discussed, such as acute cytolytic damage and molecular mimicry. Although direct causal effects of enteroviruses in type 1 diabetes are difficult to demonstrate, arguments supporting their role in type 1 diabetes pathogenesis should not be ignored; and confirmation could contribute to development of more effective preventive strategies.
Diamel Therapy in Polycystic Ovary Syndrome Reduces Hyperinsulinaemia, Insulin Resistance, and Hyperandrogenaemia
Arturo Hernández-Yero,Felipe Santana Pérez,Gisel Ovies Carballo,Eduardo Cabrera-Rode
International Journal of Endocrinology , 2012, DOI: 10.1155/2012/382719
Abstract: For to determine the effect of Diamel on the insulin resistance, insulin sensitivity, and sexual hormones results in women with polycystic ovary syndrome (PCOS). A study was carried out on 37 patients with this disorder. A triple-blind clinical trial was designed in which the Diamel food supplement was compared with a placebo. The women with reproductive ages were randomly distributed in two groups, with 18 and 19 women respectively, and they took Diamel or placebo and were followed up during 6 months with clinical and biochemical evaluation. A significant decrease in the HOMA-IR from the initial value at six months was observed in the group with Diamel. The insulin sensitivity improved considerably in this group. The rate of menstrual recovery was higher in the group with Diamel, and two patients from this group obtained pregnancy. The hormone levels shows a significant decrease in testosterone at 3 months in the group with Diamel compared with the control group. The LH also decreases in the same group when comparing the start with 6 months.We concluded that the Diamel decreases insulin resistance and improves sensitivity to this hormone in women with PCOS, with improvement in the levels of LH and testosterone. 1. Introduction Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by chronic anovulation and the cutaneous effects of hyperandrogenism [1–3]. There is a high prevalence of PCOS in women with type 2 diabetes mellitus, and there is evidence that insulin resistance and associated compensatory hyperinsulinaemia play a central role in the pathogenesis of PCOS in some women [4–7]. The metabolic aspects of this syndrome include insulin resistance, obesity, lipid abnormalities, and an increased risk for impaired glucose tolerance and type 2 diabetes mellitus [7–9]. Hyperinsulinaemia and insulin resistance are more common among women with PCOS than women without the condition regardless of whether they are obese or not [1, 8]. High insulin levels can increase the amount of androgens produced by ovarian theca cells in synergism with LH. It has been suggested that hyperandrogenism and insulin resistance occur early on in life and might even originate during foetal life and detected clinically before puberty [9, 10]. A potential mechanism for insulin resistance in PCOS women increased serine phosphorylation of the insulin receptors [8]. Serine phosphorylation of IRS-1 (insulin receptor substrate-1) has been suggested as a mechanism for TNF- -mediated insulin resistance and modulated the activity of the key regulatory enzyme of
Diabetes autoinmune del adulto en diabéticos tipo 2: frecuencia y características LADA in type 2 diabetics: frequency and characteristics
Eduardo Cabrera-Rode,Pedro Perich Amador,Oscar Díaz Horta,Gisela Molina Matos
Revista Cubana de Endocrinología , 2001,
Abstract: Se realizó este trabajo para conocer frecuencia, características clínico-bioquímicas, inmunológicas y genéticas de la diabetes autoinmune en adultos (LADA) en 1 000 diabéticos tipo 2 con edades 3 35 a os con distintos tiempos de duración de la diabetes. Se les determinó glucemia, anticuerpos antiislotes pancreáticos (ICA), anti-GAD65, anti-ICA512bdc/IA2, antimicrosomales tiroideos (AMT), antigástricos parietales (AGP), antinucleares (AN), microalbuminuria y péptido C en ayunas. Se encuestaron y se registraron algunas características clínicas. Se dividieron en 2 grupos según la presencia de ICA. Todos los diabéticos tipo 2 + para autoanticuerpos antiislotes (ICA y/o anti-GAD65) fueron identificados como LADA. Se detectó el 3,4 % de diabético tipo 2 con ICA +, en los diabéticos tipo 2 ICA- el 22,0 % presentó anticuerpos anti-GAD65. Se encontró que los diabéticos tipo 2 ICA+ eran más jóvenes, la duración de su diabetes era menor, presentaron menor IMC, disminución de los niveles de péptido C en ayunas, menos antecedentes familiares (padres) de DM2, valores menores en las tensiones arteriales diastólicas y sistólicas, mayor presencia de anticuerpos