Biodritin microencapsulated human islets of langerhans and their potential for type 1 diabetes mellitus therapy

Background. Microencapsulation of pancreatic islets with polymeric compounds constitutes an attractive alternative therapy for type 1 diabetes mellitus. The major limiting factor is the availability of a biocompatible and mechanically stable polymer. We investigated the potential of Biodritin, a novel polymer constituted of alginate and chondroitin sulfate, for islet microencapsulation. Methods. Biodritin microcapsules were obtained using an air jet droplet generator and gelated with barium or calcium chloride. Microencapsulated rat insulinoma RINm5F cells were tested for viability using the [3-(4,5-dimetyl-thiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide] [MTT] colorimetric assay. Microencapsulated rat pancreatic islets were coincubated with macrophages derived from mouse peritoneal liquid to assess the immunomodulatory potential of the microcapsules, using quantitative real time-PCR (qPCR). Biodritin biocompatibility was demonstrated by subcutaneous injection of empty microcapsules into immunocompetent Wistar rats. Insulin secretion by microencapsulated human pancreatic islets was evaluated using an electrochemoluminescent assay. Microencapsulated human islets transplanted into chemically induced diabetic mice were monitored for reversal of hyperglycemia. Results. The metabolic activity of microencapsulated RINm5F cells persisted for at least 15 days. Interleukin-1 beta expression by macrophages was observed during coculture with islets microencapsulated with Biodritin-CaCl2, but not with Biodritin-BaCl2. No statistical difference in glucose-stimulated insulin secretion was observed between nonencapsulated and microencapsulated islets. Upon microencapsulated islet transplantation, the blood glucose level of diabetic mice normalized; they remained euglycemic for at least 60 days, displaying normal oral glucose tolerance tests. Conclusion. This study demonstrated that Biodritin can be used for islet microencapsulation and reversal of diabetes; however, further investigations are required to assess its potential for long-term transplantation.

New information on carbohydrates in the Brazilian Food Composition Database

Foods that contain unavailable carbohydrates may lower the risks for some non-transmissible chronic diseases because of the potential benefits provided by the products of colonic fermentation. On the other hand, foods that are sources of available carbohydrates may have higher energy value and increase the post-prandial glycemic response. The biomarker glycemic index and the resulting glycemic load may be used to classify foods according to their potential to increase blood glucose. Information about glycemic index and glycemic load may be useful in diet therapy. Currently, food composition tables in Brazil do not provide data for individually analyzed carbohydrates even though some quality data are available in scientific publications. The objectives of this work were to produce and compile information about the concentration of individual carbohydrates in foods and their glycemic responses and to disseminate this information through the Brazilian Food Composition Database (TBCA-USP). The glycemic index and glycemic load of foods were evaluated in healthy individuals. Concentrations of available carbohydrates (soluble sugars and available starch) and unavailable carbohydrates (dietary fiber, resistant starch, beta-glucans, fructans) were quantified by official methods, and other national data were compiled. TBCA-USP (http://www.fcf.usp.br/tabela), which is used by professionals and the population in general, now offers both chemical and biological information for carbohydrates. (C) 2009 Elsevier Inc. All rights reserved.

Limitação de atividades e participação social em pacientes com diabetes

Objetivos: Avaliar a limitação de atividades e a participação social em indivíduos portadores de diabetes melito tipo 2. Métodos: Foram avaliados 79 pacientes, utilizando-se a escala SALSA (Screening of Activity Limitation and Safety Awareness - Triagem de Limitação de Atividade e Consciência de Risco), e a escala de Participação, que abrange oito das nove principais áreas da vida definidas na Classificação Internacional de Funcionalidade, Incapacidade e Saúde (CIF) da OMS. Resultados: A idade média dos participantes foi 61,6 ± 9,8 anos, sendo 55,7 por cento do sexo feminino, 68,4 por cento com companheiro(a), 32,9 por cento com renda até 3 salários mínimos e em 13,9 por cento o diabete influenciou na ocupação. O tempo médio de doença foi 10,3 ± 8,9 anos. Tratamento de 39,3 por cento dos participantes foi com insulina, 70,9 por cento com medicação oral, 51,9 por cento com dieta e 45,6 por cento com exercícios físicos. 48,1 por cento apresentavam alguma complicação da doença. A média de pontos SALSA foi 26,5 ± 11,6 e houve maior pontuação quando o tempo de doença foi superior a 10 anos. Com a evolução do diabetes, pode haver necessidade de insulinoterapia, aparecem as complicações, que podem interferir na ocupação. Estes fatores parecem contribuir para a limitação de atividade. A média de pontos na Escala de Participação foi 9,8±10,9, com maior pontuação quando os entrevistados consideraram sua saúde física alterada no último ano e faziam uso de insulina. Conclusões: A limitação de atividades no diabetes melito tipo 2 se associou ao tempo de doença, com possível contribuição de fatores que ocorrem com sua evolução. Auto-avaliação de saúde física alterada e insulinoterapia se associaram a restrição social

