Haptoglobin genotype and risk of diabetic nephropathy in patients with type 1 diabetes mellitus: a study on a Spanish population

[en] BACKGROUND: Few reports have studied the possible association between the haptoglobin (Hp) genotype and the risk of diabetic nephropathy (DN) in type 1 diabetes (T1D), with conflicting results to date. AIMS: To study whether the 2-2 Hp genotype is associated with an increased risk of overt DN in a Spanish population with T1D. METHODS: We performed a case-control study in a Spanish population. CASES: T1D patients with end-stage renal disease (stage 5 of NKF-KDOQI), awaiting reno-pancreatic transplantation or having already been transplanted (reno-pancreatic or renal alone). CONTROLS: T1D patients, matched for sex and time of diabetes evolution, with preserved renal function and normal urinary albumin excretion. Hp genotyping was done using polymerase chain reaction and electrophoresis. RESULTS: We included 57 cases and 57 controls in the study. There were no statistically significant differences in gender (70% vs. 61% males, p=1.0) or the duration of diabetes (23.0 ± 6.7 vs. 20.8 ± 9.3 years; p=0.1), although the age of onset of diabetes was lower in the cases (14.1 ± 6.8 vs. 17.7 ± 10.1 years, p=0.03). The frequency of genotypes 1-1, 1-2 and 2-2 was 19.3%, 42.1% and 38.6% in cases and 17.5%, 49.1% and 33.4% in controls, respectively, with no statistically significant differences between groups (p=0.8). Conditional logistic regression analysis showed no significant association between genotype 2-2 of Hp and the development of DN (OR 1.14, CI 0.52-2.52). CONCLUSIONS: In our sample of a Spanish population with T1D, no association was found between the Hp genotype and risk of overt DN. [spa] Antecedentes: Pocos trabajos han estudiado la asociación entre el genotipo de la haptoglobina (Hp) y el riesgo de nefropatía diabética (ND) en pacientes con diabetes tipo 1 (DM1), con resultados contradictorios hasta ahora. Objetivos: Estudiar si el genotipo 2-2 de Hp se asocia a un incremento del riesgo de ND en población española con DM1. Métodos: Se diseñó un estudio de casos y controles. CASOS: pacientes con DM1 y enfermedad renal crónica estadio 5 de la NKF-KDOQI, en espera de trasplante reno-pancreático o que han sido trasplantados (reno-pancreático o renal aislado). CONTROLES: pacientes con DM1, apareados por sexo y tiempo de evolución de la diabetes, con función renal y excreción urinaria de albúmina normales. El genotipo de Hp se realizó mediante reacción en cadena de la polimerasa y electroforesis. Resultados: Incluimos 57 casos y 57 controles, sin diferencias estadísticamente significativas en el sexo (70 % frente a 61 % varones, p = 1,0) o duración de la diabetes (23,0 ± 6,7 frente a 20,8 ± 9,3 años; p = 0,1), aunque la edad de inicio de la diabetes fue menor en los casos (14,1 ± 6,8 frente a 17,7 ± 10,1 años, p = 0,03). La frecuencia de genotipos 1-1, 1-2 y 2-2 fue de 19,3 %, 42,1 % y 38,6 % en los casos y de 17,5 %, 49,1 % y 33,4 % en los controles, respectivamente, sin diferencias significativas (p = 0,8). El análisis de regresión logística condicional no mostró asociación entre el genotipo 2-2 de Hp y el desarrollo de ND (OR 1,14, IC 0,52-2,52). Conclusiones: En nuestra muestra de población española con DM1, no se ha hallado asociación entre el genotipo de Hp y el riesgo de ND

Comparison of [18F] fluorocholine PET/CT with [99mTc] sestamibi and ultrasonography to detect parathyroid lesions in primary hyperparathyroidism: a prospective study.

