Severe hypoglycemia and hypoglycemia awareness are associated with preclinical atherosclerosis in patients with type 1 diabetes without an estimated high cardiovascular risk.

AIMS: To explore the relationship between severe hypoglycemia (SH) and hypoglycemia awareness with preclinical atherosclerosis in type 1 diabetes (T1D). MATERIALS AND METHODS: Cross-sectional study in patients with T1D without cardiovascular disease (CVD), and with ≥1 of the following: ≥40 years, diabetic kidney disease, or ≥10 years of T1D duration with another risk factor. CVD risk was estimated with the Steno T1 Risk Engine (Steno-Risk). Carotid plaque was evaluated using standardised ultrasonography protocol. Logistic regression models adjusted for CVD risk factors were constructed to test the independent associations with SH or hypoglycemia awareness assessed by the Clarke questionnaire (Clarke). The inclusion of SH and Clarke in Steno-Risk was further evaluated. RESULTS: We included 634 patients (52.4% men, age 48.3 ± 10.8 years, T1D duration 27.4 ± 11.1 years, 39.9% harbouring plaque). A stepped increase in the presence of plaque according to Steno-Risk was observed (13.5%, 37.7%, and 68.7%, for low, moderate, and high risk, respectively; p < 0.001). SH history (OR 4.4 [1.3-14.6]) and Clarke score (OR 1.7 [1.2-2.2]) were associated with plaque in low-risk patients (n = 192). Clarke score was also associated with plaque burden in low-moderate-risk participants (n = 436; ≥2 plaques: OR 1.2 [1.0-1.5], p = 0.031; ≥3 plaques: OR 1.4 [1.1-2.0], p = 0.025). The inclusion of SH and Clarke scores in Steno-Risk significantly improved the identification of low-risk individuals with atherosclerosis (area under the curve: 0.658 vs. 0.576; p = 0.036). CONCLUSIONS: In patients with T1D without an estimated high CVD risk, SH and hypoglycemia awareness assessment score were independently associated with preclinical atherosclerosis and improved identification of patients who would benefit from an intensive approach.

Adherence to an energy-restricted Mediterranean diet is associated with the presence and burden of carotid atherosclerosis in people with type 1 diabetes.

AIMS: People with type 1 diabetes (T1D) have an increased risk of cardiovascular disease (CVD). The Mediterranean diet is associated with reduced CVD; however, the evidence in T1D is scarce. We aimed to analyse the relationships between adherence to the energy-restricted Mediterranean diet (erMEDd) and carotid atherosclerosis. MATERIALS AND METHODS: We included children with T1D without CVD, with ≥1 of the following: age ≥40 years, diabetic kidney disease, or ≥10 years of disease duration with another risk factor. Plaque presence (intima-media thickness ≥1.5 mm) was determined by ultrasonography. The PREDIMED-Plus 17-item questionnaire (PP-17) was used to assess adherence to the erMEDd. RESULTS: Four hundred one individuals were included (48% males, age 48.3 ± 11 years, diabetes duration 26.8 ± 11.4 years). Those harbouring plaques (42%) showed lower adherence to the erMEDd (PP-17: 8.9 ± 2.3 of a maximum of 17 vs. 9.8 ± 2.5, p < 0.001). Greater adherence to the erMEDd was correlated with an overall better metabolic profile. After adjusting for multiple confounders, adherence to the erMEDd was independently associated with carotid atherosclerosis (OR 0.86 [0.77-0.95] for plaque presence and OR 0.85 [0.75-0.97] for ≥2 plaques). The consumption of fruit and nuts and preference of white over red meat was higher in individuals without atherosclerosis (p < 0.05). Fruit and nut consumption was associated with lower plaque prevalence in the fully adjusted models (OR 0.38 [0.19-0.73] and 0.51 [0.29-0.93]). CONCLUSIONS: Greater adherence to the erMEDd is associated with less carotid atherosclerosis in children with T1D at high risk of CVD. Strategies to improve and implement healthy dietary patterns in this population should be encouraged.

Neutrophil-to-lymphocyte ratio is independently associated with carotid atherosclerosis burden in individuals with type 1 diabetes.

