Search

The use of gamma glutamyl transpeptidase (GGT) levels as screening test for liver function is controversial. The GGT main utility is in cases in which alkaline phosphatase (ALP) is elevated. We aimed to investigate the request over time for alanine amino transferase (ALT), ALP and GGT, study the effect of a new demand management (DM) intervention for optimal GGT measurement in primary care. Our descriptive study was conducted from January 2010 to December 2020. The intervention was established in November 2019 and consisted of the laboratory information system would automatically remove GGT, if the test had been ordered simultaneously with ALP and there was no prior pathological result on record. We counted the absolute number of measured ALT, ALP and GGT, and calculated the ratios for each of the three markers related to creatinine, and GGT related to ALT in a monthly basis. The number of measured GGT increased slightly and progressively along the study until October 2019, when a decrease was observed. The ALT and ALP request from primary care also increased slightly along years. However, the GGT/ALT ratio never reached the 0.2 goal. Out of the 57,614 GGT requested in primary care patients, 38,167 (66.2%) were not measured. 7633.4€ were saved in reagent. The DM intervention to reduce the measurement of GGT when requested redundantly with ALP in primary care was successful, and the results have been maintained over time as observed by monitoring the GGT/CREA and GGT/ALT indicator results.

Objective To illustrate the changes in stat laboratory procedures over a 10 year period. Materials and Methods We implemented 5 different interventions: reporting total bilirubin through the icteric index, replacing total proteins for albumin, reporting albumin-adjusted calcium in hyper- or hypocalcemia, using lipase as a first marker and amylase-selected scenario, and measuring magnesium in hypocalcemia, hypokalemia, or high lipase values. Results Only 9.9% of total bilirubin that was requested was measured, which resulted in savings of $22,492.83. There were 30,036 albumin tests measured, and $15,625.18 was saved replacing total protein. There was $41,374.38 spent to measure lipase and amylase; the difference in costs from the lipase establishment was $16,929.62. Finally, $382.30 was spent for magnesium: 717 magnesium levels were measured given hypocalcemia or hypokalemia (42.8% hypomagnesemia), and 123 tests were added because of high lipase (35% hypomagnesemia). Overall, $53,374.15 was saved. Conclusion Progressive changes in stat laboratory procedures resulted in more efficient resources expenditures.

Objectives We aimed to share a new laboratory model based on laboratory knowledge, meaningful use of information technology, and partnership with clinicians, to lead the appropriate use of laboratory testing and clinical decision making in the diagnosis of as-yet-undiagnosed disease. More specifically, we evaluate the role of eight different opportunistic interventions to diagnose certain asymptomatic disorders, by means of the automatic registration of appropriate laboratory testing according to different scenarios. Methods This is a retrospective longitudinal study to evaluate the impact of laboratory interventions on the diagnosis of different diseases and on patient care, including data from January 2012 to September 2020. Results Overall, the above strategies have so far identified 2063 patients with clinically relevant as-yet-undiagnosed disorders who would have otherwise remained occult, such as for instance, primary hyperparathyroidism, diabetes, and hypomagnesemia. Conclusions We are facing a new laboratory model, a leading laboratory rather than a passive traditional laboratory, not just to intervene in clinical decision-making, but to make the clinical decision, through the identification of patients with occult disease.

Introduction To test the efficacy of two interventions to promote the measurement of serum vitamin B12 (s- vitamin B12) in patients with long-term proton pump inhibitor (PPI) use and to decrease inadequate s-vitamin B12 measurement by implementing a minimum retest interval. Material and Methods The Laboratory Information System (LIS) automatically registered s-vitamin B12 when not ordered by General Practitioners to all requests patients with long term (>3years) PPI treatment, and with no s-vitamin B12 testing in the previous year. Through the second intervention, the LIS reported the previous s-vitamin B12 result through an explanatory comment in the report, when the test had been requested in the previous three months. We calculated the new diagnoses of vitamin deficiency (s-vitamin B12 Results The strategy added 548 s-vitamin B12 and identified 47 new cases of vitamin B12 deficit. The number of added s-vitamin B12 needed to identify a new case by means of the intervention was 12. The total intervention reagent cost was 1446€, with a cost of 30.7€ per new case. The second intervention avoided unnecessary measurement of 611 tests, with 1613€ savings. Conclusions Through the two automated interventions we improved the diagnosis of vitamin B12 deficiency, and decreased inadequate redundant s-vitamin B12 measurement, cutting unnecessary laboratory costs.

Prompt identification of the clinical status and severity of COVID-19 can be a challenge in the emergency department (ED), as the clinical severity of the disease is variable, real-time reverse-transcription PCR (RT-PCR) results may not be immediately available, and imaging findings appear approximately 10 days after the onset of symptoms. There is currently no set of simple, readily available and fast battery of tests that can be used in the ED as prognostic factors. The purpose was to study laboratory test results in patients with COVID-19 at hospital emergency admission and to evaluate the results in non-survivors and their potential prognostic value. A profile of laboratory markers was agreed with the ED providers based on the International Federation of Clinical Chemistry and Laboratory Medicine recommendation of its usefulness, which was made in 218 patients with COVID-19. Non-survivors were significantly older, and the percentage of patients with pathological values of creatinine, albumin, lactate dehydrogenase (LDH), C reactive protein, prothrombin time, D-dimer, and arterial blood gas, PaO2/FIO2 and satO2/FIO2 indices were significantly higher among the patients with COVID-19 who died than those who survived. Patients who died also presented higher neutrophil counts. Among all studied tests, albumin and LDH were independent prognostic factors for death. The results of the study show pathology in nine laboratory markers in patients with COVID-19 admitted in the ED, valuable findings to take into consideration for its prompt identification when there is no immediate availability of RT-PCR results.

