Clinical and metabolic profile of patients with latent autoimmune diabetes in adults in specialized care in Madrid | Endocrinología, Diabetes y Nutrición (English ed.)

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Se observa una correlación negativa significativa (rho de Spearman: −0,40; p<0,001)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Alfonso Arranz Martín, Edurne Lecumberri Pascual, Miguel Ángel Brito Sanfiel, Víctor Andía Melero, Lia Nattero Chavez, Iván Sánchez López, Gloria Cánovas Molina, Francisco Arrieta Blanco, Noemí González Perez del Villar" "autores" => array:10 [ 0 => array:2 [ "nombre" => "Alfonso" "apellidos" => "Arranz Martín" ] 1 => array:2 [ "nombre" => "Edurne" "apellidos" => "Lecumberri Pascual" ] 2 => array:2 [ "nombre" => "Miguel Ángel" "apellidos" => "Brito Sanfiel" ] 3 => array:2 [ "nombre" => "Víctor" "apellidos" => "Andía Melero" ] 4 => array:2 [ "nombre" => "Lia" "apellidos" => "Nattero Chavez" ] 5 => array:2 [ "nombre" => "Iván" "apellidos" => "Sánchez López" ] 6 => array:2 [ "nombre" => "Gloria" "apellidos" => "Cánovas Molina" ] 7 => array:2 [ "nombre" => "Francisco" "apellidos" => "Arrieta Blanco" ] 8 => array:2 [ "nombre" => "Noemí" 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ZAG: zinc alpha-2 glycoprotein, UFC: 24h urinary free cortisol. Case: Cushing Syndrome (CS) subjects. Data reflect the individual distribution of ZAG in controls and CS patients. Pathological chronic levels of glucocorticoids like those in CS are associated with a higher sera ZAG level. Subjects in the control group with a normal daily production in the normal range present heterogeneous levels of ZAG, probably due to a multifactorial, regulatory mechanism." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Xavier Escoté, Gloria B. Aranda, Mireia Mora, Gregori Casals, Joaquim Enseñat, Oscar Vidal, Yaiza Esteban, Irene Halperin, Felicia A. Hanzu" "autores" => array:9 [ 0 => array:2 [ "nombre" => "Xavier" "apellidos" => "Escoté" ] 1 => array:2 [ "nombre" => "Gloria B." 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"apellidos" => "Hanzu" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2530016416300040" "doi" => "10.1016/j.endinu.2016.10.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2530016416300040?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2530018017300070?idApp=UINPBA00004N" "url" => "/25300180/0000006400000001/v1_201703170858/S2530018017300070/v1_201703170858/en/main.assets" ] "en" => array:22 [ "idiomaDefecto" => true "cabecera" => "Original Article" "titulo" => "Clinical and metabolic profile of patients with latent autoimmune diabetes in adults in specialized care in Madrid" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "34" 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"multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 896 "Ancho" => 1567 "Tamanyo" => 78680 ] ] "descripcion" => array:1 [ "en" => "Correlation between total daily dose of insulin and BMI. A positive significant correlation is seen between total insulin dose and BMI (Spearman's rho: 2.32; p<0.001)." ] ] ] "textoCompleto" => "IntroductionDiabetes mellitus (DM) is a pathophysiologically complex and heterogeneous disease that often goes beyond the somewhat rigid limits of the categories considered in the current classification.<a class="elsevierStyleCrossRef" href="#bib0105">1</a>The so-called latent autoimmune diabetes of the adult (LADA) is a slowly progressing autoimmune diabetes which is often not recognized as such and is confused with other types of DM. Positive islet cell antibodies (ICAs) have however been found in more than 10% of adults with type 2 DM (T2DM).<a class="elsevierStyleCrossRefs" href="#bib0110">2,3</a> LADA therefore represents the most prevalent form of autoimmune diabetes in adults, and is also probably the most prevalent form of autoimmune diabetes overall.<a class="elsevierStyleCrossRef" href="#bib0120">4</a>Although LADA is undoubtedly related to type 1 DM (T1DM), its clinical presentation often includes features attributable to T2DM, which often leads to a wrong diagnosis and treatment for significant periods of time. The fact that the diagnostic criteria currently used to identify this variant of diabetes are imprecise and controversial contributes to this.The purpose of this study was to help in clinical characterization of patients with LADA using specialized medical monitoring, and to study their metabolic control and the occurrence of chronic complications related to DM.MethodsA retrospective, cross-sectional study was conducted on patients with DM attending endocrinology departments of the public healthcare network of the region of Madrid. Cases were detected based on a systematic search in our clinic appointment books and databases (which did not necessarily include all cases at each hospital) for patients with the criteria listed below. The selection process lasted from May 2015 to February 2016, and the database was completed by collecting the information available at the hospital records.Patients enrolled met all three criteria of LADA proposed by the Immunology of Diabetes Society (IDS)<a class="elsevierStyleCrossRef" href="#bib0125">5</a>: diagnosis of diabetes based on the established criteria at ages older than 30years, insulin independence for at least six months after diagnosis, and positive glutamic acid decarboxylase antibodies (GADA). Patients with secondary and gestational diabetes and diabetes associated to malignancies were excluded.Data collected included age, sex, weight, height, body mass index (BMI), family history of diabetes, date of clinical diagnosis of diabetes and confirmation of LADA, GADA titer, associated autoimmune diseases or presence of organ-specific antibodies, basal plasma C-peptide levels, insulin regimen and dosage, other associated antidiabetic and cardiovascular drugs, metabolic glucose, lipid, and blood pressure control, estimated glomerular filtration rate, urinary albumin/creatinine ratio, and presence of microangiopathic and macroangiopathic complications. Biochemical and immunological data were assessed at the reference laboratories of the respective hospitals.Statistical analysis was performed using GraphPad Prism 6 software. Normally distributed data are given as mean (standard deviation). Non-normally distributed data are given as median (range). GADA titer is given as the ratio between the resulting absolute value and the upper limit of normal for each laboratory. Association or interdependence of two variables was calculated using Spearman's correlation coefficient.Results<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the demographic characteristics of our patients and information on their diabetes. Data were collected from 193 patients, of whom 108 (56%) were women. Thirty-eight percent of patients had no known family history of diabetes, 37% and 16% had a family history of T2DM and T1DM respectively, and 8.7% had a history of DM of an unknown type.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Mean age at diagnosis of DM was 48.9±11.2 years. Diagnosis of LADA, defined as the date when positive GADA were found, was made with a delay of 3.5years (range, 0–36) after clinical diagnosis of DM.GADA titer, expressed as the GADA/upper limit of normal ratio, was 5.4±2.1U/L. No correlation was seen between GADA titer, C-peptide levels, and insulin independence time.Patients were treated with diet and oral antidiabetic drugs only for a median of 12months (P10: 1; P90: 63).BMI was 25.4±4.2kg/m2. Overweight (BMI: 25–29.9) was found in 31.5% of patients, while 8% of patients were obese (BMI>30). No correlation was found between BMI and blood glucose control.Basal plasma C-peptide levels of patients were measured at different times after DM onset. Mean levels were 0.66±0.8ng/mL, but a significant heterogeneity was seen in the values found, which were clearly related to the time since onset of DM, showing a significant negative correlation (Spearman's rho: −0.52; p<0.0001). Twenty-seven percent of patients had C-peptide levels <0.05ng/mL, 49% had levels ranging from 0.05 and 1.0ng/mL, and 24% had levels >1.0ng/mL. A majority of patients (70%) in this last subgroup had a known diabetes duration shorter than one year at the time of C-peptide measurement.Basal-bolus insulin regimens were most commonly given to our patients (76.7%), followed by basal insulin (13.2%), premixes (4.2%), basal-plus regimens (2.6%), and CSII (0.5%). Only 2.6% of patients received no insulin therapy.Mean insulin dose was 35.1±19.6U/day, which corresponded to 0.51±0.24U/kg after adjustment for body weight. A positive, significant correlation (coef. 2.32; p<0.001) was found between total insulin dose and BMI (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), and there was a negative correlation between total daily insulin dose and C-peptide levels (Spearman's rho: −0.33; p<0.01).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>No concomitant non-insulin drugs were received by 66.5% of patients. Metformin was the drug most commonly used (in 25.7% of patients), followed by DPP-4 inhibitors (7.3%), GLP-1 receptor agonists (2.2%), and SGLT2 inhibitors (1.1%). Use of secretagogues and glitazones was very limited (0.6%).Fifty-seven percent of patients had other autoimmune diseases or positive organ-specific antibodies. Chronic thyroiditis was the most prevalent concomitant condition (occurring in 32.9% of patients). Other autoimmune conditions seen included atrophic gastritis (3.2%), vitiligo (2.4%), Graves’ disease (1.9%), Crohn's disease (1.2%), and celiac disease (1.2%).