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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. 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). 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

Objective Evaluate the results of a healthcare and therapeutic education program (TEP) aimed at young patients with type 1 diabetes (T1D) transferred from a pediatric center. Methodology This was a prospective, pre-postest in young T1D patients transferred from 2005–2015. The program has four phases: coordinated transfer, evaluation and objective pacting, knowledge (DKQ2) adherence (SCI-R.es) and quality of life (DQoL and SF12). Results were compared according to Multiple Daily Injections (MDI) vs. Continuous Subcutaneous Insulin Infusion (CSII) and adherence (SCI-R.es 65%). Results A total of 330 patients were transferred (age 18.19 ± 0.82 years, 49% females, glycated hemoglobin [HbA1c] 8.6 ± 1.4%). The program was completed by 68%, and 61% did a group course. While no changes in HbA1c were observed at one year (8.3 ± 1.4 vs. 8.2 ± 1.4%), there were changes in severe hypoglycaemias/patient/year (0.23 ± 0.64 to 0.05 ± 0.34 p 5 hypoglycaemias/patient/week (6.9% vs. 3.9% p = 0.09). DQK2 knowledge increased (25.7 ± 3.6 vs. 27.8 ± 3.8 p Conclusions The TEP improved some parameters of metabolic control without modifying the quality of life in young T1D patients. When comparing patients on MDI vs. CSII, there were no differences in metabolic control but there were when differences were evaluated considering treatment adherence.

Background: Although cardiovascular disease (CVD) remains the leading cause of mortality in type 1 diabetes (T1D), the use of cardioprotective drugs is scarce. We aimed to evaluate the impact of carotid ultrasonography (US) on the improvement in cardiovascular risk factors (CVRFs) in T1D.Methods: T1D patients without CVD meeting criteria for lipid treatment according to guidelines (age ≥40 years, nephropathy and/or ≥10 years of diabetes duration with ≥1 additional CVRFs) were included. The carotid-US group (US-G) underwent a standardized US protocol and CVRF assessment; recommendations were made according to subclinical atherosclerosis status. The control group (CG) followed usual clinical practice. Changes in CVRFs, specially statin use and LDL-cholesterol levels, at one year were analysed.Results: A total of 318 patients were included (51.3% female, mean age of 49.1 years and 25.5 years of diabetes duration): 211 in the US-G and 107 in the CG. Participants in the US-G had a higher baseline LDL-cholesterol than controls (114 vs. 102 mg/dL; pConclusions: Carotid-US is independently associated with an intensification of lipid-lowering therapy in a high-risk T1D population.

The purpose of this study was to evaluate specifically the relationship between glycated haemoglobin (HbA1c) levels and retinal optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in type 1 Diabetes Mellitus (DM). A total of 478 type 1 DM patients and 115 controls were included in a prospective OCTA trial (ClinicalTrials.gov NCT03422965). Subgroup analysis was performed for controls, no diabetic retinopathy (DM-no DR) and DR patients (DM-DR), and HbA1c levels. OCT and OCTA measurements were compared with HbA1c levels (current and previous 5 years). DM-no DR patients with HbA1c levels &gt, 7.5% showed lower VD than DM-DR and controls (20.16 vs. 20.22 vs. 20.71, p &lt, 0.05), and showed a significant correlation between HbA1c levels and FAZc (p = 0.04), after adjusting for age, gender, signal strength index, axial length, and DM disease duration. DM-DR patients with HbA1c &gt, 7.5% presented greater CRT than DM-no DR and controls (270.8 vs. 260 vs. 251.1, p &lt, 0.05) and showed a significant correlation between HbA1c and CRT (p = 0.03). In conclusion, greater levels of HbA1c are associated with OCTA changes in DM-no DR patients, and with structural OCT changes in DM-DR patients. The combination of OCTA and OCT measurements and HbA1c levels may be helpful to identify patients at risk of progression to greater stages of the diabetic microvascular disease.

Evaluate the weight trajectories after pancreas transplantation (PT) and their relationships with pancreas graft outcomes in type 1 diabetes (T1D).Retrospective cohort study. T1D individuals who underwent PT were recruited (T1D-PT; n = 194) and divided into three groups according to transplantation date: 1999-2004 (n = 57), 2005-2009 (n = 79), 2010-2015 (n = 58). For weight comparisons, a random sample of T1D without renal impairment was also recruited during 2015 (n = 61; T1D-control).The median follow-up for the T1D-PT group was 11.1 years. Despite significant weight loss at 6 months (65.7 ± 12.4 vs. 64.1 ± 11.4 Kg; p 0.001), a stepped increase was seen thereafter (60 months: 68.0 ± 14.0 Kg; p 0.001). Participants from the 2010-2015 period showed higher weight gain (p 0.001), outweighing that observed in the T1D-control (60 months: +4.69 ± 8.49 vs. -0.97 ± 4.59 Kg; p = 0.003). Weight gain between 6 and 36 months was directly associated with fasting glucose and HbA1c at 36 months, and with HbA1c at 60 months (p 0.05). However, in Cox-regression models adjusted for age, sex, and several recipient and PT-related variables, the third tertile of weight gain between 6 and 36 months showed a non-significant increase in the graft failure/dysfunction (HR 2.33 [0.75-7.27]).Weight gain post-PT was associated with glucose-related biochemical markers of graft dysfunction, which needs confirmation in further studies.

Cardiovascular disease is the major cause of death in patients with type 1 diabetes. Of the available risk predictors for this population, the Steno Type 1 Risk Engine (STENO T1) is the only one that includes kidney function as a risk factor, which is a well-described independent risk factor for cardiovascular disease.We explore how simultaneous pancreas-kidney transplantation (SPKT) modifies the predicted cardiovascular risk by the STENO T1 through a retrospective study including recipients of a first SPKT between 2000 and 2016.Two hundred sixty-eight SPKT recipients with a mean age of 40 y old and a median follow-up of 10 y were included. Before transplantation, the expected incidence of cardiovascular events (CVEs) at 5 and 10 y according to STENO T1 would have been 31% and 50%, respectively, contrasting with an actual incidence of 9.3% and 16% for the same timepoints, respectively (P0.05). These differences were attenuated when STENO T1 was recalculated assuming 12th-mo glomerular filtration rate (at 5 and 10 y predicted CVE incidence was 10.5% and 19.4%, respectively). Early pancreas graft failure (hazard ratio [HR] 3.00, 95% confidence interval [CI], 1.14-7.88; P = 0.02) was an independent risk factor for post-SPKT CVE, alongside kidney graft failure (HR 2.90, 95% CI, 1.53-5.48; P = 0.001), and diabetes duration (HR 1.04, 95% CI, 1.00-1.09, P = 0.04).SPKT decreases in more than two-thirds of the predicted cardiovascular risk by the STENO T1. A functioning pancreas graft further reduces CVE risk, independently of kidney graft function.

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.

