Diabetic Pts Research Articles

030: Incidence and predictors of bleeding complications in diabetic patients during long-term follow-up after DES implantation

We investigate the frequency, correlates, and clinical significance of bleeding complications in diabetic patients (pts) with long-term dual antiplatelet treatment (DAPLT) after drug-eluting stent (DES) implantation. We assessed 610 consecutive diabetic pts (male 80%, mean age 65±9 years) after DES implantation. Five years clinical follow-up (FU), obtained in 587/610 (96%) of them. At the end of FU, 211 (36%) pts were on single APLT (SAPLT) and 376 (64%) on DAPLT. Bleeding complications were defined according to PLATO and TIMI definitions The incidence of bleeding was higher in DAPLT pts (14.6% vs 3.8%, p<0.0001). Minor bleeding according to PLATO occurred in 1.9% of pts on SAPLT and 11.7% on DAPLT (p<0.0001) and according to TIMI in 2.4% vs 13.6% respectively (p< 0.0001). Major bleeding according to PLATO presented the 1.9% of pts on SAPLT and 2.9% on DAPLT; according to TIMI the incidence of major bleeding was 1.4% and 1.1% respectively (p:NS for both PLATO and TIMI definitions). The incidence of cardiovascular adverse events was similar between pts with bleeding as compared with those without bleeding. In a multivariable analysis, smoking was an independent predictor for overall as well as major bleeding according to PLATO (HR 6.2, 95% CI 1.2-30.4, p=0.024), whereas DAPLT was an independent predictor for overall and minor bleeding (HR 6.2, 95% CI 2.2–17.3, p<0.0001) Long-term DAPLT in diabetic patients treated with DES is associated with higher risk of overall and minor but not major bleeding. Smoking was an independent predictor for overall bleeding and major bleeding according to PLATO definitions

Phase I study of intravenous PI3K inhibitor BAY 80-6946: Activity in patients (pts) with advanced solid tumors and non-Hodgkin lymphoma treated in MTD expansion cohorts.

3019 Background: BAY 80-6946 (BAY) is a potent and highly selective reversible pan-Class I PI3K inhibitor, previously reported to be tolerated as a 1-hr infusion at a dose of 0.8 mg/kg on days 1, 8 and 15 every 28 days (MTD). Additional pts were treated in MTD expansion cohorts to assess safety, PK, biomarkers and clinical benefit in selected tumor types, as well as safety in Type 2 diabetics. Methods: To date, 23 nondiabetic pts with solid tumors and 5 with follicular lymphoma (FL) received BAY at the MTD, until disease progression or unacceptable toxicity. Tumor types were selected for high frequency of PIK3CA mutation, including breast cancer (BC; 16), endometrial (3), gastric (2), GU transitional cell (1) and ovarian clear cell (1). Partial enrichment for PIK3CA mutation was achieved by analysis of plasma DNA. 3 diabetic pts have been enrolled, at starting dose of 0.4 mg/kg. PK was done after the 1st and 3rd doses. FDG-PET/CT scans were done at baseline and 48 hrs after the 1st dose for pharmacodynamic assessment. Results: Safety and tolerability assessments confirmed MTD. There were no 1st cycle DLTs. Almost all nondiabetic pts had acute Grade 2/3 hyperglycemia (HG) following each dose; at least 10 of them received insulin for 1-3 days post dose. Hypertension (HTN) lasting &lt; 24 hrs was common in pts with preexisting HTN, and manageable. 2 FL pts developed interstitial pneumonitis (IP) after cycles 2 and 3, both responsive to steroids. Diabetic pts tolerated 0.4 mg/kg. Tumor SUVmax consistently fell at 48 hrs. 3 of 4 FL pts had partial response (PR) after 2 cycles, with 2 confirmed PR pts on BAY for 10+ and 8+ mos. 2 BC pts showed PR , 1 confirmed. PIK3CA mutation (n=7) does not appear to correlate with response. Average T1/2 was 36 hrs. Observation of high Cmax in very obese pts led to recommended maximum dose of 65 mg. Conclusions: BAY induced PRs in pts with BC and FL. The acute toxicities of HG in most pts and HTN in some are manageable, and IP has been limited to 2 lymphoma pts and is responsive to steroids. The observed clinical activity of BAY, along with its acceptable safety profile, provide a rationale for the ongoing development of BAY in combination with cytotoxic and targeted agents.

Evaluation of cardiovascular disease risk in older patients with HIV infection on antiretroviral therapy

BackgroundThe increasing number of older patients (pts) with HIV infection, coupled with the prevalence of cardiovascular disease (CVD) at this age, and the side effects of antiretroviral therapy (ART), mainly...

