Nueva definición, prevalencia, caracterización y tratamiento de la diabetes autoinmune latente del adulto A new definition, prevalence, characterization, and treatment of the latent autoimmune diabetes of adult

La diabetes autoinmune latente del adulto es una forma de diabetes autoinmune que está presente en algunos sujetos equívocamente clasificados como diabéticos tipo 2. La progresión del daño autoinmune de las células ß en esta entidad es más lenta que en los niños con diabetes tipo 1. Las personas que la padecen, al momento del diagnóstico, presentan una mayor preservación de la función de las células ß que aquellos con la diabetes tipo 1 clásica. Su diagnóstico actual está basado en 3 características: edad igual o superior a 30 años (aunque se pueda encontrar también en sujetos con edades inferiores a 30 años); la presencia de al menos 1 de los 5 autoanticuerpos contra los antígenos pancreáticos de las células de los islotes (autoanticuerpos antiislotes [ICA], antidescarboxilasa del ácido glutámico [AGAD], anticuerpos contra la tirosina fosfatasa [AIA2] y contra el transportador del catión zinc dentro las células de los islotes [AZnT8]), y la necesidad de requerimientos de insulina, al menos 6 meses después del diagnóstico. Está presente en el 10 % de los individuos con diabetes tipo 2 con edades ³35 años y en el 25 % de los menores de 35. Se han descrito varios genes de susceptibilidad para ella, que incluyen los genes HLA DR3/DR4 y DQB1*0201/DQB1*0302, DQB1*0602, MHC clase I relacionados con la cadena A (MICA), así como del alelo VNTR clase I, entre otros, los que la asemejan o diferencian tanto de la diabetes tipo 1 clásica como de la tipo 2. Estudios prospectivos sobre la función de las células ß muestran que los sujetos que tienen múltiples autoanticuerpos asociados a diabetes tipo 1, desarrollan un fallo de la función de las células ß dentro de los primeros 5 años de duración de la diabetes, mientras que la mayoría de aquellos con solo AGAD ó ICA desarrollan el fallo de la función de estas células después de los 5 años. En estas personas puede ocurrir un fallo de la función de las células ß hasta a los 12 años después del diagnóstico de la enfermedad, aunque el deterioro de la respuesta de las células ß a la glucosa intravenosa o al glucagón puede ser detectado en algunos sujetos al diagnóstico de la diabetes. Por tal razón, no estamos en presencia de una enfermedad latente. Existen varios estudios que sugieren que el tratamiento con insulina es el más indicado al momento del diagnóstico de la enfermedad para contrarrestar el daño de la función de las células ß. En este trabajo, se revisó lo relacionado con su definición, la genética, la presencia de autoanticuerpos antiislotes y su patogenia, así como las experiencias con la función de las células y los tratamientos en discusión. Además, como la diabetes autoinmune la podemos encontrar no solo en adultos sino también en niños y adolescentes, así como en adultos jóvenes, sugerimos el epónimo de diabetes autoinmune de progresión lenta como más apropiado.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 ß 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 ß 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 ß 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 ß 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 ß cells up to 12 years after diagnosis of disease, although deterioration of ß 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 of disease to counteract function damage of ß cells. In this paper, we reviewed all that related to its definition, genetics, presence of anti-islet auto-antibodies and its pathogeny, as well as experiences with this function, and treatment in discussion. Also, as the autoimmune diabetes may be found not only in adults but in children and adolescents, as well as in young adults, we suggested the eponymus of autoimmune diabetes of slow progression like the more suitable

Type 1 Diabetes in the Tropics: A Link with Enterovirus Infections

The global distribution of the new cases of type 1 diabetes is influenced by genetic and environmental factors. The genetic component is not restricted to HLA, as other loci participate as risk factors. The incidence of type 1 diabetes in tropical/subtropical regions is low, whereas helminth and enterovirus infections are common and widespread. Three Echovirus epidemics have been documented in Cuba over the last two decades. Echovirus infections were associated with seroconversion to diabetes-related autoantibodies. Data from Cuba indicate enteroviruses of the B species as the agents linked most frequently to type 1 diabetes. Further research is necessary to define the enterovirus types linked to type 1 diabetes, which will pave the way for designing novel preventive approaches