Background Vitamin B12 deficiency is common worldwide and is also linked to several diseases including autoimmune atrophic gastritis (AAG). The presence of anti-parietal cell antibodies (APCA) and/or intrinsic factor blocking antibodies (IFBA) is indicative of AAG that may develop into pernicious anemia. Both conditions are known to be associated with an increased risk of gastric carcinoma. The aim of this study was to estimate the frequency of individuals positive for APCA and IFBA antibodies in primary care patients with severe vitamin B12 deficiency. Methods An observational study was designed and 5468 consecutive patients from primary care with a request for vitamin B12 status were included and add-on testing for APCA and IFBA that were automatically registered if severe vitamin B12 deficiency was identified ( Results Seventy-seven patients with severe vitamin B12 deficiency were identified and out of these 44 (57%) presented with antibodies to APCA and 11 (14%) to IFBA, 25 (32.5%) had anemia, and 25 (32.5%) had macrocytosis. The majority of APCA and/or IFBA positive patients were found in the age group >70 years. Both anemia and macrocytosis were more common among APCA positive patients but the association was not statistically significant, neither was the correlation between IFBA status and anemia and/or macrocytosis. Among the patients with anemia, 10 (39%) had macrocytosis, although the rate of macrocytosis among patients with or without anemia did not differ significantly. Conclusions The automated analysis strategy of measuring antibodies to APCA and IFBA in patients with severe vitamin B12 deficiency, efficiently detected positivity in more than 60% the patients. The result point to the presence of a high rate of otherwise undetected AAG and the potential clinical utility of APCA and IFBA as markers in primary care.

Introduction The aim was to present two automated laboratory strategies designed to detect new cases of type 2 diabetes and prediabetes and improve their monitoring. Methods To improve diabetes diagnosis, we automatically registered the glycated hemoglobin (HbA1c) levels of every primary care patient between 25 and 46 years old in case of abnormal lipid testing when an HbA1c test had not been requested in the current order or during the previous year and when fasting glucose was > 100 mg/dl. We counted the number of detected cases of diabetes and prediabetes and calculated the cost per identified patient. To improve diabetes monitoring, the levels of HbA1c, total cholesterol, high- and low-density lipoprotein cholesterol and triglycerides and the spot urinary albumin-to-creatinine ratios (ACRs) were automatically registered in patients with diabetes when not ordered according to guidelines. We calculated the total economic costs according to the total number of additional registered tests and reagent cost. Results Of 103,425 requests, 224 (0.22%) met the inclusion criteria. Seventeen (7.6%) patients were identified as having new cases of diabetes and 149 (66.5%) of prediabetes, at a cost of €15.2 and €2.3, respectively, per case detected. From 13,874 requests in patients with diabetes, 91 HbA1c and 708 lipid tests and 862 ACRs were automatically registered to comply with guidelines, resulting in expenses of €1948.90. Conclusions Making use of laboratory technology, it is possible to detect new cases of type 2 diabetes and prediabetes and to improve disease monitoring.

Objective To improve clinical laboratory contribution to the treatment of primary care patients with anorexia through automated computerized strategies. Methods We recorded the number of laboratory requests due to anorexia; the demographic data, laboratory values, and presence of pathological values for the applicable patients. In a prospective study, the laboratory information management system (LIMS) automatically added thyroid-stimulating hormone (TSH) and/or ferritin testing when it was not requested by general practitioners for all primary care patients with anorexia who were younger than 16 years. Results A total of 3562 patients underwent laboratory testing due to anorexia, of whom 47% were younger than 16 years. The tests in which the results most frequently were abnormal were hemoglobin, ferritin, and TSH. TSH results were abnormal in 20% of patients younger than 16 years. Through the intervention, we detected 3 low ferritin values and 7 cases of pathological TSH levels. Conclusions The LIMS required TSH and ferritin testing in young patients even when not requested, potentially avoiding the adverse effects of iron deficiency and thyroid disorders on neurological development and cognition in those patients.

To identify new transcriptomic alterations in pancreatic islets associated with metabolic dysfunctions in people with prediabetes (PD)/type 2 diabetes (T2D).We collected information from public data repositories T2D related microarray datasets from pancreatic islets. We identified Differential Expressed Genes (DEGs) in non-diabetic (ND) vs people with T2D in each study. To identify relevant DEGs in T2D, we selected those that varied consistently in the different studies for further meta-analysis and functional enrichment analysis. DEGs were also evaluated at the PD stage.A total of seven microarray datasets were collected and analysed to find the DEGs in each study and meta-analysis was performed with 245 ND and 96 T2D cases. We identified 55 transcriptional alterations potentially associated with specific metabolic dysfunctions in T2D. Meta-analysis showed that 87% of transcripts identified as DEGs (48 out of 55) were confirmed as having statistically significant up- or down-modulation in T2D compared to ND. Notably, nine of these DEGs have not been previously reported as dysregulated in pancreatic islets from people with T2D. Consistently, the most significantly enriched pathways were related to the metabolism and/or development/maintenance of β-cells. Eighteen of the 48 selected DEGs (38%) showed an altered expression in islets from people with PD.These results provide new evidence to interpret the pathogenesis of T2D and the transition from PD to T2D. Further studies are necessary to validate its potential use for the development/implementation of efficient new strategies for the prevention, diagnosis/prognosis and treatment of T2D.

Objectives Malnutrition is an unfavorable prognostic factor associated with an increase in mortality, hospital stays, readmissions and resources consumption. The aim was to screen primary care patients for risk of malnutrition by using the control nutritional (CONUT) score, calculated through total lymphocytes count, serum albumin and total cholesterol, when the three markers were requested, and to compare results between primary care centers (PCC). Methods The clinical laboratory located in a 370-bed suburban University Community Hospital serves the Health Department inhabitants (2,34,551), attended in nine PCC. The laboratory information system (LIS) automatically calculated the CONUT score in every primary care patient over 18 years old, when all three laboratory markers were ordered by the General Practitioner. For all primary care patients, we collected demographic data, CONUT index and PCC. We classified results by PCC, and compared them. Results The clinical laboratory received 74,743 requests from primary care. The CONUT score was calculated in 7,155 (12.28%) patients. Nine hundred seventy-six (13.6%) were at risk of malnutrition according to the CONUT score, mainly male (p Conclusions It is possible to use CONUT score as a front-line population-wide laboratory marker to screen for the risk for malnutrition in primary care patients that was lower in one PCC.