<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> provides data on metabolic control of patients. Fasting blood glucose levels were 160.5±57.3mg/dL, and HbA1c values were 7.7±1.26%. Only 31.7% of patients met metabolic control criteria (HbA1c ≤7.0 in two of the last three measurements performed); 31.1% had HbA1c values ranging from 7.1 and 8.0, 23.6% values ranging from 8.1 and 9.0, and 13.4% levels >9%. A significant negative correlation (Spearman's rho: −0.40; p<0.001) was found between HbA1c and C-peptide (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>) and between fasting glucose and C-peptide (Spearman's rho: −0.27; p<0.01).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>Lipid control was usually highly satisfactory: HDL cholesterol, 65±18mg/dL; LDL cholesterol, 96±27mg/dL; triglycerides, 89±44mg/dL. Estimated glomerular filtration rate (eGFR) was 80±22mL/min, and only 5% of patients had values suggesting kidney failure (eGFR<60mL/min). Mean urinary albumin/creatinine ratio was 12.9mg/g. Criteria for microalbuminuria (ratio, 30–300mg/g) were met by 7.6% of patients, and only 0.6% had macroalbuminuria (ratio >300mg/g). Mean blood pressure values were 128/75mmHg.Overall, 44.4% of patients were being treated with antihypertensive drugs, 55% with statins, 7.8% with other lipid-lowering agents, and 18.3% with antiplatelet aggregants.A majority of patients (72.0%) had no clinical evidence of chronic complications related to diabetes (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). In the remaining 28%, most complications seen (23.1%) were microangiopathic in nature: non-proliferative retinopathy (7.2%), proliferative retinopathy (3.3%), diabetic macular edema (1.6%), incipient nephropathy (6.6%, advanced nephropathy (1.1%), sensory neuropathy (3.3%)). Only 4.9% of patients had been diagnosed some macroangiopathic complication: ischemic heart disease (3.3%), peripheral artery disease (1.6%). No patient experienced stroke.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>DiscussionLADA is currently considered as an end of the spectrum of autoimmune diabetes, but does not represent a differentiated group within the general classification of diabetes, but a variant within the T1DM category.Latent autoimmune diabetes was already described<a class="elsevierStyleCrossRef" href="#bib0120">4</a> in 1986 as a form of DM that occurred in adults with no insulin dependence during an initial period but with early failure of oral antidiabetic treatment, presence of ICA and other frequently associated organ-specific antibodies. Patients reported in the initial report had lower BMIs and less pancreatic reserve of C-peptide as compared to ICA-negative diabetic patients.The term LADA was introduced in 1995<a class="elsevierStyleCrossRef" href="#bib0130">6</a> to describe a subgroup of patients with the above mentioned clinical characteristics who had positive GADA.Because of the pathophysiological heterogeneity of diabetes, it is often an oversimplification to try and attribute the category of T1DM or T2DM only to patients who have a genetic predisposition to both types of diabetes or who are subject to the influence of environmental factors that result in development of insulin resistance. In fact, patients with LADA have been shown to share the genetic characteristics of classical T1DM,<a class="elsevierStyleCrossRefs" href="#bib0135">7,8</a> but they often also have genetic similarities with T2DM,<a class="elsevierStyleCrossRef" href="#bib0145">9</a> which suggests a mixed nature of this form of diabetes.In our study population, diagnosis of LADA was based on the finding of positive GADA in patients in whom the condition was clinically suspected (diagnosis at adult age, absence of ketoacidosis and initial insulin independence, glycemic variability with marked postprandial component, etc.). Patient characteristics are therefore not comparable to those in non-selective immune screening studies conducted in patients who phenotypically have T2DM.In this regard, as previously noted,<a class="elsevierStyleCrossRef" href="#bib0150">10</a> we think that generalized screening for LADA in the adult diabetic population is not effective. However, LADA should be routinely ruled out when an adult with diabetes does not show the usual stereotype of T2DM.Our patients had as a group lower BMIs than expected for a population with T2DM, but were frequently overweight, which agrees with other reported studies.<a class="elsevierStyleCrossRef" href="#bib0155">11</a> High BMI values should therefore not exclude or delay screening for LADA if they coexist with other suspicious clinical factors.Various studies have reported lower plasma C-peptide levels in the group of patients with LADA as compared to T2DM.<a class="elsevierStyleCrossRefs" href="#bib0160">12,13</a> Our study revealed a significant heterogeneity in pancreatic reserve, which also had a negative correlation to blood glucose control. Thus, if LADA is clinically suspected, presence of detectable C-peptide levels should not rule out the condition until the results of the immune study are available.No guidelines are currently available for the treatment of LADA, but some studies have shown that early administration of insulin or sensitizing oral drugs may be beneficial for long-term preservation of the pancreatic reserve, while sulfonylureas may decrease the insulin independence time.<a class="elsevierStyleCrossRefs" href="#bib0170">14–16</a> Our study found a negative correlation between C-peptide levels and blood glucose control, thus emphasizing the importance of early identification of LADA both to increase insulin independence time and to improve metabolic control of patients.GADA titer has been reported to be inversely related to the pancreatic reserve, and may be a marker of the risk of progression to insulin dependence.<a class="elsevierStyleCrossRefs" href="#bib0170">14,17–19</a> Our study found no association between GADA values, C-peptide levels, or insulin independence time, but it was not a prospective study, and the immune and metabolic study was not performed at the time of clinical onset, but often with a delay of up to several years.This study has other obvious limitations. It was an observational study based on the information recorded in clinical histories, which is subject to data collection problems or errors. Omission bias, especially in the presence of chronic complications, may be significant and underestimate their prevalence, disregarding subclinical forms. Patient selection was based on the most commonly agreed diagnostic criteria,<a class="elsevierStyleCrossRef" href="#bib0125">5</a> but we are aware of their limitations: the age criterion is arbitrary, insulin independence time is highly physician-dependent, and GADA levels may decrease over time and even become negative in patients with long-standing disease.<a class="elsevierStyleCrossRef" href="#bib0200">20</a> A less rigid selection would have markedly increased the number of patients enrolled, but also the number of false positives. Finally, it should be recognized that as these patients attended specialized care clinics, the study population is not probably a faithful representation of the overall group of patients with LADA.Despite these limitations, we think that our study may help define patients with LADA in order to identify them as such as early as possible and select the most adequate treatment, thus avoiding years of unawareness by patients, their relatives, and the medical team.As a conclusion, it should be noted that in the study population, diagnosis of LADA may be delayed up to several years. Patients have a quite heterogeneous pancreatic insulin reserve, which is negatively related to time since onset of disease. Treatment of patients with LADA is often difficult, as shown by the deficient blood glucose control despite high compliance with complete insulinization regimens. A successful control is however seen of other treatment goals such as blood pressure and lipid profile, together with a low incidence of macroangiopathic complications.Conflict of interestThe authors state that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres815732" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec813033" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres815733" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec813034" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interest" ] 9 => array:2 [ "identificador" => "xack273775" "titulo" => "Acknowledgment" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-05-27" "fechaAceptado" => "2016-09-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec813033" "palabras" => array:5 [ 0 => "Diabetes" 1 => "Autoimmune" 2 => "Latent" 3 => "Adult" 4 => "Latent autoimmune diabetes in adults" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec813034" "palabras" => array:5 [ 0 => "Diabetes" 1 => "Autoinmune" 2 => "Latente" 3 => "Adulto" 4 => "Diabetes autoinmune latente del adulto" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo report the clinical characteristics of patients with latent autoimmune diabetes in adults (LADA), and to ascertain their metabolic control and associated chronic complications. MethodsPatients with DM attending specialized medical care in Madrid who met the following criteria: age at diagnosis of DM >30years, initial insulin independence for at least 6months and positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis, associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic control, and presence of chronic complications were analyzed. ResultsNumber of patients; 193; 56% females. Family history of DM: 62%. Age at DM diagnosis: 49years. Delay in confirmation of LADA: 3.5years. Insulin-independence time: 12months. Baseline serum C-peptide levels: 0.66ng/ml. Basal-bolus regimen: 76.7%. Total daily dose: 35.1U/day, corresponding to 0.51U/kg. With no associated oral antidiabetic drugs: 33.5%. Other autoimmune diseases: 57%. Fasting plasma glucose: 160.5mg/dL. HbA1c: 7.7%. BMI: 25.4kg/m2 (overweight, 31.5%; obesity, 8%). Blood pressure: 128/75. HDL cholesterol: 65mg/dL. LDL cholesterol: 96mg/dL. Triglycerides: 89mg/dL. Known chronic complications: 28%. ConclusionsRecognition of LADA may be delayed by several years. There is a heterogeneous pancreatic insulin reserve which is negative related to glycemic parameters. Most patients are poorly controlled despite intensive insulin therapy. They often have overweight, but have adequate control of BP and lipid profile and a low incidence of macrovascular complications." