Jordi Mesa

High Prevalence of Hepatitis C Virus Infection in Diabetic Patients

OBJECTIVE To evaluate the prevalence of hepatitis C virus (HCV) infection in diabetic patients and to investigate the influence of several epidemiological and clinical factors on HCV infection. RESEARCH DESIGN AND METHODS A total of 176 consecutive diabetic patients were compared with 6,172 blood donors, matched by recognized risk factors to acquire HCV infection. Serologic testing for anti-HCV was done using a second-generation commercial enzyme-linked immunosorbent assay (ELISA) and an immunoblot assay was performed in anti-HCV positive samples to confirm HCV specificity. Diabetic patients were divided in two groups according to their HCV antibody status and analyzed for the following variables: age, sex, type of diabetes, duration of disease, mode of therapy, late diabetic complications, previous blood transfusions, intravenous drug addiction, hospital admissions, major surgical procedures, and liver function tests (LFTs). RESULTS A higher prevalence of HCV infection was observed in diabetic patients in comparison with blood donors (11.5 vs. 2.5%; P < 0.001; odds ratio 4.39; 95% CI 2.61–7.24). We did not detect any particular epidemiological factor for HCV infection in anti-HCV positive diabetic patients. In these patients, abnormal LFTs were observed in 72.3%, compared with only 24.7% of anti-HCV negative diabetic patients (P < 0.001). CONCLUSIONS A high prevalence of HCV infection was detected in diabetic patients, and most of anti-HCV positive patients presented with abnormal LFTs. Therefore, testing for HCV infection of diabetic patients with an abnormal LFT is mandatory. The lack of any particular epidemiological factor for HCV infection in our diabetic population suggests that HCV may have a direct role in the development of diabetes.

Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults

objective To investigate the GH response to glucagon in adult patients with GH deficiency and in controls compared with the GH response to the insulin tolerance test (ITT) in patients with GH deficiency and to determine whether the use of glucagon results in a diagnostic utility test.

Iron Deficiency in Obese Postmenopausal Women

Objective: This study evaluates whether the iron deficiency suggested in children and adolescents with overweight is also present with increasing age.

Hepatocyte growth factor in vitreous and serum from patients with proliferative diabetic retinopathy

BACKGROUND Hepatocyte growth factor (HGF) is an endothelium specific growth factor that has been implicated in angiogenesis, a crucial event for the development of proliferative diabetic retinopathy (PDR). The aim of the study is to determine the intravitreous concentrations of HGF in diabetic patients with PDR, and to investigate whether its serum levels could contribute to its intravitreous concentration. METHODS 17 diabetic patients and seven non-diabetic patients in whom a vitrectomy was performed were studied. Both groups were matched by serum levels of HGF. Venous blood and vitreous samples were collected simultaneously at the time of vitreoretinal surgery. Vitreous and serum HGF were determined by ELISA. RESULTS Intravitreous concentrations of HGF (median and range) were higher in diabetic patients (17.04 ng/ml (9.98–80)) in comparison with non-diabetic patients (5.88 ng/ml (2.57–14.20); p=0.003). Intravitreous HGF concentrations were strikingly higher than serum HGF concentrations both in diabetic patients (17.04 ng/ml (9.98–80) v0.66 ng/ml (0.26–1.26); p<0.001) and in the control group (5.88 ng/ml (2.57–14.20) v 0.68 ng/ml (0.49–0.96); p=0.003). No correlation was found between serum and vitreous levels of HGF in both groups (diabetic patients,r= −0.31; p=0.5 and control subjectsr= −0.15; p=0.5). CONCLUSION The high vitreous levels of HGF observed in diabetic patients with PDR cannot be attributed to serum diffusion across the blood-retinal barrier. Therefore, intraocular synthesis appears to be the main contributing factor for the high vitreous HGF concentrations in diabetic patients, a cytokine that seems to be directly involved in the pathogenesis of PDR.