Background: Primary hyperparathyroidism is a common endocrine disorder produced by the increase of parathyroid hormone (PTH) due to a benign adenoma of a single parathyroid gland, or as multiple gland hyperplasia, or as a rare malignant tumor. Preoperative imaging scans are frequently necessary for the minimally invasive parathyroidectomies to identify the location of enlarged parathyroid glands and to design the procedure. Methods: The diagnostic reliability of [18F]fluorocholine positron emission tomography/computed tomography (FCH PET/CT), [99mTc]sestamibi [multiplexed ion beam imaging (MIBI)] and cervical ultrasonography was analyzed in 37 patients diagnosed with primary hyperparathyroidism undergoing minimally invasive parathyroidectomy. The three preoperative imaging techniques were correlated with intraoperative and histopathological findings as well as changes in biochemical parameters (serum PTH and calcium levels). Statistical analysis was carried out with SPSS version 24.0. Results: In 30 of 37 patients (81.1%), FCH PET/CT correctly localized the pathological gland. In 3 cases of ectopic adenomas, the accuracy of the techniques was 100% (3/3) for FCH PET/CT, 66.7% (2/3) for MIBI, and 33.3% (1/3) for neck ultrasonography. Neither neck ultrasonography nor MIBI were able to locate pathological parathyroid glands in those patients with multiglandular disease, while FCH PET/CT correctly located one patient (1/3, 33.3%) with two adenomas and 3 patients (3/6, 50.0%) with hyperplasia. The three imaging techniques, FCH PET/CT, MIBI and neck ultrasound yielded a sensitivity of 92.1%, 57.9% and 32.4%, a positive predictive value of 94.6%, 84.6% and 78.6%, and a diagnostic accuracy of 96.4%, 85.7% and 79.0%, respectively. Conclusions: In this group of patients diagnosed with primary hyperparathyroidism, FCH PET/CT was superior to MIBI and neck ultrasound in detecting adenomas, particularly in the presence of ectopic glands or multiglandular disease

Adaptación metabólica y variabilidad en la pérdida de peso tras la cirugía bariátrica