BACKGROUND AND AIMS: Recent studies have identified a relationship between innate versus. Adaptative immunity and cardiovascular disease (CVD) in the general population, but information on type 1 diabetes (T1D) is lacking. We aimed to study the relationship between inflammatory biomarkers and preclinical atherosclerosis in this population. METHODS AND RESULTS: Cross-sectional study in T1D individuals without CVD and with ≥1 of the following: ≥40 years, diabetic kidney disease, or ≥10 years of diabetes duration with classical CVD risk factors. Carotid plaques were evaluated by ultrasonography. C-reactive protein, total leukocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio and systemic immune-inflammation index were assessed as inflammatory markers. Multivariate-adjusted models including age, sex, and other CVD risk factors were constructed to test their independent associations with atherosclerosis burden. We included 602 subjects (52.8% men, 48.7 ± 10.2 years old and 27.0 ± 10.5 years of diabetes duration). Carotid plaques were found in 41.2% of the individuals (12.8%, ≥3 plaques). The number of carotid plaques (none, 1-2, ≥3 plaques), was directly associated with the leukocyte count (6570 [5445-8050], 6640 [5450-8470] and 7310 [5715-8935] per mm3, respectively; p for trend = 0.021) and the NLR (1.63 [1.28-2.13], 1.78 [1.38-2.25] and 2.14 [1.58-2.92], respectively; p for trend <0.001), but only the NLR remained directly associated in fully-adjusted models (presence of plaques; OR 1.285 [1.040-1.587]; ≥3 plaques, OR 1.377 [1.036-1.829]). CONCLUSIONS: The NLR was independently and directly associated with carotid plaque burden in T1D individuals. Our data support the role of innate versus. Adaptative immunity in atherosclerosis also among the T1D population.

Validation of the Back-table Graft Arterial Anastomosis between the Splenic Artery and Superior Mesenteric Artery: Arterial Complications after a 21-year Single-center Experience of Pancreas Transplantation.

OBJECTIVE: To determine the role of the arterial splenomesenteric anastomosis (ASMA) vascular reconstruction technique in terms of arterial vascular complications in pancreas transplant (PT) recipients. SUMMARY BACKGROUND DATA: The ASMA technique was first described in 1992 by Hospital Clínic Barcelona group. Regardless that the iliac Y-graft technique is the most frequently used worldwide, evidence of arterial complications and implications of using a different back-table reconstruction is conspicuously absent in the literature. METHODS: Descriptive review of 407 PTs performed at a single center (1999-2019) by analyzing the type of arterial reconstruction technique, focusing on ASMA. The endpoints were the management of arterial complications and long-term patient and graft survival. RESULTS: ASMA was performed in 376 cases (92.4%) and a Y-graft in 31 cases (7.6%). A total of 34 arterial complications (8.3%) were diagnosed. In the ASMA group (n=30, 7.9%) they comprised: 15 acute thrombosis; 4 stenosis; 1 pseudoaneurysm and 10 diverse chronic arterial complications while in the Y-graft group (n=4, 12.9%) 3 acute thrombosis and 1 chronic artery-duodenal fistula occurred. Graft salvage was achieved in 16 patients (53.3%) from the ASMA group and in 2 (50%) from the Y-graft. After a median follow-up of 129.2 (IQR 25-75%, 77.2 -182) months the overall graft and patient survival for the whole cohort at 1, 5, and 10 years was 86.7%, 79.5%, 70.5%, and 98.5%, 95.3%, 92.5%, respectively. CONCLUSIONS: The ASMA proves to be a safe and more easily reproducible technique and should therefore be considered for first-line back-table reconstruction in the PT population.

Advanced lipoprotein profile identifies atherosclerosis better than conventional lipids in type 1 diabetes at high cardiovascular risk.

