Prediabetes is more than a pre-disease: additional evidences supporting the importance of its early diagnosis and appropriate treatment.

AIM: To identify Prediabetes (PreD) as early and serious diabetes step using clinical-biochemical characteristics in the population of the Primary Prevention Diabetes Buenos Aires (PPDBA) study. METHODS: PPDBA Study evaluated benefits of adopting healthy lifestyles to prevent T2D. It recruited people 45-75 years of age with PreD (impaired fasting glycaemia [IFG], impaired glucose tolerance [IGT] or both, American Diabetes Association criteria), using an opportunistic approach. They completed a FINDRISC questionnaire, and those with a score ≥13 points were invited to participate. When they accepted, we performed an oral glucose tolerance test (OGTT) with a complete lipid profile and HbA1c while physicians completed a clinical history. We recruited 367 persons, and depending on OGTT results, the sample was divided into normals (NGT), PreD, or with diabetes (last one was excluded in our analysis). Data were statistically analyzed using parametric and nonparametric tests and logistic regression to identify parameters associated with PreD. RESULTS: From the recruited (n = 367) 47.7% have NGT, 48.5% PreD and 3.8% unknown T2D (excluded). People with PreD were significantly older, with a higher percentage of overweight/obesity, BMI, and larger waist circumference than NGT. They also showed significantly higher fasting and 2 h post glucose load, HbA1c, and triglyceride levels. No significant differences were recorded in the blood pressure, lipid profile though both groups had abnormally high LDL-c values. They also had a larger percentage of TG/HDL-c ratios (insulin resistance indicator) (55% vs. 37.5%). Logistic regression analysis showed that PreD was significant associated with age, waist circumference, and triglyceride above target values. CONCLUSION: Our findings showed that clinical and biochemical parameters were significantly different between people with PreD and those with NGT. This evidence supports the concept that PreD is a serious dysfunction, which should be early diagnosed and treated properly to prevent its transition to T2D and its complications.

Effects of islet neogenesis associated protein depend on vascular endothelial growth factor gene expression modulated by hypoxia-inducible factor 1-alpha.

BACKGROUND: Pharmacology has provided efficient tools to improve insulin effect/secretion but the decrease in ß-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 ß-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, ß-cell mass, and mRNA levels of Bcl-2, Ngn-3, VEGF-A, VEGF-R2, CD31, Ang1 and Ang2, Laminin ß-1, and Integrin ß-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 ß-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.

Actividad física y factores de riesgo cardiovascular: evidencia de su interrelación a nivel nacional / Physical activity and cardiovascular risk factors: evidence of their interrelation nationwide

RESUMEN Antecedentes: En nuestro país la prevalencia de diabetes tipo 2 (DT2) y de factores de riesgo cardiovascular (FRCV) aumenta continuamente. Aunque el fenómeno se acompaña de adopción de estilos de vida no saludable que facilitan dicho crecimiento, es escasa la implementación de estrategias que puedan modificar la situación. Objetivo: Revisar la evidencia disponible sobre la magnitud del problema de la diabetes y los FRCV en nuestro país, su posible relación con la práctica de actividad física y potencial mecanismo de acción. Metodología: Evaluación de datos de la tercera Encuesta Nacional de Factores de Riesgo (ENFR) e información referida a factores que contribuyen al crecimiento de la prevalencia de DT2. Igualmente estrategias exitosas utilizadas a nivel mundial para su prevención. Resultados: El índice de masa corporal registrado en la población estudiada muestra un aumento del porcentaje de personas con sobrepeso/obesidad inverso a la práctica de actividad física. Igualmente los resultados de las pruebas de tolerancia a la glucosa oral muestran que sus alteraciones (prediabetes/diabetes) son menores entre quienes realizaban actividad física. El porcentaje de personas con valores de presión arterial dentro del rango normal al igual que de colesterol circulante (según valores meta de guías internacionales), es también significativamente menor entre quienes practicaban actividad física. Conclusión: La evidencia presentada demuestra objetivamente la necesidad/ventajas de implementar un programa de prevención primaria de diabetes a gran escala a nivel nacional para disminuir su crecimiento y la pertinencia de incluir la práctica de actividad física como estrategia de prevención tal como propone el PPDBA.

