Testing a new approach to translate research achievements into improved quality of care worldwide

The aim of the BRIDGES Research net is within the BRIDGES main scope: a) to improve the control and treatment of diabetes in a concerted effort to reduce the development and progression of chronic complications, thus decreasing the cost of its care and improving the quality of life of people with diabetes worldwide, b) to promote the early diagnosis of the disease and prevent its development, and c) to increase the critical mass of translational researchers worldwide. Better access of health providers and authorities to evidence-based practice, replicability and self-sustainability would be the central aim of this new initiative.Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentin

Physiological endocrine control of energy homeostasis and postprandial blood glucose levels

The aim of this review is to analyze the different components and the feedback mechanisms involved in the normal control of energy homeostasis and postprandial blood glucose levels. Such control involves exogenous and endogenous factors: while the former include quantity and quality of food intake, the latter involve the balance of glucose intestinal absorption (postprandial period), glucose production and release by the liver and its consumption by peripheral tissues. Adequate secretion and peripheral metabolic effects of insulin play a key role in the control of both processes. Insulin secretion is controlled by the level of circulating substrates and by gastrointestinal hormones. The mechanism for the immediate control of blood glucose levels is modulated by energy homeostasis, with the participation of the above mentioned hormones and others produced at the classical endocrine system and adipose tissue, whose actions integrate at the central nervous system. The alteration of such delicate mechanism of control causes diseases such as diabetes; therefore, identification of the multiple components of this mechanism and comprehension of its normal function would facilitate the selection of effective strategies for diabetes prevention and treatment.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; Argentin

Effetto di un ipoglicemizzante orale sui livelli glicemici in funzione del tempo

A constant dosage of glibenclamide (50 µg/kg i.p.) was administered to normal mice at 4-h intervals during the day. Blood samples were collected up to 360 min after the injection, for glucose determination. It was found that neither the depth nor the duration of the glibenclamide-induced hypoglycemia was constant throughout the day. These results demonstrate the existence of a circadian rhythm of the glibenclamide effect on serum glucose levels. They also suggest that a day-time schedule of therapy with this drug should result in improved control of serum glucose.Una dose costante di glibenclamide (50 µg/kg i.p.) è stata somministrata a topi normali, ad intervalli di 4 h nel corso della giornata. Prelievi di sangue per il dosaggio della glicemia sono stati praticati fino a 360 min dopo l’iniezione della sostanza. Né l’entità né la durata dell’ipoglicemia indotta dalla glibenclamide sono risultate costanti durante l’intera giornata. Questi risultati dimostrano l’esistenza di un ritmo circadiano nell’effetto della sulfanilurea sulle concentrazioni sieriche del glucosio. Essi inducono a ritenere che l’elaborazione di uno schema cronologico per la somministrazione del farmaco lungo l’arco delle 24 h dovrebbe consentire una migliore regolazione della glicemia.Une dose constante de glibenclamide (50 µg/kg i.p.) a été administrée à des rats normaux par intervalles de 4 h au cours de la journée. On a effectué des prélèvements de sang, pour le dosage du glucose, jusqu’à 360 min après l’injection. Ni le niveau, ni la durée de l’hypoglycémie provoquée par le glibenclamide sont resultés constants pendant toute la journée. Ces résultats démontren l’existence d’un rythme circadien relatif à l’effet du glibenclamide sur le niveau du glucose dans le sérum et font, en outre, penser que, en élaborant une oraire pour l’administration du médicament pendant la journée, on pourrait obtenir une meuilleure régulation de la glycémie.Ha sido suministrada a ratones normales y a intervalos de 4 h en el curso del día, una dosis constante de glibenclamida (50 µg/kg i.p.). Se han efectuado extracciones de sangre para la dosificación de la glucemia hasta los 360 min después de la inyección de la substancia. Tanto la entidad como la duración de la hipoglucemia inducida por la glibenclamida no resultaron constantes durante todo el día. Estos resultados demuestran la existencia de un ritmo circadiano en el efecto de la sulfanilurea sobre las concentraciones séricas de la glucosa y, además, nos inducen a suponer que la elaboración de un esquema cronológico para el suministro del producto en el arco de las 24 h debería permitir una regulación mejor de la glucemia.Eine gleiche Dosis Glibenclamid (50 µg/kg i.p.) wurde normalen Mäusen in 4-stündigen Abständen im Lauf des Tages verabreicht. Blutproben wurden bis zu 360 min nach der Injektion zur Blutzuckerbestimmung entnommen. Es erwies sich, dass weder Tiefe noch Dauer der von Glibenclamid verursachten Blutzuckersenkung im Lauf des Tages konstant waren. Diese Ergebnisse zeigen, dass die Wirkung des Glibenclamids auf den Serumglukosespiegel einem Tagesrhythmus unterworfen ist. Sie lassen auch vermuten, dass die Behandlung mit diesem Medikament nach einem Tagesplan zu einer besseren Regelung des Blutzuckerspiegels führen sollte.Facultad de Ciencias Médica