BACKGROUND AND AIMS: People with type 1 diabetes (T1D) present lipoprotein disturbances that could contribute to their increased cardiovascular disease (CVD) risk. We evaluated the relationship between lipoprotein alterations and atherosclerosis in patients with T1D. METHODS AND RESULTS: Cross-sectional study in subjects with T1D, without previous CVD, but high-risk (≥40 years, nephropathy, or ≥10 years of evolution of diabetes with another risk factor). The presence of plaque (intima-media thickness ≥1.5 mm) in the different carotid segments was determined by ultrasound. The advanced lipoprotein profile was analysed by magnetic resonance imaging (1H NMR). We included 189 patients (42% women, 47.8 ± 10.7 years, duration of diabetes 27.3 ± 10.1 years, HbA1c 7.5% [7-8]). Those with carotid plaques (35%) were older, with longer diabetes duration, had a higher prevalence of hypertension, and showed lower and smaller LDL particles (LDL-P) and HDL particles (HDL-P), but higher VLDL particles (VLDL-P). Some LDL, HDL and VLDL-related parameters were associated with atherosclerosis in sex, age and statin use adjusted models (p < 0.05), but after adjusting for multiple confounders, including conventional lipid parameters, only HDL-P (OR 0.440 [0.204-0.951]; p = 0.037), medium HDL-P (OR 0.754 [0.590-0.963]; p = 0.024), HDL-P cholesterol content (OR 0.692 [0.495-0.968]; p = 0.032), 1H NMR LDL-P number/conventional LDL-cholesterol (OR 1.144 [1.026-1.275]; p = 0.015), and 1H NMR non-HDL particle number/conventional non-HDL-cholesterol ratios (OR 1.178 [1.019-1.361], p = 0.026) remained associated with atherosclerosis. CONCLUSIONS: In adults with T1D at high-risk, variables related to HDL, LDL and total atherogenic particle number are independently associated with preclinical atherosclerosis. Advanced lipoprotein profiling could be used to identify those at the highest risk of CVD.

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.

Current Trends in Organ Preservation Solutions for Pancreas Transplantation: A Single-Center Retrospective Study.

Due to the high vulnerability of the pancreas to ischemia-reperfusion injury, choices regarding preservation solution markedly affect pancreas transplant success. A retrospective single-center analysis of 380 pancreas transplants (2000-2019) was performed to correlate current preservation solutions with transplant outcomes. Early graft failure requiring transplantectomy within 30 days post-transplant occurred in 7.5% for University of Wisconsin (UW) group (n = 267), 10.8% of Celsior (CS) group (n = 83), 28.5% of Histidine-Tryptophan-Ketoglutarate (HTK) group (n = 7), and none for Institut Georges Lopez-1 (IGL-1) group (n = 23). The most common causes of technical failures in this cohort included abdominal hemorrhage (8.4%); graft pancreatitis (3.7%); fluid collections (2.6%); intestinal complications (6.6%); and vascular thrombosis (20.5%). Although IGL-1 solution provided lower surgical complication rates, no significant differences were found between studied groups. Nevertheless, HTK solution was associated with elevated pancreatitis rates. The best graft survival was achieved at 1 year using UW and IGL-1, and at 3 and 5 years using IGL-1 (p = 0.017). There were no significant differences in patient survival after a median follow-up of 118.4 months. In this setting therefore, IGL-1 solution appears promising for perfusion and organ preservation in clinical pancreas transplantation, compared to other commonly used solutions.

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.

Outcomes From Brain Death Donors With Previous Cardiac Arrest Accepted for Pancreas Transplantation: A Single-center Retrospective Analysis.

OBJECTIVE: The aim of the study was to evaluate the effect of cardiac arrest time (CAT) in donors after brain death (DBD) donors on pancreas transplant outcome. SUMMARY OF BACKGROUND DATA: Results from donors after circulatory death report good outcomes despite warm ischemia times up to 57 minutes. Previous cardiac arrest in DBD has been addressed as a potential risk factor, but duration of the CAT has never been evaluated. METHODS: We conducted a retrospective analysis including 342 pancreas transplants performed at our center from 2000 to 2016, and evaluated the effect of previous cardiac arrest in DBD (caDBD) on pancreas transplant outcomes. RESULTS: A total of 49 (14.3%) caDBD were accepted for transplantation [median CAT of 5.0 min (IQR 2.5-15.0)]. Anoxic encephalopathy was most frequent and P-PASS higher (16.9 vs 15.6) in caDBD group when compared with other DBD. No differences were found in all other characteristics evaluated.Graft survival was similar between both groups, as was the incidence of early graft failure (EGF). CAT increased the risk for EGF [OR 1.09 (95% CI, 1.01-1.17)], and the duration of CPR discriminated for EGF [AUC of 0.86 (95% CI, 0.74-0.98)], with a sensitivity and specificity of 100% and 75% at a cutoff of 15 minutes. When evaluated separately, caDBD >15 min increased over 5 times the risk for EGF [HR 5.80 (95% CI, 1.82-18.56); P = 0.003], and these presented fewer days on the ICU (1.0 vs 3.0 d). CONCLUSION: CaDBD donors are suitable for routine pancreas transplantation without increasing EGF risk, and in those with longer CAT it may be prudent to postpone donation a few days to allow a thorough evaluation of organ damage following cardiac arrest.