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoDefinir las características clínicas de los pacientes con diabetes autoinmune latente del adulto (LADA), conocer su control metabólico y las complicaciones crónicas asociadas que presentan. MétodosSeleccionamos pacientes con DM seguidos en las consultas de endocrinología de hospitales públicos de la Comunidad de Madrid que reunían los siguientes criterios: edad al diagnóstico de DM >30años, independencia inicial de insulina durante al menos 6meses y positividad de anticuerpos antiGAD. Analizamos datos clínicos relativos al diagnóstico de LADA, autoinmunidad asociada, niveles de péptido C, pauta terapéutica, control metabólico y presencia de complicaciones crónicas. ResultadosNúmero de pacientes: 193. Mujeres: 56%. Antecedentes familiares de DM: 62%. Edad al diagnóstico de DM: 49años. Retraso en confirmación LADA: 3,5años. Tiempo de insulino-independencia: 12meses. Péptido C basal suero: 0,66ng/ml (0,22nmol/l). Pauta de insulina basal-bolus: 76,7%. Dosis total diaria: 35,1U/día, correspondiente a 0,51U/kg. Sin fármacos orales asociados: 33,5%. Presencia de otras patologías autoinmunes: 57%. Glucemia en ayunas: 160,5mg/dl (8,91mmol/l). HbA1c: 7,7%. IMC: 25,4kg/m2 (sobrepeso: 31,5%; obesidad: 8%). Presión arterial: 128/75. Colesterol HDL: 65mg/dl (16,9mmol/l). Colesterol LDL: 96mg/dl (24,96mmol/l). Triglicéridos: 89mg/dl (1,01mmol/l). Complicaciones crónicas: 28%; microangiopatía: 23,1%; macroangiopatía: 4,9%. ConclusionesEl reconocimiento de LADA puede retrasarse varios años. La reserva pancreática de insulina de los pacientes es heterogénea y el grado medio de control glucémico deficiente a pesar de utilizar mayoritariamente insulinoterapia intensiva. Con frecuencia presentan sobrepeso, aunque tienen un control adecuado de la presión arterial y perfil lipídico y baja incidencia de complicaciones macroangiopáticas." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Arranz Martín A, Lecumberri Pascual E, Brito Sanfiel MÁ, Andía Melero V, Nattero Chavez L, Sánchez López I, et al. Perfil clínico y metabólico de pacientes con diabetes tipo LADA atendidos en atención especializada en la comunidad de Madrid. Endocrinol Diabetes Nutr. 2017;64:34–39." ] 1 => array:3 [ "etiqueta" => "◊" "nota" => "The names of the components of the Diabetes Group of the Society of Endocrinology, Nutrition and Diabetes of Madrid (SENDIMAD) are listed in <a class="elsevierStyleCrossRef" href="#sec0030">Annex</a>." "identificador" => "fn1" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "Alpañés, Macarena; Andía, Victor, Arranz, Alfonso; Arrieta, Francisco; Brito, Miguel; Calle Alfonso; Canovas, Gloria; del Cañizo, Francisco; Cruces, Eva; Durán, María; García, Elena; Gargallo, Manuel; González, Noemí; González, Olga; Lecumberri, Edurne; Lisbona, Arturo; Maillo, Maria Angeles; Nattero, Lía; Parra, Paola; Sánchez, Iván." "etiqueta" => "Annex" "titulo" => "Members of the Working Group on Diabetes of SENDIMAD (in alphabetical order)" "identificador" => "sec0030" ] ] ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 896 "Ancho" => 1567 "Tamanyo" => 78680 ] ] "descripcion" => array:1 [ "en" => "Correlation between total daily dose of insulin and BMI. A positive significant correlation is seen between total insulin dose and BMI (Spearman's rho: 2.32; p<0.001)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 938 "Ancho" => 1600 "Tamanyo" => 69569 ] ] "descripcion" => array:1 [ "en" => "Correlation between C-peptide levels and blood glucose control (HbA1c). A negative significant correlation is seen (Spearman's rho: −0.40; p<0.001)." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients, n \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">193 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female/male, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">108/85 (56/44) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Family history of DM (%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Not known \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T2DM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1DM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Type unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age at diagnosis of DM, years (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">48.9 (11.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Delay in confirmation of LADA, years (range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.5 (0–36) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Insulin independence, months (P10–P90) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 (0–63) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Body mass index, kg/m* (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25.4 (4.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Overweight (BMI 25–30), 30% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Obesity (BMI>30), % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Plasma C-peptide, ng/mL (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.66 (0.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">GAD Ab/upper limit of normal, (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.4±2.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Associated autoimmune diseases/positive organ-specific Ab, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">56.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total daily dose of insulin, units (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35.1 (19.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Insulin units/kg (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.51 (0.24) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1370960.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical characteristics of the study population." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Alb/creat: urinary albumin/creatinine ratio; HDL-C: HDL cholesterol; LDL-C: LDL cholesterol; eGFR: estimated glomerular filtration rate; BP: blood pressure; TG: triglycerides." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">HbA1c (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Fasting blood glucose (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">BP (mmHg) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">HDL-C (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">LDL-C (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">TG (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">eGFR (mL/min) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Alb/creat (mg/g) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">7.7±1.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">160±57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">128/75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">65±18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">96±27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90±43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80±22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1370959.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Data on metabolic control of patients." ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ASA: acetiy salicylic acid; Anti-HBP: antihypertensives: Compl.: complications; Macro: macroangiopathic; Micro: microangiopathic." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">No compl. \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Micro compl. \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Macro compl. \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Anti-HBP \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Statins \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Other lipid-lowering agents \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">ASA \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">72.0% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23.1% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.9% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44.4% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">55.0% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.8% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18.3% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1370958.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Chronic complications and cardiovascular drugs." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0105" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Classification and diagnosis of diabetes" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "American Diabetes Association" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc16-S005" "Revista" => array:7 [ "tituloSerie" => "Diabetes Care" "fecha" => "2016" "volumen" => "39" "numero" => "Suppl. 1" "paginaInicial" => "S13" "paginaFinal" => "S22" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26696675" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0110" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical and pathogenic significance of pancreatic-islet-cell antibodies in diabetics treated with oral hypoglycaemic agents" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "W.J. 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Original Article

