Neuropatía autonómica cardiovascular en pacientes diabéticos sometidos a trasplante simultáneo páncreas-riñón

El trasplantament simultani de pàncrees i ronyó (SPK) és una alternativa terapèutica en pacients amb DM-1 i nefropatía diabètica terminal. No obstant això, les complicacions cròniques derivades de la DM solen estar molt avançades al moment de la realització del trasplantament. L'objectiu del treball és estudiar la neuropatía diabètica (somàtica i autonòmica) en pacients candidats a trasplantament SPK a la Comunitat Valenciana i valorar l'evolució de la mateixa al cap de 3 i 5 anys del trasplantament, prestant especial atenció a aquells pacients en els quals s'aconsegueix un estat de normoglucemia després del trasplantamentEl trasplante simultáneo de páncreas y riñón (SPK) es una alternativa terapéutica en pacientes con DM-1 con nefropatía diabética terminal. Sin embargo, las complicaciones crónicas de su DM suelen estar muy avanzadas en el momento de la realización del trasplante. El objetivo del trabajo es estudiar la neuropatía diabética (somática y autonómica) en pacientes candidatos a trasplante SPK en la Comunidad Valenciana y valorar la evolución de la misma al cabo de 3 y 5 años del trasplante, prestando especial atención a aquellos pacientes en los que se consigue un estado de normoglucemia tras el trasplante

Integration of Distributed Services and Hybrid Models Based on Process Choreography to Predict and Detect Type 2 Diabetes

[EN] Life expectancy is increasing and, so, the years that patients have to live with chronic diseases and co-morbidities. Type 2 diabetes is one of the most prevalent chronic diseases, specifically linked to being overweight and ages over sixty. Recent studies have demonstrated the effectiveness of new strategies to delay and even prevent the onset of type 2 diabetes by a combination of active and healthy lifestyle on cohorts of mid to high risk subjects. Prospective research has been driven on large groups of the population to build risk scores that aim to obtain a rule for the classification of patients according to the odds for developing the disease. Currently, there are more than two hundred models and risk scores for doing this, but a few have been properly evaluated in external groups and integrated into a clinical application for decision support. In this paper, we present a novel system architecture based on service choreography and hybrid modeling, which enables a distributed integration of clinical databases, statistical and mathematical engines and web interfaces to be deployed in a clinical setting. The system was assessed during an eight-week continuous period with eight endocrinologists of a hospital who evaluated up to 8080 patients with seven different type 2 diabetes risk models implemented in two mathematical engines. Throughput was assessed as a matter of technical key performance indicators, confirming the reliability and efficiency of the proposed architecture to integrate hybrid artificial intelligence tools into daily clinical routine to identify high risk subjects.The authors wish to acknowledge the consortium of the MOSAIC project (funded by the European Commission, Grant No. FP7-ICT 600914) for their commitment during concept development, which led to the development of the research reported in this manuscriptMartinez-Millana, A.; Bayo-Monton, JL.; Argente-Pla, M.; Fernández Llatas, C.; Merino-Torres, JF.; Traver Salcedo, V. (2018). Integration of Distributed Services and Hybrid Models Based on Process Choreography to Predict and Detect Type 2 Diabetes. Sensors. 18 (1)(79):1-26. https://doi.org/10.3390/s18010079S12618 (1)79Thomas, C. C., & Philipson, L. H. (2015). Update on Diabetes Classification. Medical Clinics of North America, 99(1), 1-16. doi:10.1016/j.mcna.2014.08.015Kahn, S. 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J., Kumari, M., … Humphries, S. E. (2010). Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study. BMJ, 340(jan14 1), b4838-b4838. doi:10.1136/bmj.b4838Sackett, D. L. (1997). Evidence-based medicine. Seminars in Perinatology, 21(1), 3-5. doi:10.1016/s0146-0005(97)80013-4Segagni, D., Ferrazzi, F., Larizza, C., Tibollo, V., Napolitano, C., Priori, S. G., & Bellazzi, R. (2011). R Engine Cell: integrating R into the i2b2 software infrastructure. Journal of the American Medical Informatics Association, 18(3), 314-317. doi:10.1136/jamia.2010.007914Semantic Webhttp://www.w3.org/2001/sw/Murphy, S. N., Weber, G., Mendis, M., Gainer, V., Chueh, H. C., Churchill, S., & Kohane, I. (2010). Serving the enterprise and beyond with informatics for integrating biology and the bedside (i2b2). 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Simultaneous Pancreas Kidney Transplantation Improves Cardiovascular Autonomic Neuropathy with Improved Valsalva Ratio as the Most Precocious Test