Factors predicting the need for insulin therapy in patients with gestational diabetes mellitus

Aim: To determine the possible factors predicting the insulin requirement in pregnancies complicated by gestational diabetes mellitus (GDM). Method: A total of 294 patients with GDM diagnosed by the 100-g/3-h oral glucose tolerance test (OGTT) were studied. The following factors were analyzed: maternal age, nulliparity, family history of diabetes, prepregnancy BMI, prior GDM, prior fetal macrosomia, multiple pregnancy, polyhydramnios, gestational age at diagnosis of GDM, smoking, hypertension, number of abnormal 100-g/3-h OGTT values, and glycated hemoglobin (HbA1c). The association between each factor and the need for insulin therapy was then analyzed individually. The performance of these factors to predict the probability of insulin therapy was estimated using a logistic regression model. Results: Univariate analysis showed a positive correlation between insulin therapy and prepregnancy BMI, family history of diabetes, hypertension, prior GDM, prior fetal macrosomia, number of abnormal 100-g/3-h OGTT values, and HbA1c (P < 0.05). Prepregnancy BMI, family history of diabetes, number of abnormal 100-g/3-h OGTT values and HbA1c were statistically significant variables in the logistic regression model. Conclusions: The probability of insulin therapy can be estimated in pregnant women with GDM based on prepregnancy BMI, family history of diabetes, number of abnormal 100-g/3-h OGTT values, and HbA1c concentration. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Effects of periodontal therapy on glycemic control and inflammatory markers

Background: Periodontitis, a complication of diabetes mellitus (DM), can induce or perpetuate systemic conditions. This double-masked, placebo-controlled study evaluated the effects of periodontal therapy (scaling and root planing [SRP]) on the serum levels of glycated hemoglobin (HbA1c) and on inflammatory biomarkers. Methods: Thirty subjects with type 2 DM and periodontitis were treated with SRP + placebo (SRP; N = 15) or with SRP + doxycycline (SRP+Doxy; N = 15), 100 mg/day, for 14 days. Clinical and laboratory data were recorded at baseline and at 3 months after treatment. Results: After 3 months, the reduction in probing depth Was 0.8 mm for the SRP group (P <0.01) and 1.1 mm for the SRP+Doxy group (P <0.01) followed by a 0.9% (SRP; P = 0.17) and 1.5% (SRP+Doxy; P<0.01) reduction in HbA1c levels. A significant reduction in interleukin (IL)-6; interferon-inducible protein 10; soluble fas ligand; granulocyte colony-stimulating factor; RANTES; and IL-12 p70 serum levels were also verified (N = 30). To our knowledge, this is the first report on the effects of periodontal therapy on multiple systemic inflammatory markers in DM. Conclusions: Periodontal therapy may influence the systemic conditions of patients with type 2 DM, but no statistical difference was observed with the adjunctive systemic doxycycline therapy. Moreover, it is possible that the observed improvement in glycemic control and in the reduction of inflammatory markers could also be due to diet, which was not controlled in our study. Therefore, a confirmatory study with a larger sample size and controlled diet is necessary.

Diet quality of persons living with HIV/AIDS on highly active antiretroviral therapy

Background This study sought to assess the diet quality of individuals living with HIV/AIDS who were receiving antiretroviral therapy in Sao Paulo Brazil,. Methods This cross-sectional study involved 56 HIV-infected adults. Demographic and anthropometric data were collected, and diet quality was measured using the Healthy Eating Index (HEI), modified for Brazilians, which included ten components: adequacy of intake of six different food groups, total fat, cholesterol, dietary fibre and dietary variety. Results Among the individuals assessed, 64.3% of the participants had a diet needing improvement, while 8.7% had a poor diet. The overall HEI score was 68.3 points (SD = 14.9). Mean scores were low for fruits, vegetables, dairy products and dietary fibre; and high for meats and eggs, total fat and cholesterol. The overall HEI score was higher among individuals who were not overweight (P = 0.003), who were also more likely to achieve dietary goals for dairy products (P = 0.039) and grains (P = 0.005). Conclusion Most of these adults living with HIV/AIDS had diets that required improvement, and being overweight was associated with poorer diet quality. Nutritional interventions aimed at maintaining healthy body weight and diet should be taken into account in caring for HIV-infected people.