Clinical and metabolic profile of patients with latent autoimmune diabetes in adults in specialized care in Madrid

Perfil clínico y metabólico de pacientes con diabetes tipo LADA atendidos en atención especializada en la comunidad de Madrid

Alfonso Arranz Martína,

Corresponding author

alfonso.arranz@salud.madrid.org

Corresponding author.

, Edurne Lecumberri Pascualb, Miguel Ángel Brito Sanfielc, Víctor Andía Melerod, Lia Nattero Chaveze, Iván Sánchez Lópezf, Gloria Cánovas Molinag, Francisco Arrieta Blancoe, Noemí González Perez del Villarh, Diabetes Group of the Society of Endocrinology, Nutrition and Diabetes of Madrid (SENDIMAD) ◊

a Servicio de Endocrinología y Nutrición, Hospital Universitario de la Princesa, Madrid, Spain

b Servicio de Endocrinología y Nutrición, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain

c Servicio de Endocrinología y Nutrición, Hospital Universitario Puerta de Hierro, Madrid, Spain

d Servicio de Endocrinología y Nutrición, Hospital General Universitario Gregorio Marañón, Madrid, Spain

e Servicio de Endocrinología y Nutrición, Hospital Universitario Ramón y Cajal, Madrid, Spain

f Servicio de Endocrinología y Nutrición, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain

g Servicio de Endocrinología y Nutrición, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain

h Servicio de Endocrinología y Nutrición, Hospital Universitario La Paz, Madrid, Spain