ABSTRACT Background: In our country, the prevalence of type 2 diabetes (DT2) and cardiovascular risk factors (CVRF) increases continuously. Although the phenomenon is accompanied by the adoption of unhealthy lifestyles that facilitate such growth, there is little implementation of strategies that can modify the situation. Objective: To review the available evidence on the magnitude of the problem of diabetes and CVRF in our country, its possible relationship with the practice of physical activity and potential mechanism of action. Methodology: Evaluation of data from the Third National Survey of Risk Factors (ENFR) and information referred to factors that promote the prevalence growth of T2D. Additionally, successful strategies have been used worldwide for its prevention. Results: The body mass index registered in the studied population shows an increase in the percentage of people with overweight/obesity inverse to the practice of physical activity. Likewise, the results of the oral glucose tolerance tests show that their alterations (prediabetes/ diabetes) are lower among those who performed physical activity. The percentage of people with blood pressure values within the normal range as well as circulating cholesterol (according to target values of international guidelines), is also significantly lower among those who practiced physical activity. Conclusion: The presented evidence objectively demonstrates the need/advantages of implementing a large-scale diabetes primary prevention program at the national level to.

Registry of people with diabetes in three Latin American countries: a suitable approach to evaluate the quality of health care provided to people with type 2 diabetes.

AIMS: To implement a patient registry and collect data related to the care provided to people with type 2 diabetes in six specialized centers of three Latin American countries, measure the quality of such care using a standardized form (QUALIDIAB) that collects information on different quality of care indicators, and analyze the potential of collecting this information for improving quality of care and conducting clinical research. METHODS: We collected data on clinical, metabolic and therapeutic indicators, micro- and macrovascular complications, rate of use of diagnostic and therapeutic elements and hospitalization of patients with type 2 diabetes in six diabetes centers, four in Argentina and one each in Colombia and Peru. RESULTS: We analyzed 1157 records from patients with type 2 diabetes (Argentina, 668; Colombia, 220; Peru, 269); 39 records were discarded because of data entry errors or inconsistencies. The data demonstrated frequency performance deficiencies in several procedures, including foot and ocular fundus examination and various cardiovascular screening tests. In contrast, HbA1c and cardiovascular risk factor assessments were performed with a greater frequency than recommended by international guidelines. Management of insulin therapy was sub-optimal, and deficiencies were also noted among diabetes education indicators. CONCLUSIONS: Patient registry was successfully implemented in these clinics following an interactive educational program. The data obtained provide useful information as to deficiencies in care and may be used to guide quality of care improvement efforts.

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: This was a randomized 2 × 2 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 (group 1), physician education (group 2), patient education (group 3), and both physician education and patient education (group 4), with identical system interventions in all four groups. Outcome measures included HbA(1c), BMI, 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: HbA(1c) decreased significantly from 4 mmol/mol to 10 mmol/mol 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 World Health Organization-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.

Patients' education, and its impact on care outcomes, resource consumption and working conditions: data from the International Diabetes Management Practices Study (IDMPS).

AIM: To evaluate the impact of diabetes education provided to patients with type 2 diabetes mellitus (T2DM) in non-controlled studies ("real-world conditions") on quality of care, resource consumption and conditions of employment. METHODS: This cross-sectional study and longitudinal follow-up describe the data (demographic and socioeconomic profiles, clinical characteristics, treatment of hyperglycaemia and associated cardiovascular risk factors, resource consumption) collected during the second phase (2006) of the International Diabetes Management Practices Study (IDMPS). Patients received diabetes education directly from the practice nurse, dietitian or educator, or were referred to ad hoc group-education programmes; all programmes emphasized healthy lifestyle changes, self-care and active participation in disease control and treatment. Educated vs non-educated T2DM patients (n=5692 in each group), paired by age, gender and diabetes duration, were randomly recruited for the IDMPS by participating primary-care physicians from 27 countries in Eastern Europe, Asia, Latin America and Africa. Outcome measures included clinical (body weight, height, waist circumference, blood pressure, foot evaluation), metabolic (HbA(1c) levels, blood lipid profile) and biochemical control measures. Treatment goals were defined according to American Diabetes Association guidelines. RESULTS: T2DM patients' education significantly improved the percentage of patients achieving target values set by international guidelines. Educated patients increased their insulin use and self-care performance, had a lower rate of chronic complications and a modest increase in cost of care, and probably higher salaries and slightly better productivity. CONCLUSION: Diabetes education is an efficient tool for improving care outcomes without having a major impact on healthcare costs.