Progression of Diet-Induced Diabetes in C57BL6J Mice Involves Functional Dissociation of Ca(2+) Channels From Secretory Vesicles

OBJECTIVE The aim of the study was to elucidate the cellular mechanism underlying the suppression of glucose-induced insulin secretion in mice fed a high-fat diet (HFD) for 15 weeks. RESEARCH DESIGN AND METHODS-C57BL6J mice were fed a HFD or a normal diet (ND) for 3 or 15 weeks. Plasma insulin and glucose levels in vivo were assessed by intraperitoneal glucose tolerance test. Insulin secretion in vitro was studied using static incubations and a perfused pancreas preparation. Membrane currents, electrical activity, and exocytosis were examined by patch-clamp technique measurements. Intracellular calcium concentration ([Ca(2+)](i)) was measured by microfluorimetry. Total internal reflection fluorescence microscope (TIRFM) was used for optical imaging of exocytosis and submembrane depolarization-evoked [Ca(2+)](i). The functional data were complemented by analyses of histology and gene transcription. RESULTS After 15 weeks, but not 3 weeks, mice on HFD exhibited hyperglycemia and hypoinsulinemia. Pancreatic islet content and beta-cell area increased 2- and 1.5-fold, respectively. These changes correlated with a 20-50% reduction of glucose-induced insulin secretion (normalized to insulin content). The latter effect was not associated with impaired electrical activity or [Ca(2+)](i) signaling. Single-cell capacitance and TIRFM measurements of exocytosis revealed a selective suppression (>70%) of exocytosis elicited by short (50 ms) depolarization, whereas the responses to longer depolarizations were (500 ms) less affected. The loss of rapid exocytosis correlated with dispersion of Ca(2+) entry in HFD beta-cells. No changes in gene transcription of key exocytotic protein were observed. CONCLUSIONS HFD results in reduced insulin secretion by causing the functional dissociation of voltage-gated Ca(2+) entry from exocytosis. These observations suggest a novel explanation to the well-established link between obesity and diabetes. Diabetes 59:1192-1201, 2010

The Na+/glucose cotransporters: from genes to therapy

Glucose enters eukaryotic cells via two types of membrane-associated carrier proteins, the Na+/glucose cotransporters (SGLT) and the facilitative glucose transporters (GLUT). The SGLT family consists of six members. Among them, the SGLT1 and SGLT2 proteins, encoded by the solute carrier genes SLC5A1 and SLC5A2, respectively, are believed to be the most important ones and have been extensively explored in studies focusing on glucose fluxes under both physiological and pathological conditions. This review considers the regulation of the expression of the SGLT promoted by protein kinases and transcription factors, as well as the alterations determined by diets of different compositions and by pathologies such as diabetes. It also considers congenital defects of sugar metabolism caused by aberrant expression of the SGLT1 in glucose-galactose malabsorption and the SGLT2 in familial renal glycosuria. Finally, it covers some pharmacological compounds that are being currently studied focusing on the interest of controlling glycemia by antagonizing SGLT in renal and intestinal tissues.

Milk intake and the risk of type 2 diabetes mellitus, hypertension and prostate cancer

Milk intake is widely recommended for a healthy diet. Recent evidences suggest that milk/dairy products are associated with a lower risk of type 2 diabetes and hypertension. On the other hand, high calcium intake has been associated with a higher risk of prostate cancer. The calcium and vitamin D content in dairy foods could have beneficial effects on glucose metabolism and renin/angiotensin system as well regulates body weight. The association between high dairy/calcium consumption and prostate cancer risk are related to the presence of estrogens and insulin like growth factor (IGF-I) in milk. Based on the current evidence, it is possible that milk/dairy products, when consumed in adequate amounts and mainly with reduced fat content, has a beneficial effect on the prevention of hypertension and diabetes. Its potential role in the pathogenesis of prostate cancer is not well supported and requires additional study.

