Insulin secretion, insulin sensitivity, and hepatic insulin extraction in first-degree relatives of type 2 diabetic patients

To identify early metabolic abnormalities in type 2 diabetes mellitus, we measured insulin secretion, sensitivity to insulin, and hepatic insulin extraction in 48 healthy normal glucose-tolerant Brazilians, first-degree relatives of type 2 diabetic patients (FH+). Each individual was matched for sex, age, weight, and body fat distribution with a person without history of type 2 diabetes (FH-). Both groups were submitted to a hyperglycemic clamp procedure (180 mg/dl). Insulin release was evaluated in its two phases. The first was calculated as the sum of plasma insulin at 2.5, 5.0, 7.5, and 10.0 min after the beginning of glucose infusion, and the second as the mean plasma insulin level in the third hour of the clamp procedure. Insulin sensitivity index (ISI) was the mean glucose infusion rate in the third hour of the clamp experiment divided by the mean plasma insulin concentration during the same period of time. Hepatic insulin extraction was determined under fasting conditions and in the third hour of the clamp procedure as the ratio between C-peptide and plasma insulin levels. FH+ individuals did not differ from FH- individuals in terms of the following parameters [median (range)]: a) first-phase insulin secretion, 174 (116-221) vs 207 (108-277) µU/ml, b) second-phase insulin secretion, 64 (41-86) vs 53 (37-83) µU/ml, and c) ISI, 14.8 (9.0-20.8) vs 16.8 (9.0-27.0) mg kg-1 min-1/µU ml-1. Hepatic insulin extraction in FH+ subjects was similar to that of FH- ones at basal conditions (median, 0.27 vs 0.27 ng/µU) and during glucose infusion (0.15 vs 0.15 ng/µU). Normal glucose-tolerant Brazilian FH+ individuals well-matched with FH- ones did not show defects of insulin secretion, insulin sensitivity, or hepatic insulin extraction as tested by hyperglycemic clamp procedures.

Differential coronary resistance microvessel remodeling between type 1 and type 2 diabetic mice: Impact of exercise training

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Behavioral and biological correlates of medicine use in type 2 diabetic patients attended by Brazilian public healthcare system

A relação entre atividade física e consumo de medicamentos não é clara. Assim, o objetivo do estudo foi investigar a relação entre nível de atividade física e uso de medicamentosem diabéticos tipo 2 atendidos pelo Sistema Único de Saúde. A amostra foi composta por 121 diabéticos do tipo 2 de ambos os sexos atendidos pelos sistema público de saúde. Gordura corporal (antropometria e bioimpedância elétrica), atividade física (Questionário de Baecke) e uso de medicamentos (15 dias prévios a avaliação) foram avaliados. Houve relação entre uso de medicamentos e sexo (r = 0.18; p = 0.045), índice de massa corporal (r = 0.22; p = 0.012), circunferência de cintura (r = 0.19; p = 0.029), percentual de gordura (r = 0.21; p = 0.016), idade (r = 0.23; p = 0.009) e atividade física (r = -0.22; p = 0.012). A regressão linear incluiu no modelo apenas idade (β = 0.718; p = 0.057), IMC BMI (β = 0.057; p = 0.022) e atividade física (β = -0.176; p = 0.044) no modelo multivariado. Conclui-se que a prática de atividade física diminui uso de medicamentos independente da idade e obesidade.

Effects of 12-week overground walking training at ventilatory threshold velocity in type 2 diabetic women

This study analyzed the effects of overground walking training at ventilatory threshold (VT) velocity on glycaemic control, body composition, physical fitness and lipid profile in DM2 women. Nineteen sedentary patients were randomly assigned to a control group (CG; n=10, 55.9±2.2 years) or a trained group (TG; n=9, 53.4±2.3 years). Both groups were subjected to anthropometric measures, a 12-h fasting blood sampling and a graded treadmill exercise test at baseline and after a 12-week period, during which TG followed a training program involving overground walking at VT velocity for 20-60min/session three times/week. Significant group×time interactions (P<0.05) in glycated hemoglobin (HbA1c), body mass, body mass index (BMI), peak oxygen uptake (VO 2peak) and exercise duration were observed as effects of training exercise, whereas intervention did not induced significant changes (P>0.05) in fasting blood glucose, submaximal fitness parameters and lipid profile. Our results suggest that overground walking training at VT velocity improves long term glycaemic control, body composition and exercise capacity, attesting for the relevance of this parameter as an effective strategy for the exercise intensity prescription in DM2 population. © 2011 Elsevier B.V.

