ABSTRACT
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.
Subject(s)
Multiple Endocrine Neoplasia Type 2a/genetics , Mutation/genetics , Proto-Oncogene Proteins c-ret/genetics , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Proto-Oncogene Mas , Retrospective Studies , Young AdultABSTRACT
OBJECTIVE: To evaluate the relation between obstructive sleep apnea (OSA) and left ventricular mass (LVM) in morbid obesity and the influence of gender, menopausal status, anthropometry, body composition, hypertension, and other cardiovascular risk factors in this relationship. DESIGN: Cross-sectional descriptive study. METHODS: Polysomnographic and echocardiographic studies were performed in a cohort of 242 patients (86 men, 100 premenopausal (PreM) and 56 postmenopausal (PostM) women), with grade II obesity and above (BMI: 43.7 ± 0.4 kg/m(2)) to investigate OSA and LVM respectively. Anthropometry, body composition, glucose tolerance, and blood pressure were also recorded. RESULTS: OSA to different degrees was diagnosed in 76.2% of the patients (n: 166), its prevalence being 90.9% (n: 70) for men, and 76% (n: 38) and 63.8% (n: 58) for PostM and PreM women, respectively (p < 0.01). LVM excess was greatest for PostM women (90.2%), followed by men (81.9%) and PreM females (69.6%) (p < 0.01). LVM values increased in accordance to OSA severity (absence, 193.7 ± 6.9 g; mild, 192.6 ± 7.8 g; moderate, 240.5 ± 12.5 g; severe, 273.6 ± 14.6 g; p < 0.01). LVM magnitude correlated with the menopausal state, age, central adiposity, hypertension (HT), type 2 diabetes (DM), desaturation index (DI), and apnea-hypopnea index (AHI) (r = 0.41; p < 0.01). The relationship between LVM and AHI persisted in the multivariate analysis (ß = 0.25; p < 0.05) after adjusting for age, gender, menopausal state, BMI, waist circumference, neck circumference, DI, fasting plasma glucose, DM, and HT. But if tobacco habits are included, the statistical difference disappears (ß = 0.22; p = 0.06). CONCLUSIONS: Morbid obesity is frequently associated with abnormal LVM, particularly in patients with OSA; this association is independent of HT, BMI, body composition, and other clinical factors, supporting a direct role of OSA on LVM in morbid obesity. This suggests that OSA and LVM might be taken as predictors of the cardiovascular risk in these patients.
Subject(s)
Cardiovascular Diseases/epidemiology , Heart Ventricles/anatomy & histology , Obesity, Morbid/epidemiology , Sleep Apnea, Obstructive/epidemiology , Adult , Anthropometry/methods , Body Composition , Cardiovascular Diseases/physiopathology , Comorbidity , Cross-Sectional Studies , Echocardiography/methods , Female , Humans , Hypertension/epidemiology , Hypertension/physiopathology , Male , Menopause , Obesity, Morbid/physiopathology , Organ Size , Polysomnography/methods , Risk Factors , Severity of Illness Index , Sex Factors , Sleep Apnea, Obstructive/physiopathology , Spain/epidemiologyABSTRACT
Introducción y objetivos. La cirugía bariátrica es una herramienta eficaz de control metabólico para pacientes obesos diabéticos. El objetivo de este trabajo es determinar la evolución del peso y el metabolismo glucídico y lipídico en pacientes obesos diabéticos intervenidos de cirugía bariátrica, durante los primeros 4 años tras la intervención. Métodos. Estudio retrospectivo de 104 pacientes (71 mujeres; media de edad, 53,0 ± 0,9 años; índice de masa corporal, 46,8 ± 0,7) con diabetes mellitus tipo 2 de una mediana de 3 años de evolución, a los que se practicó bypass gástrico proximal laparoscópico. Resultados. La glucemia y la concentración de glucohemoglobina descendieron durante los primeros 1-3 meses y se mantuvieron estables hasta los 4 años, lo que permitió eliminar el tratamiento hipoglucemiante al 80% de los pacientes. No observamos diferencias en función del índice de masa corporal, tiempo de evolución de la diabetes mellitus o el tratamiento antidiabético previo. El peso descendió hasta los 15-24 meses, con ligera recuperación posterior. Los valores de colesterol total, triglicéridos y lipoproteínas de baja densidad mejoraron significativamente, y se había obtenido valores objetivo en alrededor del 80% de los pacientes a partir de 12 meses. Estos descensos no se correlacionaron con los cambios de peso. Las lipoproteínas de alta densidad descendieron hasta los 12 meses, con una pequeña recuperación posterior, a pesar de lo cual el 85% de los pacientes presentaban valores objetivo 24 meses tras la cirugía. Conclusiones. La cirugía bariátrica es eficaz para el tratamiento de pacientes diabéticos obesos, mejora su control metabólico y reduce el riesgo cardiovascular (AU)