Early intestinal complications following pancreas transplantation: lessons learned from over 300 cases - a retrospective single-center study.

Enteric complications remain a major cause of morbidity in the post-transplant period of pancreas transplantation despite improvements surgical technique. The aim of this single-center study was to analyze retrospectively the early intestinal complications and their potential relation with vascular events. From 2000 to 2016, 337 pancreas transplants were performed with systemic venous drainage. For exocrine secretion, intestinal drainage was done with hand-sewn anastomosis duodenojejunostomy. Twenty-three patients (6.8%) had early intestinal complications. Median age was 39 years (male: 65.2%). Median cold ischemia time was 11 h [IQR: 9-12.4]. Intestinal complications were intestinal obstruction (n = 7); paralytic ileus (n = 5); intestinal fistula without anastomotic dehiscence (n = 3); ischemic graft duodenum (n = 3); dehiscence of duodenojejunostomy (n = 4); and anastomotic dehiscence in jejunum after pancreas transplantectomy (n = 1). Eighteen cases required relaparotomy: adhesiolysis (n = 6); repeated laparotomy without findings (n = 1); transplantectomy (n = 6); primary leak closure (n = 3); re-positioning of the graft (n = 1); and intestinal resection (n = 1). Of the intestinal complications, 4 were associated with vascular thrombosis, resulting in two pancreatic graft losses. Enteric drainage with duodenum-jejunum anastomosis is safe and feasible, with a low rate of intra-abdominal complications. Vascular thrombosis associated with intestinal complications presents a risk factor for the viability of pancreatic grafts, so prevention and early detection is vital.

Biomarkers of fatty acid intake are independently associated with preclinical atherosclerosis in individuals with type 1 diabetes.

PURPOSE: Information on the association between diet and cardiovascular disease (CVD) in type 1 diabetes (T1D) is scarce. We assessed the association between biomarkers of fatty acid (FA) intake and the presence of carotid plaques (a surrogate marker of future CVD events) in this high-risk population. METHODS: Cross-sectional study in 167 consecutive T1D patients without CVD and with at least one of the following: ≥ 40 years, diabetic nephropathy, or ≥ 10 years of T1D duration with another CVD risk factor. The FA profile of erythrocyte membranes was determined by gas chromatography, and the number of carotid plaques (intima-media thickness ≥ 1.5 mm) was assessed by ultrasonography. Regression models were constructed adjusting for classical (age, gender, blood pressure, smoking habit, LDL-cholesterol, body mass index and statins) and T1D-specific risk factors (diabetes duration, HbA1c and chronic complications). RESULTS: A total of 58.7% were men (mean age 48.3 ± 10.3 years, T1D duration 27.2 ± 10.1 years). Sixty-one patients (36.5%) showed carotid plaque. Linoleic acid decreased and all-C18:1trans increased with the number of carotid plaques (none, 1-2, ≥ 3 plaques; p for trend < 0.05). In multivariate regression models, linoleic acid remained inversely associated with the presence of plaque [1% increase of total FAs; OR 0.71 (0.53-0.95), p = 0.021] and ≥ 2 plaques [OR 0.70 (0.51-0.98), p = 0.039]; whereas, all-C18:1trans was positively associated with ≥ 3 plaques (0.1% increase of total FAs; OR 1.51 [1.05-2.16], p = 0.026). CONCLUSIONS: Erythrocyte FA composition, as a biomarker of FA intake, was independently associated with preclinical atherosclerosis in T1DM. Our data support the potential role of an unfavorable pattern of fat intake and CVD risk in this population.