Evaluation of Antiproliferative, Anti-Type 2 Diabetes, and Antihypertension Potentials of Ellagitannins from Strawberries (Fragaria x ananassa Duch.) Using In Vitro Models

Strawberries represent the main source of ellagic acid derivatives in the Brazilian diet, corresponding to more than 50% of all phenolic compounds found in the fruit. There is a particular interest in the determination of the ellagic acid content in fruits because of possible chemopreventive benefits. In the present study, the potential health benefits of purified ellagitannins from strawberries were evaluated in relation to the antiproliferative activity and in vitro inhibition of alpha-amylase, alpha-glucosidase, and angiotensin I-converting enzyme (ACE) relevant for potential management of hyperglycemia and hypertension. Therefore, a comparison among ellagic acid, purified ellagitannins, and a strawberry extract was done to evaluate the possible synergistic effects of phenolics. In relation to the antiproliferative activity, it was observed that ellagic acid had the highest percentage inhibition of cell proliferation. The strawberry extract had lower efficacy in inhibiting the cell proliferation, indicating that in the case of this fruit there is no synergism. Purified ellagitannins had high alpha-amylase and ACE inhibitory activities. However, these compounds had low alpha-glucosidase inhibitory activity. These results suggested that the ellagitannins and ellagic acid have good potential for the management of hyperglycemia and hypertension linked to type 2 diabetes. However, further studies with animal and human models are needed to advance the in vitro assay-based biochemical rationale from this study.

Socioeconomic Differences in Preferences and Willingness-to-Pay for Insulin Delivery Systems in Type 1 and Type 2 Diabetes

Background: An evaluation of patients' preferences is necessary to understand the demand for different insulin delivery systems. The aim of this study was to investigate the association between socioeconomic status (SES) and patients' preferences and willingness to pay (WTP) for various attributes of insulin administration for diabetes management. Methods: We conducted a discrete choice experiment (DCE) to determine patients' preferences and their WTP for hypothetical insulin treatments. Both self-reported annual household income and education completed were used to explore differences in treatment preferences and WTP for different attributes of treatment across different levels of SES. Results: The DCE questionnaire was successfully completed by 274 patients. Overall, glucose control was the most valued attribute by all socioeconomic groups, while route of insulin delivery was not as important. Patients with higher incomes were willing to pay significantly more for better glucose control and to avoid adverse events compared to lower income groups. In addition, they were willing to pay more for an oral short-acting insulin ($Can 71.65 [95% confidence interval, $40.68, $102.62]) compared to the low income group ($Can 9.85 [95% confidence interval, 14.86, 34.56; P < 0.01]). Conversely, there were no differences in preferences when the sample was stratified by level of education. Conclusions: This study revealed that preferences and WTP for insulin therapy are influenced by income but not by level of education. Specifically, the higher the income, the greater desire for an oral insulin delivery system, whereas an inhaled route becomes less important for patients.

Ionic and Histological Studies of Salivary Glands in Rats with Diabetes and Their Glycemic State After Laser Irradiation

Objectives: To evaluate the effect of laser irradiation (LI) on the glycemic state and the histological and ionic parameters of the parotid and submandibular glands in rats with diabetes. Methods: One hundred twenty female rats were divided into eight groups. Diabetes was induced by administration of streptozotocin and confirmed later according to results of glycemia testing. Twenty-nine days after the induction, the parotid and submandibular glands of the rats were irradiated with 5, 10, and 20 J/cm(2) using a laser diode (660nm/100mW) (without diabetes: C5, C10, and C20; with diabetes: D5, D10, and D20, respectively). On the following day, the rats were euthanized, and blood glucose determined. Histological and ionic analyses were performed. Results: Rats with diabetes without irradiation (D0) showed lipid droples accumulation in the parotid gland, but accumulation decreased after 5, 10, and 20 J/cm(2) of laser irradiation. A decrease in fasting glycemia level from 358.97 +/- 56.70 to 278.33 +/- 87.98mg/dL for D5 and from 409.50 +/- 124.41 to 231.80 +/- 120.18 mg/dL for D20 (p < 0.05) was also observed. Conclusion: LI should be explored as an auxiliary therapy for control of complications of diabetes because it can alter the carbohydrate and lipid metabolism of rats with diabetes.