[spa] La obesidad mórbida es un problema de salud creciente. La cirugía bariátrica es actualmente el tratamiento más eficaz para la pérdida de peso, sin embargo esta pérdida de peso es súmamente variable. En alrededor del 20% de los pacientes intervenidos la pérdida de peso es insuficiente, las causas de esta gran variabilidad no están bien definidas. Las hipótesis planteadas en esta tesis son las siguientes, 1. La variabilidad en la pérdida de peso tras la cirugía bariátrica puede ilustrarse en un número limitado de trayectorias ponderales con significación clínica. 2. La variabilidad en la pérdida de peso puede explicarse por lo menos en parte por la variabilidad en el efecto de las hormonas gastrointestinales. Los objetivos son los siguientes, 1. Describir la presencia de diferentes patrones de pérdida de peso en una cohorte de individuos operados mediante bypass gástrico y gastrectomía vertical con 5 años de seguimiento y evaluar los predictores clínicos de cada trayectoria ponderal. 2. Comparar la respuesta de las hormonas gastrointestinales en los grupos de fracaso y éxito en la pérdida de peso tras el bypass gástrico. 3. Comparar los niveles plasmáticos de citrina, marcador de la masa entérica, en los grupos de fracaso y éxito en la pérdida de peso tras el bypass gástrico. 4. Valorar el rol causal de las hormonas gastrointestinales sobre la ingesta y su repercusión sobre la respuesta ponderal en los diferentes grupos de fracaso y éxito tras el bypass gástrico a través del bloqueo de la secreción de hormonas gastrointestinales con octreótido. Los resultados y conclusiones derivadas de esta tesis se resumen en los siguientes puntos, 1- La cirugía bariátrica logra una pérdida de peso muy variable, sus efectos se atenúan y su variabilidad aumenta con el transcurso del tiempo. 2. Se pueden identificar dos trayectorias clínicamente diferentes en los que presentan escasa pérdida de peso. El fracaso primario ó resistencia a la pérdida de peso y, el fracaso secundario o mayor tendencia a reganancia de peso. 3. La cirugía bariátrica se asocia una menor pérdida del exceso de peso en los pacientes con obesidad extrema. 4. El mayor cumplimiento de las visitas de seguimiento se asocia con mayor respuesta a la cirugía bariátrica. 5. El bypass y la gastrectomía vertical consiguen resultados similares a corto y mediano plazo, sin embargo la gastrectomía vertical se asocia con mayor reganancia ponderal a medio plazo. 6. El éxito en la pérdida de peso tras el bypass gástrico se asocia a un perfil hormonal más anorexígeno en comparación con el fracaso. 7. Las hormonas gastrointestinales ejercen un papel importante en el control fisiológico de la ingesta calórica también tras el BPG. 8. Las hormonas gastrointestinales no juegan un papel crítico en las diferencias en la ingesta entre personas con éxito o fracaso secundario en la pérdida de peso tras el bypass gástrico. 9. Tras el bypass gástrico sucede una adaptación intestinal que es progresiva en el tiempo. 10. Los datos disponibles sugieren que la adaptación intestinal no ejerce un rol determinante del éxito en la pérdida de peso tras el bypass gástrico.[eng] Morbidly obesity is a growing health problem. Bariatric surgery is currently the most effective treatment for weight loss, however its results are highly variable. In about 20% of individuals weight loss is insufficient, the causes of this high variability are not well defined. The hypotheses made in this thesis are as follows, 1. Variability in weight loss after bariatric surgery can be illustrated in a limited number of weight loss patterns with clinical significance. 2. Variability in weight loss can be explained at least partly by the effect of variability in the gastrointestinal hormones. The aims were to, 1. Describe the presence of different patterns of weight loss in a cohort of individuals operated by gastric bypass and vertical gastrectomy with 5 years of follow up and evaluate clinical predictors of each weight loss path. 2. Compare the response of gastrointestinal hormones in groups of failure and success in weight loss after gastric bypass. 3. Compare the plasma levels of citrulline, marker enteric mass in groups of failure and success in weight loss after gastric bypass. 4. Assess the causal role of gastrointestinal hormones on food intake and its impact on the weight response in different groups of failure and success after gastric bypass by blocking the secretion of gastrointestinal hormones with octreotide. The results and conclusions from this thesis are summarized in the following points, 1- Bariatric surgery achieves weight loss with high variability, its effects are mitigated and variability increases with the passage of time. 2. We can identify two clinically different paths in those with low weight loss. The primary failure or resistance to weight loss, and secondary failure or greater tendency to regain weight. 3. Bariatric surgery is associated with a lower loss of excess weight in patients with extreme obesity. 4. Greater compliance with follow-up visits is associated with increased response to bariatric surgery. 5. The bypass and vertical gastrectomy get similar short and medium term results, however gastrectomy is associated with increased weight regain at medium term. 6. Successful weight loss after gastric bypass is associated with a more anorectic hormone profile compared with failure. 7. The gastrointestinal hormones play an important role in the physiological control of calorie intake also after gastric bypass. 8. Gastrointestinal hormones do not play a critical role in the differences in intake among people with secondary success or failure in weight loss after gastric bypass. 9. After gastric bypass intestinal adaptation occurs, it is progressive over time. 10. The available data suggest that intestinal adaptation does not play a decisive role to success in weight loss after gastric bypass

Haptoglobin genotype and risk of diabetic nephropathy in patients with type 1 diabetes mellitus: a study on a Spanish population