Quantification of glycoproteins by nuclear magnetic resonance associated with preclinical carotid atherosclerosis in patients with type 1 diabetes.

BACKGROUND AND AIMS: Glycoproteins play a key role in inflammatory and cardiometabolic processes. Their implication in atherosclerosis in type 1 diabetes (T1D) is unknown. We assessed the relationships between classic inflammatory markers, glycoproteins measured by nuclear magnetic resonance (1H-NMR), and preclinical atherosclerosis in these patients. METHODS AND RESULTS: We selected patients with T1D, without cardiovascular disease (CVD), with: age ≥40 years, nephropathy (micro/macroalbuminuria), or ≥10 years of evolution with another risk factor. The presence of plaque (intima-media thickness >1.5 mm) was determined by ultrasonography. Concentrations of high-sensitive C-reactive protein (hsCRP), circulating leukocytes (classical inflammation markers) and 1H-NMR-glycoproteins (GlycA, GlycB, GlycF, and the height/width [H/W] ratios of GlycA and GlycB) were determined. We included 189 patients (58% male, age 47.0 [40.7-55.2] years). Thirty-five percent presented plaques (22%, ≥2 plaques). There was no association between hsCRP or leukocytes and atherosclerosis. However, in age- and sex-adjusted models, GlycA, GlycF, and the H/W ratios of GlycA and GlycB gradually increased with the number of plaques (0, 1, ≥2 plaques) only in patients without statins (p < 0.05), with no association in patients receiving this drug (p for interaction <0.05; in ≥2 plaques). Finally, in models adjusted for other classical and T1D-specific risk factors, GlycA and GlycB H/W ratios remained associated with carotid plaque (OR 1.39 [1.12-1.90] and OR 6.89 [1.85-25.62], respectively). CONCLUSION: In T1D individuals without lipid-lowering treatment, 1H-NMR-glycoproteins were independently associated with the presence and amount of carotid atherosclerosis, unlike other classical inflammatory markers. Further studies are needed to ascertain their utility as CVD biomarkers.

Advanced lipoprotein profile 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 profile in T1DM individuals, and analysed differences 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 profiles 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 profile 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 profile than non-diabetic men, women with T1DM had a similar concentration of LDL-particles 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 LDL-cholesterol than non-diabetic subjects (prevalence of LDL-cholesterol < 100 mg/dL & LDL-particles > 1000 nmol/L: 38 vs. 21.2%; p < 0.001). All these differences were largely unchanged in participants without lipid-lowering drugs (T1DM, n = 275; controls, n = 317). CONCLUSIONS: Overall, T1DM participants showed a more favourable conventional and NMR-lipid profile than controls. However, the NMR-assessment identified several lipoprotein derangements in LDL-particles among the T1DM population (higher discrepancies in NMR-LDL-particles vs. conventional LDL-cholesterol; a worse profile in T1DM women) that were overlooked in the conventional analysis. Further studies are needed to elucidate their role in the development of CVD in this population.

Insulin resistance is associated with preclinical carotid atherosclerosis in patients with type 1 diabetes.

AIM: Although insulin resistance (IR) is a growing trait among type 1 diabetes (T1D) population, its relationship with atherosclerosis has been scarcely studied. We assessed the association between IR indexes and carotid atherosclerosis in T1D, a population at high cardiovascular disease (CVD) risk. MATERIALS AND METHODS: We evaluated 191 participants with T1D and no prior CVD with at least one of the following criteria: ≥40 years old; diabetic nephropathy; or T1D duration ≥10 years harbouring ≥1 additional CVD risk factor. IR was assessed with the metabolic syndrome (MetS) harmonized definition proposed in 2009 and the estimated glucose disposal rate (eGDR), a T1D-specific IR surrogate marker (lower values indicating higher IR). Standardized carotid ultrasonography was performed, recording intima-media thickness (IMT), plaque presence and maximum height of plaque. Comparisons between patients according to their MetS status as well as concerning eGDR values were performed. RESULTS: The participants' median age was 47.4 (41.1-53.3) years and diabetes duration 25.7 (21.6-32.5) years. Plaque prevalence was higher in patients with greater IR (49.1%, 29.1% and 20%, P = .001, for any plaque according to decreasing eGDR tertiles). Conversely, no statistically significant higher plaque prevalence was found in participants with MetS. In multivariate analyses (adjusted for general- and T1D-specific risk factors, and statin treatment), MetS was associated with neither IMT nor plaque. On the contrary, eGDR was independently related to ≥2 plaques (P = .018) and maximum plaque height (P < .01). CONCLUSIONS: In T1D, IR assessed through eGDR but not by MetS definition was independently associated with plaque burden, a predictor of CVD.