Expression of an activating mutation in the gene encoding the K(ATP) channel subunit Kir6.2 in mouse pancreatic beta cells recapitulates neonatal diabetes

Neonatal diabetes is a rare monogenic form of diabetes that usually presents within the first six months of life. It is commonly caused by gain-of-function mutations in the genes encoding the Kir6.2 and SUR1 subunits of the plasmalemmal ATP-sensitive K(+) (K(ATP)) channel. To better understand this disease, we generated a mouse expressing a Kir6.2 mutation (V59M) that causes neonatal diabetes in humans and we used Cre-lox technology to express the mutation specifically in pancreatic beta cells. These beta-V59M mice developed severe diabetes soon after birth, and by 5 weeks of age, blood glucose levels were markedly increased and insulin was undetectable. Islets isolated from beta-V59M mice secreted substantially less insulin and showed a smaller increase in intracellular calcium in response to glucose. This was due to a reduced sensitivity of K(ATP) channels in pancreatic beta cells to inhibition by ATP or glucose. In contrast, the sulfonylurea tolbutamide, a specific blocker of K(ATP) channels, closed K(ATP) channels, elevated intracellular calcium levels, and stimulated insulin release in beta-V59M beta cells, indicating that events downstream of K(ATP) channel closure remained intact. Expression of the V59M Kir6.2 mutation in pancreatic beta cells alone is thus sufficient to recapitulate the neonatal diabetes observed in humans. beta-V59M islets also displayed a reduced percentage of beta cells, abnormal morphology, lower insulin content, and decreased expression of Kir6.2, SUR1, and insulin mRNA. All these changes are expected to contribute to the diabetes of beta-V59M mice. Their cause requires further investigation.

The Pharmaceutical care of patients with type 2 diabetes mellitus

Objective To evaluate the efficiency of pharmaceutical care on the control of clinical parameters, such as fasting glycaemia and glycosylated haemoglobin in patients with Type 2 Diabetes mellitus. Setting This study was conducted at the Training and Community Health Centre of the College of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil. Methods A prospective and experimental study was conducted with 71 participants divided in two groups: (i) pharmaceutical care group (n=40), and (ii) the control group (n=31). The distribution of patients within these groups was made casually, and the patients were monitored for 12 months. Main outcome measure: Values for fasting glycaemia and glycosylated haemoglobin were collected. Results Mean values of fasting glycaemia in the pharmaceutical care group were significantly reduced whilst a small reduction was detected in the control group at the same time. A significant reduction in the levels of glycosylated haemoglobin was detected in patients in the pharmaceutical care group, and an average increase was observed in the control group. Furthermore, the follow-up of the intervention group by a pharmacist contributed to the resolution of 62.7% of 142 drug therapy problems identified. Conclusion In Brazil, the information provided by a pharmacist to patients with Type 2 Diabetes mellitus increases compliance to treatment, solving or reducing the Drug Therapy Problem and, consequently, improving glycaemic control.

A valuation of patients` willingness-to-pay for insulin delivery in diabetes

Objectives: The aim of this study was to determine the insulin-delivery system and the attributes of insulin therapy that best meet patients` preferences, and to estimate patients` willingness-to-pay (WTP) for them. Methods: This was a cross-sectional discrete choice experiment (DCE) study involving 378 Canadian patients with type 1 or type 2 diabetes. Patients were asked to choose between two hypothetical insulin treatment options made up of different combinations of the attribute levels. Regression coefficients derived using conditional logit models were used to calculate patients` WTP. Stratification of the sample was performed to evaluate WTP by predefined subgroups. Results: A total of 274 patients successfully completed the survey. Overall, patients were willing to pay the most for better blood glucose control followed by weight gain. Surprisingly, route of insulin administration was the least important attribute overall. Segmented models indicated that insulin naive diabetics were willing to pay significantly more for both oral and inhaled short-acting insulin compared with insulin users. Surprisingly, type 1 diabetics were willing to pay $C11.53 for subcutaneous short-acting insulin, while type 2 diabetics were willing to pay $C47.23 to avoid subcutaneous short-acting insulin (p < .05). These findings support the hypothesis of a psychological barrier to initiating insulin therapy, but once that this barrier has been overcome, they accommodate and accept injectable therapy as a treatment option. Conclusions: By understanding and addressing patients` preferences for insulin therapy, diabetes educators can use this information to find an optimal treatment approach for each individual patient, which may ultimately lead to improved control, through improved compliance, and better diabetes outcomes.