anti-GAD65, AMT y AGP en comparación con los diabéticos tipo 2 ICA-. Se observó que los diabéticos tipo 2 ICA+ (LADA) tienen características específicas que los asemejan a los diabéticos tipo 1, esto implicaría variaciones importantes en su tratamiento y evolución con respecto a los diabéticos tipo 2 ICA-. Se observó una baja frecuencia de ICA y alta de GAD en los diabéticos tipo 2 cubanos, las cuales fueron diferentes a la encontrada en poblaciones caucasianas. Los anticuerpos anti-GAD65 fueron superiores a los ICA para detectar los LADA. Las características clínicas e inmunológicas de estos pacientes muestran la lenta progresión de la destrucción autoinmune de las células b con implicaciones terapéuticas. This paper was aimed at knowing the frequency, clinico-biochemical, immunologic and genetic characteristics of autoimmune diabetes in adults (LADA) in 1 000 type 2 diabetic patients aged 35 or over with different times of duration of diabetes. Glycemia, anti-pancreatic islet cell antibodies (ICA), anti-GAD65 antibodies, anti-ICA512bdc/IA2 antibodies, anti-microsomal thyroid antibodies (AMT), anti-gastric parietal antibodies (AGP), antinuclear antibodies (AN), microalbuminuria and peptide C during fasting were determined. These patients were surveyed and some clinical characteristics were registered. They were divided into 2 groups according to the presence of ICA. All the type 2 + diabetics for anti-islet cell
índice cintura-cadera contra perímetro cintura para el diagnóstico del síndrome metabólico en ni os y adolescentes con familiares de primer grado diabéticos tipo 1 Waist-hip index versus waist circumference for diagnosis of metabolic syndrome in first degree-children and adolescents relatives of persons with type 1 diabetes
Eduardo Cabrera-Rode,Yadenys Bioti Torres,Sigrid Marichal Madrazo,Judith Parlá Sardi?as
Revista Cubana de Endocrinología , 2011,
Abstract: Objetivo: comparar las mediciones de perímetro cintura e índice cintura-cadera para determinar la frecuencia del síndrome metabólico en familiares de primer grado de personas con diabetes tipo 1, utilizando diferentes definiciones pediátricas. Métodos: se estudiaron 224 familiares de primer grado de personas con diabetes tipo 1, en edades comprendidas entre los 4 y los 19 a os. Se les determinó peso, talla, perímetro cintura y perímetro cadera, tensión arterial, glucemia, triglicéridos y HDL-colesterol. Se aplicaron las definiciones de síndrome metabólico según los criterios de Cook, Ford, la Federación Internacional de Diabetes y del consenso cubano. Se realizó una variante del consenso cubano utilizando: índice de masa corporal e índice cintura-cadera, según tablas cubanas, valores de glucosa 3 5,6 mmol/L y tensión arterial 3 90 percentil (tablas cubanas). Se tomaron, de forma independiente, los criterios de HDL-colesterol y triglicéridos. Empleamos el índice cintura-cadera de las tablas cubanas, el perímetro cintura sugerido por la Asociación Latinoamericana de Diabetes y el europeo para las definiciones estudiadas. Para la comparación de las frecuencias del síndrome metabólico, se usó la prueba exacta de Fisher. Resultados: la frecuencia del síndrome metabólico al aplicar la variante del consenso cubano fue de 9,37 % (21/224). Al comparar la variante del consenso cubano con las definiciones de Cook, Ford y la Federación Internacional de Diabetes (que utiliza el perímetro cintura de la Asociación Latinoamericana de Diabetes), se observó diferencia significativa con Cook y la Federación Internacional de Diabetes (4,01 %, p= 0,0360; 1,33 %, p= 0,0002 respectivamente). Al confrontar la presencia del síndrome metabólico de la variante del consenso cubano con Cook (8,48 %; 19/224) y Ford (8,93 %; 20/224), teniendo en cuenta el índice cintura-cadera de las tablas cubanas, podemos detectar frecuencias similares de familiares de primer grado de personas con diabetes tipo 1 con síndrome metabólico. En cambio, encontramos diferencias significativas cuando comparamos las frecuencias del síndrome metabólico de la variante del consenso cubano (p= 0,0019), de Cook (p= 0,0053) y de Ford (p= 0,0032), con la definición sugerida por la Federación Internacional de Diabetes (2,23 %; 5/224) empleando el índice cintura-cadera. Conclusiones: nuestros datos indican que para el diagnóstico del síndrome metabólico debemos utilizar el índice cintura-cadera y no el perímetro cintura sugerido por la Asociación Latinoamericana de Diabetes, aún sin presentar datos propios del perím
Expression of Innate Immunity Genes and Damage of Primary Human Pancreatic Islets by Epidemic Strains of Echovirus: Implication for Post-Virus Islet Autoimmunity