Safety and Efficacy of Frontline Nilotinib (Nb) for Chronic Phase (CP) Chronic Myeloid Leukemia (CML) in Diabetic Patients (pts)

Abstract 2764 Background:Nilotinib is accepted standard of care for CP-CML as initial therapy or after resistance or intolerance to imatinib. Nilotinib increases blood sugar level in diabetic and non-diabetic patients. This has caused concern about the possible adverse consequences for diabetic pts treated with nilotinib. Purpose: To investigate the impact that nilotinib therapy may have over diabetes among pts with CML receiving frontline therapy for CML. Methods: We reviewed the records of 105 CML patients treated at our institution from 7/2005 to 7/2011 who have received treatment with nilotinib 400 mg twice daily as a frontline for their CML disease. We divided our patient in two groups (Diabetes =DM- vs. non-Diabetes =non-DM-). For diabetic patients, we identified the concomitant mediations at the time of DM, DM-associated complications, occurrence of hyperglycemia during nilotinib therapy and the management of DM during their therapy with nilotinib. We compare the best and current response on nilotinib, event-free survival (EFS), treatment- free survival (TFS), and overall survival (OS) between the two groups (DM vs. non-DM). Results: The median age for the 105 pts treated was 52 yrs (range, 17 to 89), and 63 were males (60%). Nine patients (9%) were diabetic. Three of the 9 DM pts had DM complications before starting nilotinib (vitreous hemorrhage, proliferative diabetic retinopathy, and neuropathy). Median BMI was 26.9 (19.2 to 40.2) Kg/m2and 35.6(31.3 to 38.2) Kg/m2 in non-DM and DM pts respectively. Dose reductions to 400 mg or 200 mg were required in 24 non-DM pts (23 %) compared with 3 DM pts (3%). Hyperglycemia was not identified as the reason for reducing nilotinib doses in any DM pt. The median blood sugar at the start of therapy with nilotinib was 93 mg/dL (65 to167) and 123 mg/dL (64 to 329) in non-DM and DM pts respectively. The median peak blood sugar during the treatment with nilotinib was 126 mg/dL (84 to 196) in non-DM pts and 251 mg/dL (158 to 299) in DM pts. The blood sugar of two DM pts (22%) was controlled by diet without the need of using any diabetic medications and 7 pts (78%) received different kinds of oral hypoglycemia medications (biguanides, sulfonylureas, thiazolidinediones, alpha-glucosidase inhibitors, and meglitinides) before starting Nilotinib. During nilotinib therapy 1 of these 7 pts (11%) was converted to insulin due to inability to control blood sugar by using oral hypoglycemia medications 1 (11%) did not require change in DM management, and 5 pts (56%) required an increase in the dose of their DM medication or addition of other oral hypoglycemia medications. Nilotinib was not interrupted because of hyperglycemia in any pt. None of DM pts developed ketoacidosis or hyperosmolar coma. The outcome of CML for DM and non-DM pts is presented in table 1. Conclusion: Nilotinib is a safe and active medication in CML patients with DM. Close monitoring and adequate management of DM allows DM pts with CML to safely receive therapy with nilotinib and derive equal benefits as their non-DM counterparts.Table 1OutcomeDMno DMCCyR89%94%MMR89%88%CMR67%62%36 months EFS100%91%36 months TFS100%97%36 months OS100%100%EFS= Event-free survival; TFS=Transformation-free survival; OS=Overall survival CCyR= complete cytogenetic response; MMR=major molecular response; CMR=complete molecular response. Disclosures:Cortes:Deciphera: Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.

Clinical/pathologic characteristics of diabetic patients with early breast cancer (BC) and their survival outcome.

e11019 Background: Diabetes mellitus is thought to be associated with adverse outcomes in BC and it might adversely affect decisions regarding treatment. Methods: We retrospectively reviewed the medical records of the early BC patients (pts) who were treated at Marmara University Hospital between 1999 and 2007. We noted the patient, tumor, treatment-related characteristics and information on comorbidities from the medical charts. We investigated whether patient and tumor related parameters were different between diabetic and non-diabetic BC patients and whether diabetes has a negative impact on survival outcome. Results: We identified 33 diabetic early BC pts among 456 pts (7%) who had received their adjuvant therapy in our center. All diabetic BC pts were on oral antidiabetics. The median age of our study group was 51 (23-85) and median follow up was 48 months. Most diabetic BC pts were postmenopausal (p:0.004); diabetic pts were older (p:0.04) and have smaller tms compared to non-diabetic early BC pts (...