[EN] Background. Simultaneous pancreas-kidney (SPK) transplantation is a proven option of treatment for patients with type 1 diabetes mellitus (T1DM) and related end-stage renal disease. There is discrepancy between the results of different studies about the impact of prolonged normalization of glucose metabolism achieved by SPK on the course of diabetic complications including severe forms of diabetic neuropathy. The objective of the study was to evaluate the prevalence of cardiovascular autonomic neuropathy (CAN) in patients undergoing SPK transplantation and its evolution 10 years after transplantation. Methods. Prospective study of 81 patients transplanted in a single center from year 2002 to 2015. Autonomic function was assessed using cardiovascular autonomic reflex tests (CARTs). CARTs were made before SPK transplantation and during the follow-up. Evolution of tests after SPK transplantation was evaluated by contrasting hypotheses (paired tests). Multiple testing was adjusted with the Benjamini-Hochberg procedure with a false discovery rate of 10%. Results. 48 males and 33 females, mean age 37.4 +/- 5.7 years, mean BMI 24.0 +/- 3.4 kg/m2, and mean duration of diabetes 25.5 +/- 6.5 years, received SPK transplantation. Ten years after SPK transplantation, 56 patients re tained the pancreatic graft (42 of them with normofunctioning pancreas and 14 with low doses of insulin therapy). These 42 patients were selected for the autonomic study. Before transplant procedure, all CART results were abnormal. After SPK transplantation, paired test analysis showed an improvement of systolic blood pressure (SBP) response to orthostasis at the 5(th) year after SPK (p=0.03), as well as improvement of the Valsalva ratio at the 3(rd) (p<0.001) and 5(th) (p=0.001) year after SPK. After correcting for the false discovery rate, all the variables of autonomic study reached significance at different time points. Conclusions. Prevalence of CAN in patients who are candidates for SPK transplantation is high and is generally advanced. SPK transplantation improves CAN with improved Valsalva ratio as the most precocious test.Argente-Pla, M.; Pérez-Lázaro, A.; Martinez-Millana, A.; Del Olmo-García, MI.; Espí-Reig, J.; Beneyto-Castello, I.; López-Andújar, R.... (2020). Simultaneous Pancreas Kidney Transplantation Improves Cardiovascular Autonomic Neuropathy with Improved Valsalva Ratio as the Most Precocious Test. Journal of Diabetes Research. 2020:1-10. https://doi.org/10.1155/2020/7574628S1102020Freeman, R. (2014). Diabetic autonomic neuropathy. Handbook of Clinical Neurology, 63-79. doi:10.1016/b978-0-444-53480-4.00006-0Maser, R. E., Mitchell, B. D., Vinik, A. I., & Freeman, R. (2003). The Association Between Cardiovascular Autonomic Neuropathy and Mortality in Individuals With Diabetes: A meta-analysis. Diabetes Care, 26(6), 1895-1901. doi:10.2337/diacare.26.6.1895Dimitropoulos, G. (2014). Cardiac autonomic neuropathy in patients with diabetes mellitus. World J Diabetes, 5(1), 17. doi:10.4239/wjd.v5.i1.17Vinik, A. I., & Ziegler, D. (2007). Diabetic Cardiovascular Autonomic Neuropathy. Circulation, 115(3), 387-397. doi:10.1161/circulationaha.106.634949Kennedy, W. R., Navarro, X., & Sutherland, D. E. R. (1995). Neuropathy profile of diabetic patients in a pancreas transplantation program. Neurology, 45(4), 773-780. doi:10.1212/wnl.45.4.773Pop-Busui, R., Boulton, A. J. M., Feldman, E. L., Bril, V., Freeman, R., Malik, R. A., … Ziegler, D. (2016). Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care, 40(1), 136-154. doi:10.2337/dc16-2042Balcıoğlu, A. S. (2015). Diabetes and cardiac autonomic neuropathy: Clinical manifestations, cardiovascular consequences, diagnosis and treatment. World Journal of Diabetes, 6(1), 80. doi:10.4239/wjd.v6.i1.80Pop-Busui, R., Low, P. A., Waberski, B. H., Martin, C. L., Albers, J. W., Feldman, E. L., … Herman, W. H. (2009). Effects of Prior Intensive Insulin Therapy on Cardiac Autonomic Nervous System Function in Type 1 Diabetes Mellitus. Circulation, 119(22), 2886-2893. doi:10.1161/circulationaha.108.837369Maser, R. E., Lenhard, J. M., & DeCherney, S. G. (2000). Cardiovascular Autonomic Neuropathy. The Endocrinologist, 10(1), 27-33. doi:10.1097/00019616-200010010-00006Vinik, A. I., Erbas, T., & Casellini, C. M. (2013). Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease. Journal of Diabetes Investigation, 4(1), 4-18. doi:10.1111/jdi.12042Ewing, D. J., Campbell, I. W., Murray, A., Neilson, J. M., & Clarke, B. F. (1978). Immediate heart-rate response to standing: simple test for autonomic neuropathy in diabetes. BMJ, 1(6106), 145-147. doi:10.1136/bmj.1.6106.145In This Issue of Diabetes Care. (2019). Diabetes Care, 43(1), 1-2. doi:10.2337/dc20-ti01Gremizzi, C., Vergani, A., Paloschi, V., & Secchi, A. (2010). Impact of pancreas transplantation on type 1 diabetes-related complications. Current Opinion in Organ Transplantation, 15(1), 119-123. doi:10.1097/mot.0b013e32833552bcKennedy, W. R., Navarro, X., Goetz, F. C., Sutherland, D. E. R., & Najarian, J. S. (1990). Effects of Pancreatic Transplantation on Diabetic Neuropathy. New England Journal of Medicine, 322(15), 1031-1037. doi:10.1056/nejm199004123221503Bouček, P., Bartoš, V., Vaněk, I., Hýža, Z., & Skibová, J. (1991). Diabetic autonomic neuropathy after pancreas and kidney transplantation. Diabetologia, 34(S1), S121-S124. doi:10.1007/bf00587636Navarro, X., Sutherland, D. E. R., & Kennedy, W. R. (1997). Long-term effects of pancreatic transplantation on diabetic neuropathy. Annals of Neurology, 42(5), 727-736. doi:10.1002/ana.410420509Solders, G., Tyden, G., Persson, A., & Groth, C.