Frecuencia y características clínicas de la retinopatía diabética en un grupo de personas con diabetes mellitus tipo 2 de diagnóstico reciente Frequency and clinical characteristics of diabetic retinopathy in a group of persons recently diagnosed with type 2 diabetes mellitus

En los últimos años se le ha dedicado mayor atención a la presencia de complicaciones microangiopáticas en las personas con diabetes mellitus tipo 2 (DM 2), y la retinopatía diabética (RD) no es una excepción. El objetivo de este trabajo es determinar la frecuencia y las características clínicas de la RD en un grupo de personas con DM 2 de diagnóstico reciente. Se estudiaron 110 pacientes (£ 6 meses) con anticuerpos antiislotes pancreáticos (ICA) y anti-descarboxilasa del ácido glutámico (AGAD) negativos, atendidos consecutivamente en el Centro de Atención al Diabético (CAD), del Instituto Nacional de Endocrinología (INEN), y las variables utilizadas fueron: edad, sexo, hábito de fumar, índice de masa corporal (IMC), edad de debut de la DM 2, presencia de RD y de nefropatía diabética incipiente (NDI), así como la presión arterial. Se determinó ICA, AGAD, hemoglobina glucosilada (HbA1), glucemia en ayunas y posprandial 2 horas después del desayuno y 2 horas después del almuerzo y excreción urinaria de albúmina (EUA) en orina de 24 horas. No se incluyó a pacientes con ND diabética clínica (EUA ³ 300 mg/L), ni con otras causas o condiciones de aumento de EUA. Se dividieron en 2 grupos atendiendo a la presencia o no de RD, así como a su severidad y fueron utilizados los criterios propuestos por L'Esperance. El 7 % de la totalidad de la serie presentó algún tipo de RD (7 no proliferativas y 1 proliferativa). La presión arterial sistólica fue de 127,84 ± 19,43 mmHg en aquellos sin RD y de 140 ± 15,27 mmHg , en los que presentaron RDNP (p < 0,0016). La presión arterial diastólica fue de 81,99 ± 11,65 mmHg en los que no tenían RD y de 87,86 ± 13,49 mmHg en aquellos con RD (p < 0,00027). De las 7 personas que tenían RDNP, 4 tenían una NDI (EUA >20 a < 300 mg/L). Los valores de las glucemias en ayunas y posprandiales, de HbA1 y de EUA no mostraron diferencias estadísticamente significativas. La RD puede estar presente en el momento del diagnóstico clínico de la DM 2, incluso la forma proliferativa, lo que obliga a realizar un examen oftalmológico minucioso en toda persona con DM 2 en el momento de su diagnóstico clínico.<br>In the last few years, great attention has been paid to microangiopathic complications occurred in persons with type 2 diabetes mellitus, and diabetic retinopathy is not the exception. The objective of this paper is to determine the frequency and the clinical characteristics of diabetic retinopathy in a group of persons recently diagnosed with type 2 diabetes mellitus. One hundred ten patients (£ 6 months) having negative anti islet cell antibodies (ICA) and anti-glutamic acid decarboxylase antibodies (AGAD) were studied, who had been consecutively seen in the Diabetic Care Center of the National Institute of Endocrinology (INEN). The variables used were: age, sex, smoking, body mass index, age of onset of type 2 diabetes mellitus, presence of diabetic retinopathy (DR) and incipient diabetic nephropathy(IDN) as well as blood pressure. ICA, AGAD, glycosylated hemoglobin, glycemia on fasting and postprandial 2 hours after breaskfast and 2 hours after lunch, and urinary albumin excretion (UAE) in urine collected 24 hours were determined. The study did not include patients with neither clinical diabetic nephropathy (UAE ³ 300 mg/L) nor other causes and raised UAE. The patients were divided into two groups according to the presence or absence of DR as well as the severity of this illness, and the criteria suggested by L´Esperance were followed. 7% of the whole series presented with some type of DR (7 non-proliferative and 1 proliferative). Systolic blood pressure was 127,84 ± 19,43 mmHg in those patients without DR and 140 ± 15,27 mmHg in those having non-proliferative diabetic retinopathy (p &#8249; 0,0016). Diastolic blood pressure was 81,99 ± 11,65 mmHg in patients without DR and 87,86 ± 13,49 mmHg in those suffering DR (p < 0,00027). Four of the seven persons that had non-proliferative diabetic retinopathy also presented with IDN (UAE > 20 to < 300mg/L). The figures corresponding to glycemia on fasting and postprandial, HbA1 and UAE did not show statistically significant differences. DR may be present at the moment of clinical diagnosis of type 2 diabetes mellitus, even proliferative form, which makes it necessary to perform a thorough ophtalmologic test in every person suffering type 2 diabetes mellitus at the moment of diagnosis

