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

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

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

Renoprotective effect of the angiotensin-receptro antagonist ibersartan in patients with nephropathy due to type 2 diabetes

Background: It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure. Methods: We randomly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan (300 mg daily), amlodipine (10 mg daily), or placebo. The target blood pressure was 135/85 mm Hg or less in all groups. We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration, the development of end-stage renal disease, or death from any cause. We also compared them with regard to the time to a secondary, cardiovascular composite end point. Results: The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group (P=0.02) and 23 percent lower than that in the amlodipine group (P=0.006). The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group (P=0.003) and 37 percent lower in the irbesartan group than in the amlodipine group (P<0.001). Treatment with irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups (P=0.07 for both comparisons). These differences were not explained by differences in the blood pressures that were achieved. The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group (P=0.008) and 21 percent more slowly than in the amlodipine group (P=0.02). There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point. Conclusions: The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes. This protection is independent of the reduction in blood pressure it causes

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

Preemptive simultaneous pancreas kidney transplantation has survival benefit to patients

Several organ allocation protocols give priority to wait-listed simultaneous kidney-pancreas (SPK) transplant recipients to mitigate the higher cardiovascular risk of patients with diabetes mellitus on dialysis. The available information regarding the impact of preemptive simultaneous kidney-pancreas transplantation on recipient and graft outcomes is nonetheless controversial. To help resolve this, we explored the influence of preemptive simultaneous kidney-pancreas transplants on patient and graft survival through a retrospective analysis of the OPTN/UNOS database, encompassing 9690 simultaneous transplant recipients between 2000 and 2017. Statistical analysis was performed applying a propensity score analysis to minimize bias. Of these patients, 1796 (19%) were transplanted preemptively. At ten years, recipient survival was significantly superior in the preemptive group when compared to the non-preemptive group (78.9% vs 71.8%). Dialysis at simultaneous kidney-pancreas transplantation was an independent significant risk for patient survival (hazard ratio 1.66 [95% confidence interval 1.32-2.09]), especially if the dialysis duration was 12 months or longer. Preemptive transplantation was also associated with significant superior kidney graft survival compared to those on dialysis (death-censored: 84.3% vs 75.4%, respectively; estimated half-life of 38.57 [38.33 -38.81] vs 22.35 [22.17 - 22.53] years, respectively). No differences were observed between both groups neither for pancreas graft survival nor for post-transplant surgical complications. Thus, our results sustain the relevance of early referral for pancreas transplantation and the importance of pancreas allocation priority in reducing patient mortality after simultaneous kidney-pancreas transplantation

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

The efficiency of telemedicine to optimize metabolic control in patients with type 1 diabetes mellitus: Telemed study

Objective: This study evaluated the impact of an Internet-based telematic system on the economic and clinical management of patients with type 1 diabetes mellitus. Research Design and Methods: This 6-month prospective, randomized, comparative, open, multicenter study included patients with type 1 diabetes >18 years old treated with multiple insulin doses and with a glycated hemoglobin (HbA1c) level of >8%. We compared an intervention group (IG) (two face-to-face and five telematic appointments) with a control group (CG) (seven face-to-face appointments). The variables studied were (1) patient and healthcare team costs, (2) metabolic control, (3) knowledge of diabetes, (4) quality of life, and (5) self-care treatment adherence. Results: Of the 154 patients included, 118 (76.6%) completed the study (IG, 54; CG, 64). The time used by the CG to follow the program was 823±645 min versus 353±222 min in the IG (P<0.0001). Compared with the CG, the IG required less healthcare time from the professionals (288±105 min vs. 232±89 min; P<0.001). HbA1c improved in both groups (IG, 9.2±1.5% [77.0±17.0 mmol/mol] vs. 8.7±1.5% [71.6±17.0 mmol/mol] [P<0.001]; CG, 9.2±0.9% [77.0±10.0 mmol/mol] vs. 8.6±0.9% [70.5±10.0 mmol/mol] [P<0.001], as did knowledge and self-care treatment adherence. Conclusions: The use of interactive telematic appointments in subjects with type 1 diabetes and inadequate metabolic control is an efficient strategy, providing results comparable to those of face-to-face appointments in relation to improvement in glycemic control, knowledge acquisition, and self-care treatment adherence, with a significant reduction in the time used, especially by patients