Islet adaptive changes to fructose-induced insulin resistance: beta-cell mass, glucokinase, glucose metabolism, and insulin secretion.

Beta-cell mass, hexokinase/glucokinase (HK/GK) activity, glucose metabolism and insulin secretion were studied in the islets of rats with fructose-induced insulin resistance (IR). Normal male Wistar rats were fed a standard commercial diet and water without (control, C) or with 10% fructose-rich diet (FRD) for 3 weeks. Blood glucose (strips), triglyceride (commercial kit), and insulin (RIA) levels were measured at the time of death. Glucose-induced insulin release, glucose metabolism ((14)CO(2) and (3)H(2)O production from D-[U-(14)C]- and D-[5-(3)H]-glucose) and HK/GK activity (G-6-P production), transcription (RT-PCR), protein expression (Western blot), and cellular compartmentalization were measured in isolated islets (collagenase digestion). FRD rats presented normoglycemia but impaired glucose tolerance, hypertriglyceridemia, hyperinsulinemia, and increased HOMA-IR index. In these rats, beta-cell mass decreased significantly by 33%, with a 44% increase in the percentage of apoptotic cells. Glucose-induced insulin release and islet glucose metabolism were higher in FRD rats. While GK activity (total and cytosolic fraction) and protein expression were significantly higher in FRD islets, HK showed no change in any of these parameters. Our results demonstrate that the changes induced by dietary-induced IR upon beta-cell function and mass are strongly conditional on the nutrient model used. In our model (intact animals with impaired glucose tolerance), GK activity increases through mechanisms previously shown only in vitro or under highly hyperglycemic conditions. Such an increase plays a pivotal role in the adaptive increased release of insulin in response to IR, even in the presence of marked beta-cell mass reduction.

Abdominal adipose tissue: early metabolic dysfunction associated to insulin resistance and oxidative stress induced by an unbalanced diet.

The possible contribution of early changes in lipid composition, function, and antioxidant status of abdominal adipose tissue (AAT) induced by a fructose-rich diet (FRD) to the development of insulin resistance (IR) and oxidative stress (OS) was studied. Wistar rats were fed with a commercial diet with (FRD) or without 10% fructose in the drinking water for 3 weeks. The glucose (G), triglyceride (TG), and insulin (I) plasma levels, and the activity of antioxidant enzymes, lyposoluble antioxidants, total glutathione (GSH), lipid peroxidation as TBARS, fatty acid (FA) composition of AAT-TG as well as their release by incubated pieces of AAT were measured. Rats fed with a FRD have significantly higher plasma levels of G, TG, and I. Their AAT showed a marked increase in content and ratios of saturated to monounsaturated and polyunsaturated FAs, TBARS, and catalase, GSH-transferase and GSH-reductase, together with a decrease in superoxide dismutase and GSH-peroxidase activity, and total GSH, alpha-tocopherol, beta-carotene and lycopene content. Incubated AAT from FRD released in vitro higher amount of free fatty acids (FFAs) with higher ratios of saturated to monounsaturated and polyunsaturated FAs. Our data suggest that FRD induced an early prooxidative state and metabolic dysfunction in AAT that would favor the overall development of IR and OS and further development of pancreatic beta-cell failure; therefore, its early control would represent an appropriate strategy to prevent alterations such as the development of type 2 diabetes.

PRODIACOR: a patient-centered treatment program for type 2 diabetes and associated cardiovascular risk factors in the city of Corrientes, Argentina: study design and baseline data.

