Mónica Recasens

Serum Visfatin Increases With Progressive β-Cell Deterioration

Visfatin has shown to be increased in type 2 diabetes but to be unrelated to insulin sensitivity. We hypothesized that visfatin is associated with insulin secretion in humans. To this aim, a cross-sectional study was conducted in 118 nondiabetic men and 64 (35 men and 29 women) type 2 diabetic patients. Type 1 diabetic patients with long-standing disease (n = 58; 31 men and 27 women) were also studied. In nondiabetic subjects, circulating visfatin (enzyme immunoassay) was independently associated with insulin secretion (acute insulin response to glucose [AIRg] from intravenous glucose tolerance tests) but not with insulin sensitivity (Si) or other metabolic or anthropometric parameters, and AIRg alone explained 8% of visfatin variance (β = −0.29, P = 0.001). Circulating visfatin was increased in type 2 diabetes (mean 18 [95% CI 16–21] vs. 15 ng/ml [13–17] for type 2 diabetic and nondiabetic subjects, respectively; P = 0.017, adjusted for sex, age, and BMI), although this association was largely attenuated after accounting for HbA1c (A1C). Finally, circulating visfatin was found to be increased in patients with long-standing type 1 diabetes, even after adjusting for A1C values (37 ng/ml [34–40]; P < 0.0001, adjusted for sex, age, BMI, and A1C compared with either type 2 diabetic or nondiabetic subjects). In summary, circulating visfatin is increased with progressive β-cell deterioration. The study of the regulation and role of visfatin in diabetes merits further consideration.

Burden of Infection and Insulin Resistance in Healthy Middle-Aged Men

OBJECTIVE We hypothesized that burden of infection could be associated with chronic low-grade inflammation, resulting in insulin resistance. We aimed to study the effect of exposure to four infections on insulin sensitivity in apparently healthy middle-aged men (n = 124). RESEARCH DESIGN AND METHODS By inclusion criteria, all subjects were hepatitis C virus antibody seronegative. Each study subjects serum was tested for specific IgG class antibodies against herpes simplex virus (HSV)-1, HSV-2, enteroviruses, and Chlamydia pneumoniae through the use of quantitative in vitro enzyme-linked immunosorbent assays. Insulin sensitivity was evaluated using minimal model analysis. RESULTS The HSV-2 titer was negatively associated with insulin sensitivity even after controlling for BMI, age, and C-reactive protein (CRP). The associations were stronger when considering the infection burden. In particular, in those subjects who were seropositive for C. pneumoniae, the relationship between the quantitative seropositivity index (a measure of the exposure to various pathogens) and insulin sensitivity was strengthened (r = -0.50, P < 0.0001). We also observed decreasing mean insulin sensitivity index with increasing seropositivity score in subjects positive for enteroviruses. In the latter, the relationship between insulin sensitivity and seropositivity was especially significant (r = -0.71, P < 0.0001). In a multivariate regression analysis, both BMI and quantitative seropositivity index (7%) independently predicted insulin sensitivity variance in subjects with C. pneumoniae seropositivity. When controlling for CRP, this association was no longer significant. CONCLUSIONS Pathogen burden showed the strongest association with insulin resistance, especially with enteroviruses and C. pneumoniae seropositivity. We hypothesize that exposure to multiple pathogens could cause a chronic low-grade inflammation, resulting in insulin resistance.

Alpha Defensins 1, 2, and 3 Potential Roles in Dyslipidemia and Vascular Dysfunction in Humans

Objectives—&agr;-Defensins are natural antibiotics made by neutrophils that have been reported to modulate cholesterol metabolism and vascular function; however, their role in vivo remains largely unknown. We hypothesized that &agr;-defensins 1 to 3 (DEFA1–3) are associated with serum lipids and vascular reactivity in humans. Methods and Results—One hundred thirteen apparently-healthy White men, participants in a prospective study of cardiovascular risk factors, were assessed for a lipid profile, insulin sensitivity (SI, frequently-sampled intravenous glucose tolerance test), and non-stressed circulating DEFA1–3 (ELISA). In a subset of 52 subjects, vascular reactivity (high-resolution ultrasound of the brachial artery) was also assessed. Subjects in the highest quartile for plasma DEFA1–3 were found to be leaner and more insulin sensitive, and to have significantly reduced total and LDL-cholesterol, compared with subjects in the lowest quartile for circulating DEFA1–3 (P<0.0001 to P=0.002 for linear trend ANOVA). The associations with serum lipids persisted after adjustment for age, body mass index, insulin sensitivity, and smoking (which was associated with reduced plasma DEFA1–3 concentrations). Finally, endothelium-independent vasodilation increased with increasing circulating DEFA1–3 (P=0.003) and this association was not explained by age, body mass index, serum cholesterol, insulin sensitivity, or smoking. Conclusions—Circulating DEFA1–3 are associated with serum cholesterol and vascular reactivity in humans. &agr;-Defensins may have clinical implications in patients with either hypercholesterolemia or vascular dysfunction.