IMPACT OF PACLITAXEL-ELUTING STENTS IN DIABETIC AND NON-DIABETIC PATIENTS WITH ACUTE MYOCARDIAL INFARCTION UNDERGOING PRIMARY ANGIOPLASTY: 3-YEAR RESULTS FROM THE HORIZONS AMI TRIAL

Background: In the randomized HORIZONS-AMI trial, implantation of paclitaxel-eluting stents (PES) as compared to bare-metal stents (BMS) in pts with STEMI signiicantly reduced recurrent ischemia, with similar rates of death, reinfarction and stent thrombosis (ST). We assessed the impact of diabetes mellitus (DM) on clinical outcomes at 3 years in this trial. Methods: In HORIZONS-AMI, 3,006 pts were randomized in a 3:1 ratio to receive PES or BMS, stratiied by the presence of DM at the time of admission. Ischemia-driven target lesion (TLR) or target vessel revascularization (TVR), major adverse cardiovascular events (MACE: death, reinfarction, ischemic TVR or stroke) and ST were assessed according to diabetic status at 3 years. Results: Of the 3,006 randomized pts, 478 (15.9%) presented with DM. The 3-year rates of reinfarction (8.9 vs. 6.5%, p=0.09) and ST (6.0% vs. 4.7%, p=0.27) were comparable between DM vs. non-DM pts, whereas death (10.3% vs. 5.0%, p<0.0001), stroke (3.1% vs. 1.3%, p=0.004), TLR (14.2% vs. 10.8%, p=0.04), TVR (17.5% vs. 13.9%, p=0.04) and non-TVR (16.4% vs. 9.6%, p<0.0001) occurred signiicantly more often in DM pts. Outcomes at 3 years according to stent randomization are shown in the Table. Conclusions: In the HORIZONS-AMI trial, implantation of PES compared to BMS in diabetic pts resulted in a 70% reduction in TLR, 61% reduction in TVR and a 46% reduction in MACE at 3 years, with comparable rates of safety outcomes including ST. The absolute beneits of PES were greater in DM than non-DM pts. Diabetics Non-Diabetics PES n=364

Efficacy and Safety of Nilotinib In Chronic Phase (CP) Chronic Myeloid Leukemia (CML) Patients (Pts) with Type 2 Diabetes In the ENESTnd Trial.

AbstractAbstract 3430 Background:Nilotinib is a potent and selective BCR-ABL kinase inhibitor. In the randomized, multicenter phase 3 ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Philadelphia chromosome-positive CML pts) trial, nilotinib demonstrated superior efficacy, including significantly lower rates of progression on treatment to the accelerated or blastic phases of CML vs imatinib. It was previously reported that nilotinib treatment may lead to transient hyperglycemia in some pts receiving second-line nilotinib (400 mg twice daily [bid]) for resistance or intolerance to imatinib. The objective of this prospective analysis was to determine the effects of frontline nilotinib therapy on glucose metabolism in a subset of pts from ENESTnd with preexisting type 2 diabetes, and to evaluate the efficacy and safety of nilotinib therapy in these pts. Methods:Changes from baseline in glucose metabolism parameters including fasting blood glucose (FBG), insulin, C-peptide, and HbA1c levels at 12 months were assessed in the diabetic subset of pts. Changes in body weight were also assessed. Results:A total of 836 pts were included in the safety analysis of ENESTnd (279, 277, and 280 pts in the nilotinib 300 mg bid, nilotinib 400 mg bid, and imatinib arms, respectively) with a median follow-up of 18 months. In this population, all grade hyperglycemia occurred in 38%, 42%, and 22% of pts in the nilotinib 300 mg bid, 400 mg bid, and imatinib arms, respectively (grade 3/4 in 6%, 4%, and 0%). Importantly, no patient from any treatment arm discontinued study due to hyperglycemia and there were no diabetic serious adverse events (eg, diabetic ketoacidosis, hyperosmolar events, and/or hospitalization due to diabetes). The subset of pts with preexisting type 2 diabetes (n = 57; 23, 18, and 16 pts in the nilotinib 300 mg bid, nilotinib 400 mg bid, and imatinib arms, respectively) was analyzed for glucose metabolism parameters and efficacy. Median age was higher (approximately 60 years) in this subset of pts compared to the entire pt population (approximately 47 years). At study entry, 68% (39/57) of pts were on diabetes medications; 18% (7/39) of whom were on insulin. The majority of diabetic pts (74%) did not have a change in diabetes therapy on study. Changes in glucose metabolism parameters were minimal (Table), and no meaningful changes in body weight or HbA1c were noted in any arm. In the subset of pts with preexisting type 2 diabetes, response rates were similar to the overall population, with MMR rates by 12 months of 69.6%, 55.6%, and 25%, and CCyR rates by 12 months of 69.6%, 77.8%, and 68.8% in the nilotinib 300 mg bid, nilotinib 400 mg bid, and imatinib arms, respectively. No pt in the diabetic subset has progressed to advanced disease. Overall, 8, 5, and 6 diabetic pts discontinued nilotinib 300 mg bid, nilotinib 400 mg bid, and imatinib, respectively. Of these, 3, 5, and 4 pts discontinued due to an adverse event or laboratory abnormality unrelated to diabetes. One diabetic pt in each of the nilotinib arms experienced an ischemic heart disease event (grade 1 or 2). Two diabetic pts died, 1 due to intestinal obstruction and 1 due to suicide, both in the nilotinib 300 mg bid arm. Conclusions:Hyperglycemia occurring during nilotinib treatment was usually mild, transient, manageable and did not lead to treatment discontinuation in patients with or without preexisting type 2 diabetes. Moreover, the efficacy and safety of nilotinib in this subset of pts was similar to the overall population in ENESTnd. These data suggest that nilotinib is efficacious and well-tolerated in pts with type 2 diabetes. Disclosures:Saglio:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Larson:Novartis: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding. Hughes:Ariad: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria, Research Funding. Marin:Novartis: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding. Kalaycio:Novartis: Honoraria, Speakers Bureau. Gallagher:Novartis Pharma AG: Employment, Equity Ownership. Kayath:Novartis: Employment. Zheng:Novartis: Employment, Equity Ownership. Kantarjian:Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding; Pfizer: Research Funding. Hochhaus:Novartis: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding.