OBJECTIVE: To implement a controlled clinical trial (PRODIACOR) in a primary care setting designed 1) to improve type 2 diabetes care and 2) to collect cost data in order to be able to measure cost-effectiveness of three system interventions (checkbook of indicated procedures, patient/provider feedback and complete coverage of medications and supplies) and physician and/or patient education to improve psychological, clinical, metabolic and therapeutic indicators. All three Argentinean health subsectors (public health, social security and the private, prepaid system) are participants in the study. Patients of participating physicians were randomly selected and assigned to one of four groups: control, provider education, patient education, and provider/patient education; the system interventions were provided to all four groups. BASELINE RESULTS: Mean BMI was 29.8 kg/m(2); most subjects had blood pressure, fasting glucose and total cholesterol above targets recommended by international standards. Only 1% had had microalbuminuria measured, 57% performed glucose self-monitoring, 37% had had an eye examination and 31% a foot examination in the preceding year. Ten percent, 26% and 73% of people with hyperglycemia, hypertension and dyslipidemia, respectively, were not on medications. Most patients treated with either insulin or oral antidiabetic agents were on monotherapy as were those treated for hypertension and dyslipidemia. WHO-5 questionnaire scores indicated that 13% of the subjects needed psychological intervention. CONCLUSIONS: Baseline data show multiple deficiencies in the process and outcomes of care that could be targeted and improved by PRODIACOR intervention.

Enhanced expression of hexokinase I in pancreatic islets induced by sucrose administration.

Administration of a sucrose-rich diet (SRD) to normal hamsters induces an insulin-resistant state and a significant increase of insulin secretion and beta-cell mass. Islets isolated from these animals had a marked increase in glucose metabolism and glucose-induced insulin secretion, at both low and high glucose concentrations. They also presented increased hexokinase (HK) activity, without measurable changes in glucokinase (GK) activity. In this study we measured HK and GK activity in homogenates of islets isolated from normal control and SRD-fed hamsters, as well as in their particulate and cytosolic fractions. We also measured transcription rate (mRNA by reverse transcriptase PCR) and expression levels (Western blotting) of both enzymes in these islets. We found an increase in HK activity and expression levels, without measurable changes in HK mRNA level in SRD-fed animals. Whereas a similar GK activity was measured in homogenates of islets isolated from both groups, such activity was significantly higher in the cytosolic fraction of SRD islets. On the other hand, GK transcription rate and expression level were similar in both experimental groups. Our results suggest that the increased beta-cell secretory response to low glucose can be partly ascribed to an increased activity of islet HK consecutive to an enhanced expression of the enzyme, while the enhanced response to high glucose could be due to changes in GK compartmentalization.

PROPAT: a study to improve the quality and reduce the cost of diabetes care.

OBJECTIVE: In PROPAT we implemented an integrated approach to diabetes care designed to improve the quality and reduce the cost of care. STUDY DESIGN AND METHODS: PROPAT was a case-control study matching patients by age and gender (diabetes:control ratio 1:2) within IOMA, a public employment-based health maintenance organization (HMO) of the Province of Buenos Aires, Argentina. Costs were evaluated using prevalence data from an HMO perspective. We currently report clinical and biochemical data and costs from the first 297 patients enrolled who completed 1 year in PROPAT, and compare them with those derived from control patients. RESULTS: All recommended practices recorded as care provided at baseline increased significantly 1 year after implementing PROPAT, with a parallel significant improvement in several clinical and biochemical parameters, and markedly lower total annual per capita costs. CONCLUSIONS: These results demonstrate that the implementation of a comprehensive diabetes care program can simultaneously improve quality while reducing costs.

Plasma membrane calcium pump activity in rat pancreatic islets: an accurate method to measure its calcium-dependent modulation.

The aim of this study was to quantify the glucose modulation of the plasma membrane calcium pump (PMCA) function in rat pancreatic islets. Ca2+-ATPase activity and levels of phosphorylated PMCA intermediates both transiently declined to a minimum in response to stimulation by glucose. Strictly dependent on Ca2+ concentration, this inhibitory effect was fully expressed at physiological concentrations of the cation (less than 0.5 muM), then progressively diminished at higher concentrations. These results, together with those previously reported on the effects of insulin secretagogues and blockers on the activity, expression and cellular distribution of the PMCA, support the concept that the PMCA plays a key role in the regulation of Ca2+ signaling and insulin secretion in pancreatic islets.

Islet neogenesis: an apparent key component of long-term pancreas adaptation to increased insulin demand.