Insulin lispro is as effective as regular insulin in optimising metabolic control and preserving β-cell function at onset of type 1 diabetes mellitus

The aim of the study was to examine the effects of intensive insulin therapy using lispro on metabolic control, immunogenicity and beta-cell function of newly diagnosed type 1 diabetic subjects in comparison with intensive insulin therapy using regular insulin. An open study was conducted in 45 newly diagnosed type 1 diabetic subjects. Patients were randomly assigned to intensive insulin therapy using insulin lispro (lispro) (lispro, n=22; 22.8 years) or intensive insulin therapy using regular insulin (regular) (regular, n=23; 24.4 years): three to five injections of subcutaneous rapid-acting insulin before meals and Neutral Protamine Hagedorn (NPH) before dinner/bed-time. GAD, IA2, insulin antibodies, basal and stimulated plasma C-peptide and HbA(1c) were measured initially and at months 1, 4, 8 and 12. Daily blood glucose profiles tended to be lower in the lispro group, particularly values after breakfast, without reaching statistical significance. There were no differences in terms of HbA(1c) throughout the study. The proportion of subjects achieving an HbA(1c)<6% at the end of the study was similar in both groups (regular 73.9%, lispro 68.0%). The number of mild hypoglycemic episodes tended to be lower with lispro, but not significantly. beta-Cell function was not significantly different in both groups. During follow-up there were no differences in antibodies, including IAAb. In summary, insulin lispro used in intensive insulin therapy is as effective as regular insulin in optimizing metabolic control and preserving beta-cell function at diagnosis of type 1 diabetes.

Efectos del trasplante de riñón y páncreas en los índices neurofisiológicos de polineuropatía y función autonómica cardiorreguladora en pacientes diabéticos con insuficiencia renal terminal

Fundamento Los pacientes con diabetes mellitus tipo 1 (DM1) e insuficiencia renal cronica terminal(IRCT) suelen presentar polineuropatia (PNP) grave, cuya progresion puede detenersetras el trasplante de rinon y pancreas (TRP). Hemos analizado la modificacion de los indicesneurofisiologicos de PNP y de funcion autonoma cardiorreguladora (FAC) en los pacientes conDM1 e IRCT en el curso del primer ano despues de TRP. Pacientes y metodo Se estudio a 26 pacientes sometidos a TRP que mantuvieron los organosnormofuncionantes durante al menos un ano despues del trasplante. Se realizaron examenesneurofisiologicos en tres periodos: a) antes del TRP; b) 1-3 meses post-TRP, y c) 12 mesespost-TRP. Se midieron la velocidad de conduccion (VC) y la amplitud de los potenciales de accion(APA) de los nervios peroneal comun, tibial posterior y sural, asi como la variacion observadaen el intervalo entre complejos QRS del electrocardiograma durante la respiracion tranquilay la maniobra de Valsalva. Resultados Todos los pacientes presentaban PNP grave pre-TRP. Diez pacientes (38,4%) presentaronuna reduccion significativa de la APA y de la FAC en el examen realizado entre uno ytres meses post-TRP, mientras que todos los pacientes presentaron un aumento en la VC, APAy FAC al ano del TRP. Conclusion El TRP induce una mejoria estadisticamente significativa de los signos neurofisiologicosde PNP y de FAC al ano del trasplante. En algunos pacientes, la mejoria va precedidade un incremento en la afeccion axonopatica, que sucede en los primeros meses despues deltrasplante y podria estar relacionado con la agresion periquirurgica.

Macrovascular events after kidney-pancreas transplantation in type 1 diabetic patients

BACKGROUND There are few studies concerning the effect of kidney-pancreas transplantation (KPTx) on the progression of macrovascular disease in type 1 diabetic patients. The aim of our study was to retrospectively evaluate the incidence of macrovascular events after functioning KPTx. MATERIALS AND METHODS We studied 146 patients (96 men and 50 women) who had undergone KPTx from February 1983 to September 2001, with more than 1 year of evolution of both grafts functioning normally. The mean follow-up of the patients after KPTx was 5+/-3 years. RESULTS Before KPTx, 29 patients displayed 42 macrovascular events. During the follow-up after transplantation, intermittent claudication remained in 25 patients (86.2%) with 11 new macrovascular events (1 stroke, 1 angina pectoris, 1 myocardial infarction, and 8 minor amputations) in 10 patients (34%). Among the 117 patients without antecedent macrovascular events prior to KPTx, 38 (32.5%) experienced a total of 63 macrovascular events (26 intermittent claudication, 4 stroke, 8 angina pectoris, 7 myocardial infarction, 11 minor amputations, and 7 major amputations). Before transplantation, 88.4% of the patients presented with hypertension, 42.5% a history of smoking, and 14.4% previous treatment for dyslipidmia. After transplantation, we observed an important reduction in the percentage of patients with hypertension (48.6%) and smoking (25.5%), without a change in the prevalence of dyslipemia (19.9%). Hypertension after transplantation was clearly associated with the appearance or persistence of macrovascular events. CONCLUSION In our experience, 43% of the transplant recipients present with macrovascular events. It is important to note the elevated prevalence of cardiovascular risk factors in the patients who underwent KPTx.