Background Risk of malnutrition can be evaluated through Controlling Nutritional (CONUT) Score based on total peripheral lymphocytes, serum albumin, and total cholesterol. Our aim was to automatically calculate CONUT in primary care when involved markers were requested and compare its performance with albumin to identify patients at risk of malnutrition. CONUT was evaluated according to patient age, and calculated the potential expenses to calculate CONUT, when serum markers were no requested, and measured. Methods We calculated CONUT when the three laboratory markers were requested, compared CONUT and albumin, considering risk of malnutrition CONUT ≥ 2, and albumin

Islet Neogenesis Associated Protein pentadecapeptide (INGAP-PP) increases β-cell mass and function in experimental animals. A short clinical trial also yielded promising results. However, HTD4010, a new peptide derived from INGAP-PP, was developed in order to optimize its specific effects by minimizing its side effects. To study and compare the tertiary structure, stability dynamics, and plasma stability of HTD4010, an INGAP-PP analogue. Both peptides were pre-incubated in human, rat and mouse plasma at 37 °C, and their presence was identified and quantified by high performance liquid chromatography at different time-points. GROMACS 2019 package and the Gromos 54A7 force field were used to evaluate overall correlated motion of the peptide molecule during molecular dynamics simulation by essential dynamics. HTD4010 exhibited significantly larger plasma stability than INGAP-PP, and its structural stability was almost 3.36-fold higher than INGAP-PP. These results suggest that HTD4010 may facilitate longer tissue interaction, thereby developing higher potential biological effects. If so, HTD4010 may become a promising therapeutic agent to treat people with diabetes. Communicated by Ramaswamy H. Sarma.

Background. The aim was to study the demographic and laboratory pattern of primary care patients with alopecia undergoing laboratory testing, more specifically, the request of hemoglobin and ferritin and values showing anemia and iron deficiency, and to evaluate the effects of an intervention involving automatic ferritin registration and measurement when not requested. Methods. Retrospective and prospective observational cross-sectional studies were conducted, as well as an intervention to automatically register and measure ferritin when not requested by the general practitioner. Results. There were 343 and 1032 primary care laboratory requests prompted by alopecia in the retrospective and prospective studies. Hemoglobin was requested in almost every patient and ferritin in 88%. 5% of the cohort had anemia, and 25% had iron deficiency. The intervention registered and measured that 123 ferritin and 24 iron deficiencies were detected in patients with alopecia, all women, at a cost of 10.6€. Conclusion. Primary care patients with alopecia and laboratory tests request were mainly young female. Our intervention added ferritin when not requested, detecting iron deficiency in 27.9% of women, potentially avoiding the adverse effects of iron deficiency on hair loss.

INTRODUCTION: The significance of hypomagnesemia and the need for treatment are under-recognized in clinical practice. Our objective was to design, establish, and test two interventions to screen for patients with hypomagnesemia and increase the rate of treatment of hypomagnesemia in the Emergency Department (ED). MATERIAL AND METHODS: A prospective two-year study was conducted. The Laboratory Information System was set to automatically order plasma magnesium in ED patients with plasma calcium

Islet-Neogenesis Associated Protein-Pentadecapeptide (INGAP-PP) increases β-cell mass and enhances glucose and amino acids-induced insulin secretion. Our aim was to demonstrate its effect on liver metabolism. For that purpose, adult male Wistar rats were injected twice-daily (10 days) with saline solution or INGAP-PP (250 μg). Thereafter, serum glucose, triglyceride and insulin levels were measured and homeostasis model assessment (HOMA-IR) and hepatic insulin sensitivity (HIS) were determined. Liver glucokinase and glucose-6-phosphatase (G-6-Pase) expression and activity, phosphoenolpyruvate carboxykinase (PEPCK) expression, phosphofructokinase-2 (PFK-2) protein content, P-Akt/Akt and glycogen synthase kinase-3β (P-GSK3/GSK3) protein ratios and glycogen deposit were also determined. Additionally, glucokinase activity and G-6-Pase and PEPCK gene expression were also determined in isolated hepatocytes from normal rats incubated with INGAP-PP (5 μg/ml). INGAP-PP administration did not modify any of the serum parameters tested but significantly increased activity of liver glucokinase and the protein level of its cytosolic activator, PFK-2. Conversely, INGAP-PP treated rats decreased gene expression and enzyme activity of gluconeogenic enzymes, G-6-Pase and PEPCK. They also showed a higher glycogen deposit and P-GSK3/GSK3 and P-Akt/Akt ratio. In isolated hepatocytes, INGAP-PP increased GK activity and decreased G-6-Pase and PEPCK expression. These results demonstrate a direct effect of INGAP-PP on the liver acting through P-Akt signaling pathway. INGAP-PP enhances liver glucose metabolism and deposit and reduces its production/output, thereby contributing to maintain normal glucose homeostasis. These results reinforce the concept that INGAP-PP might become a useful tool to treat people with impaired islet/liver glucose metabolism as it occurs in T2D. Fil: Villagarcía, Hernán Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: Román, Carolina Lisi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: Castro, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: González Arbeláez, Luisa Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina Fil: Ronco, Maria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina Fil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina Fil: Massa, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: Maiztegui, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: Flores, Luis Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: Francini, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina

Background To study the variability in the request of serum uric acid (SUA) in primary care. Method A cross-sectional study was designed and conducted at a main core laboratory. Spanish laboratories were invited to report their number of serum glucose (SG) and SUA tests requested from primary care during 2014. A survey was sent to every participant in November 2016 regarding the inclusion of SUA in order profiles/panels. The ratio of SUA/SG requests (SUA/SG) was calculated and compared between regions, and laboratories depending on whether SUA was included or not in a health check profile. Results 110 laboratories participated in the study (59.8% Spanish population). The median SUA/SG ratio was 0.82 (IQR: 0.25), and 41 laboratories had a ratio over 0.9. There was a significant regional variability (P = .008). Laboratories where SUA was not included in the "health check profile" had lower SUA/SG indicators (P = .003). Conclusion There was significant regional variability in the request of SUA, and an overall over-request. Different regional customs or habits and the inclusion of SUA in the health check profile were probable causes behind the observed over-request.