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          3 => array:3 [
            "entidad" => "Servicio de Endocrinolog&#237;a y Nutrici&#243;n&#44; Hospital General Universitario Gregorio Mara&#241;&#243;n&#44; Madrid&#44; Spain"
            "etiqueta" => "d"
            "identificador" => "aff0020"
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          4 => array:3 [
            "entidad" => "Servicio de Endocrinolog&#237;a y Nutrici&#243;n&#44; Hospital Universitario Ram&#243;n y Cajal&#44; Madrid&#44; Spain"
            "etiqueta" => "e"
            "identificador" => "aff0025"
          ]
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            "entidad" => "Servicio de Endocrinolog&#237;a y Nutrici&#243;n&#44; Hospital Universitario Fundaci&#243;n Alcorc&#243;n&#44; Alcorc&#243;n&#44; Madrid&#44; Spain"
            "etiqueta" => "f"
            "identificador" => "aff0030"
          ]
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            "entidad" => "Servicio de Endocrinolog&#237;a y Nutrici&#243;n&#44; Hospital Universitario de Fuenlabrada&#44; Fuenlabrada&#44; Madrid&#44; Spain"
            "etiqueta" => "g"
            "identificador" => "aff0035"
          ]
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            "entidad" => "Servicio de Endocrinolog&#237;a y Nutrici&#243;n&#44; Hospital Universitario La Paz&#44; Madrid&#44; Spain"
            "etiqueta" => "h"
            "identificador" => "aff0040"
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            "identificador" => "cor0005"
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            "correspondencia" => "Corresponding author&#46;"
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        "titulo" => "Perfil cl&#237;nico y metab&#243;lico de pacientes con diabetes tipo LADA atendidos en atenci&#243;n especializada en la comunidad de Madrid"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Correlation between total daily dose of insulin and BMI&#46; A positive significant correlation is seen between total insulin dose and BMI &#40;Spearman&#39;s rho&#58; 2&#46;32&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Diabetes mellitus &#40;DM&#41; is a pathophysiologically complex and heterogeneous disease that often goes beyond the somewhat rigid limits of the categories considered in the current classification&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The so-called latent autoimmune diabetes of the adult &#40;LADA&#41; is a slowly progressing autoimmune diabetes which is often not recognized as such and is confused with other types of DM&#46; Positive islet cell antibodies &#40;ICAs&#41; have however been found in more than 10&#37; of adults with type 2 DM &#40;T2DM&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">2&#44;3</span></a> LADA therefore represents the most prevalent form of autoimmune diabetes in adults&#44; and is also probably the most prevalent form of autoimmune diabetes overall&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Although LADA is undoubtedly related to type 1 DM &#40;T1DM&#41;&#44; its clinical presentation often includes features attributable to T2DM&#44; which often leads to a wrong diagnosis and treatment for significant periods of time&#46; The fact that the diagnostic criteria currently used to identify this variant of diabetes are imprecise and controversial contributes to this&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The purpose of this study was to help in clinical characterization of patients with LADA using specialized medical monitoring&#44; and to study their metabolic control and the occurrence of chronic complications related to DM&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">A retrospective&#44; cross-sectional study was conducted on patients with DM attending endocrinology departments of the public healthcare network of the region of Madrid&#46; Cases were detected based on a systematic search in our clinic appointment books and databases &#40;which did not necessarily include all cases at each hospital&#41; for patients with the criteria listed below&#46; The selection process lasted from May 2015 to February 2016&#44; and the database was completed by collecting the information available at the hospital records&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Patients enrolled met all three criteria of LADA proposed by the Immunology of Diabetes Society &#40;IDS&#41;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a>&#58; diagnosis of diabetes based on the established criteria at ages older than 30<span class="elsevierStyleHsp" style=""></span>years&#44; insulin independence for at least six months after diagnosis&#44; and positive glutamic acid decarboxylase antibodies &#40;GADA&#41;&#46; Patients with secondary and gestational diabetes and diabetes associated to malignancies were excluded&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Data collected included age&#44; sex&#44; weight&#44; height&#44; body mass index &#40;BMI&#41;&#44; family history of diabetes&#44; date of clinical diagnosis of diabetes and confirmation of LADA&#44; GADA titer&#44; associated autoimmune diseases or presence of organ-specific antibodies&#44; basal plasma C-peptide levels&#44; insulin regimen and dosage&#44; other associated antidiabetic and cardiovascular drugs&#44; metabolic glucose&#44; lipid&#44; and blood pressure control&#44; estimated glomerular filtration rate&#44; urinary albumin&#47;creatinine ratio&#44; and presence of microangiopathic and macroangiopathic complications&#46; Biochemical and immunological data were assessed at the reference laboratories of the respective hospitals&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Statistical analysis was performed using GraphPad Prism 6 software&#46; Normally distributed data are given as mean &#40;standard deviation&#41;&#46; Non-normally distributed data are given as median &#40;range&#41;&#46; GADA titer is given as the ratio between the resulting absolute value and the upper limit of normal for each laboratory&#46; Association or interdependence of two variables was calculated using Spearman&#39;s correlation coefficient&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the demographic characteristics of our patients and information on their diabetes&#46; Data were collected from 193 patients&#44; of whom 108 &#40;56&#37;&#41; were women&#46; Thirty-eight percent of patients had no known family history of diabetes&#44; 37&#37; and 16&#37; had a family history of T2DM and T1DM respectively&#44; and 8&#46;7&#37; had a history of DM of an unknown type&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Mean age at diagnosis of DM was 48&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;2 years&#46; Diagnosis of LADA&#44; defined as the date when positive GADA were found&#44; was made with a delay of 3&#46;5<span class="elsevierStyleHsp" style=""></span>years &#40;range&#44; 0&#8211;36&#41; after clinical diagnosis of DM&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">GADA titer&#44; expressed as the GADA&#47;upper limit of normal ratio&#44; was 5&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;1<span class="elsevierStyleHsp" style=""></span>U&#47;L&#46; No correlation was seen between GADA titer&#44; C-peptide levels&#44; and insulin independence time&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Patients were treated with diet and oral antidiabetic drugs only for a median of 12<span class="elsevierStyleHsp" style=""></span>months &#40;P10&#58; 1&#59; P90&#58; 63&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">BMI was 25&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;2<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#46; Overweight &#40;BMI&#58; 25&#8211;29&#46;9&#41; was found in 31&#46;5&#37; of patients&#44; while 8&#37; of patients were obese &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>30&#41;&#46; No correlation was found between BMI and blood glucose control&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Basal plasma C-peptide levels of patients were measured at different times after DM onset&#46; Mean levels were 0&#46;66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;8<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; but a significant heterogeneity was seen in the values found&#44; which were clearly related to the time since onset of DM&#44; showing a significant negative correlation &#40;Spearman&#39;s rho&#58; &#8722;0&#46;52&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46; Twenty-seven percent of patients had C-peptide levels &#60;0&#46;05<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; 49&#37; had levels ranging from 0&#46;05 and 1&#46;0<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; and 24&#37; had levels &#62;1&#46;0<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46; A majority of patients &#40;70&#37;&#41; in this last subgroup had a known diabetes duration shorter than one year at the time of C-peptide measurement&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Basal-bolus insulin regimens were most commonly given to our patients &#40;76&#46;7&#37;&#41;&#44; followed by basal insulin &#40;13&#46;2&#37;&#41;&#44; premixes &#40;4&#46;2&#37;&#41;&#44; basal-plus regimens &#40;2&#46;6&#37;&#41;&#44; and CSII &#40;0&#46;5&#37;&#41;&#46; Only 2&#46;6&#37; of patients received no insulin therapy&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Mean insulin dose was 35&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;6<span class="elsevierStyleHsp" style=""></span>U&#47;day&#44; which corresponded to 0&#46;51<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;24<span class="elsevierStyleHsp" style=""></span>U&#47;kg after adjustment for body weight&#46; A positive&#44; significant correlation &#40;coef&#46; 2&#46;32&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; was found between total insulin dose and BMI &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; and there was a negative correlation between total daily insulin dose and C-peptide levels &#40;Spearman&#39;s rho&#58; &#8722;0&#46;33&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">No concomitant non-insulin drugs were received by 66&#46;5&#37; of patients&#46; Metformin was the drug most commonly used &#40;in 25&#46;7&#37; of patients&#41;&#44; followed by DPP-4 inhibitors &#40;7&#46;3&#37;&#41;&#44; GLP-1 receptor agonists &#40;2&#46;2&#37;&#41;&#44; and SGLT2 inhibitors &#40;1&#46;1&#37;&#41;&#46; Use of secretagogues and glitazones was very limited &#40;0&#46;6&#37;&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Fifty-seven percent of patients had other autoimmune diseases or positive organ-specific antibodies&#46; Chronic thyroiditis was the most prevalent concomitant condition &#40;occurring in 32&#46;9&#37; of patients&#41;&#46; Other autoimmune conditions seen included atrophic gastritis &#40;3&#46;2&#37;&#41;&#44; vitiligo &#40;2&#46;4&#37;&#41;&#44; Graves&#8217; disease &#40;1&#46;9&#37;&#41;&#44; Crohn&#39;s disease &#40;1&#46;2&#37;&#41;&#44; and celiac disease &#40;1&#46;2&#37;&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> provides data on metabolic control of patients&#46; Fasting blood glucose levels were 