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

Evaluation of microvascular changes in the perifoveal vascular network using optical coherence tomography angiography (OCTA) in type I diabetes mellitus: a large scale prospective trial

Background: Diabetic retinopathy (DR) is the leading cause of blindness in type 1 Diabetes Mellitus (DM) patients, as a consequence of impaired blood flow in the retina. Optical coherence tomography angiography (OCTA) is a newly developed, non-invasive, retinal imaging technique that permits adequate delineation of the perifoveal vascular network. It allows the detection of paramacular areas of capillary non perfusion and/or enlargement of the foveal avascular zone (FAZ), representing an excellent tool for assessment of DR. The relationship of these microvascular changes with systemic factors such as metabolic control or duration of the disease still needs to be elucidated. Methods: Prospective, consecutive, large-scale OCTA study. A complete ocular examination including a comprehensive series of OCTA images of different scan sizes captured with 2 OCT devices (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA, USA, and Triton Deep Range Imaging OCT, Topcon Corp, Topcon, Japan) will be obtained as part of the yearly routine follow up visits in type 1 DM patients seen in the Diabetes Unit of the Endocrinology department which give written informed consent to participate in the project. The aim of this study is to investigate the relationship between OCTA-derived parameters and systemic factors, as metabolic control (Hb1Ac, lipid profile, cholesterol, etc), and other relevant clinical factors as demographics or duration of the disease. Discussion: This study is directed to investigate the relationship between the status of the perifoveal vascular network and systemic markers of the disease, and in particular to study whether these changes reflect those occurring elsewhere in the body affected by diabetic microvascular disease, as the kidneys or the brain. If these relationships were demonstrated, early detection of these microvascular changes by OCTA could lead to modifications in the pharmacological management of type 1 diabetic patients, as a way to reduce the risk of future complications in both the eye and other organs

Advanced lipoprotein profle disturbances in type 1 diabetes mellitus: a focus on LDL particles

Background: Lipoprotein disturbances have been associated with increased cardiovascular disease (CVD) risk in type 1 diabetes mellitus (T1DM). We assessed the advanced lipoprotein profle in T1DM individuals, and analysed diferences with non-diabetic counterparts. Methods: This cross-sectional study involved 508 adults with T1DM and 347 controls, recruited from institutions in a Mediterranean region of Spain. Conventional and advanced (assessed by nuclear magnetic resonance [NMR] spectroscopy) lipoprotein profles were analysed. Crude and adjusted (by age, sex, statin use, body mass index and leukocyte count) comparisons were performed. Results: The median (interquartile range) age of the study participants was 45 (38–53) years, 48.2% were men. In the T1DM group, the median diabetes duration was 23 (16–31) years, and 8.1% and 40.2% of individuals had nephropathy and retinopathy, respectively. The proportion of participants with hypertension (29.5 vs. 9.2%), and statin use (45.7% vs. 8.1%) was higher in the T1DM vs. controls (p<0.001). The T1DM group had a better conventional (all parameters, p<0.001) and NMR-lipid profle than the control group. Thus, T1DM individuals showed lower concentrations of atherogenic lipoproteins (VLDL-particles and LDL-particles) and higher concentrations of anti-atherogenic lipoproteins (HDL-particles) vs. controls, even after adjusting for several confounders (p<0.001 for all). While non-diabetic women had a more favourable lipid profle than non-diabetic men, women with T1DM had a similar concentration of LDL-par‑ ticles compared to men with T1DM (1231 [1125–1383] vs. 1257 [1128–1383] nmol/L, p=0.849), and a similar concentration of small-LDL-particles to non-diabetic women (672.8 [614.2–733.9] vs. 671.2 [593.5–761.4] nmol/L, respectively; p=0.790). Finally, T1DM individuals showed higher discrepancies between NMR-LDL-particles and conventional LDLcholesterol than non-diabetic subjects (prevalence of LDL-cholesterol1000 nmol/L: 38 vs. 21.2%; p<0.001). All these diferences were largely unchanged in participants without lipid-lowering drugs (T1DM, n=275; controls, n=317).This research was supported by grants from the Carlos III National Institute of Health (PI12/0183 and PI15/0625). CIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM) and CIBER on Pathophysiology of Obesity and Nutrition (CIBEROBN) are initiatives of ISCIII, Spain. AJA received a research grant from the Associació Catalana de Diabetis (ACD), “Ajut per a la recerca en diabetis modalitat clínica 2018”

Optical Coherence Tomography Angiography in Type 1 Diabetes Mellitus-Report 2: Diabetic Kidney Disease.