Introduction and objectives. Bariatric surgery is a valuable tool for metabolic control in obese diabetic patients. The aim of this study was to determine changes in weight and carbohydrate and lipid metabolism in obese diabetic patients during the first 4 years after bariatric surgery. Methods. A retrospective study was performed in 104 patients (71 women; mean age, 53.0 [0.9] years; mean body mass index, 46.8 [0.7]) with type 2 diabetes mellitus (median duration, 3 years) who underwent laparoscopic proximal gastric bypass. Results. Blood glucose levels and glycated hemoglobin concentrations decreased during the first 1-3 postoperative months. Values stabilized for the rest of the study period, allowing hypoglycemic treatment to be discontinued in 80% of the patients. No significant differences were observed as a function of the body mass index, diabetes mellitus duration, or previous antidiabetic treatment. Weight decreased during the first 15-24 months and slightly increased afterward. Levels of total cholesterol, triglycerides, and low-density lipoprotein significantly decreased, and target values were reached after 12 months in 80% of the patients. No correlation was found between these reductions and weight loss. Similarly, high-density lipoprotein concentrations decreased until 12 months after surgery. Although concentrations showed a subsequent slight increase, target or lower high-density lipoprotein values were achieved at 24 months postintervention in 85% of the patients. Conclusions. Bariatric surgery is effective for the treatment of obese diabetic patients, contributing to their metabolic control and reducing their cardiovascular risk (AU)
Subject(s)
Humans , Male , Female , Obesity/complications , Bariatric Surgery , Risk Factors , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Hypercholesterolemia/complications , Hypercholesterolemia/diagnosis , Hypoglycemia/complications , Hypoglycemia/diagnosis , Lipoproteins, HDL/analysis , Lipoproteins, LDL/analysis , Retrospective Studies , Diabetes Complications/diagnosis , Body Mass Index , Blood Glucose/analysis , Glycemic IndexABSTRACT
INTRODUCTION AND OBJECTIVES: Bariatric surgery is a valuable tool for metabolic control in obese diabetic patients. The aim of this study was to determine changes in weight and carbohydrate and lipid metabolism in obese diabetic patients during the first 4 years after bariatric surgery. METHODS: A retrospective study was performed in 104 patients (71 women; mean age, 53.0 [0.9] years; mean body mass index, 46.8 [0.7]) with type 2 diabetes mellitus (median duration, 3 years) who underwent laparoscopic proximal gastric bypass. RESULTS: Blood glucose levels and glycated hemoglobin concentrations decreased during the first 1-3 postoperative months. Values stabilized for the rest of the study period, allowing hypoglycemic treatment to be discontinued in 80% of the patients. No significant differences were observed as a function of the body mass index, diabetes mellitus duration, or previous antidiabetic treatment. Weight decreased during the first 15-24 months and slightly increased afterward. Levels of total cholesterol, triglycerides, and low-density lipoprotein significantly decreased, and target values were reached after 12 months in 80% of the patients. No correlation was found between these reductions and weight loss. Similarly, high-density lipoprotein concentrations decreased until 12 months after surgery. Although concentrations showed a subsequent slight increase, target or lower high-density lipoprotein values were achieved at 24 months postintervention in 85% of the patients. CONCLUSIONS: Bariatric surgery is effective for the treatment of obese diabetic patients, contributing to their metabolic control and reducing their cardiovascular risk.