E0472 Two-year clinical efficacy of sirolimus—versus paclitaxel—versus zotarolimus-eluting stents in diabetic patients

BackgroundDrug-eluting stents (DESs) have drastically improved the angiographic and clinical outcomes of percutaneous coronary intervention (PCI) in patients (pts) with diabetes mellitus. However, little has been known whether the different...

THERAPEUTIC DECISION FOR UNCONTROLLED AND UNTREATED HYPERTENSIVE PATIENTS: DIFFERENCES BETWEEN CARDIOLOGISTS AND GPS – REFLEXE STUDY: PP.33.343

The study aim was to observe the therapeutic decision made by GPs or cardiologists for uncontrolled and untreated hypertensive patients (pts) (BP> = 140/90 for non diabetic (DB) and BP>=130/80mmHg for DB pts). Three treatment approaches were assessed: lifestyle and diet recommendations without treatment (LD), implementation of a single drug antihypertensive treatment (SD) or prescription of two antihypertensive agents (TD). French cross sectional study conducted with 1048 GPs and 155 cardiologists in 2008. Each physician included the first 5 consecutive hypertensive pts according to above inclusion criteria. Cardiovascular (CV) risk factors (RF) and associated diseases were collected to compare pts characteristics in the 3 groups. 5201 pts were included by GPs and 764 pts by cardiologists (see table below).Overall physicians mostly chose to start an antihypertensive treatment: only 7.9% of pts followed by GPs remained without treatment versus 10.6% of pts managed by cardiologists. Cardiologists were more disposed to immediately prescribe a two-drug regimen than GPs, respectively 32.7 and 22.9%, even though their patients didn't have more severe HTN or more associated cardiovascular risk factors or diseases. Therapeutic management for uncontrolled and untreated hypertensive patients differ between cardiologist and GPs, with cardiologists adopting a more aggressive approach despite the same cardiovascular risk of their pts. The more frequent ambulatory BP measurement prescribed by cardiologists could explain partly the differences observed in therapeutic decision.

INCREASED AORTIC STIFFNESS IS ASSOCIATED WITH INCREASED RISK FOR RECURRENT CARDIOVASCULAR EVENTS IN DIABETIC PATIENTS WITH ISCHEMIC HEART DISEASE: PP.17.139