-G. (1992). Improvement of Nerve Conduction in Diabetic Neuropathy: A Follow-up Study 4 Yr After Combined Pancreatic and Renal Transplantation. Diabetes, 41(8), 946-951. doi:10.2337/diab.41.8.946Argente-Pla, M., Martínez-Millana, A., Del Olmo-García, M. I., Espí-Reig, J., Pérez-Rojas, J., Traver-Salcedo, V., & Merino-Torres, J. F. (2019). Autoimmune Diabetes Recurrence After Pancreas Transplantation: Diagnosis, Management, and Literature Review. Annals of Transplantation, 24, 608-616. doi:10.12659/aot.920106Sundkvist, G., & Lilja, B. (1985). Autonomic Neuropathy in Diabetes Mellitus: A Follow-up Study. Diabetes Care, 8(2), 129-133. doi:10.2337/diacare.8.2.129Boulton, A. J. M., Vinik, A. I., Arezzo, J. C., Bril, V., Feldman, E. L., Freeman, R., … Ziegler, D. (2005). Diabetic Neuropathies: A statement by the American Diabetes Association. Diabetes Care, 28(4), 956-962. doi:10.2337/diacare.28.4.956Ewing, D. J., Martyn, C. N., Young, R. J., & Clarke, B. F. (1985). The Value of Cardiovascular Autonomic Function Tests: 10 Years Experience in Diabetes. Diabetes Care, 8(5), 491-498. doi:10.2337/diacare.8.5.491Spallone, V., Bellavere, F., Scionti, L., Maule, S., Quadri, R., Bax, G., … Morganti, R. (2011). Recommendations for the use of cardiovascular tests in diagnosing diabetic autonomic neuropathy☆. Nutrition, Metabolism and Cardiovascular Diseases, 21(1), 69-78. doi:10.1016/j.numecd.2010.07.005Agashe, S., & Petak, S. (2018). Cardiac Autonomic Neuropathy in Diabetes Mellitus. Methodist DeBakey Cardiovascular Journal, 14(4), 251. doi:10.14797/mdcj-14-4-251Valensi, P., Pariès, J., & Attali, J. . (2003). Cardiac autonomic neuropathy in diabetic patients: influence of diabetes duration, obesity, and microangiopathic complications—the french multicenter study. Metabolism, 52(7), 815-820. doi:10.1016/s0026-0495(03)00095-7Tesfaye, S., Boulton, A. J. M., Dyck, P. J., Freeman, R., Horowitz, M., … Kempler, P. (2010). Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria, Estimation of Severity, and Treatments. Diabetes Care, 33(10), 2285-2293. doi:10.2337/dc10-1303Benjamini, Y., & Hochberg, Y. (1995). Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society: Series B (Methodological), 57(1), 289-300. doi:10.1111/j.2517-6161.1995.tb02031.xAdler, G. K., Bonyhay, I., Failing, H., Waring, E., Dotson, S., & Freeman, R. (2008). Antecedent Hypoglycemia Impairs Autonomic Cardiovascular Function: Implications for Rigorous Glycemic Control. Diabetes, 58(2), 360-366. doi:10.2337/db08-1153HATHAWAY, D. K., ABELL, T., CARDOSO, S., HARTWIG, M. S., GEBELY, S. E., & Gaber, A. O. (1994). IMPROVEMENT IN AUTONOMIC AND GASTRIC FUNCTION FOLLOWING PANCREAS-KIDNEY VERSUS KIDNEY-ALONE TRANSPLANTATION AND THE CORRELATION WITH QUALITY OF LIFE1,2. Transplantation, 57(6), 816-822. doi:10.1097/00007890-199403270-00008Arnold, R., Pussell, B. A., Pianta, T. J., Lin, C. S.-Y., Kiernan, M. C., & Krishnan, A. V. (2013). Association Between Calcineurin Inhibitor Treatment and Peripheral Nerve Dysfunction in Renal Transplant Recipients. American Journal of Transplantation, 13(9), 2426-2432. doi:10.1111/ajt.12324Vinik, A. I., Maser, R. E., Mitchell, B. D., & Freeman, R. (2003). Diabetic Autonomic Neuropathy. Diabetes Care, 26(5), 1553-1579. doi:10.2337/diacare.26.5.1553Suarez, G. A. (2005). Sudden cardiac death in diabetes mellitus: risk factors in the Rochester diabetic neuropathy study. Journal of Neurology, Neurosurgery & Psychiatry, 76(2), 240-245. doi:10.1136/jnnp.2004.039339Dinh, W., Füth, R., Lankisch, M., Bansemir, L., Nickl, W., Scheffold, T., … Ziegler, D. (2010). Cardiovascular autonomic neuropathy contributes to left ventricular diastolic dysfunction in subjects with Type 2 diabetes and impaired glucose tolerance undergoing coronary angiography. Diabetic Medicine, no-no. doi:10.1111/j.1464-5491.2010.03221.xWackers, F. J. T., Young, L. H., Inzucchi, S. E., Chyun, D. A., Davey, J. A., Barrett, E. J., … Iskandrian, A. E. (2004). Detection of Silent Myocardial Ischemia in Asymptomatic Diabetic Subjects: The DIAD study. Diabetes Care, 27(8), 1954-1961. doi:10.2337/diacare.27.8.1954Astrup, A. S., Tarnow, L., Rossing, P., Hansen, B. V., Hilsted, J., & Parving, H.-H. (2006). Cardiac Autonomic Neuropathy Predicts Cardiovascular Morbidity and Mortality in Type 1 Diabetic Patients With Diabetic Nephropathy. Diabetes Care, 29(2), 334-339. doi:10.2337/diacare.29.02.06.dc05-1242Pop-Busui, R., Evans, G. W., Gerstein, H. C., Fonseca, V., Fleg, J. L., … Hoogwerf, B. J. (2010). Effects of Cardiac Autonomic Dysfunction on Mortality Risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial. Diabetes Care, 33(7), 1578-1584. doi:10.2337/dc10-0125Kempler, P., Tesfaye, S., Chaturvedi, N., Stevens, L. K., Webb, D. J., … Eaton, S. (2002). Autonomic neuropathy is associated with increased cardiovascular risk factors: the EURODIAB IDDM Complications Study. Diabetic Medicine, 19(11), 900-909. doi:10.1046/j.1464-5491.2002.00821.xPop-Busui, R., Cleary, P. A., Braffett, B. H., Martin, C. L., Herman, W. H., Low, P. A., … Bluemke, D. A. (2013). Association Between Cardiovascular Autonomic Neuropathy and Left Ventricular Dysfunction. Journal of the American College of Cardiology, 61(4), 447-454. doi:10.1016/j.jacc.2012.10.02