Subject(s)
Bariatric Surgery/methods , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Obesity, Morbid/surgery , Risk Assessment , Adult , Blood Glucose/metabolism , Body Mass Index , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/prevention & control , Cohort Studies , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/metabolism , Female , Follow-Up Studies , Humans , Lipoproteins, HDL/metabolism , Male , Middle Aged , Obesity, Morbid/diagnosis , Obesity, Morbid/epidemiology , Obesity, Morbid/metabolism , Retrospective Studies , Risk Reduction Behavior , Survival Analysis , Time Factors , Treatment Outcome , Weight LossSubject(s)
Adenocarcinoma, Follicular/secondary , Bone Neoplasms/secondary , Thyroid Neoplasms/diagnosis , Adenocarcinoma, Follicular/diagnosis , Adenocarcinoma, Follicular/radiotherapy , Adenocarcinoma, Follicular/surgery , Aged , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/radiotherapy , Combined Modality Therapy , Fatal Outcome , Female , Femoral Neoplasms/radiotherapy , Femoral Neoplasms/secondary , Femoral Neoplasms/surgery , Fractures, Spontaneous/etiology , Humans , Ilium/diagnostic imaging , Iodine Radioisotopes/therapeutic use , Male , Middle Aged , Radiotherapy, Adjuvant , Sacrum/diagnostic imaging , Spinal Cord Compression/etiology , Spinal Neoplasms/diagnostic imaging , Spinal Neoplasms/radiotherapy , Spinal Neoplasms/secondary , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Thyroidectomy , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Pheochromocytoma occurs in nearly 50% of MEN 2A (multiple endocrine neoplasia, type 2A) cases. Many issues related to this tumor are still the subject of debate: the diagnostic management in patients who have had positive genetic study results (RET mutation), variations related to mutation, the best surgical option, and the real relapse rate during long-term follow-up. The aim of this study is to present our experience with this unusual disease, looking for answers to some of these questions. PATIENTS AND METHODS: Of 169 patients belonging to 19 MEN 2A families, 54 (32%) presented with pheochromocytoma. The following variables have been studied: (1) clinical and diagnostic data [age, mutation, clinical features, results of catecholamines and catabolites in a 24-h urine sample, computerized tomography (CT) scan and iodine-131 meta-iodobenzylguanidine (MIBG) scintigraphy results, and the means of diagnostic, clinical, or genetic screening]; (2) surgical treatment; and (3) follow-up and recurrence. The mean follow-up time was 92.5 months (range: 12-120 months). RESULTS: The mean age of the 54 patients was 37.9 years (range: 14-71 years); 33 were women. Most (96.3%) mutations were found in exon 11. The most frequent mutations were Cys634Tyr (in 33 cases [61.1%]) and Cys634Arg (in 14 [25.9%]). The diagnosis of pheocromocytoma was made after the diagnosis of MTC in 26 cases (48.2%), simultaneously in 21 (38.9%), and prior in the 7 remaining cases (12.9%). At the time of diagnosis 28 patients (51.8%) were asymptomatic and 26 (48.2%) had clinical features related to pheochromocytoma. In 6 patients (11.1%), the values of catecholamines and catabolites in urine were normal. In the cases with high values, the most useful isolated determination was that of metanephrines (82%), followed by adrenaline (76%). The CT scan did not provide a correct diagnosis in 6 patients with bilateral lesions, and one patient with a bilateral tumor was not diagnosed by MIBG. The combination of CT scan and MIBG diagnosed 100% of cases. The pheochromocytoma was bilateral in 27 cases, with a total number of 81 pathological glands detected. A laparascopic approach was used in 30 cases and a laparotomy in 24. The mean tumor size was 4.5 cm (range: 1-18 cm). Five patients with unilateral resection relapsed (18.5%), and the mean relapse time was 43.2 months (range: 12-120 months). There was a greater frequency of pheochromocytoma in those subjects who had the Cys634Arg mutation (p < 0.03). In addition, the Cys634Arg mutation is more frequent in bilateral cases. There are no prognostic factors for recurrence. CONCLUSIONS: Pheochromocytoma in MEN 2A is related to the type of mutation, which can be early onset and is frequently asymptomatic. Its diagnosis requires catecholamines determinations as well as a CT scan. Correct diagnosis of bilaterality is established by CT and MIBG. Laparoscopic adrenalectomy is the treatment of choice.