BACKGROUND AND AIMS Tools to detect type 1 diabetes (T1D) individuals at overt cardiovascular disease (CVD) risk are scarce. We aimed to assess the usefulness of the score 'Steno Type 1 Risk Engine' (Steno-Risk) to identify T1D patients with advanced carotid atherosclerosis. MATERIAL AND METHODS T1D patients without CVD with at least one of the following were included: ≥40 years, diabetic nephropathy, or diabetes duration ≥10 years with ≥1 CVD risk factor. Intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) were assessed by standardized B-mode ultrasonography. Steno-Risk was used to estimate 10-year risk (

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.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.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).Pancreas graft outcomes are worse for PAldK when compared with PAddK and SPK patients.

Aims Information on the impact of insulin therapy before pancreas donation on pancreas outcomes is scarce. We aim to explore the influence of insulin therapy before donation on recipient and pancreas graft survival. Methods Registry study including 12,841 pancreas recipients from the OPTN/UNOS registry performed between 2000 and 2017. Inverse probability of treatment weighting (IPTW) was used to account for covariate imbalance between recipients from a donor with and without insulin requirements. Results A total of 7765 (60%) patients received a pancreas from a donor with insulin before donation (IBD). Pancreas graft survival (death-censored) was similar between recipients from IBD and non-IBD donors at 1, 5 and 10 years (89% vs 89%, 78% vs 79 and 69% vs 70%, respectively, P = 0.35). Recipients from IBD donors presented a similar 90-days pancreas graft survival. After IPTW weighting, IBD donors were neither associated with any post-transplant surgical complication (HR 1.11 [95% CI 0.98–1.24], P = 0.06), nor with risk for recipient death (HR 0.94 [95% CI 0.85–1.04], P = 0.26), nor pancreas graft failure (HR 1.06 [95% CI 0.98–1.16], P = 0.15). Conclusions Insulin therapy before donation in accepted pancreas donors was not associated, per se, with an impaired pancreas graft and patient survival.

Resumen Introduccion Despues de transcurridos mas de 50 anos desde el primer trasplante de pancreas realizado en la Universidad de Minnesota, las tecnicas quirurgicas empleadas han experimentado muchas modificaciones. La colocacion del injerto en posicion retroperitoneal reproduce la fisiologia del pancreas «nativo». El objetivo del estudio es presentar la experiencia de la aplicacion de una tecnica modificada, con el injerto pancreatico en posicion retroperitoneal, con drenaje venoso sistemico y duodenoduodenostomia para el drenaje enterico. Metodos Analisis retrospectivo de los trasplantes de pancreas realizados entre mayo de 2016 y enero de 2017 en una sola institucion. Resultados Se incluyen un total de 10 trasplantes (6 hombres: mediana de edad de 41 anos [IQR 36-54]). El tiempo de isquemia fria fue de 10,30 h [IQR 5,30-12,10]. La solucion de preservacion utilizada fue Celsior (n = 7), IGL-1 (n = 2) y UW (n = 1). No se han identificado complicaciones relacionadas directamente con la posicion retroperitoneal y la derivacion duodenoduodenal. Un paciente requirio trasplantectomia a las 12 h por trombosis del injerto proveniente de un donante con paro cardiorrespiratorio prolongado. Otro procedimiento fue abortado debido a una trombosis arterial intraoperatoria en un paciente con ateromatosis iliaca grave. Los restantes pacientes presentaron una correcta funcion del injerto, sin requerimientos de insulina. La estancia hospitalaria fue de 13,50 dias (IQR 10-27). Conclusiones La colocacion del injerto retroperitoneal es una tecnica factible, que permite un facil acceso para la diseccion de los vasos y posterior reconstruccion vascular y que minimiza, a su vez, el riesgo de oclusion intestinal.

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 “native” 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 time was 10.30 h [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 12 h 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 8 patients. 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.

To evaluate the changes in cardiovascular risk factors (CVRFs) and cardiovascular disease (CVD) in patients with type 1 diabetes (T1D) and end-stage renal disease (ESRD) who were candidates for kidney-pancreas transplantation (KPTx) from 1999 to 2017.Patients with T1D referred for KPTx evaluation were included. The cohort was divided into five groups according to the year of evaluation (1999-2002, 2003-2006, 2007-2010, 2011-2014 and 2015-2017). The control of CVRFs and the prevalence of prior CVD were evaluated.We evaluated 360 patients (64.4% men, age 38.9 ± 7.1 years). LDL-cholesterol100 mg/dl increased from 22.7% to 76.9% (1999-2002 vs. 2015-2017; p 0.001), as did the use of statins (from 24.7% to 74.5%; p 0.001). Systolic blood pressure decreased from 138.8 ± 27.6 to 125.1 ± 27.9 mmHg (p = 0.001) and current smokers from 48% to 25% (p = 0.018). Intensive insulin treatment increased from 34.4% to 93.6% (p 0.001). Diabetes duration before the initiation of renal replacement therapy increased from 23 ± 5.5 to 26.9 ± 8.9 years (p = 0.001). Overall, 30.3% had previous CVD, without significant changes over time (p = 0.699), albeit patients were older and had longer diabetes duration.Patients with T1D and ESRD referred for KPTx have better control of CVRFs over time, which might lead to a decrease in cardiovascular events.

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.

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 Conclusions In T1D, IR assessed through eGDR but not by MetS definition was independently associated with plaque burden, a predictor of CVD.

Nocturnal hypertension (night systolic [S]/diastolic [D] blood pressure [BP]≥120/70 mm Hg), nondipper status (nocturnal BP fall10% of daytime values), and pulse pressure ([PP]; difference between 24-h SBP and DBP readings) are associated with increased risk of cardiovascular disease. We evaluated the 1-year effect of significant surgical weight loss (WL) on abnormal BP patterns in patients with and without hypertension and identified the factors involved.University hospital, Spain.This prospective study included 42 patients (28 normotensive [NT] and 14 hypertensive [HT]), 71% women with a mean age (standard deviation [SD]) of 48 (11) years undergoing bariatric surgery (BS): 22 laparoscopy Roux-en-Y gastric bypass (LRYGB) and 20 sleeve gastrectomy (SG). SG: 20. Before and 12 months post-BS, anthropometric data, BP (24-h ambulatory BP measurement), and metabolic parameters were determined. At 12 months post-BS ultrasonographic carotid assessment was performed in a subgroup of patients (22).Both groups experienced significant WL (percent of excess body weight loss [%EBWL] 68%), a fall in 24-h SBP of-13 (11)/DBP-3 (7) mm Hg, and improvement in all the metabolic parameters evaluated and the homeostatic model assessment of insulin resistance (HOMA-IR). However, nondipper status remained high in NT (54%) and HT (64%) as well as 60% of the patients with carotid plaque. Additionally, in HT patients nocturnal hypertension and PP remained significantly higher, and basal fasting insulin values and the HOMA-IR score were significantly higher in those not normalizing dipper status.Surgery-induced WL was associated with a sizeable decline in BP and metabolic parameters improvement. However, independent of the presence of hypertension, the prevalence of abnormal 24-h BP patterns remained high, and thus, cardiovascular risk continued to be high in these 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 Conclusion:Corticosteroid withdrawal has no significant effect on glucose metabolism and on anti-GAD profile among SPK patients.