Background: The aim was to study the regional variability in the request of the ten most frequently ordered laboratory tests in primary care in Spain. Methods: Spain is divided into autonomous communities (AACC), first level health care divisions. Every AACC is divided into health departments (HDs). A laboratory attends the needs of every HD inhabitant. Laboratories from different HDs participated in the study. They reported the request of the ten most commonly requested laboratory tests in primary care during the year 2014 according to prior evidence: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol, creatinine, γ-glutamyl transpeptidase (GGT), glucose, HDL-cholesterol, triglycerides, uric acid and urinalysis. Test-utilization rates were calculated as tests per 1000 inhabitants. Laboratories were grouped in the different AACC and the results for each region were compared using the coefficient of quartile dispersion (CQD), calculated using the first (Q1) and third (Q3) quartiles for each data set, as follows: (Q3−Q1)/(Q3+Q1). Results: One hundred and ten laboratories participated, corresponding to 27,798,262 inhabitants (59.8% Spanish population) from 15 AACC. 82,710,869 tests were requested. AST, GGT and uric acid showed the greatest variation. Conclusions: There were significant regional differences in how the most common laboratory tests were ordered in Spain.

AimTo study the regional variability of requests for anaemia chemistry tests in primary care in Spain and the associated economic costs of potential over-requesting.MethodsRequests for anaemia tests were examined in a cross-sectional study. Clinical laboratories from different autonomous communities (AACCs) were invited to report on primary care anaemia chemistry tests requested during 2014. Demand for iron, ferritin, vitamin B12 and folate tests per 1000 inhabitants and the ratios of the folate/vitamin B12 and transferrin/ferritin requests were compared between AACCs. We also calculated reagent costs and the number of iron, transferrin and folate tests and the economic saving if every AACC had obtained the results achieved by the AACC with best practice.Results110 laboratories participated (59.8% of the Spanish population). More than 12 million tests were requested, resulting in reagent costs exceeding €16.5 million. The serum iron test was the most often requested, and the ferritin test was the most costly (over €7 million). Close to €4.5 million could potentially have been saved if iron, transferrin and folate had been appropriately requested (€6 million when extrapolated to the whole Spanish population).ConclusionsThe demand for and expenditure on anaemia chemistry tests in primary care in Spain is high, with significant regional differences between different AACCs.

Background Preparation of the patient for laboratory tests is crucial. Our aim was to investigate the current practice and regional variability of recommendations regarding patient preparation for laboratory testing. Methods A call for data was posted by email. Spanish laboratories were invited to fill out and submit a survey. Results Sixty-eight laboratories participated in the study. In 73% of those laboratories, fasting was always recommended regardless of the requested tests. Only one-third of the laboratories systematically recommended a 12-hour fast before the tests. In 71% of the laboratories, water intake was allowed without restrictions during the fasting period. In 57% of the laboratories, computerized order entry offered the possibility to print customized recommendations automatically in the primary care doctor’s office according to the requested tests. Seventy-two percent of the laboratories agreed with the proposed recommendation. Conclusions There was high variability in patient preparation for laboratory testing. A significant proportion of centers did not follow international guidelines.

Background Pharmacology has provided efficient tools to improve insulin effect/secretion but the decrease in β-cell mass remains elusive. INGAP-PP could provide a therapeutic alternative to meet that challenge. Aim To further understand the mechanism that links INGAP-PP effects upon β-cell mass and function with islet angiogenesis. Methodology Normal male Wistar rats were divided into 2 groups and injected with a single dose of 100 mg/Kg suramin or saline. Both groups were divided into 2 subgroups that received daily doses of 2 mg/kg INGAP-PP or saline for ten days. Plasma glucose, triacylglycerol, TBARS, and insulin levels were measured. Pancreas immunomorphometric analyses were also performed. Pancreatic islets were isolated to measure glucose-stimulated insulin secretion (GSIS). Specific islet mRNA levels were studied by qRT-PCR. Statistical analysis was done using ANOVA. Results No differences were recorded in body weight, food intake, or any other plasma parameter measured in all groups. Islets from INGAP-PP-treated rats significantly increased GSIS, β-cell mass, and mRNA levels of Bcl-2, Ngn-3, VEGF-A, VEGF-R2, CD31, Ang1 and Ang2, Laminin β-1, and Integrin β-1, and decreased mRNA levels of Caspase-8, Bad, and Bax. Islets from suramin-treated rats showed significant opposite effects, but INGAPP-PP administration rescued most of the suramin effects in animals treated with both compounds. Conclusion Our results reinforce the concept that INGAP-PP enhances insulin secretion and β-cell mass, acting through PI3K/Akt/mTOR pathways and simultaneously activating angiogenesis through HIF-1α-mediated VEGF-A secretion. Therefore, INGAP-PP might be a suitable antidiabetic agent able to overcome two major alterations present in T2D. Fil: Román, Carolina Lisi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: Maiztegui, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: Mencucci, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: Ahrtz, Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: Algañarás, Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: del Zotto, Hector Herminio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: Flores, Luis Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina

