José Miguel González-Clemente

Arterial Stiffness Is Increased in Patients With Type 1 Diabetes Without Cardiovascular Disease: A potential role of low-grade inflammation

OBJECTIVE To investigate the relationship between arterial stiffness and low-grade inflammation in subjects with type 1 diabetes without clinical cardiovascular disease. RESEARCH DESIGN AND METHODS Sixty-eight patients with type 1 diabetes and 68 age- and sex-matched healthy subjects were evaluated. Arterial stiffness was assessed by aortic pulse wave velocity (aPWV). Serum concentrations of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and soluble fractions of tumor necrosis factor-α receptors 1 and 2 (sTNFαR1 and sTNFαR2, respectively) were measured. All statistical analyses were stratified by sex. RESULTS Subjects with diabetes had a higher aPWV compared with healthy control subjects (men: 6.9 vs. 6.3 m/s, P < 0.001; women: 6.4 vs. 6.0 m/s, P = 0.023). These differences remained significant after adjusting for cardiovascular risk factors. Men with diabetes had higher concentrations of hsCRP (1.2 vs. 0.6 mg/L; P = 0.036), IL-6 (0.6 vs. 0.3 pg/mL; P = 0.002), sTNFαR1 (2,739 vs. 1,410 pg/mL; P < 0.001), and sTNFαR2 (2,774 vs. 2,060 pg/mL; P < 0.001). Women with diabetes only had higher concentrations of IL-6 (0.6 vs. 0.4 pg/mL; P = 0.039). In men with diabetes, aPWV correlated positively with hsCRP (r = 0.389; P = 0.031) and IL-6 (r = 0.447; P = 0.008), whereas in women with diabetes no significant correlation was found. In men, multiple linear regression analysis showed that the following variables were associated independently with aPWV: age, BMI, type 1 diabetes, and low-grade inflammation (R2 = 0.543). In women, these variables were age, BMI, mean arterial pressure, and type 1 diabetes (R2 = 0.550). CONCLUSIONS Arterial stiffness assessed as aPWV is increased in patients with type 1 diabetes without clinical cardiovascular disease, independently of classical cardiovascular risk factors. In men with type 1 diabetes, low-grade inflammation is independently associated with arterial stiffness.

¿La diabetes mellitus es un equivalente de riesgo coronario? Resultados de un metaanálisis de estudios prospectivos

Introduccion y objetivos Varias guias sobre el tratamiento de los factores de riesgo cardiovascular basan sus recomendaciones en el concepto de que la diabetes mellitus (DM) es un equivalente de riesgo coronario o de riesgo cardiovascular. Hasta el presente no se ha realizado ninguna revision sistematica sobre los estudios en los que se sustenta dicho concepto. Metodos Se ha realizado una busqueda sistematica en PubMed hasta febrero de 2006 para localizar los estudios prospectivos que cumplian los siguientes criterios: a) periodo de seguimiento > 5 anos; b) incluir un grupo de pacientes con DM y sin enfermedad coronaria (DM+EC–), otro sin DM y con enfermedad coronaria (DM–EC+), y otro sin ninguno de los 2 factores de riesgo (DM–EC–), y c) proporcionar datos sobre mortalidad coronaria o cardiovascular. Se ha evaluado las caracteristicas de los estudios y se las ha combinado separadamente, segun el sexo, con un modelo de efectos aleatorios, y tomando el grupo DM–EC– como de referencia. Resultados Trece estudios han cumplido los criterios de inclusion. Los varones del grupo DM+EC– presentan una menor mortalidad coronaria y cardiovascular que los del grupo DM–EC+, pero las diferencias no son significativas (hazard ratio [intervalo de confianza del 95%]: mortalidad coronaria, 3,06 [2,45-3,83] frente a 4,28 [3,24-5,66], respectivamente, p = 0,066; mortalidad cardiovascular, 2,55 [2-3,26] frente a 3,61 [2,81-4,62], respectivamente, p = 0,051). Las mujeres no presentan diferencias significativas entre los dos grupos DM+EC– y DM–EC+ en relacion con la mortalidad coronaria (4,68 [3,40-6,45] frente a 3,51 [1,75-7,04], respectivamente; p = 0,42) y la cardiovascular (4,70 [4,23-5,22] frente a 3,39 [1,51-9,02], respectivamente; p = 0,59). Conclusiones Este metaanalisis apoya la idea de que las mujeres del grupo DM+EC– tienen una mortalidad coronaria y cardiovascular similar a la de las mujeres en el grupo DM–EC+, mientras que los varones del grupo DM+EC– tienen una tendencia no estadisticamente significativa a presentar una menor mortalidad coronaria y cardiovascular que los varones en el grupo DM–EC+.