Purpose The purpose of this study was to evaluate specifically in type 1 diabetes mellitus (DM) individuals the relationship between perifoveal superficial capillary plexus (SCP) parameters assessed by optical coherence tomography angiography (OCTA) and diabetic retinopathy (DR) grade. Methods Cross-sectional analysis of a large scale prospective OCTA trial cohort (ClinicalTrials.gov NCT03422965). A total of 1186 eyes (593 individuals), 956 type 1 DM eyes (478 patients), and 230 control eyes (115 healthy volunteers) were included in this study. DR stage was graded according to the International Classification. OCTA imaging was performed with a commercially available device (Cirrus HD-OCT). Vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) area, perimeter and circularity measurements were quantified in the SCP and receiver operating characteristic (ROC) curves were constructed for each OCTA parameter. Results VD and PD (in both 3 × 3 and 6 × 6 mm captures) were inversely associated with DR stage (P < 0.001 in all cases) in a multiple regression analysis after controlling by age, gender, signal strength index, axial length, and DM duration. Greater FAZ area and perimeter and conversely lower circularity measurements were observed as DR severity increased in both scanning protocols (P < 0.05 in all cases). Conclusions In type 1 DM individuals, OCTA provides an objective, continuous, and reliable method for accurate quantification of VD, PD, and FAZ parameters in the SCP, which ultimately correlate with DR stages. Translational Relevance Objective OCTA measurements of the retinal microvasculature could substitute the clinical DR classification in patients with type 1 DM, identify patients at risk of DR progression, and inform treatment decisions to modify the evolution of the disease.

ObjectiveImprovement in insulin alternatives is leading to a delayed presentation of microvascular and macrovascular complications of diabetes. The objective of this study was to evaluate the long-term outcomes of older (≥50 years) diabetic patients who receive a pancreas transplantation (PT).Research design and methodsWe retrospectively evaluated all 338 PTs performed at our center between 2000 and 2016 (mean follow-up 9.4±4.9 years). Recipient and graft survivals were estimated for up to 10 years after PT. Major adverse cardiovascular events (MACEs) before and after PT were included in the analysis.ResultsThirty-nine patients (12%) were ≥50 years old (52.7±2.3 years) at the day of PT, of which 29 received a simultaneous pancreas–kidney transplantation (SPK) and 10 a pancreas after kidney transplantation (PAK). SPK recipients were first transplants, whereas in the PAK up to 50% were pancreas re-transplantations. Recipient and pancreas graft survivals at 10 years were similar between the group 0.05). The prevalence of MACE prior to PT was similar between both groups (31% vs 29%). Following PT, older recipients presented inferior post-transplant MACE-free survival. In a multivariate regression model, diabetes vintage (HR 1.054, p=0.03) and pre-transplantation MACE (HR 1.98, p=0.011), but not recipient age (HR 1.45, p=0.339), were associated with post-transplant MACE.ConclusionsLong-term survival of older pancreas transplant recipients are similar to younger counterparts. Diabetes vintage, but not age, increased the risk of post-transplantation MACE. These results suggest pancreas transplantation is a valuable treatment alternative to older diabetic patients.

The use of statins in non-selected type 1 diabetes (T1D) populations is low. We assessed the prevalence and factors associated with statin treatment in patients meeting criteria for this therapy for primary prevention of cardiovascular disease (CVD).From 2015 to 2018, T1D patients from a tertiary hospital were selected. Inclusion criteria were: ≥40 years-old, diabetic nephropathy, or T1D duration ≥10 years with ≥1 cardiovascular risk factor (CVRF). A standardized cardiovascular risk evaluation protocol was performed. Prevalence of statin treatment was evaluated according to presence of several CVRFs, and multivariable models were constructed to assess independent determinants of statin use.We included 241 patients (50% women, age 48.2±9.9 years, T1D duration 26.6±9.0 years). Diabetic retinopathy and nephropathy, active smoking, and hypertension were present in 38%, 12%, 28%, and 27%, respectively. Overall, 43% of patients were on statins and 27% had LDL-cholesterol100mg/dl. Statin users were older, and had higher body mass index (BMI), prevalence of kidney dysfunction, and hypertension (p0.05 for all). However, among both T1D-related and classical CVRFs, only hypertension (odds ratio [OR], 2.96; 95% confidence interval [CI] 1.48-5.91) and BMI (OR, 1.08; CI, 1.01-1.16) were independently associated with statin use in multiple regression analysis.Less than half of T1D patients from a tertiary hospital who met criteria for statin use were on treatment. Hypertension and BMI emerged as the only CVRFs independently associated with statin therapy. New strategies are needed to better address CVD prevention in this very high-risk population.

Despite the favorable evidence available, our public health care system has no specific programs including therapeutic education for patients newly diagnosed with type 2 diabetes (T2DM), which would be crucial for the subsequent course of the disease.To assess the effectiveness of a "Health care and Therapeutic Education Program for newly diagnosed type 2 diabetes (PAET-Debut DM2)" agreed by the primary care centers and the reference hospital in a given geographical area.A prospective pilot study in patients over 18 years of age diagnosed with T2DM between February 2012 and 2013. The PAET-DebutDM2 is planned and set up in four primary care centers in the area covered by Hospital Clínic in Barcelona. Reference persons (family doctor and nurse) are designated at each center and specific training is provided to standardize the clinical processes and therapeutic education methods. First results are assessed and compared at 6 and 12 months.The program was proposed to 345 patients, of which 191 (55.3%) were enrolled in it and 134 (70.2%) completed the program. At the end of the program, 84% achieved the control goal (HbA1c7%) and 88% passed the screening of chronic complications. Improvements were seen in body weight, physical activity (p0,001), and disease awareness (p0.05), and there were less hospital emergencies due to DM as compared to patients not included in the program (p=0.023).The PAET-DebutDM2 standardizes intervention and education and is effective in terms of clinical and educational results and patient satisfaction. The program emphasizes the importance of early education and intervention, reorganizing resources without increasing care pressure in the primary care centers, thus reducing hospital care.