160&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>57&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; and HbA1c values were 7&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;26&#37;&#46; Only 31&#46;7&#37; of patients met metabolic control criteria &#40;HbA1c &#8804;7&#46;0 in two of the last three measurements performed&#41;&#59; 31&#46;1&#37; had HbA1c values ranging from 7&#46;1 and 8&#46;0&#44; 23&#46;6&#37; values ranging from 8&#46;1 and 9&#46;0&#44; and 13&#46;4&#37; levels &#62;9&#37;&#46; A significant negative correlation &#40;Spearman&#39;s rho&#58; &#8722;0&#46;40&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; was found between HbA1c and C-peptide &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41; and between fasting glucose and C-peptide &#40;Spearman&#39;s rho&#58; &#8722;0&#46;27&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Lipid control was usually highly satisfactory&#58; HDL cholesterol&#44; 65<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#59; LDL cholesterol&#44; 96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#59; triglycerides&#44; 89<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>44<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; Estimated glomerular filtration rate &#40;eGFR&#41; was 80<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>22<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#44; and only 5&#37; of patients had values suggesting kidney failure &#40;eGFR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>60<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#41;&#46; Mean urinary albumin&#47;creatinine ratio was 12&#46;9<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#46; Criteria for microalbuminuria &#40;ratio&#44; 30&#8211;300<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#41; were met by 7&#46;6&#37; of patients&#44; and only 0&#46;6&#37; had macroalbuminuria &#40;ratio &#62;300<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#41;&#46; Mean blood pressure values were 128&#47;75<span class="elsevierStyleHsp" style=""></span>mmHg&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Overall&#44; 44&#46;4&#37; of patients were being treated with antihypertensive drugs&#44; 55&#37; with statins&#44; 7&#46;8&#37; with other lipid-lowering agents&#44; and 18&#46;3&#37; with antiplatelet aggregants&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">A majority of patients &#40;72&#46;0&#37;&#41; had no clinical evidence of chronic complications related to diabetes &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; In the remaining 28&#37;&#44; most complications seen &#40;23&#46;1&#37;&#41; were microangiopathic in nature&#58; non-proliferative retinopathy &#40;7&#46;2&#37;&#41;&#44; proliferative retinopathy &#40;3&#46;3&#37;&#41;&#44; diabetic macular edema &#40;1&#46;6&#37;&#41;&#44; incipient nephropathy &#40;6&#46;6&#37;&#44; advanced nephropathy &#40;1&#46;1&#37;&#41;&#44; sensory neuropathy &#40;3&#46;3&#37;&#41;&#41;&#46; Only 4&#46;9&#37; of patients had been diagnosed some macroangiopathic complication&#58; ischemic heart disease &#40;3&#46;3&#37;&#41;&#44; peripheral artery disease &#40;1&#46;6&#37;&#41;&#46; No patient experienced stroke&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0115" class="elsevierStylePara elsevierViewall">LADA is currently considered as an end of the spectrum of autoimmune diabetes&#44; but does not represent a differentiated group within the general classification of diabetes&#44; but a variant within the T1DM category&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Latent autoimmune diabetes was already described<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> in 1986 as a form of DM that occurred in adults with no insulin dependence during an initial period but with early failure of oral antidiabetic treatment&#44; presence of ICA and other frequently associated organ-specific antibodies&#46; Patients reported in the initial report had lower BMIs and less pancreatic reserve of C-peptide as compared to ICA-negative diabetic patients&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The term LADA was introduced in 1995<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> to describe a subgroup of patients with the above mentioned clinical characteristics who had positive GADA&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Because of the pathophysiological heterogeneity of diabetes&#44; it is often an oversimplification to try and attribute the category of T1DM or T2DM only to patients who have a genetic predisposition to both types of diabetes or who are subject to the influence of environmental factors that result in development of insulin resistance&#46; In fact&#44; patients with LADA have been shown to share the genetic characteristics of classical T1DM&#44;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">7&#44;8</span></a> but they often also have genetic similarities with T2DM&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a> which suggests a mixed nature of this form of diabetes&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">In our study population&#44; diagnosis of LADA was based on the finding of positive GADA in patients in whom the condition was clinically suspected &#40;diagnosis at adult age&#44; absence of ketoacidosis and initial insulin independence&#44; glycemic variability with marked postprandial component&#44; etc&#46;&#41;&#46; Patient characteristics are therefore not comparable to those in non-selective immune screening studies conducted in patients who phenotypically have T2DM&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In this regard&#44; as previously noted&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">10</span></a> we think that generalized screening for LADA in the adult diabetic population is not effective&#46; However&#44; LADA should be routinely ruled out when an adult with diabetes does not show the usual stereotype of T2DM&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Our patients had as a group lower BMIs than expected for a population with T2DM&#44; but were frequently overweight&#44; which agrees with other reported studies&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">11</span></a> High BMI values should therefore not exclude or delay screening for LADA if they coexist with other suspicious clinical factors&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Various studies have reported lower plasma C-peptide levels in the group of patients with LADA as compared to T2DM&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">12&#44;13</span></a> Our study revealed a significant heterogeneity in pancreatic reserve&#44; which also had a negative correlation to blood glucose control&#46; Thus&#44; if LADA is clinically suspected&#44; presence of detectable C-peptide levels should not rule out the condition until the results of the immune study are available&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">No guidelines are currently available for the treatment of LADA&#44; but some studies have shown that early administration of insulin or sensitizing oral drugs may be beneficial for long-term preservation of the pancreatic reserve&#44; while sulfonylureas may decrease the insulin independence time&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">14&#8211;16</span></a> Our study found a negative correlation between C-peptide levels and blood glucose control&#44; thus emphasizing the importance of early identification of LADA both to increase insulin independence time and to improve metabolic control of patients&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">GADA titer has been reported to be inversely related to the pancreatic reserve&#44; and may be a marker of the risk of progression to insulin dependence&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">14&#44;17&#8211;19</span></a> Our study found no association between GADA values&#44; C-peptide levels&#44; or insulin independence time&#44; but it was not a prospective study&#44; and the immune and metabolic study was not performed at the time of clinical onset&#44; but often with a delay of up to several years&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">This study has other obvious limitations&#46; It was an observational study based on the information recorded in clinical histories&#44; which is subject to data collection problems or errors&#46; Omission bias&#44; especially in the presence of chronic complications&#44; may be significant and underestimate their prevalence&#44; disregarding subclinical forms&#46; Patient selection was based on the most commonly agreed diagnostic criteria&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a> but we are aware of their limitations&#58; the age criterion is arbitrary&#44; insulin independence time is highly physician-dependent&#44; and GADA levels may decrease over time and even become negative in patients with long-standing disease&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a> A less rigid selection would have markedly increased the number of patients enrolled&#44; but also the number of false positives&#46; Finally&#44; it should be recognized that as these patients attended specialized care clinics&#44; the study population is not probably a faithful representation of the overall group of patients with LADA&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Despite these limitations&#44; we think that our study may help define patients with LADA in order to identify them as such as early as possible and select the most adequate treatment&#44; thus avoiding years of unawareness by patients&#44; their relatives&#44; and the medical team&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">As a conclusion&#44; it should be noted that in the study population&#44; diagnosis of LADA may be delayed up to several years&#46; Patients have a quite heterogeneous pancreatic insulin reserve&#44; which is negatively related to time since onset of disease&#46; Treatment of patients with LADA is often difficult&#44; as shown by the deficient blood glucose control despite high compliance with complete insulinization regimens&#46; A successful control is however seen of other treatment goals such as blood pressure and lipid profile&#44; together with a low incidence of macroangiopathic complications&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interest</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors state that they have no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Conflict of interest"
        ]
        9 => array:2 [
          "identificador" => "xack273775"
          "titulo" => "Acknowledgment"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2016-05-27"
    "fechaAceptado" => "2016-09-27"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec813033"
          "palabras" => array:5 [
            0 => "Diabetes"
            1 => "Autoimmune"
            2 => "Latent"
            3 => "Adult"
            4 => "Latent autoimmune diabetes in adults"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec813034"
          "palabras" => array:5 [
            0 => "Diabetes"
            1 => "Autoinmune"
            2 => "Latente"
            3 => "Adulto"