Weight loss in prepubertal obese children is associated with a decrease in adipocyte fatty-acid-binding protein without changes in lipocalin-2: a 2-year longitudinal study

CONTEXT Lipocalin-2 and adipocyte fatty-acid-binding protein (A-FABP or FABP4) are adipokines potentially involved in the pathophysiology of obesity and metabolic syndrome in adults. In children, they have been scarcely studied. OBJECTIVE To analyze lipocalin-2 and A-FABP circulating levels before and after 2 years of a dieting and lifestyle intervention in a prepubertal obese cohort. DESIGN AND SETTING Case-control study with a prospective follow-up of cases for 2 years in our referral pediatric endocrine outpatient center. PATIENTS AND METHODS Seventy-three prepubertal obese children, 8.03 ± 1.08-years old, and 47 age- and gender-matched lean controls were studied. Anthropometric parameters, blood pressure, fasting oral glucose tolerance test, homeostatic model insulin resistance index (HOMA-IR), lipid profile, lipocalin-2, and A-FABP were evaluated. Weight loss was considered if z-score body mass index (BMI) decreased at least 0.5 s.d. RESULTS At baseline, lipocalin-2 and A-FABP were higher in prepubertal obese children than those in lean controls (P<0.001). A-FABP showed a gradual increase, according to the obesity degree (r(2)=0.632; P<0.001). After 2 years, obese patients who lost weight showed a decrease in A-FABP (a mean 2% reduction in BMI was associated with a mean 29% decrease in A-FABP (P<0.001)) without changes in lipocalin-2 levels. Regression model analysis adjusted by age, sex, BMI, and HOMA showed that A-FABP was lower in males (β=-5.77 (CI 95%: -9.7; -1.84)) and was modified by BMI (β=2.7 (CI 95%: 1.77-3.62), r(2)=0.659). Lipocalin-2 was not modified by any of these variables. CONCLUSIONS Prepubertal obese children show high plasma lipocalin-2 and A-FABP levels, but only A-FABP is influenced by weight loss.

Serum soluble transferrin receptor concentrations are increased in central obesity. Results from a screening programme for hereditary hemochromatosis in men with hyperferritinemia.

BACKGROUND A decrease in the serum concentrations of the soluble transferrin receptor (sTfR) is considered a good index of tissue iron. Because obesity is associated with hyperferritinemia and this is considered a sign of iron overload, a decrease in sTfR would be expected for the obese. We evaluated whether obese men with hyperferritinemia, detected in a genetic screening programme for hereditary hemochromatosis (HH), have lower serum concentrations of sTfR than their non-obese counterparts. METHODS 75 men (age: 55.4+/-12.4 years) with hyperferritinemia (serum ferritin--SF > 200 microg/L) and no known conditions of iron overload were evaluated for body mass index (BMI), waist circumference (WC), blood pressure, traditional indices of iron status, sTfR, fasting plasma glucose, lipid profile, insulin resistance (HOMA-IR), highly-sensitive C-reactive protein, hepatic enzymes and HFE gene mutations of HH. RESULTS sTfR correlated with BMI (r=0.289; p=0.014) and with WC (r=0.420; p<0.001). Thirty-two subjects were obese (BM > or = 30 kg/m(2)) and had a significantly higher sTfR (2.95 (2.22-3.28) vs 2.28 (1.88-2.91) mg/L; p=0.013), hemoglobin (157+/-12 vs 152+/-11 gr/L; p=0.049) and HOMA-IR (1.38 (1.04-2.69) vs 1.02 (0.60-1.55) mg/L; p=0.009) than the non-obese. WC explained separately more variability of the sTfR than BMI (r(2)=0.177; p=0.002 and r=0.077; p=0.042, respectively), after adjusting for potential confounders. CONCLUSION An increase in serum concentrations of sTfR is associated with central obesity in men with hyperferritinemia.

Is Diabetes Mellitus a Coronary Heart Disease Equivalent? Results of a Meta-Analysis of Prospective Studies