This study aimed to determine the relative importance of different functional and morphological pancreatic changes induced by the chronic administration of a sucrose-rich diet (SRD) to maintain normal glucose homeostasis. Male Wistar rats were fed either sucrose (SRD) or starch (CD) for 6 and 12 months. At both periods, serum glucose and triacylglycerol levels were significantly higher (P<0.05; paired and unpaired Student's t-test) in SRD rats. Serum insulin levels were significantly lower in SRD only at 12 months. At 6 months, the insulin secretion dose-response curve in SRD rats showed a shift to the left that was no longer observed at 12 months, when SRD islets decreased their response to 16 mM glucose. At 6 months, SRD rats showed a significant increase in beta-cell volume density (Vvi) and islet cell replication rate, together with a decrease in beta-cell apoptotic rate. Changes were not detected in the percentage of PDX-1- and islet neogenesis associated protein (INGAP)-positive cells. Conversely, at 12 months, there was a significant decrease in beta-cell Vvi and in the percentage of PDX-1-positive cells; the islet cell replication rate was not modified, and the number of apoptotic beta-cells increased significantly. No signs of increased neogenesis or INGAP-positive cells were recorded at any period in SRD rats. Our results show that SRD rats are unable to develop functional and morphological pancreatic reactive changes sufficient to maintain normal glucose and triacylglycerol levels for a long period. Such failure could be ascribed to their inability to increase the rate of neogenesis and of INGAP production.

Hospitalization and re-hospitalization of people with and without diabetes in La Plata, Argentina: comparison of their clinical characteristics and costs.

OBJECTIVE: To examine the prevalence, characteristics, and costs of hospitalization and re-hospitalization of diabetic and non-diabetic patients in La Plata, Argentina, and to compare the data with those of developed countries. RESEARCH DESIGN AND METHODS: We studied all in-hospital registries of diabetic patients enrolled in a health maintenance organization of the Province of Buenos Aires (IOMA, November 1996). For each diabetic patient (127 persons), the characteristics of two other hospitalized non-diabetic patients matched by age and gender were simultaneously recorded. RESULTS: Of the 2200 recorded hospitalizations, 5.8% were for diabetic patients, accounting for 10.5% of the hospitalization cost. Cardiovascular diseases were the major cause of hospitalization in both groups. The per capita hospitalization cost of diabetic patients was significantly higher: 1628.5+/-1754.0 US dollars versus 833+/-842 US dollars; P=0.00002. Percent re-hospitalizations were five and a half times higher in diabetic patients (P=0.0001), and significantly associated with history of severe episodes of acute (odds ratio: 3.61; 95% CI: 1.11-11.70; P=0.03) and chronic (odds ratio: 4.26; 95% CI: 1.60-11.29; P=0.004) complications. CONCLUSIONS: The combination of higher and longer hospitalization rates and frequent re-hospitalizations resulted in increased costs for our diabetic population. Implementation of care programs based on education (for physicians and patients) could effectively decrease current and future costs of the disease.

Evaluación de un programa de educación de tratamiento intensivo en adolescentes con diabetes tipo 1. Seguimiento por dos años / Evaluation of an intensive treatment education program for type 1 diabetes in a group of adolescents. A two year follow up

During the past decade several reports were published showing that intensive treatment of type 1 diabetes can prevent and delay disease-related microvascular complications. However, several problems were reported in children and adolescents such as frequent hypoglycemic episodes and weight gain. The aim of this study was to describe the results of intensified treatment for type 1 diabetes in a group of Argentinean adolescents after a follow-up of two years. Twenty five adolescents with type 1 diabetes older than 10 years with at least one year from diagnosis were selected. All patients received a one-week teaching program during admission to our center. All patients were followed-up monthly during two years. Treatment schedule included 4-5 controls in fasting conditions, two doses of NPH insulin and four doses of regular insulin according to glycemia and the amount of calculated carbohydrate intake. Median age was 13.5 years (range 10 to 19 years). Mean time from diagnosis to inclusion in the study was 3.8 years (range 1.25 to 9 years). Mean total dose of NPH insulin decreased significantly when measured at the inclusion in the study (0.9 IU/kg) and after a year of follow-up 0.8 IU/kg (p 0.04). However, there were no changes in NPH insulin dose after two years follow-up (0.85 IU/kg). On the contrary, the dose of regular insulin administered on fasting conditions with normal glycemia increased from 0 to 0.21/kg after a year (p 0.0001) and to 0.69 after two years (non significant). Median HbA1C showed a significant reduction from 10 +/- 1.62% to 8.53 +/- 1.04% after a year (p 0.03) and to 8.72 +/- 0.81% after two years. BMI Z score increased from significantly from 0.7 +/- 0.9 to 1.06 +/- 1.15 after a year (p 0.03) with a further reduction without a significant difference from the basal value after two years. We found no significant differences in the frequency of hypoglycemia or other metabolic features. Our results show that intensive treatment of type 1 diab...