The purpose of this study is to investigate potential associations between optical coherence tomography angiography (OCTA) parameters and diabetic kidney disease (DKD) categories in type 1 diabetes mellitus (T1DM) patients and controls. A complete ocular and systemic examination, including OCTA imaging tests and bloods, was performed. OCTA parameters included vessel density (VD), perfusion density (PD), foveal avascular zone area (FAZa), perimeter (FAZp) and circularity (FAZc) in the superficial vascular plexus, and DKD categories were defined according to glomerular filtration rate (GFR), albumin-creatinine ratio (ACR) and KDIGO prognosis risk classifications. A total of 425 individuals (1 eye/1 patient) were included. Reduced VD and FAZc were associated with greater categories of GFR (p = 0.002, p = 0.04), ACR (p = 0.003, p = 0.005) and KDIGO risk prognosis classifications (p = 0.002, p = 0.005). FAZc was significantly reduced in greater KDIGO prognosis risk categories (low risk vs. moderate risk, 0.65 ± 0.09 vs. 0.60 ± 0.07, p < 0.05). VD and FAZc presented the best diagnostic performance in ROCs. In conclusion, OCTA parameters, such as VD and FAZc, are able to detect different GFR, ACR, and KDIGO categories in T1DM patients and controls in a non-invasive, objective quantitative way. FAZc is able to discriminate within T1DM patients those with greater DKD categories and greater risk of DKD progression

Validation of Backtable Graft Arterial Anastomosis Between Splenic Artery and Superior Mesenteric Artery: A 21-year Single-center Experience of Pancreas Transplantation

Resumen del trabajo presentado en el IPITA 2021 VIRTUAL CONGRESS, celebrado de forma virtual del 20 al 23 de octubre de 2021Aim: To determine the role of the arterial spleno-mesenteric anastomosis reconstruction technique compared to other types of backtable arterial anastomosis, in terms of vascular complications and long-term patient and graft survival in a single institution. Methods: Retrospective analysis including all pancreas transplants performed over 21 years (1999–2019). For the bench reconstruction: (1) the distal superior mesenteric artery (SMA) was distally dissected and sewn to the splenic artery (SA), or (2) the arteries were reconstructed with an iliac arterial “Y” graft. Results: A total of 412 pancreas transplantations were done. At the bench procedure SMA/SA anastomosis was performed in 376 of patients, arterial iliac “Y” graft in 32 of patients, and no arterial reconstruction was required in 4 of patients. A total of 90 patients presented vascular complications within the 30 days following transplant: (venous (n=64), arterial (n=11), both (n=15), without statistically significant differences between the SMA/SA anastomosis group and others. Regarding acute arterial events:(1) for the SMA/SA anastomosis group, a total of 24 patients presented with thrombosis (n=16), stenosis (n=5), pseudoaneurysm (n=2); (2) for the iliac “Y” graft group, there were 3 patients with thrombosis. Focusing on chronic arterial events:(1)for the SMA/SA anastomosis group, a total of 2 patients presented with chronic thrombosis, 2 with pseudoaneurysm, 2 with arterioenteral fistula and one with arteriovenous fistula;(2)for the iliac “Y” graft group, and one patient with arterioenteral fistula. After a median follow-up of 129.2 [77.2–182] months, no statically differences were found between SMA/SA anastomosis and iliac “Y” graft arterial reconstruction groups at 1, 3, 5 and 10 years in terms of patient and graft survival. Conclusions: The back table procedure used in our institution (SMA/SA) is an easy, effective and safe surgical technique that can be used as the first option for arterial reconstruction or as a good alternative for surgeons to the widely used arterial “Y” graft.Peer reviewe

Patients' and physicians' preferences for type 2 diabetes mellitus treatments in Spain and Portugal: a discrete choice experiment