Determinants of blood pressure in type 2 diabetic subjects with high occurrence of inadequate glycemic control

Study design: Association study Objective: To analyze the association between different biological/behavioral risk factors and blood pressure in a sample of type 2 diabetes mellitus patients with poor glycemic control. Methods: A sample of 121 type 2 diabetic patients was selected in the Public Healthcare System in a middle size Brazilian city. Blood pressure was measured using an aneroid device, previously calibrated. Six determinants of blood pressure were taken into count: age, hypoglycemic agents, general obesity, abdominal obesity, eating behaviors and physical activity level. Results: The type 2 diabetic patients presented mean age of 60.1±8.9 years-old and, at least, one risk factor. Eating behaviors (OR adj= 0.31 [0.12-0.75]) and sports practice (OR adj= 0.12 [0.02-0.75]) constituted protective factors associated with lower systolic blood pressure. On the other hand, age was positively associated with high systolic blood pressure (OR adj= 3.81 [1.39-10.38]). Patients with 5-6 risk factors, presented higher values of systolic and (F= 3.857; p= 0.011 [post hoc with p= 0.039]), diastolic blood pressure (F= 4.158; p= 0.008 [post hoc with p= 0.036]) and increased occurrence of hypertension (p= 0.010). Conclusion: Our findings indicate that, behavioral variables were important determinants of blood pressure in type 2 diabetic patients with poor glycemic control and clustering of behavioral and biological risk factors increase the hypertension occurrence.

Monotoring adherence to prescribed medication in type 2 diabetic patients treated with sulfonylureas

Data on adherence to prescribed medication amongst diabetics are scarce. The purpose of this study was to collect information about the dynamics and patterns of compliance of elderly patients with type 2 diabetes mellitus on oral treatment by using different assessment techniques.

Quality of care for uninsured type 2 diabetic patients in a financial assistance medical home model

The medically uninsured population in the United States is 16% or 42 million people and consists of a significant number of Type 2 diabetic patients which is the predominant form of diabetes with 798,000 new cases diagnosed each year. There is limited health services research on uninsured populations concerning health system measures or specific disease conditions. ^ The purpose of this investigation was to determine the impact a newly implemented health care program had on the quality of care provided to patients with Type 2 diabetes. The primary study objective was to compare the quality of care while controlling for utilization, and health status of patients in the new program to their status during the previous financial assistance program. The research design was a retrospective matched-pairs design. The study population consisted of 225 patients who received medical care during 1996 and 1997 at the University Health System in San Antonio, Texas. ^ Six quality of care measures individually failed to demonstrate a statistically significant difference when compared between the two periods. However, an index measure reflecting the number of patients who received all six of the quality of care measures demonstrated a statistically significant increase in 1997 (p-value < 0.05). In 1996, 8 patients (2.6%) received all six medical management components. In 1997, 38 patients (16.8%) received all six medical management components. Four regression models were analyzed; two out of the four models demonstrated inconsistent results based on the program membership variable. ^ It is concluded that there has been a small effect of the Carelink program demonstrated by an increase from 8 to 38 patients receiving all quality of care components for Type 2 diabetics at the UHS. It is recommended that additional research be conducted in order to evaluate the quality of care provided to Type 2 diabetic patients. ^

The performance of interferon-gamma release assays in tuberculosis patients with type II diabetes

The sensitivity of Interferon-γ release assays for detection of Mycobacterium tuberculosis (MTB) infection or disease is affected by conditions that depress host immunity (such as HIV). It is critical to determine whether these assays are affected by diabetes and related conditions (i.e. hyperglycemia, chronic hyperglycemia, or being overweight/obese) given that immune impairment is thought to underline susceptibility to tuberculosis (TB) in people with diabetes. This is important for tuberculosis control due to the millions of type 2 diabetes patients at risk for tuberculosis worldwide.^ The objective of this study was to identify host characteristics, including diabetes, that may affect the sensitivity of two commercially available Interferon-γ (IFN-γ) release assays (IGRA), the QuantiFERON®-TB Gold (QFT-G) and the T-SPOT®.TB in active TB patients. We further explored whether IFN-γ secretion in response to MTB antigens (ESAT-6 and CFP-10) is associated with diabetes and its defining characteristics (high blood glucose, high HbA1c, high BMI). To achieve these objectives, the sensitivity of QFT-G and T-SPOT. TB assays were evaluated in newly diagnosed, tuberculosis confirmed (by positive smear for acid fast bacilli and/or positive culture for MTB) adults enrolled at Texas and Mexico study sites between March 2006 and April 2009. Univariate and multivariate models were constructed to identify host characteristics associated with IGRA result and level of IFN-γ secretion.^ QFT-G was positive in 68% of tuberculosis patients. Those with diabetes, chronic hyperglycemia or obesity were more likely to have a positive QFT-G result, and to secrete higher levels of IFN-γ in response to the mycobacterial antigens (p<0.05). Previous history of BCG vaccination was the only other host characteristic associated with QFT-G result, whereby a higher proportion of non-BCG vaccinated persons were QFT-G positive, in comparison to vaccinated persons. In a separate group of patients, the T-SPOT.TB was 94% sensitive, with similar performance in all tuberculosis patients, regardless of host characteristics.^ In summary, we have demonstrated the validity of QFT-G and T-SPOT. TB to support the diagnosis of TB in patients with a range of host characteristics, but most notably in patients with diabetes. We also confirmed that TB patients with diabetes and associated characteristics (chronic hyperglycemia or BMI) secreted higher titers of IFN-γ when stimulated with MTB specific antigens, in comparison to patients without these characteristics. Together, these findings suggest that the mechanism by which diabetes increases risk to TB may not be explained by the inability to secrete IFN-γ, a key cytokine for TB control.^