Durante la década pasada, se publicaron numerosos trabajos demostrando que el tratamiento intensivo de la diabetes tipo 1 puede prevenir y retrasar el desarrollo de las complicaciones microvasculares asociadas a la misma. Sin embargo en el grupo de niños y adolescentes se hallaron algunos problemas como el incremento de la frecuencia de los episodios de hipoglucemia y el excesivo aumento de peso. El propósito del presente estudio fue describir los resultados del tratamiento intensificado llevado a cabo durante 2 años en una población de niños y adolescentes argentinos con diabetes tipo 1. Fueron seleccionados 25 pacientes mayores de 10 años de edad con diabetes de más de 1 año de evolución. Todos ellos realizaron un programa de educación durante una semana de internación. El seguimiento posterior fue mensual durante los siguientes dos años. El esquema de tratamiento insulínico consistió en 4 a 5 controles preprandiales diarios, dos dosis de insulina NPH cubriendo requerimientos basales y cuatro dosis de insulina regular preprandial ajustadas de acuerdo al cálculode hidratos de carbono a ingerir, la actividad física y el valor de glucemia. La media de edad fue de 13.5años (r: 10-19 años). El tiempo medio transcurrido desde el diagnóstico hasta la intensificación del tratamientofue de 3.8 años ( r: 1.2 –9 años). La dosis media total de NPH disminuyó significativamente desde 0.9 U/kg en elinicio a 0.8 U/kg al año de seguimiento (p = 0.04), sin diferencias al segundo año de seguimiento (0.85 U/kg). Porel contrario, la dosis de insulina regular administrada en forma preprandial en normoglucemia aumentó de 0 a0.21 U/kg en el primer año (p 0.0001) y a 0.69 U/kg a los dos años (p NS). La media de HbA1C mostró unasignificativa reducción desde 10±1.62% a 8.53±1.04% en el primer año (p = 0.03) y 8.72± 0.81% a los dos años.El Z score de IMC aumentó significativamente de 0.7 ± 0.9 a 1.06 ± 1.15 luego de un año (p = 0.03) descendiendo a valores no...

Evaluación de un programa de educación de tratamiento intensivo en adolescentes con diabetes tipo 1. Seguimiento por dos años / Evaluation of an intensive treatment education program for type 1 diabetes in a group of adolescents. A two year follow up

During the past decade several reports were published showing that intensive treatment of type 1 diabetes can prevent and delay disease-related microvascular complications. However, several problems were reported in children and adolescents such as frequent hypoglycemic episodes and weight gain. The aim of this study was to describe the results of intensified treatment for type 1 diabetes in a group of Argentinean adolescents after a follow-up of two years. Twenty five adolescents with type 1 diabetes older than 10 years with at least one year from diagnosis were selected. All patients received a one-week teaching program during admission to our center. All patients were followed-up monthly during two years. Treatment schedule included 4-5 controls in fasting conditions, two doses of NPH insulin and four doses of regular insulin according to glycemia and the amount of calculated carbohydrate intake. Median age was 13.5 years (range 10 to 19 years). Mean time from diagnosis to inclusion in the study was 3.8 years (range 1.25 to 9 years). Mean total dose of NPH insulin decreased significantly when measured at the inclusion in the study (0.9 IU/kg) and after a year of follow-up 0.8 IU/kg (p 0.04). However, there were no changes in NPH insulin dose after two years follow-up (0.85 IU/kg). On the contrary, the dose of regular insulin administered on fasting conditions with normal glycemia increased from 0 to 0.21/kg after a year (p 0.0001) and to 0.69 after two years (non significant). Median HbA1C showed a significant reduction from 10 +/- 1.62% to 8.53 +/- 1.04% after a year (p 0.03) and to 8.72 +/- 0.81% after two years. BMI Z score increased from significantly from 0.7 +/- 0.9 to 1.06 +/- 1.15 after a year (p 0.03) with a further reduction without a significant difference from the basal value after two years. We found no significant differences in the frequency of hypoglycemia or other metabolic features. Our results show that intensive treatment of type 1 diab...(AU)