Frecuencia y características clínicas de la nefropatìa incipiente en personas con diabetes mellitus tipo 2 de diagnóstico reciente Frequency and clinical characteristics of incipient neuropathy in persons recently diagnosed with diabetes mellitus type 2

El objetivo de este trabajo fue determinar la frecuencia y las características clínicas de la nefropatía diabética incipiente (NDI) en personas con diabetes mellitus tipo 2 (DM2) de diagnóstico reciente, negativos en relación con los anticuerpos antislotes pancreáticos (ICA) y la antidescarboxilasa del ácido glutámico (AGAD). Se estudiaron 183 personas con DM2 (ICA y AGAD negativos), atendidas en el Centro de Atención al Diabético, con la evaluación de las siguientes variables: edad, sexo, hábito de fumar, índice de masa corporal (IMC), edad al debut, tipo de tratamiento de la DM, presencia de retinopatía diabética (RD) y la presión arterial, así como la glucemia en ayunas y posprandial. Se determinó ICA, AGAD, hemoglobina glucosilada (HbA1), glucemia en ayuna y postprandial 2 horas después del desayuno y del almuerzo, así como excreción urinaria de albúmina (EUA) en orina de 24 horas. No se incluyó a pacientes con ND diabética clínica (EUA ³ 300 mg/L), con nefropatía no diabética, ni con otras causas o condiciones de aumento de EUA. Los sujetos se dividieron en 2 grupos: normoalbuminúricos (EUA £ 20 mg/L) N = 163, y microalbuminúricos (NDI incipiente EUA > 20 a The objective of this paper was to determine the frequency and clinical characteristics of incipient diabetic nephropathy(IDN) in persons with type 2 diabetes mellitus of recent diagnosis negatives for pancreatic islet cell antibodies (ICA) and glutamic acid decarboxylase antibodies(AGAD). One-hundred and three persons with DM2 (negative ICA and AGAD), seen at the Diabetic Care Center, were studied and evaluated according to the following variables: age, sex, smoking, body mass index (BMI); age of onset of diabetes, type of DM treatment, presence of diabetic retinopathy (DR) and blood pressure as well as glucemia at fasting and postprandial. The study determined ICA, AGAD, glycosylated hemoglobin(HbA1), glucemia at fasting and postprandial two hours after breakfast and lunch as well as urinary albumin excretion (UAE) in urine collected for 24 hours. Patients with clinical diabetic nephropathy (UAE ³ 300 mg/L), non-diabetic nephropathy or other causes or conditions leading to increased UAE were excluded. The patients were divided into two groups: normoalbuminuric (UAE £ 20 mg/L) N = 163 and microalbuminuric (incipient DN, UAE >20 a < 300 mg/L) N = 20. IDN in persons recently diagnosed with DM2 was observed in 10,9% of cases (20/183). Statistically significant differences were found when comparing normoalbuminurics to microalbuminurics at ages 52,6 ± 9,9 years vs. 57,5 ± 7,5 years (p< 0,03); their systolic: 127 ± 19,8 vs 139,0 ± 22,9 mmHg (p< 0,01) and diastolic blood pressure: 81,4 ± 11,3 vs 88,0 ± 11,0 mmHg (p < 0,01) as well as their BMI: 27,0 ± 5,0 vs 32,2 ± 6,4 (p< 0,00001). It was observed some sort of DR in 26 patients (20 normoalbuminurics and 6 microalbuminurics. HbA1 was higher in microalbuminurics with 9,4± 8,7% than in normoalbuminurics with 7,2± 1,5% (p < 0,002.) IDN may be present in a high percentage of persons recently diagnosed with DM2. Age, increased systolic and diastolic blood pressure values, the increase of BMI and raised HbA1 values are the main risk factors associated to IDN. Some of them can be changed if an adequate therapy is applied

Expression of Innate Immunity Genes and Damage of Primary Human Pancreatic Islets by Epidemic Strains of Echovirus: Implication for Post-Virus Islet Autoimmunity

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&lt;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&lt;0.033 and P&lt;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