Possible modulatory effect of endogenous islet catecholamines on insulin secretion

Background: The possible participation of endogenous islet catecholamines (CAs) in the control of insulin secretion was tested. Methods: Glucose-induced insulin secretion was measured in the presence of 3-lodo-L-Tyrosine (MIT), a specific inhibitor of tyrosine-hydroxylase activity, in fresh and precultured islets isolated from normal rats. Incubated islets were also used to measure CAs release in the presence of low and high glucose, and the effect of α 2-(yohimbine [Y] and idazoxan [I]) and α1-adrenergic antagonists (prazosin [P] and terazosin [T]) upon insulin secretion elicited by high glucose. Results: Fresh islets incubated with 16.7 mM glucose released significantly more insulin in the presence of 1 μM MIT (6.66 ± 0.39 vs 5.01 ± 0.43 ng/islet/h, p < 0.02), but did not affect significantly the insulin response to low glucose. A similar enhancing effect of MIT upon insulin secretion was obtained using precultured islets devoid of neural cells, but absolute values were lower than those from fresh islets, suggesting that MIT inhibits islet rather than neural tyrosine hydroxylase. CAs concentration in the incubation media of fresh isolated islets was significantly higher in the presence of 16.7 than 3.3 mM glucose: dopamine 1.67 ± 0.13 vs 0.69 ± 0.13 pg/islet/h, p < 0.001, and noradrenaline 1.25 ± 0.17 vs 0.49 ± 0.04 pg/islet/h, p < 0.02. Y and I enhanced the release of insulin elicited by 16.7 mM glucose while P and T decreased such secretion. Conclusion: Our results suggest that islet-originated CAs directly modulate insulin release in a paracrine manner.Facultad de Ciencias Médica

Relation between cost of drug treatment and body mass index in people with type 2 diabetes in Latin America

Aims Despite the frequent association of obesity with type 2 diabetes (T2D), the effect of the former on the cost of drug treatment of the latest has not been specifically addressed. We studied the association of overweight/obesity on the cost of drug treatment of hyperglycemia, hypertension and dyslipidemia in a population with T2D. Methods This observational study utilized data from the QUALIDIAB database on 3,099 T2D patients seen in Diabetes Centers in Argentina, Chile, Colombia, Peru, and Venezuela. Data were grouped according to body mass index (BMI) as Normal (18.5BMI<25), Overweight (25BMI<30), and Obese (BMI30). Thereafter, we assessed clinical and metabolic data and cost of drug treatment in each category. Statistical analyses included group comparisons for continuous variables (parametric or non-parametric tests), Chi-square tests for differences between proportions, and multivariable regression analysis to assess the association between BMI and monthly cost of drug treatment. Results Although all groups showed comparable degree of glycometabolic control (FBG, HbA1c), we found significant differences in other metabolic control indicators. Total cost of drug treatment of hyperglycemia and associated cardiovascular risk factors (CVRF) increased significantly (p<0.001) with increment of BMI. Hyperglycemia treatment cost showed a significant increase concordant with BMI whereas hypertension and dyslipidemia did not. Despite different values and percentages of increase, this growing cost profile was reproduced in every participating country. BMI significantly and independently affected hyperglycemia treatment cost. Conclusions Our study shows for the first time that BMI significantly increases total expenditure on drugs for T2D and its associated CVRF treatment in Latin America.Fil: Elgart, Jorge Federico. 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; ArgentinaFil: Prestes, Mariana. 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; ArgentinaFil: Gonzalez, Lorena. 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; ArgentinaFil: Rucci, Enzo. 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; ArgentinaFil: 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; Argentin