Durante la década pasada, se publicaron numerosos trabajos demostrando que el tratamiento intensivo de la diabetes tipo 1 puede prevenir y retrasar el desarrollo de las complicaciones microvasculares asociadas a la misma. Sin embargo en el grupo de niños y adolescentes se hallaron algunos problemas como el incremento de la frecuencia de los episodios de hipoglucemia y el excesivo aumento de peso. El propósito del presente estudio fue describir los resultados del tratamiento intensificado llevado a cabo durante 2 años en una población de niños y adolescentes argentinos con diabetes tipo 1. Fueron seleccionados 25 pacientes mayores de 10 años de edad con diabetes de más de 1 año de evolución. Todos ellos realizaron un programa de educación durante una semana de internación. El seguimiento posterior fue mensual durante los siguientes dos años. El esquema de tratamiento insulínico consistió en 4 a 5 controles preprandiales diarios, dos dosis de insulina NPH cubriendo requerimientos basales y cuatro dosis de insulina regular preprandial ajustadas de acuerdo al cálculode hidratos de carbono a ingerir, la actividad física y el valor de glucemia. La media de edad fue de 13.5años (r: 10-19 años). El tiempo medio transcurrido desde el diagnóstico hasta la intensificación del tratamientofue de 3.8 años ( r: 1.2 ¹9 años). La dosis media total de NPH disminuyó significativamente desde 0.9 U/kg en elinicio a 0.8 U/kg al año de seguimiento (p = 0.04), sin diferencias al segundo año de seguimiento (0.85 U/kg). Porel contrario, la dosis de insulina regular administrada en forma preprandial en normoglucemia aumentó de 0 a0.21 U/kg en el primer año (p 0.0001) y a 0.69 U/kg a los dos años (p NS). La media de HbA1C mostró unasignificativa reducción desde 10±1.62% a 8.53±1.04% en el primer año (p = 0.03) y 8.72± 0.81% a los dos años.El Z score de IMC aumentó significativamente de 0.7 ± 0.9 a 1.06 ± 1.15 luego de un año (p = 0.03) descendiendo a valores no...(AU)

Expression of islet neogenesis-associated protein in islets of normal hamsters.

The aim of the present study was to test the possible presence and expression of islet neogenesis-associated protein (INGAP) in islet cells of normal adult hamsters. Pancreata from normal male Syrian hamsters were removed to perform the following studies. (i) Western blot analysis using the cytosolic fraction from homogenates of isolated islets, exocrine tIssue and whole pancreas, and rabbit INGAP-specific antibody. (ii) Immunohistochemical identification of INGAP-positive cells in fixed sections of intact pancreata, fresh and 72 h cultured islets (isolated by collagenase digestion), and smears of exocrine pancreatic cells, using the same INGAP-specific antibody and streptavidin-biotin complex. (iii) RT-PCR using total RNA extracted from isolated islets and from exocrine tIssue as template, and a specific pair of primers. (iv) Control of the sequence of the PCR products. INGAP protein was identified by Western blot in the cytosolic fraction of homogenates from fresh isolated islets, exocrine cells and whole fresh pancreas. INGAP-immunopositive cells were observed in duct, exocrine and islet cells in either fixed intact or digested pancreatic tIssue. INGAP mRNA was identified in samples of total RNA from fresh and cultured isolated islets and from exocrine cells. Our data demonstrate that INGAP is present and expressed in islets and in exocrine pancreatic cells of normal hamsters. The ubiquitous localization of INGAP suggests its possible role in the physiological process of islet growth and its protective effect upon streptozotocin-induced diabetes.

Pancreatic duodenal homeobox-1 and islet neogenesis-associated protein: a possible combined marker of activateable pancreatic cell precursors.