INTRODUCTION AND OBJECTIVES Several guidelines on the treatment of cardiovascular risk factors base their recommendations on the assertion that diabetes mellitus (DM) is a coronary heart disease (CHD) or cardiovascular disease (CVD) risk equivalent. To date, no systematic review of studies substantiating this assertion has been carried out. METHODS A systematic search of the PubMed database up to February 2006 was performed to identify prospective studies meeting the following criteria: a) follow-up was >5 years; b) groups of subjects with DM and without CHD (i.e., DM+CHD-), without DM and with CHD (DM-CHD+), and without either DM or CHD (DM-CHD-) were all included; and c) data on CHD or CVD mortality was reported. The characteristics of the studies were assessed, and data were combined separately for men and women using a random effects model and taking the DM-CHD- group as a reference. RESULTS In total, 13 studies met the inclusion criteria. Overall, CHD mortality was non-significantly lower in DM+CHD- men than in DM-CHD+ men, hazard ratio [HR] (95% confidence interval [CI]), 3.06 (2.45-3.83) vs 4.28 (3.24-5.66), respectively (P=.066); as was CVD mortality, HR (95% CI), 2.55 (2.00-3.26) vs 3.61 (2.81-4.62), respectively (P=.051). In women, there was no significant difference between the DM+CHD- and DM-CHD+ groups with regard to either CHD mortality, HR (95% CI), 4.68 (3.40-6.45) vs 3.51 (1.75-7.04), respectively (P=.42), or CVD mortality, HR (95% CI), 4.70 (4.23-5.22) vs 3.39 (1.51-9.02), respectively (P=.59). CONCLUSIONS The findings of this meta-analysis support the view that women in the DM+CHD- group have similar CHD and CVD mortality to those in the DM-CHD+ group, whereas men in the DM+CHD- group demonstrated a non-significant trend towards lower CHD and CVD mortality than those in the DM-CHD+ group.

Men with hyperferritinemia and diabetes in the Mediterranean area do not have a higher iron overload than those without diabetes

AIM To assess the role of iron overload in type 2 diabetic men with hyperferritinemia. METHODS 150 men were recruited from a genetic screening programme for hereditary hemocromatosis (HH) and were tested for type 2 diabetes, other components of the metabolic syndrome, beta cell function (BCF), insulin sensitivity, high-sensitivity C-reactive protein and iron overload. RESULTS Fifty-one men had type 2 diabetes. They were older (p=0.017) and 99 had lower BCF (p<0.001) than non-diabetic men. None of the iron overload indexes was associated with diabetes. CONCLUSIONS Our findings dispute a role of iron overload in the pathogenesis of type 2 diabetes.

Angiopoietin-like protein 8/betatrophin as a new determinant of type 2 diabetes remission after bariatric surgery

&NA; This work aimed to explore the link between angiopoietin‐like protein 8 (ANGPTL8) and weight loss after metabolic surgery. In the cross‐sectional study (n = 100), circulating ANGPTL8 concentrations were significantly lower in morbidly obese than in lean subjects, and strikingly lower in morbidly obese patients with type 2 diabetes mellitus (T2DM). Conversely, ANGPTL8 expression in subcutaneous adipose tissue (SAT) was higher in morbidly obese patients, particularly in those with T2DM, whereas its expression in visceral adipose tissue was unchanged. The main predictors for circulating levels of ANGPTL8 were BMI and T2DM, whereas ANGPTL8 expression in SAT was determined by the presence of T2DM. The prospective cohort studies before and 1 year after bariatric surgery in morbidly obese patients with (n = 45) and without (n = 30) T2DM, revealed a significant increase of circulating ANGPTL8 levels 1 year after the bariatric surgery. Intriguingly, this increment, which was predicted by basal ANGPTL8 concentrations, appeared as a determinant of T2DM remission. In conclusion, circulating ANGPTL8 levels have an inverse relationship with SAT expression. Low basal levels of ANGPTL8 rebound after bariatric surgery. The increment in ANGPTL8 concentrations at 1 month of follow‐up after weight loss emerged as a significant predictor of the T2DM remission at 1 year of follow‐up.

ANGPTL8 as a new determinant of type 2 diabetes remission after bariatric surgery

&NA; This work aimed to explore the link between angiopoietin‐like protein 8 (ANGPTL8) and weight loss after metabolic surgery. In the cross‐sectional study (n = 100), circulating ANGPTL8 concentrations were significantly lower in morbidly obese than in lean subjects, and strikingly lower in morbidly obese patients with type 2 diabetes mellitus (T2DM). Conversely, ANGPTL8 expression in subcutaneous adipose tissue (SAT) was higher in morbidly obese patients, particularly in those with T2DM, whereas its expression in visceral adipose tissue was unchanged. The main predictors for circulating levels of ANGPTL8 were BMI and T2DM, whereas ANGPTL8 expression in SAT was determined by the presence of T2DM. The prospective cohort studies before and 1 year after bariatric surgery in morbidly obese patients with (n = 45) and without (n = 30) T2DM, revealed a significant increase of circulating ANGPTL8 levels 1 year after the bariatric surgery. Intriguingly, this increment, which was predicted by basal ANGPTL8 concentrations, appeared as a determinant of T2DM remission. In conclusion, circulating ANGPTL8 levels have an inverse relationship with SAT expression. Low basal levels of ANGPTL8 rebound after bariatric surgery. The increment in ANGPTL8 concentrations at 1 month of follow‐up after weight loss emerged as a significant predictor of the T2DM remission at 1 year of follow‐up.