A model educational program for people with type 2 diabetes : A cooperative Latin American implementation study (PEDNID-LA)

Objective - To implement an educational program in 10 Latin American countries and to evaluate its effect on the clinical, biochemical, and therapeutic aspects as well as the economic cost of diabetes. Research design and methods - Educators from each participating country were previously trained to implement the educational model. The patient population included 446 individuals with type 2 diabetes; all patients were <65 years of age, did not require insulin for metabolic control, did not have severe complications of diabetes or life-limiting illnesses, and had not previously participated in diabetes education courses. Clinical and therapeutic data and the cost of their pharmacological treatment were collected 6 months before participation in the educational program (-6 months), on entry into the program (time 0), and at 4, 8, and 12 months after initiation of the program. Results - All parameters measured had improved significantly (P 1c 9.0 ±2.0 vs. 7.8 ± 1.6%; body weight 84.6 ±14.7 vs. 81.2 ±15.2 kg; systolic blood pressure 149.6 ±33.6 vs. 142.9 ± 18.8 mmHg; total cholesterol 6.1 ±1.1 vs. 5.4 ±1.0 mmol/l; and triglycerides 2.7 ± 1.8 vs. 2.1 ±1.2 mmol/l. At 12 months, the decrease in pharmacotherapy required for control of diabetes, hypertension, and hyperlipidemia represented a 62% decrease in the annual cost of treatment ($107,939.99 vs.$41,106.30 [U.S.]). After deducting the additional cost of glucosuria monitoring ($30,604), there was still a 34% annual savings. Conclusions - The beneficial results of this educational model, implemented in 10 Latin American countries, reinforce the value of patient education as an essential part of diabetes care. They also suggest that an educational approach promoting healthy lifestyle habits and patient empowerment is an effective strategy with the potential to decrease the development of complications related to diabetes as well as the socioeconomic costs of the disease.Facultad de Ciencias MédicasCentro de Endocrinología Experimental y Aplicad

Glucagon and insulin secretion during acid-base alterations

Previously, we reported that change from the normal pH of 7.4 surrounding the islet cells to 7.8 results in a decreased B-cell response to 16.6 mM glucose, 10 mM arginine or 400 µg/ml tolbutamide. In the present report we studied the effect of modifications in the extracellular pH on glucose- and arginine-induced glucagon and insulin secretion by the perfused rat pancreas. It was found that at pH 7.8, arginine-induced glucagon secretion was significantly greater than at pH 7.4. On the other hand, the switch from pH 7.4 to 7.8 in a pancreas already stimulated by either low glucose or arginine, produced fast and transient glucagon release. Sequential extracellular pH changes from 7.4 to 7.8 and back to 7.4 in the presence of 8.3 mM glucose and a 5 mM arginine stimulus demonstrated that A- and B-cells rapidly modify their secretion in response to extracellular alkalosis in opposite directions. While glucagon output was enhanced (mean secretory rates at pH 7.4, 0.692 ± 0.042 ng/min and 0.948 ± 0.57 at pH 7.8), insulin secretion was clearly reduced (72.6 ± 6.2 ng/min and 35.7 ± 2.8 ng/min at pH 7.4 and 7.8, respectively). The above observations, together with our previously reported data, indicate that extracellular pH plays an important role in the regulation of glucagon and insulin release. Particularly, extracellular alkalosis enhances A-cell response to 2.3 mM glucose and 5 mM arginine while partially inhibiting B-cell secretion in the perfused rat pancreas.Centro de Endocrinología Experimental y Aplicad