The combination of obesity and hypertension (HT) places patients at a higher risk for adverse cardiovascular outcomes and raises the need to establish the pathogenic mechanisms of this relationship. The aim of this study was to assess the effects of important weight loss on longitudinal changes in blood pressure (BP) and investigate the pathogenic factors associated with these changes.We performed a prospective, open-label study including 37 obese hypertensive patients (28 females, mean age 52±8 yr) undergoing BS. Before BS, and at 4 and 12 months postoperatively, the body mass index (BMI), 24-h ambulatory BP, renin-angiotensin-aldosterone system (RAAS: plasma rennin activity, aldosterone, angiotensin II, and angiotensin converting enzyme), sympathetic nervous system (SNS: metanephrines, normetanephrines, and norepinephrine) components, leptin, insulin, and abdominal fat were measured.Before BS, HT-duration was 6±6 years, the BMI 45±5 kg/m2 and excess weight (EBW) was 53±12 kg. At 12 months, the excess BMI loss was 14 kg/m2 and the EBW loss was 70 %; HT remission was observed in 70%; 24-h (systolic 19±13/diastolic 7±9 mm Hg), day and night BP levels and aldosterone, norepinephrine, leptin, insulin, subcutaneous and visceral abdominal fat (VAT) significantly decreased (P.05). Mixed models for repeated measures revealed that HT-duration, baseline BP, BMI, and VAT area were the main variables associated with longitudinal changes in BP.These results demonstrate that the hypotensive response after weight loss in severely hypertensive obese patients is mainly regulated by HT-duration, baseline BP, BMI and VAT area, independently of suppression of hyperinsulinemia or changes in RAAS and SNS components.

ResumenLa enfermedad renal crónica (ERC) es un importante problema de salud pública que puede afectar en sus diferentes estadios a cerca del 10% de la población española y que supone una elevada morbimortalidad, así como un importante consumo de recursos al Sistema Nacional de Salud. Diez sociedades científicas involucradas en el manejo del paciente renal nos hemos puesto de acuerdo para hacer una puesta al día del anterior documento de consenso sobre ERC de 2007. El presente es la edición abreviada del documento general extenso, que puede ser consultado en las páginas Web de cada una de las sociedades firmantes. Contiene los siguientes aspectos: definición, epidemiología y factores de riesgo de la ERC; criterios de diagnóstico, evaluación y estadificación de la ERC, albuminuria y estimación del filtrado glomerular; concepto y factores de progresión; criterios de derivación a nefrología; seguimiento del paciente, actitudes y objetivos por especialidad; prevención de la nefrotoxicidad; detección del daño cardiovascular; actitudes, estilo de vida y tratamiento: manejo de la hipertensión arterial, dislipidemia, hiperglucemia, tabaquismo, obesidad, hiperuricemia, anemia, alteraciones del metabolismo mineral y óseo; seguimiento coordinado por atención primaria-otras especialidades-nefrología; manejo del paciente en tratamiento renal sustitutivo, hemodiálisis, diálisis peritoneal y trasplante renal; tratamiento paliativo de la uremia terminal. Esperamos que sirva de gran ayuda en el manejo multidisciplinar del paciente con ERC, a la vista de las recomendaciones más actualizadas.AbstractChronic 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.

There is scarce information about predictive factors of hypertension (HT) remission after bariatric surgery (BS). The aims of this study were to determine the clinical characteristics differentiating obese patients with and without HT and to evaluate the predictive factors associated with the risk of persistence of HT after BS.From January 2007 to December 2009, a review of patients who had undergone BS was performed. Patients were classified as hypertensive if having permanent use of antiHT drugs or clinical BP ≥ 140/90 mm Hg. Weight, waist circumference (WC), and blood pressure were determined with standardized procedures.Five hundred twenty-6 patients met the inclusion criteria; 264 (50%) were hypertensive, 74 (34%) of whom had type 2 diabetes. Before BS, older age, male gender, and greater WC differentiated hypertensive from normotensive patients. The prevalence of HT significantly fell to 35% (P.0001) at 12 months after BS. The use of multivariate logistic regression showed that age ≥ 40, male gender and WC ≥ 130 cm were significant predictors of having HT before surgery. Regarding persistence of HT at the 12-month follow-up, the only independent predictors observed were time since diagnosis of HT ≥ 10 years and the number of antiHT drugs used. Presurgical BMI, WC, excess weight (EW), EW loss, surgical procedure, type 2 diabetes, and vitamin D status were not significant predictors.Bariatric surgery is associated with a high rate of HT remission. Older age, male gender, and higher WC differentiated hypertensive-obese from normotensive patients. After BS, longer duration and severity of HT were independently associated with no remission of HT.

OBJECTIVE The creatinine excretion rate (CER) is inversely associated with mortality in the general and renal transplant population. The CER is a marker for muscle mass. It is unknown whether the CER is associated with outcome in diabetes. We therefore investigated whether the CER is a determinant of all-cause mortality in diabetic patients. RESEARCH DESIGN AND METHODS We used data from the combined Reduction of Endpoints in Non-insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL) and Irbesartan Diabetic Nephropathy Trial (IDNT) studies. A total of 1,872 patients (58% of the overall population) with type 2 diabetes and nephropathy with valid 24-h urinary creatinine excretion data were included. The primary end point of the analyses was all-cause mortality. RESULTS Mean age was 60 ± 8 years and median CER was 1,407 (total range 400–3,406) mg/day. Body surface area, hemoglobin, black race, and albuminuria were positive independent determinants of the CER, whereas female sex and age were inverse independent determinants of the CER. During a median follow-up of 36 (29–45) months, 300 patients died. In a Kaplan-Meier analysis of sex-stratified tertiles of the CER, risk for all-cause mortality increased with decreasing CER (P < 0.001). In a multivariable Cox regression analysis, lower CER (as a continuous variable) was independently associated with increased risk for all-cause mortality (hazard ratio 0.39 [95% CI 0.29–0.52], P < 0.001). Adjustment for potential collection errors did not materially change these associations. CONCLUSIONS Lower CER was strongly associated with increased all-cause mortality in patients with type 2 diabetes and nephropathy. As the CER can be considered a proxy for muscle mass, this puts renewed emphasis on physical condition and exercise in this population.

REACH is the largest international registry designed to identify the clinical characteristics of atherothrombosis in the real-life setting. The present study describes the baseline and 1-year follow-up characteristics of 67,888 patients with coronary, cerebrovascular or peripheral vascular disease (VD group) or with three or more risk factors for developing atherothrombosis (RFO group) followed-up by 5,473 physicians. At baseline the patients had a high prevalence of risk factors, especially obesity, insufficient treatment (69.4% statins and 78.6% platelet antiaggregants) and involvement of more than one vascular territory in 15.9%. At 1 year of follow-up, 4.24% had a combination of cardiovascular death, myocardial infarction or stroke (4.69% in the VD group and 2.15% in the ORF group). This finding was related to the number of diseased vascular territories (2.15% in the ORF group and 9.21% in patients with three diseased territories). The REACH registry shows that the patients studied had multiple vascular involvement, undertreatment and high morbidity.