Background: Aortic stiffness (AS) has been correlated with recurrence of coronary events in non-diabetic patients (pts). Its predictive value for cardiovascular (CV) morbidity in diabetic pts with ischaemic heard disease is not yet established. Methods: One hundred diabetic men with no history of CV disease, admitted to the coronary care unit between February 2006 and June 2007, were evaluated at discharge for AS by calculating carotid-femoral pulse wave velocity (PWV).Telephone interviews at 12 months after discharge assessed the primary endpoints: re-hospitalisation for any CV event (unstable angina UA, revascularization RV, myocardial infarction MI, stroke S) or death. Results: Mean age was 63.86 ± 10.09 yrs, mean diabetes duration 11.93 ± 9.64 yrs, body mass index (BMI) 28.42 ± 4.65 Kgr/m2, waist circumference 105.81 ± 11.77 cm, A1c glycaeted hemoglobin (HbA1c) 7.50 ± 2.31 %, serum glucose at admission 166.95 ± 52.04 mg/dl, total cholesterol 184.45 ± 55.85 mg/dl, triglycerides 147.77 ± 87.69, HDL-C 36.27 ± 11.74 mg/dl, LDL-C 83.99 ± 62.99 mg/dl. Smokers were 36.7%, hypertensives 58.8%, and dyslipidemics 44%. To facilitate analysis, PWV values were divided into two halves, upper and lower with cut off point 11.5m/sec. Overall 12 cardiovascular events (UA:6, MI:3, RV:2, S: 1) and 2 deaths were recorded. Those in the upper compared to those in the lower half of PWV were older (68.22 ± 7.18 vs. 58.96 ± 10.36 years, p < 0.001), had a longer diabetes duration (13.6 ± 10.43 vs. 6.71 ± 5.95 years, p = 0.003), and had more increased TC (178.26 ± 52.50 vs. 216.66 ± 56.7 mg/dl, p = 0.025). No statistical significant differences were detected for waist, BMI, serum glucose levels at initial admission, troponine I, HbA1c, triglycerids, HDL-C, frequency of hypertension and smoking. After adjustment for age, diabetes duration, TC, and smoking, PWV was independently associated with the risk for recurrent cardiovascular morbidity (hazard ratio = 2.408, 95%CI = 1.313–6.88, p = 0.032). Conclusions: Increased aortic stiffness was associated with increased one-year risk for recurrent cardiovascular event in diabetic men. We propose that aortic stiffness could be routinely used for risk stratification in the management of diabetic men after the first coronary event.

OP-001 PROGNOSTIC STRATIFICATION IN DIABETIC PATIENTS ADMITTED FOR ACUTE CORONARY SYNDROME

Objective: To assess the different prognostic role of clinical, angiographic and metabolic parameters on prognosis in diabetic pts with preserved (EF >45%) or impaired LV systolic function (EF 75 years, presence of smoke, hypercholesterolemia, renal insufficiency, Insulin therapy, previous CAD, CABG, PAD, EPA at admission) dichotomized on basis of EF impaired or preserved. Differently from pts with preserved LV function, in pts with LV systolic dysfunction (EF 7%) and smoking at the time of admission and history of CAD had a negative prognostic value, while previous CABG and hypercholesterolemia favourably affected the survival. Moreover Renal Insufficiency, age and insulin therapy didn’t show any predictive value when EF was <45%. Conclusions: The different predictive role of many important prognostic variables between pts with and without LV systolic dysfunction underline the importance of risk stratification considering this parameter. This may allow to better finalize our preventive interventions.

“Non-Hodgkin's Lymphomas and Diabetes of Type 2 in Elderly Patients: Impact On Management in the Real Life”.