Introduction The request of Urinary albumin in primary care in Spain is insufficient to monitor patients with diabetes and hypertension (HTN). Our aim was to evaluate a strategy designed in consensus with general practitioners (GPs) to improve the request of urinary albumin in primary care patients with HTN according to guidelines, and to study its financial implications. Materials and methods In a meeting with GPs, we decided that the Laboratory Information System (LIS) would automatically register the albumin-to-creatinine ratio (ACR) test in patients with HTN when the former had not been requested in the previous year. We counted the number of ACRs requested by the GPs, those that were automatically added through the intervention, and if they were measured through the strip assay or additionally through quantification. We calculated the economic cost of the additional registered ACR based on reagent cost. Results In the 6 months study period, the laboratory received 48,075 requests for primary care patients. For 3816 (7.9%), HTN was the indication that prompted the request. 386 ACR were automatically registered through the intervention. Use of strip analysis cost of 275.8 € but resulted in savings of 1450.3€ in albumin reagent. Conclusions By making use of the laboratory technology, the strategy achieved a better adherence to the guidelines at no additional cost.

Introduction To compare the inter-practice variability in lipid metabolism laboratory tests requested by General Practitioners in Spain using appropriateness indicators and investigate the variability according to the different characteristics of the geographical regions. Materials and methods 141 clinical laboratories were invited to participate from diverse regions across Spain. We obtained the number of serum cholesterol, high-density cholesterol (HDL-cholesterol) and triglycerides requested by General Practitioners for the year 2012. Two types of appropriateness indicators were calculated: test requests per 1000 inhabitants and ratio of related tests requests (HDL-cholesterol/cholesterol, triglycerides /cholesterol). The indicators results obtained in different setting, with different type of management and in different geographical areas were compared. Results We obtained production statistics from 76 laboratories who attended a population of 17,679,195 inhabitants from 13 Communities throughout Spain. 5,823,053 cholesterol, 4,544,663 HDL-cholesterol and 5,599,358 triglycerides tests were ordered. Cholesterol, HDL-cholesterol and triglycerides per 1000 inhabitants indicators results ranged from 106.3 to 550.7; 20.4 to 417.5 and from 94.0 to 439.2 respectively. HDL-cholesterol/cholesterol, triglycerides/cholesterol indicators results ranged from 0.19 to 1.00 and from 0.54 to 1.00 respectively. Cholesterol, HDL-cholesterol and triglycerides were higher requested in rural areas. No significant differences in tests requests were observed based on Spanish Community. Conclusion There was a high variability in cholesterol, triglycerides and HDL-cholesterol requesting in primary care in Spain. Cholesterol was probably inappropriately under requested to screen for hypercholesterolemia in certain areas that would suggests a potential risk for inappropriate dyslipidemia screening in general population, emphasizing the need to establish interventions.

Background and objectives Laboratory tests are crucial for diagnosis and monitoring of thyroid disorders. It is therefore necessary to study the pattern and variability in requests of thyroid function tests. The study objectives were to compare the inter-regional variability in the request of laboratory thyroid tests by general practitioners (GPs) in Spain, and to investigate the potential economic savings if the goals set for some suitability indicators were reached. Methods Test requests per 1000 inhabitants and test ratios (free thyroxine (FT4)/thyrotropin (TSH), free triiodothyronine (FT3)/TSH, thyroglobulin antibody (TgAb)/peroxidase antibody (TPOAb)) were compared between the different areas, according to their setting, location, and management. The resulting savings if each department achieved the goals for indicator (0.25 for FT4/TSH, 0.1 for FT3/TSH) were estimated. Results Seventy-six laboratories covering a population of 17,679,195 inhabitants participated in the study. TSH was requested significantly less in urban-rural areas, and the requests for FT3/1000 inhabitants, FT3/TSH, and TgAb/TPOAb were higher in departments with private management. The savings generated if specifications for the ratios of related tests were met would be 937,260.5 €. Conclusions The high variability reported in requests for thyroid function and autoimmunity tests in Spain suggests the need for implementing strategies to improve use of such tests.

Introduction Many additional tasks in the Stat laboratory (SL) increase the workload. It is necessary to control them because they can affect the service provided by the laboratory. Our aim is to calculate these tasks, study their evolution over a 10 year period, and compare turnaround times (TAT) in summer period to the rest of the year. Materials and methods Additional tasks were classified as "additional test request" and "additional sample". We collected those incidences from the laboratory information system (LIS), and calculated their evolution over time. We also calculated the monthly TAT for troponin for Emergency department (ED) patients, as the difference between the verification and LIS registration time. A median time of 30 minutes was our indicator target. TAT results and tests workload in summer were compared to the rest of the year. Results Over a 10-year period, the technologists in the SL performed 51,385 additional tasks, a median of 475 per month. The workload was significantly higher during the summer (45,496 tests) than the rest of the year (44,555 tests) (P = 0.019). The troponin TAT did not show this variation between summer and the rest of the year, complying always with our 30 minutes indicator target. Conclusion The technicians accomplished a significant number of additional tasks, and the workload kept increasing over the period of 10 years. That did not affect the TAT results.

Introducción: el INGAP-PP es un péptido derivado de INGAP que, en animales normales y con diabetes, aumenta la masa celular ß, la capacidad angiogénica insular y potencia la secreción de insulina estimulada por glucosa (SIEG) y otros secretagogos. Esto le adjudica un potencial terapéutico que actuaría específicamente en la patogenia celular de la diabetes. Conocer su posible efecto sobre los cambios globales en los perfiles de expresión génica insular facilitaría la comprensión de su mecanismo de acción.Objetivos: conocer, a través de un estudio transcriptómico, el efecto del INGAP-PP sobre la expresión génica de las células insulares y la posible regulación de distintas vías de señalización implicadas.Materiales y métodos: islotes aislados (colagenasa) de rata Wistar normales fueron cultivados 4 días en medio RPMI en ausencia (C) o presencia de INGAP-PP 50 µg/ml (I) y glucosa 11 mM. A su término se utilizaron 100 islotes de cada grupo para estudiar la SIEG en presencia de glucosa 3,3 mMó 16,6 mM (RIA). Del resto de los islotes se extrajo ARN total, una alícuota fue sometida a secuenciación masiva de ARN (RNA-seq) y otra fue retrotranscripta a ADNc para utilizarlo como molde en qPCR de marcadores de desarrollo, regeneración y angiogénesis.