Resumen Fundamento y objetivo REACH es el mayor registro mundial disenado para obtener informacion sobre el control de factores de riesgo vascular y tratamiento preventivo en una poblacion con aterotrombosis sintomatica o de riesgo alto para desarrollarla. El objetivo del presente estudio es conocer la tasa de episodios cardiovasculares en la muestra de la poblacion espanola incluida en el registro, tras un ano de seguimiento e intervencion. Material y metodo El registro REACH Espana es un estudio de cohorte prospectivo de sujetos con solo factores de riesgo vascular (SFR) para aterotrombosis o con enfermedad vascular (EV) sintomatica: enfermedad coronaria (EC) y/o cerebrovascular (ECV) y/o arterial periferica (EAP). Las variables principales del estudio fueron la tasa de mortalidad global, cardiovascular y la del conjunto de mortalidad cardiovascular mas infarto de miocardio (IM), mas accidente cerebrovascular, mas hospitalizacion cardiovascular al ano de seguimiento. Resultados Espana incluyo a 2.516 sujetos, de los cuales 2.252 completaron el ano de seguimiento, con una edad media de 68,1 anos (73,8% de varones). El 11,6% presentaban SFR y el 88,5% EV establecida, el 55% EC, el 33% ECV y el 17% EAP. La tasa anual en los grupos EV y SFR fue, respectivamente, para la mortalidad global del 3,57 y el 1,98% (p=NS), para la mortalidad cardiovascular del 2,69% y el 0,62% (p Conclusiones Los datos del registro REACH espanol al ano de seguimiento en sujetos con aterotrombosis establecida o con factores de riesgo para desarrollarla muestran una alta tasa de mortalidad total y de la combinacion de episodios cardiovasculares mayores, que se acentua cuando mayor es el numero de territorios vasculares afectados.

Background Some studies suggest that schizophrenia may be associated with an increased risk of diabetes, independently of antipsychotic medications and other confounding factors. Previous studies have also suggested that there is an increased prevalence of diabetes in the relatives of schizophrenia probands. Method First-degree siblings of schizophrenia probands ( N = 6) and control subjects ( N = 12) were administered a glucose tolerance test. Subjects were matched for gender, age, body mass index, neighborhood of residence, socio-economic status and smoking habits. Results The siblings of schizophrenia probands had a significantly increased two-hour mean glucose concentration compared to the control subjects (respective means [SD] were 100.5 mg/dL [27.7] vs. 78.0 [12.3]; p Conclusions Although confirmation with larger samples is needed, these results and other studies suggest that diabetes may share familial risk factors with schizophrenia.

Fundamento y objetivo La hiperglucemia en el momento del ingreso se ha asociado con mal pronostico en pacientes con infarto de miocardio (IM). El beneficio clinico del tratamiento intensive con insulina se ha evaluado en pacientes diabeticos ingresados en unidades de cuidados intensivos. Nuestro objetivo ha sido evaluar los efectos a corto plazo y la seguridad del control glucemico estricto en pacientes con IM e hiperglucemia sin diabetes conocida. Pacientes y metodo Se aleatorizo a un total de 28 pacientes sin diabetes conocida que habian ingresado con IM e hiperglucemia a 2 grupos de tratamiento durante las primeras 48 h: a) grupo de tratamiento intensivo (n = 13), que recibio insulina intravenosa con el objetivo de mantener la glucemia entre 80 y 110 mg/dl, y b) grupo de tratamiento convencional (n = 15), que recibio insulina subcutanea solo si la glucemia era mayor o igual a 160 mg/dl. La proteina C reactiva ultrasensible se determino a las 48 h del ingreso y al alta. Se realizo un test de tolerancia oral a la glucosa al cabo de un mes. Resultados Durante las primeras 48 h la glucemia fue significativamente menor en el grupo de tratamiento intensivo, con una media (desviacion estandar) de 104 (8) mg/dl, frente a 153 (54) mg/dl en el grupo de tratamiento convencional (p = 0,002), sin episodios de hipoglucemias sintomaticas. A las 48 h la proteina C reactiva ultrasensible fue significativamente menor en el grupo de tratamiento intensivo que en el de tratamiento convencional –media de 44,3 (35,7) y 20,3 (20,3) μg/ml, respectivamente (p = 0,04)–. Al cabo de 4 semanas solo el 28,6% de los pacientes presentaba tolerancia normal a la glucosa. Conclusiones El tratamiento intensivo con insulina con valores cercanos a la normoglucemia en pacientes no diabeticos con IM e hiperglucemia es factible, seguro y mas efectivo que el tratamiento convencional. Ademas, atenua la respuesta inflamatoria. El estudio confirma la alta prevalencia de alteraciones de la tolerancia a la glucosa no conocidas en pacientes con IM.

Fundamento y objetivo REACH es el mayor registro mundial disenado para obtener informacion sobre el control de factores de riesgo cardiovascular y tratamiento preventivo en una poblacion con aterotrombosis sintomatica o alto riesgo de desarrollarla. El objetivo del presente estudio es mostrar los resultados obtenidos en la muestra de la poblacion espanola incluida en el registro. Pacientes y metodo Registro de pacientes consecutivos con solo factores de riesgo cardiovascular (SFR) para aterotrombosis o con enfermedad vascular (EV) sintomatica: enfermedad coronaria (EC) y/o cerebrovascular (ECV) y/o arterial periferica (EAP). Se evaluo el control de factores de riesgo cardiovascular y tratamientos antitrombotico e hipolipemiante. Resultados Espana incluyo a 2.515 pacientes: 297 con SFR y 2.218 con EV (un 61,4% con EC,un 36,6% con ECV y un 18,7% con EAP). En los grupos SFR y EV los porcentajes de falta de control de la presion arterial, los valores plasmaticos de glucosa, de colesterol total y de trigliceridos fueron del 76,5 frente al 57,1% (p Conclusiones El control de los factores de riesgo cardiovascular en personas espanolas de alto riesgo o con EV establecida, especialmente EAP, es inadecuado. Mientras que el uso de estatinas es insuficiente, el de medicacion antitrombotica es aceptable en prevencion secundaria,pero bastante deficiente en prevencion primaria.