Abstract 4998 PurposePrevalence of patients (pts) suffering of non-Hodgkin's lymphoma (NHL) and diabetes is increasing. Previous investigations were mainly focused on possible association with an increased risk of NHL in pts with type 2 diabetes. In another way, it is well known that NHL patients (pts) with co-morbidity are treated less intensively and have worse prognosis. We propose a retrospective analysis of a homogeneous aggressive lymphoma cohort based on a multicentric regional network database to assess the cross-impact of diabetes and NHL in term of pts management and survival. Patients and methodsAll pts with high-grade NHL cases, histologically proven, diagnosed between 2003 and 2008 in the Hematology Department of regional network HEMATOLIM, have been included. Diabetes of type 2 has been defined according to international criteria. Data about diabetes and lymphoma treatments, toxicity, relapse, progression or death, have been collected from the Database Structure Régionale de Référence sur les Lymphomes en Limousin. Statistical analysis had been done by StatView and SAS 9.1.2 softwares. ResultsWe included 251 NHL pts with aggressive NHL concerning 69.3% Diffuse Large B Cell Lymphoma (DLBCL) (n=174), 7.6% Mantle cell (n=19), 5.2% Peripheral T-cell (n=13), 5.2% Burkitt (n=13) and 12.7% others (anaplastic (n=9), Follicular grade 3B (n=8),T angioimmunoblastic (n=8), primary mediastinal NHL (n=3), nasal NK-T (n=2), T-cell-rich BCL (n=1), centroblastic BCL (n=1)). Among these NHL, 16.7% had type 2 diabetes (n=42). Sex ratio was 1 for diabetic pts (dp) versus (vs) 1.4 for non-diabetic pts (ndp), the average age was 65.1±15.8, 71.3±8.4 for dp vs 63.8±16.6 for ndp (p=0.005). All received first-line chemotherapy mainly Cyclophosphamide/Oncovin/ Adriamycine/Prednisone ± Rituximab (54.6%, n=137), with no difference between dp and ndp (respectively 59.5% vs 57.0%). Chemo-resistance was reported for 22.7% of pts (28.6% dp (n=12) and 21.5% ndp (n=45)). Chemotherapy-related toxicities were more frequent in dp (71.4%, n=30, vs 47.8%, n=100 ndp) (p=0.005), mainly fever and/or bleeding and infectious complications or back to hospitalization. Dose reductions were more frequent in dp, 31.0%, (n=13) vs ndp 12.0%, n=25) (p=0.0017) and adjustements in time-interval (54.8%, n=23, vs 38.8%, n=81 ndp) (p=0.05) of chemotherapy course. A logistic regression analysis showed that dose reductions and treatment-related toxicities were associated to diabetes status (p=0.015 and p=0.026, respectively). Complete remission (CR) was achieved for 66% ndp (n=138) vs 40.5% dp (n=17) with significant difference (p=0.0019). Relapses: no significant difference between both groups with 13.9% ndp (n=29) vs 19% dp (n=8). Mortality rate was significantly increased: 41.6 % ndp vs 59.5% dp (p=0.033), mainly due to NHL complications, 41.6% ndp (n=87) vs 59.5% dp (n=25) (p=0.033). With a median follow-up of 17 months (m) (range 0-72), median overall survival (OS) was not reached for ndp vs 12±9 m for dp (p=0.006), median event-free survival (EFS) was 41±6.2 m for ndp vs 11±4.3 m for dp (p=0.002). In a multivariate analysis, the differences disappeared on OS and EFS after adjustment on age. A logistic regression analysis showed an important increasing of complications, adjustment of doses, and CR but these chemotherapy-related toxicities had no impact on dp survival. The impact of chemotherapy mainly including corticosteroids on the long term diabetes status has been assessed at the end of NHL treatment, 35.7% increased oral medication to oral insulin or received an intensified dose of the antidiabetic treatment (9.5%, n=4). Some dp with oral treatment improved their glycemia (7.1%, n=3), and used only hygiene-dietary measures. Long term insulin treatment was introduced after glycemia disorders for 3.8% ndp (n=8). ConclusionAggressive NHL were more frequently associated with type 2 diabetes (16%) in our regional cohort probably due to the study population median age around 68 years. A real impact of incidence of the chemotherapy-related toxicities, back to hospitalization, a less dose-intensity chemotherapy on dp CR has been significantly demonstrated. EFS and OS were not significant in multivariate analysis especially with adjustment on age. These results claim for a cautious management of diabetes at the initial assessment and during chemotherapy for decreasing complications and by an intensive patient education. DisclosuresNo relevant conflicts of interest to declare.

Evaluation of the relationship between gastric emptying, metabolic status and diabetic neuropathy

Introduction: The possible correlations between the metabolic status, the gastric emptying and the neuropathy are still not clearly explored by the studies of the past decades. The aims of this study were to perform a continuous glucose monitoring during the determination of gastric emptying and to evaluate the severity of neuropathy in patients (pts) with type-1 diabetes mellitus (DM). Patients and methods: 13 young pts with type-1 DM were included (duration of DM: 15.1±2.9 years; mean±SE). The emptying of the stomach was evaluated by scintigraphy. The subcutaneous glucose levels were determined by a CGMS method (Medtronic Hungária Kft) during the interval of the gastric emptying. Cardiovascular reflex tests were applied for the assessment of autonomic neuropathy (AN). Sensory nerve integrity was studied with a Neurometer (Neurotron Inc., Baltimore). Results: There was a longer period of gastric emptying in diabetic pts than in healthy subjects, but this difference did not reach significance (T1/2: 84.4±12.4 vs. 49.6±5.5min., p=0.06, pts vs. control). The glucose levels recorded during the gastric emptying (the lowest and highest, the mean, the highest difference) and the HbA1c did not correlate with the gastric motility. Moderately severe AN was found in pts (AN score: 2.9±0.5 vs. 0.3±0.2p<0.001, heart rate response to beathing: 16.4±1.9 vs. 26.3±2.3 beats/min, p<0.01; 30/15 ratio: 1.04±0.02 vs. 1.21±0.04, p<0.01; Valsalva ratio: 1.34±0.06 vs. 1.71±0.1, p<0.01; handgrip: 15.6±2.8 vs. 28.3±3.5mm Hg, p<0.05). The current perception thresholds (CPT) at 5Hz on the peroneal nerve of the pts differed from controls (CPT: 3.12±0.9 vs. 0.68±0.07 mA, p<0.05). Conclusions: Parameters of the continuously measured glucose levels did not correlate with the gastric emptying. Slightly slower gastric emptying was found in the presence of a moderately severe autonomic and sensory neuropathy in pts after a 15-year-long duration of DM. These data may strengthen the hypothesis that the current glucose levels have a less important role than neuropathy in the pathogenesis of delayed gastric emptying.