Complicaciones nutricionales después del tratamiento quirúrgico de la obesidad: ¿qué ocurre en el bypass gástrico?

Fundamento y objetivos Las deficiencias en macronutrientes y micronutrientes son complicaciones frecuentes de la cirugia de la obesidad. El objetivo de este trabajo es estudiar la repercusion del bypass gastrico en la evolucion ponderal y las concentraciones de proteinas, vitaminas y minerales, asi como documentar el porcentaje de pacientes que precisan suplementacion nutricional. Material y metodo Se estudio a 109 pacientes a los que se practico bypass gastrico antes del 1 de marzo de 2004 y se siguio durante al menos 2 anos. Se valoro la evolucion del peso, el indice de masa corporal (IMC), la albumina, la ferritina, el acido folico, la vitamina B 12 , la 25-OH-vitamina D 3 , vitamina A y vitamina E, a los 0, 6, 12, 18 y 24 meses tras la cirugia. Resultados El peso y el IMC se estabilizan entre 12 y 18 meses tras la intervencion. El porcentaje de sobrepeso perdido a los 6, 12, 18 y 24 meses fue del 53, el 66, el 70 y el 69%, respectivamente. Las concentraciones deferritina y 25-OH-vitamina D 3 fueron significativamente menores que las basales a partir de los 6 meses tras cirugia. El 54,7% de los pacientes requirio ferroterapia oral y el 9,5% recibio hierro via intravenosa. Al 31,1% se le prescribio vitamina B 12 intramuscular y al 31,7%, hidroferol oral a dosis altas. El 10,4% de los pacientes requirio suplementacion proteinica y el 7,6%, suplementos de vitamina A. Conclusiones El bypass gastrico consigue unos buenos resultados ponderales durante los primeros 24 meses despues de la intervencion. Este periodo coincide con el de mayores carencias nutricionales, y la ferropenia, la deplecion de vitamina B 12 y 25-OH-vitamina D 3 son las complicaciones nutricionales mas frecuentes.

Características clínicas, metabólicas, inmunológicas y genotípicas de un grupo de adolescentes y adultos con diabetes mellitus tipo 1A. Inicio y pronóstico a corto plazo

Fundamento y objetivo: Aproximadamente la mitad de los nuevos diagnosticos de diabetes mellitus tipo 1A (DM1A) en nuestro medio se realizan en sujetos mayores de 15 anos. En este contexto su caracterizacion tiene un interes indudable. Los objetivos de nuestro estudio fueron: a) caracterizar un grupo de sujetos, en edad no pediatrica, con DM1A al inicio de la enfermedad; b) valorar su pronostico tras instaurar tratamiento intensivo con insulina, y c) investigar la presencia de mutaciones en el gen de HNF-1* en los sujetos sin datos de autoinmunidad pancreatica. Pacientes y metodo: Se estudio a todos los pacientes con edades comprendidas entre los 15 y 35 anos, ambas inclusive, con un inicio reciente de DM1A (1998-2001). La funcion s pancreatica se evaluo mediante una prueba de estimulacion con glucagon (al inicio y a los 12 meses). Se determino la presencia de autoanticuerpos pancreaticos incluyendo GAD, IA2 y AAI. La tipificacion genomica de los genes HLA de clase II y el estudio de los 10 exones del gen HNF-1* se efectuaron a partir de ADN genomico. Todos los pacientes fueron incluidos en un programa de tratamiento convencional intensivo con insulina en multiples dosis. Resultados: Se incluyo a 86 pacientes (32 mujeres, con una edad media [DE] de 23,9 [5,3] anos). Un 80% de los pacientes presentaba positividad para alguno de los autoanticuerpos pancreaticos. Solos o en combinacion, GAD fue positivo en el 68,6% de los pacientes; IA2, en el 45,3%, y AAI, en el 27,9%. El haplotipo mas frecuente fue DRB1*0301-DQA1*0501-DQB*0201. La presencia o ausencia de anticuerpos antipancreaticos no condiciono diferencias clinicas, metabolicas o genotipicas (inicio y 12 meses). En ninguno de los pacientes estudiados (con o sin la presencia de autoanticuerpos pancreaticos) encontramos mutaciones en el gen HNF-1*. Despues de un ano de seguimiento la funcion s pancreatica permanecio inalterada. Conclusiones: Las caracteristicas clinicas, inmunologicas y de HLA en una poblacion de edad no pediatrica con DM1A concuerda con lo esperado. La ausencia de marcadores de autoinmunidad pancreatica no descarta la presencia de una DM1A ni se asocia a mutaciones del gen MODY-3. La instauracion de un tratamiento intensivo con insulina previene el deterioro de la capacidad de secrecion de insulina.