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. TRIAL REGISTRATION: ClinicalTrials.gov, trial number NCT03422965.

Pancreas outcomes between living and deceased kidney donor in pancreas after kidney transplantation patients.

Background: Pancreas outcomes in pancreas after kidney transplantation (PAK) patients have been reported as being inferior to those of patients who receive simultaneous pancreas and kidney transplantation (SPK). The influence of the kidney donor (i.e. living versus deceased) has never been previously addressed. Methods: We retrospectively analysed all pancreas transplants performed in a single centre since 2007 and compared the outcomes between those patients who had previously received a living-donor kidney transplant (pancreas transplantation after living-donor kidney transplantation, PAldK; n = 18) or a deceased-donor kidney transplant (pancreas transplantation after deceased-donor kidney transplantation, PAddK; n = 28), using SPK (n = 139) recipients as a reference. Results: Pancreas survival was similar between all groups, but inferior for PAldK when including only those with a functioning graft at day 90 post-transplantation (P = 0.004). Pancreas acute rejection was significantly increased in PAldK (67%; 1.8 ± 1.4 episodes/graft) when compared with PAddK (25%) and SPK (32%) (P < 0.05) patients. In a multivariate Cox regression model including known risk factors for pancreas rejection, PAldK was the only predictor of acute rejection (hazard ratio 6.82, 95% confidence interval 1.51-30.70, P < 0.05). No association was found between donor-recipient HLA mismatches and graft rejection. Repeated HLA mismatches between kidney and pancreas donors (0 versus 1-6) did not correlate with pancreas graft rejection or survival in either PAK transplantation group (P > 0.05). Conclusion: Pancreas graft outcomes are worse for PAldK when compared with PAddK and SPK patients.

Pancreas transplantation: Advantages of a retroperitoneal graft position. / Trasplante de páncreas: ventajas de la posición retroperitoneal del injerto.

INTRODUCTION: In the 50 years since the first pancreas transplant performed at the University of Minnesota, the surgical techniques employed have undergone many modifications. Techniques such as retroperitoneal graft placement have further improved the ability to reproduce the physiology of the «native¼ pancreas. We herein present our experience of a modified technique for pancreatic transplant, with the organ placed into a fully retroperitoneal position with systemic venous and enteric drainage of the graft by duodeno-duodenostomy. METHODS: All pancreas transplantations performed between May 2016 and January 2017 were prospectively entered into our transplant database and retrospectively analyzed. RESULTS: A total of 10 transplants were performed using the retroperitoneal technique (6 men: median age of 41 years [IQR 36-54]). Median cold ischemia times was 10,30h [IQR 5,30-12,10]. The preservation solution used was Celsior (n=7), IGL-1 (n=2), and UW (n=1). No complications related to the new surgical technique were identified. In one patient, transplantectomy at 12h was performed due to graft thrombosis, probably related to ischemic conditions from a donor with prolonged cardio-respiratory arrest. Another procedure was aborted without completing the graft implant due to an intraoperative immediate arterial thrombosis in a patient with severe iliac atheromatosis. No primary pancreas non-function occurred in the remaining 8patients. The median hospital stay was 13,50 days [IQR 10-27]. CONCLUSIONS: Retroperitoneal graft placement appears feasible with easy access for dissection the vascular site; comfortable technical vascular reconstruction; and a decreased risk of intestinal obstruction by separation of the small bowel from the pancreas graft.

The Effect of Corticosteroid Withdrawal on Glucose Metabolism and Anti-GAD Antibodies in Simultaneous Pancreas-Kidney Transplant Patients.