Preoperative Thyrotropin Serum Concentrations Gradually Increase from Benign Thyroid Nodules to Papillary Thyroid Microcarcinomas Then to Papillary Thyroid Cancers of Larger Size

We evaluated the preoperative serum thyrotropin (TSH) levels in 386 patients operated on for nodular thyroid disease (NTD). TSH levels for cases with final benign disease and differentiated thyroid carcinoma (DTC) were compared. No evidence of cancer was detected in 310 patients (80.3%), whereas malignancy was present in 76 cases (19.7%). Mean TSH concentration was 1.36 ± 1.62 mU/L in benign patients and 2.08 ± 2.1 in cases with malignant lesions (P = 0.0013). The group of malignancy was subdivided in papillary thyroid carcinoma (PTMC) versus thyroid cancer of larger size (TCLS). Mean TSH was 1.71 ± 1.52 in PTMC and 2.42 ± 2.5 in TCLS. Significant differences were found when all groups (benign, PTMC and TCLS) were compared (P < 0.001). However, pairwise comparisons between them showed that differences were only significant between benign and TCLS groups (P < 0.01). In conclusion, TSH levels were higher in patients with a final diagnosis of DTC. Moreover, it appears that there exists an increment in tumor size as a function of increment in the TSH level.

Free insulin-like growth factor 1 in the vitreous fluid of diabetic patients with proliferative diabetic retinopathy: a case-control study

The aim of the study was to evaluate the vitreous levels of free insulin-like growth factor 1 (IGF-1) in patients with proliferative diabetic retinopathy (PDR). For this, a total of 36 diabetic patients with PDR (group A) and 28 non-diabetic patients (group B) in whom a vitrectomy was performed were compared. Both groups were matched by age, sex and serum-free IGF-1. In a subgroup of diabetic patients (n =21) and non-diabetic patients (n =13), vitreous and serum total IGF-1, IGF-binding protein 1 (IGFBP-1) and IGFBP-3 were also determined. Serum and vitreous levels of free IGF-1, total IGF-1, IGFBP-1 and IGFBP-3 were measured by immunological methods. Vitreal proteins were assessed by a turbidimetric method and adjusted for vitreous haemoglobin. Vitreous levels of free IGF-1 were elevated in group A (median, 0.16 ng/ml; range 0.06-0.57 ng/ml) in comparison with group B (median, 0.12 ng/ml; range 0.06-0.22 ng/ml; P <0.001); however, after adjusting for vitreal proteins, free IGF-1 levels were significantly lower in group A in comparison with group B [0.05 ng/mg (0.01-0.45 ng/mg) versus 0.15 ng/mg (0.07-0.66 ng/mg); P <0.001]. The relatively lower free IGF-1 level observed in group A could not be attributed to differences in the distribution of intravitreous IGFBP-1 and IGFBP-3 in relation to total IGF-1. Notably, the contribution of free IGF-1 to total IGF-1 in vitreous fluid was 10% in group A and 42% in group B; these percentages largely exceed that obtained in serum (<1%). Our results suggest that although there is an enhancement of intravitreous free IGF-1 in diabetic patients due to serum diffusion, a deficit in its intraocular production also exists. In addition, these findings support the concept that intraocular-produced free IGF-1 plays a relevant role in retinal homoeostasis.

Clinical significance of RET/PTC and p53 protein expression in sporadic papillary thyroid carcinoma

Aims:  Rearranged during Transfection (RET)/papillary thyroid carcinoma (PTC) and p53 are two genes involved in the pathogenesis of PTC. It has been suggested that RET/PTC expression is associated with higher rates of local extension and lymph node involvement, whereas p53 mutations are more frequent in poorly differentiated and anaplastic carcinomas. In addition, experimental studies have shown that p53 activity can modify the behaviour of PTC carrying RET/PTC. The aim of this study was to investigate the expression of both RET/PTC and p53 in order to evaluate their usefulness as prognostic factors.

RET Cys634Arg mutation confers a more aggressive multiple endocrine neoplasia type 2A phenotype than Cys634Tyr mutation

OBJECTIVE Specific germline mutations in the RET proto-oncogene are correlated with clinical features in multiple endocrine neoplasia type 2A (MEN2A); however, data are scarce regarding differences in clinical profiles dependent on the type of nucleotide and amino acid substitution at the same codon. We aimed to analyse differences in clinical risk profiles and outcomes among different amino acids encoded by codon 634. DESIGN The study was retrospective and multicentric. METHODS We collected data included in the Spanish Online National Database from patients with MEN2A carrying a RET proto-oncogene mutation on codon 634. The mean follow-up time was 7.6±6.9 years (1-32). RESULTS Patients (n=173) from 49 unrelated families were C634Y carriers, and 26 patients from eight different families had C634R mutation. We found higher penetrance of medullary thyroid carcinoma, phaeochromocytoma and hyperparathyroidism (P<0.001, P=0.007 and P<0.001 respectively) in C634R carriers than in C634Y carriers. The Kaplan-Meier estimate of cumulative lymph node and distant metastases rates showed that these events occurred earlier in patients harbouring the C634R mutation (P<0.001). A multivariate adjusted Cox regression analysis indicated that the C634R mutation was an independent factor for persistent/recurrent disease (hazard ratio, 3.17; 95% CI: 1.66-6.03; P<0.001). CONCLUSIONS Our results suggest that there could be clinical differences caused by different amino acid substitutions at codon 634; specifically, the C634R mutation was associated with a more aggressive MEN2A phenotype than the C634Y mutation.