Introducción: la disfunción de las células ß está condicionada por alteraciones en la expresión génica y en sus mecanismos reguladores. Los micro ARNs (miARNs) son ARN no codificantes que regulan la expresión génica interactuando con ARNs mensajeros (ARNms) específicos. Una adecuada integración de estudios de perfiles de expresión de ARNms y miARNs facilita la identificación de alteraciones biológicas relevantes.Objetivos: identificar nuevas alteraciones transcriptómicas y miARNs involucrados en la patogenia de la diabetes tipo 2 (DM2) a través de la integración de datos disponibles en bases de datos públicas.Materiales y métodos: 1) analizamos 7 estudios de "microarray" realizados a partir de islotes de personas sin diabetes (ND; n=245) y con DM2 (n=96). Identificamos los genes diferencialmente expresados (GDEs) (ND vs DM2), seleccionamos aquellos que variaban consistentemente en los diferentes estudios y realizamos un meta-análisis. 2) Posteriormente, para identificar miARNs funcionalmente relevantes, se integró información de perfiles de expresión de miARNs y ARNms con la predicción computacional de interacciones miARN-ARNm. Este análisis se realizó sobre un estudio realizado en un modelo murino de DM2, en el que se analizaron ambos tipos de ARNs en el mismo tejido pancreático, mediante técnicas de "NextGenerationSequencing".

Introducción: la asociación de la diabetes tipo 2 (DM2) con otros factores de riesgo cardiovascular como sobrepeso/obesidad, promueven el desarrollo de disfunción endocrino-metabólica. No es claro el efecto directo sobre la masa/función de las células insulares que podrían efectuar las adipoquinas producidas por los adipocitos blancos (AB) del tejido adiposo visceral y las batoquinas producidas por adipocitos pardos (AP) y beige (A beige).Objetivos: demostrar el posible efecto directo de metabolitos, adipoquinas y batoquinas sobre marcadores de la función/masa de células insulares, su respuesta inflamatoria y los mediadores intracelulares de insulina.Materiales y métodos: removimos el páncreas y los tejidos adiposos visceral (TAV) e interescapular (TAI) de ratas Wistar y los digerimos con colagenasa (aislamiento de islotes y adipocitos). El fenotipo de los adipocitos fue verificado por qPCR de marcadores de AB (UCP-2 y Wdnm1); de AP (UCP-1 y Cidea) y de A beige (TMEM-26). Los AB y AP fueron incubados 1 h en medio KRB para obtener los correspondientes medios condicionados (MC-AB y MC-AP) para su utilización en forma individual o combinada (1:1), como medios de incubación de islotes en presencia de glucosa 16,6 mM. De los islotes incubados obtuvimos el ARN total para evaluar la expresión de genes (qPCR) reguladores de apoptosis, mediadores de la acción de insulina y de respuesta inflamatoria.

Introducción: la prediabetes inducida en ratas normales mediante la administración de una dieta rica en fructosa (DRF) durante 21 días promueve insulinorresistencia (IR), hiperinsulinemia, hipertrigliceridemia, aumento del estrés oxidativo y de la respuesta inflamatoria.Objetivos: verificar los posibles cambios desarrollados en el tejido adiposo pardo (TAP) en el estadio de prediabetes.Materiales y métodos: ratas SpragueDowley macho normales de 60 días de edad, consumieron durante 21 días una dieta comercial estándar (C) o dicha dieta más 10% de fructosa en el agua de bebida (DRF). Finalizado el tratamiento, se sacrificaron midiéndose los niveles plasmáticos de glucosa (G), triglicéridos (TG), colesterol total, c-HDL y la relación TG/colesterol HDL (indicador de IR). También se extrajo el TAP determinándose la relación peso tejido/peso animal, su composición de ácidos grasos (AG) y la expresión génica de marcadores de la cascada de insulina, inflamación y apoptosis mediante qPCR.

Simposio 17: Falla de la célula betaAl rescate de la célula betaLas células β pancreáticas están especializadas para liberar insulina ante cualquier aumento de la glucemia mediante un complejo mecanismo altamente regulado que asegura el mantenimiento de su homeostasis. Existen múltiples factores genéticos y ambientales que atentan contra la integridad funcional de las células β y que son responsables de la progresión del estado normal al de prediabetes o de diabetes mellitus tipo 2 (DM2).En la actualidad disponemos de diversas herramientas farmacológicas que pueden recuperar su función secretora, pero ninguna es capaz de recuperar su masa, por lo cual resulta fundamental prevenir su pérdida. El consumo de dietas desbalanceadas, particularmente de dietas ricas en bebidas edulcoradas con jarabe de alto contenido de fructosa (DRF), promueve la ruptura de la homeostasis metabólica y el surgimiento de un estado de insulinorresistencia (IR) que ya se manifiesta en el estadio de prediabetes.