Luis Sarmiento, Gun Frisk, Mahesh Anagandula, Eduardo Cabrera-Rode, Merja Roivainen, Corrado M. Cilio
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0077850
Abstract: Three large-scale Echovirus (E) epidemics (E4,E16,E30), each differently associated to the acute development of diabetes related autoantibodies, have been documented in Cuba. The prevalence of islet cell autoantibodies was moderate during the E4 epidemic but high in the E16 and E30 epidemic. The aim of this study was to evaluate the effect of epidemic strains of echovirus on beta-cell lysis, beta-cell function and innate immunity gene expression in primary human pancreatic islets. Human islets from non-diabetic donors (n = 7) were infected with the virus strains E4, E16 and E30, all isolated from patients with aseptic meningitis who seroconverted to islet cell antibody positivity. Viral replication, degree of cytolysis, insulin release in response to high glucose as well as mRNA expression of innate immunity genes (IFN-b, RANTES, RIG-I, MDA5, TLR3 and OAS) were measured. The strains of E16 and E30 did replicate well in all islets examined, resulting in marked cytotoxic effects. E4 did not cause any effects on cell lysis, however it was able to replicate in 2 out of 7 islet donors. Beta-cell function was hampered in all infected islets (P<0.05); however the effect of E16 and E30 on insulin secretion appeared to be higher than the strain of E4. TLR3 and IFN-beta mRNA expression increased significantly following infection with E16 and E30 (P<0.033 and P<0.039 respectively). In contrast, the expression of none of the innate immunity genes studied was altered in E4-infected islets. These findings suggest that the extent of the epidemic-associated islet autoimmunity may depend on the ability of the viral strains to damage islet cells and induce pro-inflammatory innate immune responses within the infected islets.
índice cintura-cadera contra perímetro cintura para el diagnóstico del síndrome metabólico en ni?os y adolescentes con familiares de primer grado diabéticos tipo 1
Cabrera-Rode,Eduardo; Bioti Torres,Yadenys; Marichal Madrazo,Sigrid; Parlá Sardi?as,Judith; Arranz Calzado,Celeste; Olano Justiniani,Raysa; González Fernández,Pedro; Vera González,Manuel;
Revista Cubana de Endocrinolog?-a , 2011,
Abstract: objective: to compare the measurements of waist circumference and waist-hip circumference to determine the frequency of metabolic syndrome in first degree relatives of persons with type 1diabetes, using different pediatric definitions. methods: two hundred twenty four first degree relatives of persons with type 1 diabetes were studied in ages from 4 to 10 years. weight, height, waist-hip circumference, blood pressure, glycemia, triglycerides and hdl-cholesterol were determined. the definitions of metabolic syndrome according to cook, ford, international federation of diabetes and the cuban consensus were applied. a variant of cuban consensus was performed using: body mass index and waist-hip index according the cuban tables, values of glucose 3 5,6 mmol/l and blood pressure 3 90 percentile (cuban tables). in an independent way, criteria of hdl-cholesterol and triglycerides were taken into account. the waist-hip index of cuban tables, the waist circumference suggested by the latin-american and european association of diabetes for study definitions were applied. for comparison of frequencies of metabolic syndrome the fisher exact test was used. results: the frequency of metabolic syndrome with application of cuban consensus variant was of 9,37 % (21/224). comparing the above variant with the definitions of cook, ford and of the international federation of diabetes (using the waist circumference of the latin-american association of diabetes, there was a significant difference between cook and the international federation of diabetes (4,01 %, p= 0,0360; 1,33 %, p= 0,0002, respectively). comparing the presence of metabolic syndrome of the cuban consensus variant with cook (8,48 %; 19/224) and ford (8,93 %; 20/224) taking into account the waist-hip index of the cuban tables, it is possible to detect similar frequencies of first degree relatives of persons with type 1 diabetes with metabolic syndrome. on the other hand, we found significant differences comparing the freque
Diabetes autoinmune del adulto en diabéticos tipo 2: frecuencia y características
Cabrera-Rode,Eduardo; Perich Amador,Pedro; Díaz Horta,Oscar; Molina Matos,Gisela; Suárez Fonseca,Leonel; Tiberti,Claudio; Arranz Calzado,Celeste; Licea Puig,Manuel; Puig Domingo,Manuel; de Leiva,Alberto; Di Mario,Umberto;