            4 => "Diabetes autoinmune latente del adulto"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To report the clinical characteristics of patients with latent autoimmune diabetes in adults &#40;LADA&#41;&#44; and to ascertain their metabolic control and associated chronic complications&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Patients with DM attending specialized medical care in Madrid who met the following criteria&#58; age at diagnosis of DM &#62;30<span class="elsevierStyleHsp" style=""></span>years&#44; initial insulin independence for at least 6<span class="elsevierStyleHsp" style=""></span>months and positive GAD antibodies were enrolled&#46; Clinical profiles&#44; data on LADA diagnosis&#44; associated autoimmunity&#44; C-peptide levels&#44; therapeutic regimen&#44; metabolic control&#44; and presence of chronic complications were analyzed&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Number of patients&#59; 193&#59; 56&#37; females&#46; Family history of DM&#58; 62&#37;&#46; Age at DM diagnosis&#58; 49<span class="elsevierStyleHsp" style=""></span>years&#46; Delay in confirmation of LADA&#58; 3&#46;5<span class="elsevierStyleHsp" style=""></span>years&#46; Insulin-independence time&#58; 12<span class="elsevierStyleHsp" style=""></span>months&#46; Baseline serum C-peptide levels&#58; 0&#46;66<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; Basal-bolus regimen&#58; 76&#46;7&#37;&#46; Total daily dose&#58; 35&#46;1<span class="elsevierStyleHsp" style=""></span>U&#47;day&#44; corresponding to 0&#46;51<span class="elsevierStyleHsp" style=""></span>U&#47;kg&#46; With no associated oral antidiabetic drugs&#58; 33&#46;5&#37;&#46; Other autoimmune diseases&#58; 57&#37;&#46; Fasting plasma glucose&#58; 160&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; HbA1c&#58; 7&#46;7&#37;&#46; BMI&#58; 25&#46;4<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> &#40;overweight&#44; 31&#46;5&#37;&#59; obesity&#44; 8&#37;&#41;&#46; Blood pressure&#58; 128&#47;75&#46; HDL cholesterol&#58; 65<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; LDL cholesterol&#58; 96<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; Triglycerides&#58; 89<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; Known chronic complications&#58; 28&#37;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Recognition of LADA may be delayed by several years&#46; There is a heterogeneous pancreatic insulin reserve which is negative related to glycemic parameters&#46; Most patients are poorly controlled despite intensive insulin therapy&#46; They often have overweight&#44; but have adequate control of BP and lipid profile and a low incidence of macrovascular complications&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Definir las caracter&#237;sticas cl&#237;nicas de los pacientes con diabetes autoinmune latente del adulto &#40;LADA&#41;&#44; conocer su control metab&#243;lico y las complicaciones cr&#243;nicas asociadas que presentan&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Seleccionamos pacientes con DM seguidos en las consultas de endocrinolog&#237;a de hospitales p&#250;blicos de la Comunidad de Madrid que reun&#237;an los siguientes criterios&#58; edad al diagn&#243;stico de DM &#62;30<span class="elsevierStyleHsp" style=""></span>a&#241;os&#44; independencia inicial de insulina durante al menos 6<span class="elsevierStyleHsp" style=""></span>meses y positividad de anticuerpos antiGAD&#46; Analizamos datos cl&#237;nicos relativos al diagn&#243;stico de LADA&#44; autoinmunidad asociada&#44; niveles de p&#233;ptido C&#44; pauta terap&#233;utica&#44; control metab&#243;lico y presencia de complicaciones cr&#243;nicas&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">N&#250;mero de pacientes&#58; 193&#46; Mujeres&#58; 56&#37;&#46; Antecedentes familiares de DM&#58; 62&#37;&#46; Edad al diagn&#243;stico de DM&#58; 49<span class="elsevierStyleHsp" style=""></span>a&#241;os&#46; Retraso en confirmaci&#243;n LADA&#58; 3&#44;5<span class="elsevierStyleHsp" style=""></span>a&#241;os&#46; Tiempo de insulino-independencia&#58; 12<span class="elsevierStyleHsp" style=""></span>meses&#46; P&#233;ptido C basal suero&#58; 0&#44;66<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;0&#44;22<span class="elsevierStyleHsp" style=""></span>nmol&#47;l&#41;&#46; Pauta de insulina basal-bolus&#58; 76&#44;7&#37;&#46; Dosis total diaria&#58; 35&#44;1<span class="elsevierStyleHsp" style=""></span>U&#47;d&#237;a&#44; correspondiente a 0&#44;51<span class="elsevierStyleHsp" style=""></span>U&#47;kg&#46; Sin f&#225;rmacos orales asociados&#58; 33&#44;5&#37;&#46; Presencia de otras patolog&#237;as autoinmunes&#58; 57&#37;&#46; Glucemia en ayunas&#58; 160&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;8&#44;91<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#41;&#46; HbA1c&#58; 7&#44;7&#37;&#46; IMC&#58; 25&#44;4<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> &#40;sobrepeso&#58; 31&#44;5&#37;&#59; obesidad&#58; 8&#37;&#41;&#46; Presi&#243;n arterial&#58; 128&#47;75&#46; Colesterol HDL&#58; 65<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;16&#44;9<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#41;&#46; Colesterol LDL&#58; 96<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;24&#44;96<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#41;&#46; Triglic&#233;ridos&#58; 89<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;1&#44;01<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#41;&#46; Complicaciones cr&#243;nicas&#58; 28&#37;&#59; microangiopat&#237;a&#58; 23&#44;1&#37;&#59; macroangiopat&#237;a&#58; 4&#44;9&#37;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El reconocimiento de LADA puede retrasarse varios a&#241;os&#46; La reserva pancre&#225;tica de insulina de los pacientes es heterog&#233;nea y el grado medio de control gluc&#233;mico deficiente a pesar de utilizar mayoritariamente insulinoterapia intensiva&#46; Con frecuencia presentan sobrepeso&#44; aunque tienen un control adecuado de la presi&#243;n arterial y perfil lip&#237;dico y baja incidencia de complicaciones macroangiop&#225;ticas&#46;</p></span>"
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            "titulo" => "Resultados"
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            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
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    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Arranz Mart&#237;n A&#44; Lecumberri Pascual E&#44; Brito Sanfiel M&#193;&#44; And&#237;a Melero V&#44; Nattero Chavez L&#44; S&#225;nchez L&#243;pez I&#44; et al&#46; Perfil cl&#237;nico y metab&#243;lico de pacientes con diabetes tipo LADA atendidos en atenci&#243;n especializada en la comunidad de Madrid&#46; Endocrinol Diabetes Nutr&#46; 2017&#59;64&#58;34&#8211;39&#46;</p>"
      ]
      1 => array:3 [
        "etiqueta" => "&#9674;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">The names of the components of the Diabetes Group of the Society of Endocrinology&#44; Nutrition and Diabetes of Madrid &#40;SENDIMAD&#41; are listed in <a class="elsevierStyleCrossRef" href="#sec0030">Annex</a>&#46;</p>"
        "identificador" => "fn1"
      ]
    ]
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            "apendice" => "<p id="par0190" class="elsevierStylePara elsevierViewall">Alpa&#241;&#233;s&#44; Macarena&#59; And&#237;a&#44; Victor&#44; Arranz&#44; Alfonso&#59; Arrieta&#44; Francisco&#59; Brito&#44; Miguel&#59; Calle Alfonso&#59; Canovas&#44; Gloria&#59; del Ca&#241;izo&#44; Francisco&#59; Cruces&#44; Eva&#59; Dur&#225;n&#44; Mar&#237;a&#59; Garc&#237;a&#44; Elena&#59; Gargallo&#44; Manuel&#59; Gonz&#225;lez&#44; Noem&#237;&#59; Gonz&#225;lez&#44; Olga&#59; Lecumberri&#44; Edurne&#59; Lisbona&#44; Arturo&#59; Maillo&#44; Maria Angeles&#59; Nattero&#44; L&#237;a&#59; Parra&#44; Paola&#59; S&#225;nchez&#44; Iv&#225;n&#46;</p>"
            "etiqueta" => "Annex"
            "titulo" => "Members of the Working Group on Diabetes of SENDIMAD &#40;in alphabetical order&#41;"
            "identificador" => "sec0030"
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        ]
      ]
    ]
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Correlation between total daily dose of insulin and BMI&#46; A positive significant correlation is seen between total insulin dose and BMI &#40;Spearman&#39;s rho&#58; 2&#46;32&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p>"
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        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Correlation between C-peptide levels and blood glucose control &#40;HbA1c&#41;&#46; A negative significant correlation is seen &#40;Spearman&#39;s rho&#58; &#8722;0&#46;40&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p>"
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Patients&#44; n</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">193&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Female&#47;male&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">108&#47;85 &#40;56&#47;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Family history of DM &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Not known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T2DM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T1DM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Type unknown&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Age at diagnosis of DM&#44; years &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">48&#46;9 &#40;11&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Delay in confirmation of LADA&#44; years &#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;5 &#40;0&#8211;36&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Insulin independence&#44; months &#40;P10&#8211;P90&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12 &#40;0&#8211;63&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Body mass index&#44; kg&#47;m&#42; &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&#46;4 &#40;4&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Overweight &#40;BMI 25&#8211;30&#41;&#44; 30&#37;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">31&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Obesity &#40;BMI</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#62;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">30&#41;&#44; &#37;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Plasma C-peptide&#44; ng&#47;mL &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;66 &#40;0&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">GAD Ab&#47;upper limit of normal&#44; &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Associated autoimmune diseases&#47;positive organ-specific Ab&#44; &#37;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">56&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Total daily dose of insulin&#44; units &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35&#46;1 &#40;19&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Insulin units&#47;kg &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;51 &#40;0&#46;24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics of the study population&#46;</p>"
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      ]
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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Article information