The aim of this work was to study the possible relationship between pancreatic duodenal homeobox-1 (Pdx-1) and islet neogenesis-associated protein (INGAP) during induced islet neogenesis. Pregnant hamsters were fed with (S) and without (C) sucrose, and glycemia, insulin secretion in vitro, and pancreas immunomorphometric parameters were measured in their 7-day-old offspring. S offspring had significantly lower glycemic levels than C animals. Insulin release in response to increasing glucose concentrations in the incubation medium (2-16 mM glucose) did not increase in pancreata from either C or S offspring. However, pancreata from S offspring released more insulin than those from C animals. In S offspring, beta-cell mass, beta-cell replication rate and islet neogenesis increased significantly, with a simultaneous decrease in beta-cell apoptotic rate. INGAP- and Pdx-1-positive cell mass also increased in the islets and among acinar and duct cells. We found two subpopulations of Pdx-1 cells: INGAP-positive and INGAP-negative. Pdx-1/INGAP-positive cells did not stain with insulin, glucagon, somatostatin, pancreatic polypeptide, or neurogenin 3 antibodies. The increment of Pdx-1/INGAP-positive cells represented the major contribution to the Pdx-1 cell mass increase. Such increments varied among pancreas subsectors: ductal>insular>extrainsular. Our results suggested that INGAP participates in the regulation of islet neogenesis, and Pdx-1/INGAP-positive cells represent a new stem cell subpopulation at an early stage of development, highly activateable in neogenesis.

Mechanisms involved in the beta-cell mass increase induced by chronic sucrose feeding to normal rats.

The aim of the present study was to clarify the mechanisms by which a sucrose-rich diet (SRD) produces an increase in the pancreatic beta-cell mass in the rat. Normal Wistar rats were fed for 30 weeks either an SRD (SRD rats; 63% wt/wt), or the same diet but with starch instead of sucrose in the same proportion (CD rats). We studied body weight, serum glucose and triacylglycerol levels, endocrine tissue and beta-cell mass, beta-cell replication rate (proliferating cell nuclear antigen; PCNA), islet neogenesis (cytokeratin immunostaining) and beta-cell apoptosis (propidium iodide). Body weight (g) recorded in the SRD rats was significantly (P<0.05) larger than that of the CD group (556.0+/-8.3 vs 470.0+/-13.1). Both serum glucose and triacylglycerol levels (mmol/l) were also significantly higher (P<0.05) in SRD than in CD rats (serum glucose, 8.11+/-0.14 vs 6.62+/-0.17; triacylglycerol, 1.57+/-0.18 vs 0.47+/-0.04). The number of pancreatic islets per unit area increased significantly (P<0.05) in SRD rats (3.29+/-0.1 vs 2.01+/-0.2). A significant increment (2.6 times) in the mass of endocrine tissue was detected in SRD animals, mainly due to an increase in the beta-cell mass (P=0.0025). The islet cell replication rate, measured as the percentage of PCNA-labelled beta cells increased 6.8 times in SRD rats (P<0.03). The number of apoptotic cells in the endocrine pancreas decreased significantly (three times) in the SRD animals (P=0.03). The cytokeratin-positive area did not show significant differences between CD and SRD rats. The increase of beta-cell mass induced by SRD was accomplished by an enhanced replication of beta cells together with a decrease in the rate of beta-cell apoptosis, without any evident participation of islet neogenesis. This pancreatic reaction was unable to maintain serum glucose levels of these rats at the level measured in CD animals.

Expression and cellular distribution pattern of plasma membrane calcium pump isoforms in rat pancreatic islets.

This work is aimed at identifying the presence and cellular distribution pattern of plasma membrane calcium pump (PMCA) isoforms in normal rat pancreatic islet. Microsomal fractions of isolated islets and exocrine tissue were analyzed to detect different PMCA isoforms. The cellular distribution pattern of these PMCAs in the islets was also studied in fixed pancreas sections incubated with antibodies against PMCAs and insulin. Antibody 5F10, which reacts with all PMCA variants, showed multiple bands in the blots in the 127-134 kDa region, indicating the presence of several isoforms. Microsomes also reacted positively with specific antibodies for individual PMCA isoforms, generating a band of the expected size. Antibody 5F10 immunocytochemically labeled the plasma cell membrane of both b- and non-b-cells, but predominantly the former. All islet cells were also labeled with antibodies against isoforms 1 and 4, while the antibody reacting with isoform 3 labeled exclusively b-cells. A few b- and non-b-cells were positively labeled with the antibody reacting with PMCA b variant. Negative results were obtained with the antibody against isoform 2. Further studies, together with previous reports on the modulatory effect of insulin secretagogues and blockers upon PMCA activity, may provide evidence of the importance of this particular PMCA expression for islet function under normal and pathological conditions.