Neuropatía autonómica cardiovascular en pacientes diabéticos sometidos a trasplante simultáneo páncreas-riñón

El trasplantament simultani de pàncrees i ronyó (SPK) és una alternativa terapèutica en pacients amb DM-1 i nefropatía diabètica terminal. No obstant això, les complicacions cròniques derivades de la DM solen estar molt avançades al moment de la realització del trasplantament. L'objectiu del treball és estudiar la neuropatía diabètica (somàtica i autonòmica) en pacients candidats a trasplantament SPK a la Comunitat Valenciana i valorar l'evolució de la mateixa al cap de 3 i 5 anys del trasplantament, prestant especial atenció a aquells pacients en els quals s'aconsegueix un estat de normoglucemia després del trasplantamentEl trasplante simultáneo de páncreas y riñón (SPK) es una alternativa terapéutica en pacientes con DM-1 con nefropatía diabética terminal. Sin embargo, las complicaciones crónicas de su DM suelen estar muy avanzadas en el momento de la realización del trasplante. El objetivo del trabajo es estudiar la neuropatía diabética (somática y autonómica) en pacientes candidatos a trasplante SPK en la Comunidad Valenciana y valorar la evolución de la misma al cabo de 3 y 5 años del trasplante, prestando especial atención a aquellos pacientes en los que se consigue un estado de normoglucemia tras el trasplante