ISSN: 25300180
Original language: English

DOI:10.1016/j.endien.2017.02.001

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Year/Month	Html	Pdf	Total

2024 October	18	1	19
2024 September	24	12	36
2024 August	17	5	22
2024 July	18	6	24
2024 June	21	5	26
2024 May	10	2	12
2024 April	9	3	12
2024 March	23	8	31
2024 February	24	5	29
2024 January	8	7	15
2023 December	15	2	17
2023 November	20	3	23
2023 October	21	5	26
2023 September	12	8	20
2023 August	18	4	22
2023 July	7	8	15
2023 June	19	2	21
2023 May	28	4	32
2023 April	18	0	18
2023 March	23	8	31
2023 February	21	9	30
2023 January	11	2	13
2022 December	24	6	30
2022 November	54	6	60
2022 October	23	13	36
2022 September	13	13	26
2022 August	15	8	23
2022 July	9	8	17
2022 June	9	5	14
2022 May	21	8	29
2022 April	17	8	25
2022 March	24	6	30
2022 February	36	6	42
2022 January	49	8	57
2021 December	43	16	59
2021 November	28	8	36
2021 October	56	16	72
2021 September	44	16	60
2021 August	76	6	82
2021 July	47	9	56
2021 June	17	11	28
2021 May	25	6	31
2021 April	100	22	122
2021 March	25	8	33
2021 February	40	10	50
2021 January	50	14	64
2020 December	30	10	40
2020 November	23	11	34
2020 October	21	7	28
2020 September	20	10	30
2020 August	23	8	31
2020 July	9	9	18
2020 June	18	6	24
2020 May	30	6	36
2020 April	23	3	26
2020 March	17	7	24
2020 February	23	6	29
2020 January	18	9	27
2019 December	29	11	40
2019 November	17	2	19
2019 October	14	7	21
2019 September	15	4	19
2019 August	7	2	9
2019 July	16	8	24
2019 June	30	11	41
2019 May	99	25	124
2019 April	46	15	61
2019 March	5	6	11
2019 February	6	1	7
2019 January	5	6	11
2018 November	6	4	10
2018 October	10	1	11
2018 September	17	5	22
2018 August	6	7	13
2018 July	24	7	31
2018 June	11	3	14
2018 May	12	5	17
2018 April	11	4	15
2018 March	10	3	13
2018 February	14	2	16
2018 January	10	1	11
2017 December	12	1	13
2017 November	9	0	9
2017 October	8	3	11
2017 September	10	2	12
2017 August	11	2	13
2017 July	8	5	13

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