Background The clinical laboratory plays a crucial role in the diagnosis and monitoring of chronic kidney disease. The quantitative measurement of urine albumin in a spot sample, expressed as ratio per creatinine (ACR) is the most frequently used biomarker for such a purpose. Our aim was to evaluate the diagnostic performances of a strip for measuring ACR for differentiating patients who are candidates for subsequent albumin quantification, and to evaluate the economic effects of its implementation. Methods We systematically measured strip analysis when quantitative urinary albumin was requested. Semiquantitative urinary albumin was measured using a UC-3500 (Sysmex, Kobe, Japan), based on the protein error of a pH indicator. We collected and reviewed all the values of quantified urinary albumin and their corresponding results in ACR strip tests. We calculated the diagnostic indicators for ACR at different albumin and creatinine values using the quantitative ACR measurement as a “gold standard”. We also studied the economic effects based on both tests prices (€1.31 for quantitative albumin plus creatinine, and €0.04 for an albumin strip). Results The study included 9148 patients (mean age 63, 46.3% men). The results at different albumin and creatinine cutoffs showed the best performance when 10 mg/L and above 50 mg/dL, respectively. Based on our results, we would have saved 3506 urine albumin and creatinine tests in the study period, corresponding to €4226.94. Conclusions The present study supports the use of the ACR strip test to identify pathological albuminuria values to be measured through quantitative methods. Considerable economic savings are possible.

To characterize the intrinsic mechanism by which sucrose induces β-cell dysfunction. Normal rats received for 3 weeks a standard diet supplemented with 10% sucrose in the drinking water (high sucrose (HS)) with/out an antioxidant agent (R/S α-lipoic acid). We measured plasma glucose, insulin, triglyceride, leptin, and lipid peroxidation levels; homeostasis model assessment (HOMA)-insulin resistance (HOMA-IR) and HOMA for β-cell function (HOMA-β) indexes were also determined. Insulin secretion, β-cell apoptosis, intracellular insulin and leptin mediators, and oxidative stress (OS) markers were also measured in islets isolated from each experimental group. HS rats had increased plasma triglyceride, insulin, leptin, and lipid peroxidation (OS marker) levels associated with an insulin-resistant state. Their islets developed an initial compensatory increase in glucose-induced insulin secretion and mRNA and protein levels of β-cell apoptotic markers. They also showed a significant decrease in mRNA and protein levels of insulin and leptin signaling pathway mediators. Uncoupling protein 2 (UCP2), peroxisome proliferator-activated receptor (PPAR)-α and -δ mRNA and protein levels were increased whereas mRNA levels of Sirtuin-1 (Sirt-1), glutathione peroxidase, and catalase were significantly lower in these animals. Development of all these endocrine-metabolic abnormalities was prevented by co-administration of R/S a-lipoic acid together with sucrose. OS may be actively involved in the mechanism by which unbalanced/unhealthy diet induces β-cell dysfunction. Since metabolic-endocrine dysfunctions recorded in HS rats resembled those measured in human pre-diabetes, knowledge of its molecular mechanism could help to develop appropriate strategies to prevent the progression of this metabolic state toward type 2 diabetes (T2D)., Centro de Endocrinología Experimental y Aplicada

The objective of this review article is to address the most frequently asked questions that pathologists and primary care physicians might face when dealing with a patient with suspicion of vitamin B12 deficiency. More specifically, the article mainly discusses the importance and prevalence of the deficit, how to recognize it, and the important role of a prompt diagnosis confirmation based on laboratory biomarkers for efficient replacement therapy.

BACKGROUND To study the urinalysis request, pre-analytical sample conditions, and analytical procedures. METHODS Laboratories were asked to provide the number of primary care urinalyses requested, and to fill out a questionnaire regarding pre-analytical conditions and analytical procedures. RESULTS 110 laboratories participated in the study. 232.5 urinalyses/1,000 inhabitants were reported. 75.4% used the first morning urine. The sample reached the laboratory in less than 2 hours in 18.8%, between 2 - 4 hours in 78.3%, and between 4 - 6 hours in the remaining 2.9%. 92.5% combined the use of test strip and particle analysis, and only 7.5% used the strip exclusively. All participants except one performed automated particle analysis depending on strip results; in 16.2% the procedure was only manual. CONCLUSIONS Urinalysis was highly requested. There was a lack of compliance with guidelines regarding time between micturition and analysis that usually involved the combination of strip followed by particle analysis.

Aims Liver laboratory tests are used to screen for liver disease, suggest the underlying cause, estimate the severity, assess prognosis, and monitor the efficacy of therapy. The aim of this study was to compare the liver laboratory tests requesting patterns by GPs in Spain, according to geographic and hospital characteristics, to investigate the degree of requesting appropriateness. Materials and methods One hundred and forty-one clinical laboratories were invited to participate from diverse regions across Spain. They filed out the number of laboratory liver tests requested by GPs for the year 2012. Two types of appropriateness indicators were calculated: every test request per 1000 inhabitants or ratios of related tests requests. The indicator results obtained were compared between the different hospitals, according to their setting, location, and management. The savings generated, if each area would have achieved indicator targets, were calculated. Results We recruited 76 laboratories covering a population of 17,679,195 inhabitants. GPs requested 20,916,780 laboratory liver tests in the year 2012. No differences were obtained according to their setting. Lactate dehydrogenase and direct bilirubin per 1000 inhabitants were significantly higher in institutions with private management. Largest differences were observed between communities. Nine, 31, 0, and 13 laboratories, respectively, achieved the aspartate aminotransferase, lactate dehydrogenase, γ-glutamyl transpeptidase, and total bilirubin-related alanine aminotransferase indicator targets. Reaching ratios would have resulted in savings of €1,028,468. Conclusion There was a high variability in the request of liver tests. This emphasizes the need to implement interventions to improve appropriate use of liver tests.

Introduction The study was performed to compare and analyze the inter-departmental variability in the request of rarely requested laboratory tests in primary care, as opposed to other more common and highly requested tests. Materials and methods Data from production statistics for the year 2012 from 76 Spanish laboratories was used. The number of antinuclear antibodies, antistreptolysin O, creatinine, cyclic citrullinated peptide antibodies, deaminated peptide gliadine IgA antibodies, glucose, protein electrophoresis, rheumatoid factor, transglutaminase IgA antibodies, urinalysis and uric acid tests requested was collected. The number of test requests per 1000 inhabitants was calculated. In order to explore the variability the coefficient of quartile dispersion was calculated. Results The smallest variation was seen for creatinine, glucose, uric acid and urinalysis; the most requested tests. The tests that were least requested showed the greatest variability. Conclusion Our study shows through a very simplified approach, in a population close to twenty million inhabitants, how in primary care, the variability in the request of laboratory tests is inversely proportional to the request rate.