Resultados del trasplante de páncreas en pacientes con diabetes mellitus tipo 1 en la Comunidad Valenciana

Compendi d'articlesLa hiperglucemia crónica característica de la diabetes mellitus(DM) se asocia, a largo plazo,con la aparición de complicaciones que van a disminuir la calidad y esperanza de vida del paciente. Existen diversos tipos de tratamiento para la DM encaminados a conseguir un buen control glucémico y a evitar las complicaciones crónicas.El tratamiento insulínico intensificado consigue un mejor control glucémico pero a expensas de un mayor número de episodios hipoglucémicos,que aumentan la morbi-mortalidad de estos pacientes. Actualmente, el trasplante de páncreas es el único tratamiento que restablece el estado de euglucemia sin aumentar el riesgo de hipoglucemias.También reduce los factores de riesgo cardiovascular, mejora la función cardiaca y reduce la mortalidad,aumentando la calidad de vida de estos pacientes. La presente tesis doctoral se basa en un compendio de tres publicaciones científicas.El objetivo general es estudiar la evolución de los pacientes con DM-1 sometidos a trasplante simultáneo de páncreas-riñón en la Comunidad Valenciana.The chronic hyperglycemia characteristic of Diabetes mellitus(DM) is associated,in the long term,with the appearance of complications, which will decrease the patient’ quality and life expectancy. There are several types of treatment for DM, aimed at achieving good glycemic control and avoiding chronic complications.Intensified insulin therapy achieves better glycemic control, but it is at the expense of a greater number of hypoglycemic episodes, which increase the morbidity and mortality of these patients. Pancreas transplantation is currently the only treatment capable of restoring euglycemia without increasing the risk of hypoglycemia. It has also been shown to reduce cardiovascular risk factors, improve cardiac function and reduce mortality, increasing the quality of life of these patients. This doctoral thesis is based on a compendium of three scientific publications. The general purpose is to study the evolution of type 1 DM patients undergoing simultaneous pancreas-kidney transplantation in the Comunidad Valenciana.Programa de Doctorat en Ciències Biomèdiques i Salu