Thiazolidinedione Therapy Associated with Improved Clinical Outcomes in Heart Failure Patients with Diabetes

Background: The role of thiazolidinediones (TZDs) in the treatment of diabetic patients (pts) with Heart Failure (HF) is controversial. Though their favorable endovascular effects may contribute to delayed HF progression, their use has been associated with fluid retention and clinical decompensation. Concern regarding fluid retention, particularly when used in combination with Insulin (I), has led to several guideline recommendations against the use of TZDs in HF. To date, there have been no trials assessing the impact of TZD therapy on HF outcomes. We analyzed our experience with TZDs to better define the role of these agents in HF. Methods: We retrospectively analyzed 97 consecutive diabetic pts referred to our Heart Failure Treatment Program with systolic dysfunction (LVEF ≤ 35%) and NYHA class II-IV HF. 37% were treated with TZDs and 15% with TZD+I. The TZD+ and TZD− groups were well-matched with regard to baseline LVEF (TZD+ 23.7%, TZD− 25.9%, p=NS), glycosylated hemoglobin (TZD+ 7.1, TZD− 6.9, p=NS), and NYHA class (TZD+ 2.56, TZD− 2.79, p=NS). Baseline renal function was slightly worse in the TZD− group (1.15 vs 1.33 mg/dl, p=0.03). All pts were treated with ACE-inhibitors or ARBs and 97% with beta blockers. We assessed clinical outcomes at one year. Results: All 97 pts were alive at one year. Clinical outcomes were analyzed by TZD use both alone and in combination with I:Clinical Outcomes by Thiazolidinedione UseTZD+TZD−ΔNYHA class−0.21−0.12p=NSAll-cause hospitalizations (per patient)0.190.71p=0.01HF hospitalizations (per patient)0.030.16p=0.04Total hospital days0.672.72p=0.02Clinical Outcomes by Combined TZD and I UseTZD,I+TZD,I−ΔNYHA Class−0.13−0.16p=NSAll-cause hospitalizations (per patient)0.200.59p=0.11HF hospitalizations (per patient)0.200.43p=NSTotal Hospital Days (per patient)0.072.30p=0.0005There was a trend toward increased diuretic requirements in the TZD,I+ group (69.3mg vs 45.5 mg furosemide/day, p=0.08). This was not seen in pts treated with TZDs alone. Conclusions: We saw no adverse effect of TZDs on outcomes. In fact, TZD use was associated with reductions in both hospitalizations and hospital days. The hospital day reduction was independent of I use. These findings challenge recommendations against TZD use in HF. Clinial trials will determine the degree to which these findings can be extrapolated to broader HF populations.

COMPARABLE KIDNEY GRAFT SURVIVAL OF TYPE I DIABETICS TREATED WITH SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION (SPK) AND NON DIABETIC PATIENTS TREATED WITH CADAVERIC RENAL TRANSPLANTATION (KTX)

P362 Aims: SPK is an accepted therapy for the treatment of type I diabetics with end stage renal failure (ESRD). Compared to type I diabetics treated with KTX alone or remaining on dialysis, SPK shows a superior patient survival when suitable candidates are selected. Furthermore SPK is supposed to prevent the recurrence of diabetic lesions in the renal transplant resulting in better renal transplant survival, when compared to diabetics treated by KTX only (UNOS annual report 2000). However this presumption could not be confirmed by the analysis of Bunnapradist (2003), who found no differences in the 1 to 5 year survival of kidney graft survival between SPK-patients (pts) and KTX-pts, when equally matched for donor and recipient risk factors. In this study we compared the renal graft outcome between type I diabetics treated with SPK and non diabetic pts treated with KTX alone. Methods: All type I diabetics with SPK and all non diabetic pts with KTX, who received their transplants between 1.1.98 and 31.12.01 were included in this retrospective analysis. The follow up period ended at 31.12.02, the mean observation time was 33,5 month. Pts with living donation or retransplantation were not considered. Results: 95 type I diabetics with SPK and 231 non diabetic pts with KTX could be included in this study. The renal graft survival of the SPK-pts was significantly better than the graft survival of the KTX-pts. The one- and three-year kidney graft survival was 95% and 91 % in the SPK- and 87% and 83% in the KTX-group(p<0.05). The patient survival did not differ between both groups. Compared to the KTX group the SPK group showed a lower donor (35 vs. 46 years) and recipient age (42 vs. 51 years), a shorter cold ischemic time (11 vs. 13h), but a higher number of HLA-mismatches (4 vs. 2), a longer initial hospitalisation (53 vs. 28 days) and a higher hospital readmission rate (2 vs. 1) [p-value for all differences <0.01]. Limiting the recipient age for KTX-pts to < 65 years (the oldest SPK-pts was 62 years old), renal graft survival as well as patient survival showed no difference between both groups. Conclusions: Donor and recipient age as well the cold ischemic time might have more impact on the early outcome of the renal transplants than the HLA match and a more complicated postoperative course (indicated by longer posttransplant hospitalisation). Furthermore according to our data and the data of Bunnapradist (2003), the outcome of renal transplants during the first years after transplantation seems to be independent from the underlying disease which caused the ESRD and the modality of transplantation (SPK vs. KTX).