It is not unusual for simultaneous pancreas and kidney transplantation (SPK) to be performed in patients with type 2 diabetes (T2D), clinically classified as having type 1 diabetes (T1D). C-peptide determination is useful to identify these patients. We describe the prevalence and characteristics of patients with C-peptide levels >3 ng/mL, classified with T2D in 172 patients referred for SPK from 1998-2006. Nine patients (5.2%) fulfilled this criteria (mean free C-peptide 9.08 ng/mL) and were older at diabetes onset (23.5 vs. 12 yr, p < 0.001) and at assessment (42.2 vs. 37.6 yr, p = 0.047) with shorter time between diabetes onset and renal failure (17.8 vs. 22.7 yr, p = 0.3) compared with T1D patients (mean free C-peptide 0.24 ng/mL). In our experience the prevalence of T2D in candidates for SPK is not negligible. Despite some clinical differences with T1D these T2D patients can phenotypically be confounded with T1D in the absence of C-peptide determination.

ducir la morbimortalidad cardiovascular asociada a las cifras elevadas de presion arterial (PA). Para alcanzarlo es preciso aplicar una serie de medidas encaminadas tanto a reducir la PA como a minimizar el impacto de otros posibles factores de riesgo cardiovascular asociados . Practicamente todas las guias nacionales e internacionales coinciden en que el objetivo terapeutico para todos los pacientes con hipertension arterial (HTA) esencial mayores de 18 anos de edad es lograr un descenso de la PA, estable y sostenido, a menos de 140 mmHg de presion arterial sistolica (PAS) y de 90 mmHg de presion arterial diastolica (PAD). Ademas, muchas de ellas senalan la conveniencia de alcanzar la PA optima y estabilizarla a valores del orden de 120/80 mmHg o inferiores en la poblacion de hipertensos con menos de 60 anos. Finalmente, todas las recomendaciones indican con firmeza reducir la PA a menos de 130/80 mmHg para los pacientes diabeticos o con enfermedad cardiovascular establecida, y a menos de 125/75 mmHg para los pacientes con insuficiencia renal y proteinuria superior a 1 g/24 horas. En cualquier caso, el objetivo de mantener a los hipertensos tratados por debajo de los 140/90 mmHg esta universalmente aceptado. No se conoce con precision el efecto real del tratamiento antihipertensivo sobre la poblacion espanola de pacientes hipertensos, aunque los datos disponibles considerados en su conjunto apuntan a tasas de control de PA entre el 13% y el 39%. Esta amplia variacion obedece a factores de diversa indole tales como: a) utilizacion de distintos criterios de control a lo largo del tiempo (160/95 mmHg frente a 140/90 mmHg); b) utilizacion en algunos estudios de muestras de pequeno tamano no representativas de la poblacion hipertensa; c) diferentes ambitos de los estudios (poblacion general, Atencion Primaria, Unidades de Hipertension, etc.); d) comparacion de pacientes procedentes de areas geograficas con distinta prevalencia de HTA que impide extrapolar los datos al conjunto del territorio nacional; e) heterogeneidad metodologica en la medicion de la PA, y f) descripcion de tasas de control respecto del grupo de hipertensos tratados o del total de hipertensos detectados. Con los criterios generales de control utilizados en la actualidad (PA < 140/90 mmHg), mucho mas estrictos que los recomendados antigua

Objective To assess the effects of telecare on the results of intensive follow-up in T1D patients with poor metabolic control. Methods After initial evaluation, 40 T1D were randomised to either a Telecare (TG) or Conventional Group (CG). Patients had an intensive 6-month follow-up and helped to make decisions concerning treatment self-management. The TG had 12 appointments: 9 telematic with the GlucoBeep system + 3 ambulatory. The CG had 12 outpatient appointments. At 0, 6 (end of study) and 12 months, metabolic control, self-management and quality of life were evaluated. Cost analysis was made at study end. Results Thirty patients completed the study (16 TG, 14 CG). Intention to treat analysis included 19 TG and 16 CG. Improvement in HbA1c was similar in both groups TG: 8.4 ± 1.2%; 7.5 ± 1.4%; 7.6 ± 0.9%, p = 0.008; CG: 8.9 ± 1.3%; 7.7 ± 0.9%; 7.6 ± 0.7%, p = 0.001; with a decrease in hypoglycaemic events and improvement in self-management and quality of life. Patient costs were lower in the TG versus CG in appointment length (0.25 h versus 0.5 h). However, 30% of the diabetes team and patient appointments were longer than expected due to technical difficulties: (0.25 h versus 1 h). Conclusions Intensive telematic follow-up achieves similar results to those of intensive face-to-face follow-up with lower patient costs. However, communication technology must be improved.

Fundamento y objetivo El estudio PREVENCAT se diseno para estimar el control de los principales factores de riesgo cardiovascular (FRCV) y el tratamiento de estos en la poblacion asistida en atencion primaria (AP) que presenta hipertension arterial (HTA), diabetes mellitus tipo 2 (DM2) o hipercolesterolemia (HC). Pacientes y metodo Estudio transversal en pacientes con HTA, DM2 y/o HC, reclutados de forma consecutiva por medicos de AP en Espana. Se evaluo el tratamiento de la HTA, la DM2 y la HC y se analizo la relacion entre el control de estos FRCV y diversos factores potencialmente predictivos. Resultados Se incluyo a 2.649 pacientes. La frecuencia del tratamiento farmacologico fue del 95% en la HTA, del 84% en la DM2 y del 71,4% n la HC, y los farmacos mas utilizados fueron los diureticos, las sulfonilureas y las estatinas, respectivamente. En el tratamiento de la HTA predomino la monoterapia. La frecuencia del tratamiento de la HTA y de la DM2 fue homogenea en los subgrupos definidos por la presencia o ausencia de los otros dos diagnosticos. Sin embargo, el tratamiento de la HC fue mas frecuente en presencia de DM2 (p = 0,001). La edad, la enfermedad cardiovascular (ECV), la DM2, la obesidad y el sedentarismo fueron predictivos del control de la presion arterial (PA), mientras que el tratamiento con farmacos, la edad, la ECV, la HTA y el sedentarismo lo fueron del control de la HC. El tratamiento con farmacos fue el unico factor predictivo del control de la glucemia basal. Conclusiones El tratamiento de los FRCV considerados fue elevado aunque muy heterogeneo y no basado en la mejor evidencia disponible. La DM2, la ECV y la obesidad se asociaron al mal control de la PA.

Elevated arterial pressure is a major risk factor for progression to ESRD in diabetic nephropathy. However, the component of arterial pressure and level of BP control for optimal renal outcomes are disputed. Data from 1590 hypertensive patients with type 2 diabetes in the Irbesartan Diabetic Nephropathy Trial (IDNT), a randomized, double-blind, placebo-controlled trial performed in 209 clinics worldwide, were examined, and the effects of baseline and mean follow-up systolic BP (SBP) and diastolic BP and the interaction of assigned study medications (irbesartan, amlodipine, and placebo) on progressive renal failure and all-cause mortality were assessed. Other antihypertensive agents were added to achieve predetermined BP goals. Entry criteria included elevated baseline serum creatinine concentration up to 266 micromol/L (3.0 mg/dl) and urine protein excretion >900 mg/d. Baseline BP averaged 159/87 +/- 20/11 mmHg. Median patient follow-up was 2.6 yr. Follow-up achieved SBP most strongly predicted renal outcomes. SBP >149 mmHg was associated with a 2.2-fold increase in the risk for doubling serum creatinine or ESRD compared with SBP