Possible modulatory effect of endogenous islet catecholamines on insulin secretion

Background: The possible participation of endogenous islet catecholamines (CAs) in the control of insulin secretion was tested. Methods: Glucose-induced insulin secretion was measured in the presence of 3-lodo-L-Tyrosine (MIT), a specific inhibitor of tyrosine-hydroxylase activity, in fresh and precultured islets isolated from normal rats. Incubated islets were also used to measure CAs release in the presence of low and high glucose, and the effect of α 2-(yohimbine [Y] and idazoxan [I]) and α1-adrenergic antagonists (prazosin [P] and terazosin [T]) upon insulin secretion elicited by high glucose. Results: Fresh islets incubated with 16.7 mM glucose released significantly more insulin in the presence of 1 μM MIT (6.66 ± 0.39 vs 5.01 ± 0.43 ng/islet/h, p < 0.02), but did not affect significantly the insulin response to low glucose. A similar enhancing effect of MIT upon insulin secretion was obtained using precultured islets devoid of neural cells, but absolute values were lower than those from fresh islets, suggesting that MIT inhibits islet rather than neural tyrosine hydroxylase. CAs concentration in the incubation media of fresh isolated islets was significantly higher in the presence of 16.7 than 3.3 mM glucose: dopamine 1.67 ± 0.13 vs 0.69 ± 0.13 pg/islet/h, p < 0.001, and noradrenaline 1.25 ± 0.17 vs 0.49 ± 0.04 pg/islet/h, p < 0.02. Y and I enhanced the release of insulin elicited by 16.7 mM glucose while P and T decreased such secretion. Conclusion: Our results suggest that islet-originated CAs directly modulate insulin release in a paracrine manner.Facultad de Ciencias Médica

Clinical, metabolic and psychological outcomes and treatment costs of a prospective-randomized trial based on different educational strategies to improve diabetes care (PRODIACOR)

Aim To evaluate the effect of system interventions (formalized data collection and 100% coverage of medications and supplies) combined with physician and/or patient education on therapeutic indicators and costs in Type 2 diabetes. Methods Randomized 2x2 design in public health, social security or private prepaid primary care clinics in Corrientes, Argentina. Thirty-six general practitioners and 468 adults with Type 2 diabetes participated. Patients of nine participating physicians were selected randomly and assigned to one of four structured group education programmes (117 patients each): control, physician education, patient education and both, with identical system interventions in all four groups. Outcome measures included glycated haemoglobin, body mass index, blood pressure, fasting glucose, lipid profile, drug consumption, resource use and patient well-being at baseline and every 6 months up to 42 months. Results Glycated haemoglobin decreased significantly from 0.34 to 0.84% by 42 months (P < 0.05); the largest and more consistent decrease was in the groups where patients and physicians were educated. Blood pressure and triglycerides decreased significantly in all groups; the largest changes were recorded in the combined education group. The WHO-5-Lowe score showed significant improvements, without differences among groups. The lowest treatment cost was seen in the combined education group. Conclusions In a primary care setting, educational interventions combined with comprehensive care coverage resulted in long-term improvement in clinical, metabolic and psychological outcomes at the best cost-effectiveness ratio. Trial registration NCT01456806 Keywords Type 2 diabetes management, patient and healthcare provider education, quality of care, patient satisfaction, psychological impactFil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Lapertosa, Silvia. Ministerio de Salud de la Provincia de Corrientes; ArgentinaFil: Pfirter, Guillermina . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Villagra, Mirta. Ministerio de Salud de la Provincia de Corrientes; ArgentinaFil: Caporale, Joaquín E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Gonzalez, Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Elgart, Jorge Elgart. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Gonzalez, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Cernadas, C.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Rucci, Enzo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Clark, C.. Indiana University; Estados Unido

The beta-receptors in the rat pancreas

Se estudio el efecto del isoproterenol (ISO) sobre la secrecion de insulina in vitro. Los resultados indican que el ISO es capaz de estimular la secrecion de insulina en forma similar a la glucosa en altas concentraciones.Facultad de Ciencias Médica