Relationship between electrogastrography (EGG) alteration and neuropathy in patients with pancreatic diabetes

Timing and criteria of testing for gastric dysmotility and the management of diabetic pts with pancreatic insufficiency is not well established.

CORRELATES OF SURVIVAL IN HEMODIALYSIS (HD) PATIENTS (PTS)

Disappointingly poor survival during treatment for end stage renal disease (ESRD) in the United States has been attributed to various causes including inadequate dialysis and malnutrition. The objective of this study was to identify the factors that are associated with long-term survival on HD. We have prospectively examined enrollment demographic, and visceral and somatic nutritional markers in 530 HD pts from 1987 onwards (monitored through October, 1999). For the prealbumin study, 126 pts were enrolled from June 1991. Pre-albumin was measured by rate nephelometry on a Beckman Array Protein System. Serum intact PTH was measured by radioimmunoassay. Mean age was 60±16 (SD) yrs; female, 54%; African American, 57%; diabetic, 47%. Enrollment levels of nutritional markers were significantly lower in diabetics compared to non-diabetics (P < 0.001). Over 12 years of observation, the observed survival (Kaplan Meier) of diabetic pts was significantly lower than that of non-diabetics (P < 0.0001). Survival was positively influenced by enrollment levels of biochemical markers of nutrition such as albumin (P < 0.001), prealbumin (P < 0.001) and creatinine (PO.001) as well as PTH (P=0.002) (Univariate Cox's proportional hazard model). Over 12 years of observation, the survival of HD pts with lower enrollment levels of albumin (P < 0.0001), creatinine (P < 0.0001) and PTH (P=0.009) was significantly lower compared to those with higher levels of these markers (Kaplan Meier method). After adjustment for confounding variables the results were similar. Over 8 years of observation, pts with higher levels of enrollment prealbumin had significantly (P=0.008) increased survival compared to those with lower prealbumin levels. After adjustment for confounding variables the results were similar (P=0.025). Serum PTH and serum prealbumin levels correlated positively with other nutritional markers. After longer follow-up and with more enrolled pts, this study confirms our findings regarding the prognostic importance of enrollment nutritional markers in HD pts. Diabetic HD pts had poorer nutritional status, which may be partly responsible for the excess mortality seen in this population.

Therapeutic experience with fluconazole in the treatment of fungal infections in diabetic patients.

Diabetes mellitus is associated with a higher incidence of certain infections, including fungal infections like rhinocerebral zygomycosis (RCZ) and cutaneous candidosis. As the pathophysiology of increased susceptibility to infection of diabetic patients is very complex, a general therapeutic approach is not existing yet. Appropriate diabetes control remains as the best preventive measure. Nevertheless, effective drug therapy is very often required. Fluconazole has proven efficacy in prophylaxis, treatment and suppressive therapy of both systemic and superficial fungal infections, especially in candidosis and cryptococcosis. Therefore it is used routinely against fungal infections in diabetes (FID). Clinical efficacy of fluconazole against cutaeneous candidosis, oropharyngeal candidosis (OPC) and vulvovaginal candidosis (VVC) has been confirmed in more than 100 studies, involving more than 10.000 patients (pts). The overall success rate is 90%, with a mean dosage of 100-200 mg/d. In severe cases, e.g. in OPC in late-stage AIDS pts or in recurrent VVC, higher dosages of up to 800mg/d may be required. In the treatment of RCZ, therapeutic experience with fluconazole is limited1,2 . Four diabetic pts have been treated with dosages of 200-300 mg/d and all of them recovered. Nevertheless, treatment of RCZ should include surgical debridement combined with aggressive antifungal therapy. In conclusion, proven efficacy and the excellent safety profile justify the routine use of fluconazole in the treatment of FID.