[en] BACKGROUND: Few reports have studied the possible association between the haptoglobin (Hp) genotype and the risk of diabetic nephropathy (DN) in type 1 diabetes (T1D), with conflicting results to date. AIMS: To study whether the 2-2 Hp genotype is associated with an increased risk of overt DN in a Spanish population with T1D. METHODS: We performed a case-control study in a Spanish population. CASES: T1D patients with end-stage renal disease (stage 5 of NKF-KDOQI), awaiting reno-pancreatic transplantation or having already been transplanted (reno-pancreatic or renal alone). CONTROLS: T1D patients, matched for sex and time of diabetes evolution, with preserved renal function and normal urinary albumin excretion. Hp genotyping was done using polymerase chain reaction and electrophoresis. RESULTS: We included 57 cases and 57 controls in the study. There were no statistically significant differences in gender (70% vs. 61% males, p=1.0) or the duration of diabetes (23.0 ± 6.7 vs. 20.8 ± 9.3 years; p=0.1), although the age of onset of diabetes was lower in the cases (14.1 ± 6.8 vs. 17.7 ± 10.1 years, p=0.03). The frequency of genotypes 1-1, 1-2 and 2-2 was 19.3%, 42.1% and 38.6% in cases and 17.5%, 49.1% and 33.4% in controls, respectively, with no statistically significant differences between groups (p=0.8). Conditional logistic regression analysis showed no significant association between genotype 2-2 of Hp and the development of DN (OR 1.14, CI 0.52-2.52). CONCLUSIONS: In our sample of a Spanish population with T1D, no association was found between the Hp genotype and risk of overt DN. [spa] Antecedentes: Pocos trabajos han estudiado la asociación entre el genotipo de la haptoglobina (Hp) y el riesgo de nefropatía diabética (ND) en pacientes con diabetes tipo 1 (DM1), con resultados contradictorios hasta ahora. Objetivos: Estudiar si el genotipo 2-2 de Hp se asocia a un incremento del riesgo de ND en población española con DM1. Métodos: Se diseñó un estudio de casos y controles. CASOS: pacientes con DM1 y enfermedad renal crónica estadio 5 de la NKF-KDOQI, en espera de trasplante reno-pancreático o que han sido trasplantados (reno-pancreático o renal aislado). CONTROLES: pacientes con DM1, apareados por sexo y tiempo de evolución de la diabetes, con función renal y excreción urinaria de albúmina normales. El genotipo de Hp se realizó mediante reacción en cadena de la polimerasa y electroforesis. Resultados: Incluimos 57 casos y 57 controles, sin diferencias estadísticamente significativas en el sexo (70 % frente a 61 % varones, p = 1,0) o duración de la diabetes (23,0 ± 6,7 frente a 20,8 ± 9,3 años; p = 0,1), aunque la edad de inicio de la diabetes fue menor en los casos (14,1 ± 6,8 frente a 17,7 ± 10,1 años, p = 0,03). La frecuencia de genotipos 1-1, 1-2 y 2-2 fue de 19,3 %, 42,1 % y 38,6 % en los casos y de 17,5 %, 49,1 % y 33,4 % en los controles, respectivamente, sin diferencias significativas (p = 0,8). El análisis de regresión logística condicional no mostró asociación entre el genotipo 2-2 de Hp y el desarrollo de ND (OR 1,14, IC 0,52-2,52). Conclusiones: En nuestra muestra de población española con DM1, no se ha hallado asociación entre el genotipo de Hp y el riesgo de ND

Obesity impacts brain metabolism and structure independently of amyloid and tau pathology in healthy elderly

Aims/hypothesis: Midlife obesity is a risk factor for dementia. We investigated the impact of obesity on brain structure, metabolism, and cerebrospinal fluid (CSF) core Alzheimer's disease (AD) biomarkers in healthy elderly. Methods: We selected controls from ADNI2 with CSF AD biomarkers and/or fluorodeoxyglucose positron emission tomography (FDG-PET) and 3T-MRI. We measured cortical thickness, FDG uptake, and CSF amyloid beta (Aβ)1-42, p-tau, and t-tau levels. We performed regression analyses between these biomarkers and body mass index (BMI). Results: We included 201 individuals (mean age 73.5 years, mean BMI 27.4 kg/m2). Higher BMI was related to less cortical thickness and higher metabolism in brain areas typically not involved in AD (family-wise error [FWE] <0.05), but not to AD CSF biomarkers. It is notable that the impact of obesity on brain metabolism and structure was also found in amyloid negative individuals. Conclusions/interpretation: In the cognitively unimpaired elderly, obesity has differential effects on brain metabolism and structure independent of an underlying AD pathophysiology