Subject(s)
Adrenal Gland Neoplasms/diagnosis , Adrenal Gland Neoplasms/surgery , Adrenalectomy , Multiple Endocrine Neoplasia Type 2a/complications , Pheochromocytoma/diagnosis , Pheochromocytoma/surgery , Adolescent , Adrenal Gland Neoplasms/genetics , Adult , Aged , Cohort Studies , Female , Humans , Laparoscopy , Male , Middle Aged , Multiple Endocrine Neoplasia Type 2a/pathology , Multiple Endocrine Neoplasia Type 2a/therapy , Mutation/genetics , Pheochromocytoma/genetics , Proto-Oncogene Proteins c-ret/genetics , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: The term conjugated linoleic acid (CLA) refers to several positional and geometric conjugated dienoic isomers of linoleic acid (LA), of which the trans-10,cis-12 isomer has been reported to reduce adiposity and increase lean mass in mice and other animals when included at Subject(s)
Body Composition/drug effects
, Body Weight/drug effects
, Linoleic Acids, Conjugated
, Obesity/metabolism
, Adipose Tissue/metabolism
, Animals
, Body Composition/physiology
, Body Weight/physiology
, Evidence-Based Medicine
, Humans
, Isomerism
, Linoleic Acids, Conjugated/chemistry
, Linoleic Acids, Conjugated/metabolism
, Linoleic Acids, Conjugated/pharmacology
, Muscle, Skeletal/metabolism
ABSTRACT
The aim of this cross-sectional study was to describe the prevalence of total, known and unknown diabetes mellitus and impaired fasting glucose (IFG) in the population of Murcia (SE Spain), a Mediterranean area with a high prevalence of obesity. Therefore, 2562 subjects (>or=20 years) were selected by stratified random sampling and a survey was carried out by telephone, together with a physical examination and biochemical determinations. The ADA-1997 diagnostic criteria were used. The crude prevalence of total diabetes was 11% (9.5-12.6%), known diabetes 7.8% (6.5-9.2%), unknown diabetes 3.2% (2.4-4.2%) and IFG 4.9% (3.9-6.1%). Both total diabetes and IFG were higher in men than in women, with prevalence rates increasing with age. People with diabetes and IFG had higher BMI, blood pressure, total cholesterol, LDL-cholesterol and triglyceride values than the rest of the population. No difference in the prevalence of diabetes was observed between the rural and urban populations. The prevalence of diabetes in Murcia is high compared to the rest of Spain and the world, suggesting that the possible benefits attributed to some characteristics of the diet of this Mediterranean population are not sufficient to counteract the risk factors associated with the disease.
Subject(s)
Diabetes Mellitus/epidemiology , Obesity/epidemiology , Adult , Aged , Blood Glucose/metabolism , Female , Humans , Male , Mediterranean Region/epidemiology , Middle Aged , Prevalence , Rural Population , Sex Characteristics , Spain/epidemiology , Surveys and Questionnaires , Urban PopulationABSTRACT
BACKGROUND: Genetic study of the RET proto-oncogene has modified the management, treatment, and prognosis of medullary thyroid carcinoma (MTC), multiple endocrine neoplasia 2A (MEN 2A), for patients with less advanced tumor stages. Classically, the diagnosis was based on an increase in basal and poststimulus peak calcitonin (bCT and pCT). Prophylactic thyroidectomy, based on results of genetic testing, may reduce recurrences in MTC. STUDY DESIGN: Of 82 MTC (MEN 2A) patients genetically diagnosed and surgically treated at our center, 22 received a prophylactic thyroidectomy (RET +, bCT and pCT with normal values and asymptomatic). We analyzed age, gender, phenotype, RET mutation, cervical ultrasound, laboratory tests (bCT, pCT, and CEA), surgery, histologic data, TNM, and followup. RESULTS: The 22 patients belonged to 8 families with MTC (MEN 2A). Mean age was 15.2 years (range 5 to 36 years). The RET mutation in 21 patients was Cys-->Tyr and in the remaining patient both in codon 634 in exon 11. The median values of bCT and pCT were 38 pg/mL (range < 15 to 75 pg/mL) and 148.5 pg/mL (range < 15 to 250 pg/mL), respectively. Total thyroidectomy was performed in 8 patients (age < or = 10 years) and associated central neck dissection in 14 patients (age> 10 years). Histologic study showed 7 C-cell hyperplasias and 15 MTCs (8 bilateral); the median size was 0.2 cm (range < 0.1 to 0.7cm); 1 patient had metastatic adenopathies. According to TNM, 7 were stage 0, 14 were stage I, and 1 was stage III. Postsurgery bCT and pCT values were normal in all patients, with a curative rate of 100%. MTC patients compared with C-cell hyperplasia patients were older on average, had higher mean bCT, mean pCT, and mean CEA. CONCLUSIONS: Prophylactic thyroidectomy based on genetic testing allows identification and treatment of patients at an early stage of the disease and decreases recurrence rates. pCT values above the upper limit of normal may be markers for the presence of MTC and should be considered in selecting operative procedures for these patients.