Relationship between lipoprotein(a) phenotypes and plaminogen activator inhibitor type 1 in diabetic patients.

It has been demonstrated in vitro that lipoprotein(a) [Lp(a)] increases the endothelial synthesis of plasminogen activator inhibitor 1 (PAI-1). However, this effect in vivo is controversial, and the possible relationship between PAI-1 and Lp(a) phenotypes has not been evaluated. The aim of the study was to determine the influence of Lp(a) and its phenotypes on PAI-1 serum concentrations in diabetic patients. For this purpose we include 75 Caucasian diabetic patients (34 consecutive type I and 41 consecutive type II) without late diabetic complications. Lp(a) and PAI-1 were assessed by ELISA. Lp(a) phenotypes were determined by SDS-PAGE followed by immunoblotting, and grouped according to size in small (F,B,S1,S2), big (S3,S4), and null. A linear correlation between Lp(a) and PAI-1 was not observed either as a whole or when type I and type II diabetic patients were analyzed separately. However, significant differences were detected in PAI-1 levels when Lp(a) phenotypes were considered (small: 42.1+/-31.8 ng/mL; big: 37.2+/-26.1 ng/mL; null: 14.4+/-14.4; p< 0.05). The significant differences were due to the low PAI-1 concentrations observed in patients with null phenotype. Our results suggest that fibrinolytic activity might be preserved in diabetic patients with null Lp(a) phenotype. Furthermore, it could be speculated that diabetic patients with null phenotype should be considered at low risk to develop cardiovascular disease.

Deficiencia de la hormona de crecimiento en el adulto: efectos del tratamiento sustitutivo sobre la composición corporal y la calidad de vida relacionada con la salud

Fundamento y objetivo La deficiencia de hormona de crecimiento (GH) en el adulto se acompanade alteraciones en la composicion corporal y de una disminucion de la calidad de vida relacionadacon la salud (CVRS) que pueden ser revertidas mediante la administracion de GH. Elobjetivo de este estudio fue valorar la respuesta bioquimica y sobre la composicion corporal, asicomo la CVRS y la seguridad del tratamiento sustitutivo con GH. Pacientes y metodo Se estudio a 165 pacientes con hipopituitarismo y deficiencia de GH. El disenofue de doble ciego, aleatorio, placebo-control durante un periodo de 6 meses, seguido de otros 6 enel que todos los pacientes recibieron GH. La dosis inicial fue de 0,125 UI/kg/semana, seguida de0,25 UI/kg/semana. La composicion corporal se determino mediante impedanciometria bioelectrica,y la CVRS se evaluo con los cuestionarios Perfil de Salud de Nottingham (PSN) y QoL-AGHDA. Resultados Las concentraciones de IGF-1 se incrementaron a los 6 meses en el grupo GH/GHpero no en el placebo/GH, y fueron normales para un grupo control de su mismo sexo y edad.Se observo un incremento significativo de la masa libre de grasa durante el tratamiento con GHy simultaneamente una disminucion de la masa grasa. El agua corporal total presento un aumentodurante el tratamiento. A los 6 meses se produjeron cambios en las dimensiones deenergia y reaccion emocional en ambos grupos, valoradas con el PSN, sin apreciarse modificacionesen el resto de las dimensiones. Con el QoL-AGHDA se aprecio una mejoria progresiva enla CVRS en el grupo tratado y no en el grupo placebo. Los efectos adversos se debieron fundamentalmentea retencion hidrica y se resolvieron al disminuir las dosis. Conclusiones El tratamiento con GH en adultos con deficit de esta hormona fue generalmentebien tolerado y produjo efectos beneficiosos sobre la composicion corporal y la CVRS.