Elevated arterial pressure enhances the risk for cardiovascular (CV) events in patients with diabetic nephropathy. The optimal BP and the component of the elevated BP that affect the risk have not been defined. A post hoc analysis was performed to assess the impact of achieved systolic, diastolic, and pulse pressures on CV outcomes in 1590 adults who had overt diabetic nephropathy and were enrolled in the Irbesartan Diabetic Nephropathy Trial (IDNT) and had a baseline serum creatinine above the normal range, up to 266 micromol/L (3.0 mg/dL), 24-h urine protein >900 mg/d, and at least 6 mo of follow-up. Patients were randomized to irbesartan, amlodipine, or placebo, with other antihypertensive agents to a BP goal of < or =135/85 mmHg. Progressively lower achieved systolic BP (SBP) to 120 mmHg predicted a decrease in CV mortality and congestive heart failure (CHF) but not myocardial infarctions (MI). A SBP below this threshold was associated with increased risk for CV deaths and CHF events. Achieved diastolic BP

AIMS The aims of the study were to determine whether transforming growth factor beta1 TGF-beta1 levels are raised at diagnosis of Type 1 diabetes mellitus and are related to blood glucose. SUBJECTS AND METHODS Fourteen patients (mean age 24.3 +/- 4.9 years) admitted to hospital for onset of Type 1 diabetes were studied. On the first day of hospitalization, before insulin therapy, and at 1, 4 and 16 weeks, fasting blood glucose, HbA(1c), lipid profile and TGF-beta1 levels and TGF-beta1 levels in 24-h urine were determined. The control group included 14 non-diabetic subjects with similar characteristics to those of the diabetic group. RESULTS Plasma and urinary TGF-beta1 levels were significantly lower in controls (4.7 (1.6-6.8) ng/ml P < 0.001; 5.7 (1.5-8.5) ng/mg urinary creatinine, P < 0.01) than in patients with Type 1 diabetes mellitus [10.5 (1.8-24.9) ng/ml; 10.1 (4.2-29.8) ng/mg urinary creatinine]. On study completion, HbA(1c) fell from 11.6 +/- 2.0 to 5.4 +/- 0.6% (P < 0.001). Improved metabolic control was not associated with changes in plasma (9.4 (2.6-19.5)/5.9 (1.6-21.5)/7.0 (2.3-30.2)/10.5 (1.8-24.9) ng/ml at baseline, 1, 4 and 16 weeks, respectively) or urinary (12.0 (4.7-29.5)/10.9 (1.5-20.5)/8.7 (4.3-16.9)/10.1 (4.2-29.8) ng/mg urinary creatinine) TGF-beta1 levels. A statistically significant correlation was observed between plasma TGF-beta1 and insulin dosage (U/kg/day) (r = 0.52, P = 0.037). CONCLUSIONS The increased TGF-beta1 production observed herein was not modulated by glycaemic reduction and could be a response to immuno-inflammatory activation present at the onset of Type 1 diabetes.

Epidemiological studies have shown that cigarette smoke, an oxidant agent, is a risk factor for the development of diabetic nephropathy (DN), in which pathogenesis transforming growth factor beta(1) (TGFbeta(1)) plays a key role. In our experimental model we exposed mesangial cell cultures to cigarette smoke concentrate (CSC) to study the effect of smoking on the pathogenesis of DN. Thus, we analyzed the effect of CSC on TGFbeta(1) and lipid peroxidation (8-epi-PGF(2alpha)) in rat mesangial cells. Furthermore, since the protein kinase C (PKC) pathway appears to be a key factor for the enhanced production of TGFbeta(1), we also analyzed the effect of the selective PKCbeta inhibitor LY379196 on TGFbeta(1) response to CSC. CSC induced an increase of both TGFbeta(1) and 8-epi-PGF(2) compared to basal conditions (5 mM glucose). The CSC-induced increase in TGFbeta(1) secretion was significantly suppressed by LY379196. These data suggest that smoking could increase TGFbeta(1) production, probably due to oxidative stress and PKCbeta activation. This finding supports the concept that smoking is a risk factor for DN development.

BACKGROUND: Oxidative stress and transforming growth factor-beta 1 (TGF-beta1) are associated with diabetic complications, and smoking is a risk factor. AIMS: This study aimed (i) to compare urinary 8-epi-PGF2alpha and plasma and urinary TGF-beta1 levels obtained in heavy smokers with Type 1 diabetes with those observed in age-matched non-smoker patients with Type 1 diabetes and controls, and (ii) to investigate the effects of smoking cessation (SC) on the above-mentioned parameters in patients with Type 1 diabetes. METHODS AND RESULTS: Compared with control subjects (n = 12), non-smoker diabetic patients (n = 12) presented higher values of urinary 8-epi-PGF2alpha (74.2 +/- 29.6 vs. 29.6 +/- 11.1 pg/mg urinary creatinine, P = 0.01), plasma TGF-beta1 (7.7 +/- 4.7 vs. 3.6 +/- 1.7 ng/ml, P = 0.001) and urinary TGF-beta1 (15.3 +/- 6.3 vs. 8.1 +/- 4.4 ng/mg urinary creatinine, P = 0.02). Compared with non-smoker diabetic patients, smoker diabetic patients (n = 16) showed higher levels of urinary 8-epi-PGF2alpha (107.8 +/- 40.2 vs. 74.2 +/- 29.6 pg/mg urinary creatinine, P = 0.0001), plasma TGF-beta1 (12.6 +/- 4.9 vs. 7.7 +/- 4.7 ng/ml, P = 0.001) and urinary TGF-beta1 (27.5 +/- 16.0 vs. 15.3 +/- 6.3 ng/mg urinary creatinine, P = 0.01). Smoker patients were included in a smoking cessation programme. In the 10 patients that gave up smoking there was a reduction of urinary 8-epi-PGF2alpha (basal: 110.47 +/- 47.0 vs. week 12: 73.2 +/- 25.6; P < 0.001), plasma TGF-beta1 (basal: 11.2 +/- 5.9 vs. week 12: 4.89 +/- 2.25; P < 0.01) and urinary TGF-beta1 (basal: 18.12 +/- 9.27 vs. week 12: 10.32 +/- 2.0; P < 0.01) levels. CONCLUSIONS: In patients with Type 1 diabetes, smoking increased oxidative stress, evaluated by lipid peroxidation, and TGF-beta1 production. Smoking cessation decreased these parameters, providing additional support to encourage diabetic patients to give up smoking.