Revista Cubana de Endocrinolog?-a , 2001,
Abstract: this paper was aimed at knowing the frequency, clinico-biochemical, immunologic and genetic characteristics of autoimmune diabetes in adults (lada) in 1 000 type 2 diabetic patients aged 35 or over with different times of duration of diabetes. glycemia, anti-pancreatic islet cell antibodies (ica), anti-gad65 antibodies, anti-ica512bdc/ia2 antibodies, anti-microsomal thyroid antibodies (amt), anti-gastric parietal antibodies (agp), antinuclear antibodies (an), microalbuminuria and peptide c during fasting were determined. these patients were surveyed and some clinical characteristics were registered. they were divided into 2 groups according to the presence of ica. all the type 2 + diabetics for anti-islet cell autoantibodies (ica and/or antigad65) were identified as lada. 3.4 % of type 2 ica + were detected. 22.0 % of type 2 ica - diabetics had anti-gad65 antibodies. it was found that type 2 ica + diabetics were younger, that their diabetes was shorter, that they had lower bmi, reduced levels of fasting peptide c, less dm2 history family (parents), lower values of diastolic and systolic arterial pressure, higher presence of anti-gad65 antibodies, amt and agp in comparison with type 2 ica - diabetics. it was observed that type 2 ica+ diabetics (lada) have specific characteristics that make them similar to type 1 diabetics, which would lead to important variations in their treatment and evolution as regards type 2 ica - diabetics. among the cuban type 2 diabetics it was detected a low frequency of ica and a high frequency of gad, which were different to those found in the caucasian populations. the anti-gad65 antibodies were higher than ica to detect lada. the clinical and immunological characteristics of these patients show the slow progression of the autoimmune destruction of b-cells with therapeutic implications.
Problemas actuales en la diabetes autoinmune latente del adulto Present problems in latent autoimmune diabetes of the adult
Eduardo Cabrera Rode
Revista Cubana de Endocrinología , 2002,
Abstract:
Nueva definición, prevalencia, caracterización y tratamiento de la diabetes autoinmune latente del adulto
Cabrera Rode,Eduardo; Licea Puig,Manuel E;
Revista Cubana de Endocrinolog?-a , 2008,
Abstract: latent autoimmune diabetes of adult is a way of autoimmune diabetes present in some subjects erroneously classified as type 2 diabetics. progression of autoimmune damage of ? cells in this entity is slower than in children presenting with type 1 diabetes. at diagnosis, persons affected by this condition, have a greater preservation of ? cells function than those presenting with the classic type 1 diabetes. their present diagnosis is based on 3 features: age similar o greater than 30 years (however, it may be present in subjects in ages lower than 30 years); presence of at least 1 of the 5 antibodies to pancreatic antigens of islet-cells (anti-islet [ai] auto-antibodies, anti-descarboxylase of glutamic acid [agad], antibodies to phosphatase tyrosine [aia2], and to zinc-cation transporter within ? islet-cells [aznt8]), and the need of insulin requirements, at least 6 months after diagnosis. it is present in 10 % of subjects presenting with type 2 diabetes in 335 years, and in 25 % of those younger than 35 years. some genes of susceptibility for it are described, including genes hla dr3/dr4 and dqb1*0201/dqb1*0302, dqb1*0602, class i mhc related to a chain (mica), as well as class i vntr allele, among others, those similar o different of the classic type 1 diabetes or the type 2. prospective studies on function of ? cells show that subject carriers of it with multiple auto-antibodies associated to type 1 diabetes develops a failure of function above mentioned within the first 5 years of duration of diabetes, while the most of those with on agad or ica develop a failure in this function after 5 years. in these persons may to occur a failure in function of ? cells up to 12 years after diagnosis of disease, although deterioration of ? cells response to i.v. glucose or glucagon, may be detected in some subjects at diagnosis of diabetes. thus, we aren't in presence of a latent disease. there are studies suggesting that insulin-treatment is the more appropriate at diagnosis
Diabetes autoinmune latente del adulto: estamos diagnosticándola correctamente? Latent autoimmune diabetes of the adult: are we diagnosing it right?
Eduardo Cabrera Rode,Manuel E. Licea Puig
Revista Cubana de Endocrinología , 2008,
Abstract:
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