CONTEXT: Corticosteroid withdrawal may reduce insulin resistance; however, it could also influence pancreatic autoantibody profile in simultaneous pancreas-kidney (SPK) transplant patients. OBJECTIVE: To evaluate the effect of corticosteroid withdrawal on glucose metabolism and anti-glutamic acid decarboxylase (GAD) antibody titers in SPK patients with type 1 diabetes after 12 months of follow-up. DESIGN: In this retrospective study, fasting glucose and glycated hemoglobin (A1c) were compared before and after 3, 6, and 12 months of corticosteroid withdrawal in 80 SPK patients. In addition, weight, anti-GAD, and C-peptide levels were compared before and after withdrawal. Finally, fasting and postglucose, insulin, and C-peptide levels were compared before and after withdrawal in 25 patients undergoing oral glucose tolerance test (OGTT). RESULTS: Fasting glucose levels did not change during corticosteroid discontinuation. After 12 months, A1c slightly increased from 4.6% (0.4%) to 4.8% (0.6%) (P < .01) and C-peptide decreased from 2.8 (1.1) ng/mL to 2.4 (1.3) ng/mL (P <. 01). In patients submitted to OGTT, glucose, insulin, and C-peptide levels did not change. There was no alteration in the proportion of anti-GAD positive tests (41% vs 45%). Anti-GAD titers remained stable or decreased in 70% of positive patients. CONCLUSION: Corticosteroid withdrawal has no significant effect on glucose metabolism and on anti-GAD profile among SPK patients.

[Consensus document for the detection and management of chronic kidney disease]. / Documento de consenso para la detección y manejo de la enfermedad renal crónica.

Chronic kidney disease (CKD) is an important global health problem, involving to 10% of the Spanish population, promoting high morbidity and mortality for the patient and an elevate consumption of the total health resources for the National Health System. This is a summary of an executive consensus document of ten scientific societies involved in the care of the renal patient, that actualizes the consensus document published in 2007. The central extended document can be consulted in the web page of each society. The aspects included in the document are: Concept, epidemiology and risk factors for CKD. Diagnostic criteria, evaluation and stages of CKD, albuminuria and glomerular filtration rate estimation. Progression factors for renal damage. Patient remission criteria. Follow-up and objectives of each speciality control. Nephrotoxicity prevention. Cardio-vascular damage detection. Diet, life-style and treatment attitudes: hypertension, dyslipidaemia, hyperglycemia, smoking, obesity, hyperuricemia, anemia, mineral and bone disorders. Multidisciplinary management for Primary Care, other specialities and Nephrology. Integrated management of CKD patient in haemodialysis, peritoneal dialysis and renal transplant patients. Management of the uremic patient in palliative care. We hope that this document may be of help for the multidisciplinary management of CKD patients by summarizing the most updated recommendations.

Dose-Dependent association of cumulative tobacco consumption with the presence of carotid atherosclerosis in individuals with type 1 diabetes.

AIMS: Evaluate the association between cumulative tobacco consumption (CTC; packs-year) and atherosclerosis in type 1 diabetes (T1D), and study whether the inclusion of CTC in the Steno T1 Risk Engine (ST1RE) equation improves the identification of plaques. METHODS: Cross-sectional study in T1D patients without cardiovascular disease (CVD), with ≥ 1 of the following: ≥40 years-old, diabetic kidney disease, and/or T1D duration ≥ 10 years + cardiovascular risk factors.Preclinical atherosclerosis was evaluated by carotid ultrasonography. RESULTS: N = 584 patients were included (46.1 % women, age 48.7 ±â€¯10.5 years, T1D duration 27.3 ±â€¯10.8 years, 26.2 % active smokers). The overall plaque prevalence was 40.9 %. In models adjusted for age, sex, lipids, blood pressure, kidney function, statin use, microvascular complications and HbA1c, CTC was dose-dependently associated with the number of plaques (none, 1-2, ≥3) overall and in both active and former smokers (p < 0.001). This association remained after adjusting for ST1RE (OR 1.11 [1.02-1.19]). Although the inclusion of CTC in the ST1RE did not improve plaque identification overall (p = 0.180), it did so when analyzing active smokers separately (AUC 0.738 vs. 0.768; p < 0.01). CONCLUSIONS: In T1D patients, CTC is dose-dependently associated with atherosclerosis. Further prospective studies are needed to determine if CTC could identify T1D individuals more prone to accelerated atherosclerosis.