Angiopoietin-like protein 8 as a new determinant of type 2 diabetes remission after bariatric surgery

&NA; This work aimed to explore the link between angiopoietin‐like protein 8 (ANGPTL8) and weight loss after metabolic surgery. In the cross‐sectional study (n = 100), circulating ANGPTL8 concentrations were significantly lower in morbidly obese than in lean subjects, and strikingly lower in morbidly obese patients with type 2 diabetes mellitus (T2DM). Conversely, ANGPTL8 expression in subcutaneous adipose tissue (SAT) was higher in morbidly obese patients, particularly in those with T2DM, whereas its expression in visceral adipose tissue was unchanged. The main predictors for circulating levels of ANGPTL8 were BMI and T2DM, whereas ANGPTL8 expression in SAT was determined by the presence of T2DM. The prospective cohort studies before and 1 year after bariatric surgery in morbidly obese patients with (n = 45) and without (n = 30) T2DM, revealed a significant increase of circulating ANGPTL8 levels 1 year after the bariatric surgery. Intriguingly, this increment, which was predicted by basal ANGPTL8 concentrations, appeared as a determinant of T2DM remission. In conclusion, circulating ANGPTL8 levels have an inverse relationship with SAT expression. Low basal levels of ANGPTL8 rebound after bariatric surgery. The increment in ANGPTL8 concentrations at 1 month of follow‐up after weight loss emerged as a significant predictor of the T2DM remission at 1 year of follow‐up.

Escasa caracterización clínica de los pacientes con diabetes mellitus incluidos en los principales ensayos clínicos sobre hipertensión arterial

Fundamento y objetivo: Los pacientes con diabetes mellitus (DM) presentan un elevado pero heterogeneo riesgo cardiovascular. Entre los factores que pueden modificarlo se encuentran la edad, el sexo, la etnia, el tipo y la duracion de la enfermedad, el grado de control glucemico, tipo de tratamiento hipoglucemiante y la presencia de nefropatia o de acontecimientos cardiovasculares previos. No se conoce hasta que punto estas caracteristicas estan descritas en los principales ensayos clinicos sobre tratamiento de la hipertension que incluyen pacientes con DM. Material y metodo: Se analizaron los ensayos clinicos aleatorizados y con grupo control, publicados hasta mayo de 2003, sobre el tratamiento de la hipertension que incluian a pacientes con DM y tenian, dentro de su criterio principal de valoracion, cualquiera de los siguientes acontecimientos cardiovasculares: infarto agudo de miocardio, accidente cerebrovascular o mortalidad total. En esos ensayos se valoro la informacion de los pacientes con DM en relacion con las variables referidas en el apartado anterior. Resultados: Se analizo un total de 16 estudios que se clasificaron en 3 grupos: a) ensayos exclusivamente para pacientes con DM (RENAAL, UKPDS 38, UKPDS 39, IDNT); b) ensayos con analisis de subgrupo para pacientes con DM (SHEP, Syst-Eur, MICRO-HOPE, HOT, STOP-2, LIFE), y c) ensayos sin analisis de subgrupo para pacientes con DM (CAPP, NORDIL, INSIGHT, ALLHAT, SANBPSG, CONVINCE). En todos estos estudios se incluyo a un total de 33.984 pacientes con DM, la mayoria de 55 o mas anos y con un porcentaje de mujeres entre el 33,5 y el 71,9%, aunque en dos estudios no consto este porcentaje (12,5%). No se preciso el origen etnico de los participantes en 10 ensayos (62,5%), el tipo de DM en 7 (43,8%), el tiempo de evolucion de la DM en 13 (81,3%), el grado de control glucemico en 10 (62,5%), el tipo de tratamiento en 11 (68,8%), la presencia o ausencia de nefropatia en 11 (68,8%) y no se preciso el porcentaje de acontecimientos cardiovasculares previos en 3 (18,8%). En general, los ensayos que no presentaron un analisis de subgrupos para pacientes con DM presentaron una peor definicion de las caracteristicas clinicas de los pacientes que el resto. Conclusiones: La caracterizacion clinica de los pacientes con DM incluidos en los principales ensayos clinicos sobre hipertension es deficiente, lo que limita su validez externa. Esa caracterizacion deberia tenerse en cuenta si se pretende mejorar las recomendaciones terapeuticas de la hipertension en la DM.