Background: Severe vitamin B12 deficiency can result in serious complications If undiagnosed or untreated. Our aim was to test the efficacy of interventions in the laboratory process to improve the detection and the treatment of severe vitamin B12 deficiency. Methods: Quasi-experimental investigation with a retrospective 7-year pre-intervention period and 29-month post-intervention follow-up in a university hospital. Two interventions were designed to improve the detection and treatment of subjects with vitamin B12 deficiency: the laboratory information system (LIS) automatically added seru vitamin B12 (s-vitamin B12) based on certain conditions; and created a comment in the report and scheduled an appointment with the general practitioner (GP). We calculated the number of new diagnoses of severe vitamin deficiency (s-vitamin B12

Objective To compare the ratios of requests of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) and urea to creatinine (Crea); to investigate the variability among regions and to calculate the potential savings if a target is reached. Methods Laboratories were invited to fill out a registration form on the number of AST, ALT, Urea and Crea requested in 2014, and to provide the reagent price of urea and AST. AST:ALT and Urea:Crea were calculated and compared; also compared were potential savings if each laboratory would have reached the target. Results: A significant difference was found among regions in Urea:Crea. Twenty-one laboratories reached the goal in AST:ALT, and 6 in Urea:Crea. The potential savings if each indicator would have reached the target would have been $553,827 and $745,184, respectively. Conclusion Variability was found in AST:ALT and Urea:Crea, which resulted in a significant unnecessary financial burden and suggests the need to promote the optimal requesting rate.

BACKGROUND Our aim is to study the regional variability in the request of thyroid laboratory tests from primary care facilities in Spain and to investigate a potential inappropriate request and its economic societal impact. METHODS Spain is divided into 17 autonomous communities (AACCs) which are in turn divided in Health Departments that cover a geographic area and its population and a laboratory that attends the needs of every inhabitant. Each participating laboratory was required to report the number of thyroid tests requested from primary care during year 2014 and to provide organizational data. The request of every test per 1000 inhabitants and ratio of related tests (free thyroxine (FT4)/thyrotropin (TSH), triiodothironine (FT3)/TSH, antithyroglobulin antibody (ATG)/antiperoxidase antibody (TPO)) were calculated and compared in different AACCs with more than 4 participants. The economic costs taking into account reagent cost were calculated. RESULTS 110 laboratories participated (27,798,262 inhabitants). Close to 6 million TSH tests were requested, representing an expense of more than 10 million euros. That corresponds to 18 million euros when extrapolating for the whole Spanish population, only in reagent cost. The number of TSH requests per 1000 inhabitants in the different AACCs ranged from 198 to 289. FT4 was ordered more than twice as frequently in some regions compared to others. TPO request per 1000 inhabitants ranged from 0.2 to 11.2. CONCLUSIONS There was a significant over-request and regional variability of thyroid laboratory tests in primary care in Spain, resulting in a high economic impact on society.

Background Glycated haemoglobin (HbA1c) is one of the most useful and relevant laboratory tests currently available. The aim of the actual research was to study the variability and appropriateness in the request of HbA1c in primary care, and differences between regions, to assess if there would be an opportunity to improve the request. Methods A cross-sectional study was conducted enrolling clinical Spanish laboratories. The number of HbA1c requested in 2014 by all general practitioners was reported by each participant. Test-utilization rate was expressed as tests per 1000 inhabitants. The index of variability was calculated, as the top decile divided by the bottom decile. HbA1c per 1000 inhabitants was compared between the different regions. To investigate whether HbA1c was appropriately requested to manage patients with diabetes, the real request was compared to the theoretically ideal number, according to prevalence of known diabetes mellitus in Spain and guideline recommendations. Results A total of 110 laboratories participated in the study, corresponding to a catchment area of 27 798 262 inhabitants (59.8% of the Spanish population) from 15 different autonomous communities (AACCs). 2 655 547 HbA1c were requested, a median of 93.9 (interquartile range (IQR): 33.4) per 1000 inhabitants. The variability index was 1.97. The HbA1c/1000 inhabitants was significantly different among the AACCs, ranging from 73.4 to 126.3. A total of 4 336 529 additional HbA1c would have been necessary to manage patients with diabetes according to guidelines, and 3 861 769 for diagnosis in asymptomatic patients. Conclusions There was a high variability and significant differences between Spanish AACCs. Also a significant under-request of HbA1c was observed in Primary Care in Spain.

Our aim was to determine whether islet angiogenesis and VEGFA production/release participate in the mechanism by which INGAP-PP enhances β-cell function and mass. We used two models: a) in vivo (normal rats injected with INGAP-PP for 10 days) and b) in vitro (normal islets cultured for 4 days with INGAP-PP, VEGFA, Rapamycin, and the specific VEGF-Receptor inhibitor, SU5416). INGAP-PP administration enhanced insulin secretion, β-cell mass, islet vascularization, and angiogenesis without affecting glucose homeostasis. Normal islets cultured with INGAP-PP and VEGFA increased insulin and VEGFA secretion while apoptosis decreased. INGAP-PP-induced effects were prevented by both Rapamycin and SU5416. INGAP-PP effects on β-cell mass and function were significantly associated with a positive effect on islet angiogenesis and VEGFA production/release. VEGF-A possibly potentiates INGAP-PP effect through mTORC pathway. Fil: Román, Carolina Lisi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: Maiztegui, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: del Zotto, Hector Herminio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: Flores, Luis Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; Argentina