Background: After pancreas transplantation (PTx) some patients report occasional symptoms of hypoglycaemia and at times, serious hypoglycaemia. Continuous blood glucose monitoring (CBGM) allows determination of the daily glucose profile and detection of unrecognized hypoglycaemia. The aims of our study were to determine the incidence of hypoglycaemia in PTx and evaluate whether the use of CBGM helps to detect unrecognized nocturnal hypoglycaemia. Patients and methods: We studied 12 patients (six males) with normal functioning PTx and kidney transplantation for more than 3 yr, with systemic drainage of endocrine secretion and stable immunosuppression. A 24-h CBGM using a microdialysis technique (GlucoDay, A. Menarini Diagnostics, Florence, Italy) was performed in all the patients. Results: Three patients had asymptomatic recorded glucose levels below 3.3 nmol/L during the nocturnal period (01:00–07:00 hours) with the glucose levels during these episodes being 2.6, 2.5 and 2.5 nmol/L, and the duration of nocturnal hypoglycaemia being 27, 62 and 93 min, respectively, rising spontaneously without intervention. Patients with hypoglycaemia presented lower glycosylated haemoglobin levels when compared with those not presenting hypoglycaemic episodes, although basal glucose and insulin levels and insulin antibody titres were similar. In one of the three patients presenting hypoglycaemia CBGM was re-evaluated after including an extra snack at bedtime, with subsequent normalization of the blood glucose profile being observed. Conclusion: Unrecognized nocturnal hypoglycaemia is relatively frequent in patients with PTx and 24-h CBMG may be useful to detect these episodes.

Fundamento Los pacientes con diabetes mellitus tipo 1 (DM1) e insuficiencia renal cronica terminal(IRCT) suelen presentar polineuropatia (PNP) grave, cuya progresion puede detenersetras el trasplante de rinon y pancreas (TRP). Hemos analizado la modificacion de los indicesneurofisiologicos de PNP y de funcion autonoma cardiorreguladora (FAC) en los pacientes conDM1 e IRCT en el curso del primer ano despues de TRP. Pacientes y metodo Se estudio a 26 pacientes sometidos a TRP que mantuvieron los organosnormofuncionantes durante al menos un ano despues del trasplante. Se realizaron examenesneurofisiologicos en tres periodos: a) antes del TRP; b) 1-3 meses post-TRP, y c) 12 mesespost-TRP. Se midieron la velocidad de conduccion (VC) y la amplitud de los potenciales de accion(APA) de los nervios peroneal comun, tibial posterior y sural, asi como la variacion observadaen el intervalo entre complejos QRS del electrocardiograma durante la respiracion tranquilay la maniobra de Valsalva. Resultados Todos los pacientes presentaban PNP grave pre-TRP. Diez pacientes (38,4%) presentaronuna reduccion significativa de la APA y de la FAC en el examen realizado entre uno ytres meses post-TRP, mientras que todos los pacientes presentaron un aumento en la VC, APAy FAC al ano del TRP. Conclusion El TRP induce una mejoria estadisticamente significativa de los signos neurofisiologicosde PNP y de FAC al ano del trasplante. En algunos pacientes, la mejoria va precedidade un incremento en la afeccion axonopatica, que sucede en los primeros meses despues deltrasplante y podria estar relacionado con la agresion periquirurgica.

Background. The aim of the present study was to determine the effect of losartan on transforming growth factor-β1 (TGF-β1) plasma levels and urinary albumin excretion (UAE) in patients with type 2 diabetes mellitus, mild hypertension and microalbuminuria. Methods. Fourteen patients (eight males, aged 55 ± 6 years) with type 2 diabetes mellitus, mild arterial hypertension and microalbuminuria, participating in an open, uncontrolled, pilot study were included. Patients were treated for 8 weeks with losartan. TGF-β1 plasma levels, UAE and 24-h blood pressure monitoring were determined at baseline and at 4 and 8 weeks. Results. At 4 and 8 weeks of treatment, a reduction was observed in TGF-β1 plasma levels (5.5 ± 4.5 vs 2.0 ± 0.6 and 2.6 ± 1.0 ng/ml, P

OBJECTIVE: Pregnancy in type 1 diabetes is associated with an increased risk of developing pregnancy-induced hypertension (PIH). Ambulatory blood pressure monitoring (ABPM) has been used to screen for preeclampsia in nondiabetic pregnancy. To date, there are no data regarding ABPM during pregnancy in normotensive type 1 diabetic women. This study sought to establish blood pressure (BP) profiles for pregnant type 1 diabetic women using ABPM and determine whether the BP pattern can define a population at risk for developing PIH. RESEARCH DESIGN AND METHODS: ABPM was carried out for one 24-h period during each trimester--in the first trimester between weeks 7 and 12, in the second trimester between weeks 20 and 24, and in the third trimester between weeks 30 and 34--in 22 normotensive pregnant type 1 diabetic and 10 pregnant nondiabetic women. RESULTS: The incidence of PIH was fourfold greater in type 1 diabetic women than in control subjects. Diabetic women showed higher daily diastolic BP in the third trimester compared with nondiabetic pregnant women. Diabetic women who developed PIH in the third trimester showed significantly higher BP profiles throughout gestation than those who remained normotensive. Receiver operator characteristics curves for nighttime systolic BP showed the best predictive capacity for PIH, with a cutoff > 105 mmHg (85% sensitivity and 92% specificity). CONCLUSIONS: Our study confirms the early increase of BP in patients who will develop PIH and suggests that nighttime systolic BP >105 mmHg in the second trimester is a useful predictor of PIH. ABPM may be useful in screening for PIH in pregnant diabetic women.

Objective: To evaluate the possible effect of short- and long-term insulin treatment on arterial blood pressure (BP) and endothelin-1 (ET-1) plasma levels in type 2 diabetic patients. Research design and methods: Seven type 2 diabetic patients with secondary failure to oral hypoglycemic drugs (SFOH) were studied. Twenty-four-hour arterial BP monitorization (Spacelabs 90207) was performed before initiation of insulin treatment (time 0), 6 days after (time 1) and 1 year later (time 2). Moreover, ET-1 plasma levels were measured. Results: Insulin treatment did not produce any variation in systolic (124.3±11.6; 120.7±7.9; 127.0±13.4 mmHg) and diastolic (72.8±5.9; 71.5±3.4; 71.8±5.2 mmHg) 24-h BP monitorization at times 0, 1 and 2, respectively. The systolic and diastolic day/night differences did not change in the three times studied. Neither were significant differences observed in ET-1 plasma levels. Conclusions: In patients with SFOH, insulin treatment did not induce any short- or long-term increase in BP or any variation in plasma ET-1 levels.

The aim of this cross-sectional study was to establish the prevalence of renal involvement and to identify associations with its most important possible risk factors in a group of patients with Type II diabetes mellitus, representative of the population living in Catalonia. One thousand two hundred and three patients (47% males, mean age: 61 ± 6 years, diabetes duration 9 ± 6 years) were studied. Overnight urine samples were collected to determine urinary albumin excretion (UAE). If UAE was > 15 μg/min, a new 24-h urine collection for UAE measurement to establish the existence of microalbuminuria (20–200 μg/min) or macroalbuminuria (> 200 μg/min) was obtained. Clinic and metabolic evaluations were also performed. The prevalence (%) of microalbuminuria, macroalbuminuria and hypertension were, respectively, 23, 1, 5.4 and 42. In comparison with normoalbuminurics, patients with microalbuminuria were predominately male (P