Driving Type 2 Diabetes Risk Scores into Clinical Practice: Performance Analysis in Hospital Settings

Electronic health records and computational modelling have paved the way for the development of Type 2 Diabetes risk scores to identify subjects at high risk. Unfortunately, few risk scores have been externally validated, and their performance can be compromised when routine clinical data is used. The aim of this study was to assess the performance of well-established risk scores for Type 2 Diabetes using routinely collected clinical data and to quantify their impact on the decision making process of endocrinologists. We tested six risk models that have been validated in external cohorts, as opposed to model development, on electronic health records collected from 2008-2015 from a population of 10,730 subjects. Unavailable or missing data in electronic health records was imputed using an existing validated Bayesian Network. Risk scores were assessed on the basis of statistical performance to differentiate between subjects who developed diabetes and those who did not. Eight endocrinologists provided clinical recommendations based on the risk score output. Due to inaccuracies and discrepancies regarding the exact date of Type 2 Diabetes onset, 76 subjects from the initial population were eligible for the study. Risk scores were useful for identifying subjects who developed diabetes (Framingham risk score yielded a c-statistic of 85%), however, our findings suggest that electronic health records are not prepared to massively use this type of risk scores. Use of a Bayesian Network was key for completion of the risk estimation and did not affect the risk score calculation (p &gt; 0.05). Risk score estimation did not have a significant effect on the clinical recommendation except for starting pharmacological treatment (p = 0.004) and dietary counselling (p = 0.039). Despite their potential use, electronic health records should be carefully analyzed before the massive use of Type 2 Diabetes risk scores for the identification of high-risk subjects, and subsequent targeting of preventive actions

Autoimmune Diabetes Recurrence After Pancreas Transplantation: Diagnosis, Management, and Literature Review

[EN] Background: Pancreas transplantation can be a viable treatment option for patients with type 1 diabetes mellitus (T1DM), especially for those who are candidates for kidney transplantation. T1DM may rarely recur after pancreas transplantation, causing the loss of pancreatic graft. The aim of this study was to describe the prevalence of T1DM recurrence after pancreas transplantation in our series. Material/Methods: Eighty-one patients transplanted from 2002 to 2015 were included. Autoantibody testing (GADA and IA-2) was performed before pancreas transplantation and during the follow-up. Results: The series includes 48 males and 33 females, mean age 37.4+5.7 years and mean duration of diabetes 25.5 +/- 6.5 years. Patients received simultaneous pancreas kidney (SPK) transplantation. After SPK transplantation, 56 patients retained pancreatic graft, 8 patients died, and 17 patients lost their pancreatic graft. T1DM recurrence occurred in 2 of the 81 transplanted patients, yielding a prevalence of 2.5%, with an average time of appearance of 3.3 years after transplant. Pancreatic enzymes were normal in the 2 patients, ruling out pancreatic rejection. T1DM recurrence was confirmed histologically, showing selective lymphoid infiltration of the pancreatic islets. Conclusions: T1DM recurrence after pancreas transplantation is infrequent; however, it is one of the causes of pancreatic graft loss that should always be ruled out. Negative autoimmunity prior to transplantation does not ensure that T1DM does not recur.Argente-Pla, M.; Martinez-Millana, A.; María Isabel Del Olmo-García; Espí-Reig, J.; Pérez-Rojas, J.; Traver Salcedo, V.; Merino-Torres, JF. (2019). Autoimmune Diabetes Recurrence After Pancreas Transplantation: Diagnosis, Management, and Literature Review. Annals of Transplantation. 24:608-616. https://doi.org/10.12659/AOT.920106S6086162