Objective To assess Spanish and Portuguese patients’ and physicians’ preferences regarding type 2 diabetes mellitus (T2DM) treatments and the monthly willingness to pay (WTP) to gain benefits or avoid side effects. Methods An observational, multicenter, exploratory study focused on routine clinical practice in Spain and Portugal. Physicians were recruited from multiple hospitals and outpatient clinics, while patients were recruited from eleven centers operating in the public health care system in different autonomous communities in Spain and Portugal. Preferences were measured via a discrete choice experiment by rating multiple T2DM medication attributes. Data were analyzed using the conditional logit model. Results Three-hundred and thirty (n=330) patients (49.7% female; mean age 62.4 [SD: 10.3] years, mean T2DM duration 13.9 [8.2] years, mean body mass index 32.5 [6.8] kg/m2, 41.8% received oral + injected medication, 40.3% received oral, and 17.6% injected treatments) and 221 physicians from Spain and Portugal (62% female; mean age 41.9 [SD: 10.5] years, 33.5% endocrinologists, 66.5% primary-care doctors) participated. Patients valued avoiding a gain in bodyweight of 3 kg/6 months (WTP: €68.14 [95% confidence interval: 54.55–85.08]) the most, followed by avoiding one hypoglycemic event/month (WTP: €54.80 [23.29–82.26]). Physicians valued avoiding one hypoglycemia/week (WTP: €287.18 [95% confidence interval: 160.31–1,387.21]) the most, followed by avoiding a 3 kg/6 months gain in bodyweight and decreasing cardiovascular risk (WTP: €166.87 [88.63–843.09] and €154.30 [98.13–434.19], respectively). Physicians and patients were willing to pay €125.92 (73.30–622.75) and €24.28 (18.41–30.31), respectively, to avoid a 1% increase in glycated hemoglobin, and €143.30 (73.39–543.62) and €42.74 (23.89–61.77) to avoid nausea. Conclusion Both patients and physicians in Spain and Portugal are willing to pay for the health benefits associated with improved diabetes treatment, the most important being to avoid hypoglycemia and gaining weight. Decreased cardiovascular risk and weight reduction became the third most valued attributes for physicians and patients, respectively

Patient Experience in Pancreas-Kidney Transplantation-A Methodological Approach Towards Innovation in an Established Program

Simultaneous pancreas-kidney transplantation (SPKT) leads to increased survival and quality of life, and is an alternative treatment for insulin-dependent diabetes mellitus and end-stage kidney disease. Due to the particularities of this population (often with multiple comorbidities) and of the surgery (only performed in a few centers), a comprehensive analysis of patients' experience along the SPKT process is crucial to improve patient care and add value to this procedure. Therefore, we applied a systematic and iterative methodology with the participation of both patients and professional teams working together to explore and identify unmet needs and value-adding steps along the transplant patient journey at an established pancreas transplant program. Four main steps (to comprehend, to explore, to experiment and to assess) led to several interventions around three major areas: Administration and logistics, information and communication, and perceived quality of assistance. As a result, both displacements to the hospital for diagnostic purposes and the time delay involved in joining the patient waiting list for transplantation were reduced in parallel to the administrative procedures. In conclusion, the methodological implementation of key organizational changes has great impact on overall patient experience. Further quantitative analysis from the patient's perspective will consolidate our program and may add new prototype service design components

Impact of Achieved Blood Pressure on Cardiovascular Outcomes in the Irbesartan Diabetic Nephropathy Trial

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Consensus document for the detection and management of chronic kidney disease.

Chronic kidney disease (CKD) is a major public health problem that, in its different stages, may affect up to 10% of the Spanish population and results in high morbidity and mortality, as well as high consumption of National Health System resources. Ten scientific societies involved in the management of kidney patients agreed to update the 2007 CKD consensus document. The current version is an abridged edition of the detailed general document, which can be consulted on the webpages of each signatory society. It includes the following aspects: CKD definition, epidemiology and risk factors and criteria on diagnosis, assessment and staging of CKD, albuminuria and glomerular filtration estimation. Progression factors and concept. Criteria for referral to Nephrology. Patient follow-up, attitudes and objectives by specialty. Prevention of nephrotoxicity. Detection of cardiovascular damage. Attitudes, lifestyle and treatment: management of high blood pressure, dyslipidaemia, hyperglycaemia, smoking, obesity, hyperuricaemia, anaemia and mineral and bone metabolism disorders. Coordinated follow-up by Primary Care - other specialties - Nephrology. Management of renal replacement therapy, haemodialysis, peritoneal dialysis and renal transplantation patients. Palliative treatment of terminal uraemia. We hope that this document will be very useful in the multidisciplinary management of CKD patients, in view of the updated recommendations