Reduced postprandial proinsulinaemia and 32-33 split proinsulinaemia after a mixed meal in type 2 diabetic patients following sensitization to insulin with pioglitazone

Objective: Reduced insulin sensitivity associated with fasting hyperproinsulinaemia is common in type 2 diabetes. Proinsulinaemia is an established independent cardiovascular risk factor. The objective was to investigate fasting and postprandial release of insulin, proinsulin (PI) and 32-33 split proinsulin (SPI) before and after sensitization to insulin with pioglitazone compared to a group treated with glibenclamide. Design and patients: A randomized double-blind placebo-controlled trial. Twenty-two type 2 diabetic patients were recruited along with 10 normal subjects. After 4 weeks washout, patients received a mixed meal and were assigned to receive pioglitazone or glibenclamide for 20 weeks, after which patients received another identical test meal. The treatment regimes were designed to maintain glycaemic control (HbA1c) at pretreatment levels so that ß-cells received an equivalent glycaemic stimulus for both test meals. Measurements: Plasma insulin, PI, SPI and glucose concentrations were measured over an 8-h postprandial period. The output of PI and SPI was measured as the integrated postprandial response (area under the curve, AUC). Results: Pioglitazone treatment resulted in a significant reduction in fasting levels of PI and SPI compared to those of the controls. Postprandially, pioglitazone treatment had no effect on the insulin AUC response to the meal but significantly reduced the PI and SPI AUCs. Glibenclamide increased fasting insulin and the postprandial insulin AUC but had no effect on the PI and SPI AUCs. Conclusions: Sensitization to insulin with pioglitazone reduces the amount of insulin precursor species present in fasting and postprandially and may reduce cardiovascular risk. © 2007 The Authors.

The Genetic Landscape of Renal Complications in Type 1 Diabetes

Diabetes is the leading cause of end stage renal disease. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2,843 subjects, we estimated that the heritability of diabetic kidney disease was 35% ( p=6x10-3 ). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index ( p=2.2×10-5) and the risk of type 2 diabetes (p=6.1x10-4 ) were associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation ( p=1.1×10-4 ). Pathway analysis implicated ascorbate and aldarate metabolism ( p=9×10-6), and pentose and glucuronate interconversions ( p=3×10-6) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.  

Adhésion au traitement antidiabétique oral chez les adultes atteints de diabète de type 2 : déterminants et interventions visant à l'améliorer

Introduction : Le diabète de type 2 est une maladie évolutive débilitante et souvent mortelle qui atteint de plus en plus de personnes dans le monde. Le traitement antidiabétique non-insulinique (TADNI) notamment le traitement antidiabétique oral (TADO) est le plus fréquemment utilisé chez les adultes atteints de cette maladie. Toutefois, plusieurs de ces personnes ne prennent pas leur TADO tel que prescrit posant ainsi la problématique d’une adhésion sous-optimale. Ceci entraîne des conséquences néfastes aussi bien pour les patients que pour la société dans laquelle ils vivent. Il serait donc pertinent d’identifier des pistes de solution à cette problématique. Objectifs : Trois objectifs de recherche ont été étudiés : 1) Explorer la capacité de la théorie du comportement planifié (TCP) à prédire l’adhésion future au TADNI chez les adultes atteints de diabète de type 2, 2) Évaluer l’efficacité globale des interventions visant à améliorer l’adhésion au TADO chez les adultes atteints de diabète de type 2 et étudier l’influence des techniques de changement de comportement sur cette efficacité globale, et 3) Évaluer l’efficacité globale de l’entretien motivationnel sur l’adhésion au traitement médicamenteux chez les adultes atteints de maladie chronique et étudier l’influence des caractéristiques de cette intervention sur son efficacité globale. Méthodes : Pour l’objectif 1 : Il s’agissait d’une enquête web, suivie d’une évaluation de l’adhésion au TADNI sur une période de 30 jours, chez des adultes atteints de diabète de type 2, membres de Diabète Québec. L’enquête consistait à la complétion d’un questionnaire auto-administré incluant les variables de la TCP (intention, contrôle comportemental perçu et attitude) ainsi que d’autres variables dites «externes». Les informations relatives au calcul de l’adhésion provenaient des dossiers de pharmacie des participants transmis via la plateforme ReMed. Une régression linéaire multivariée a été utilisée pour estimer la mesure d’association entre l’intention et l’adhésion future au TADNI ainsi que l’interaction entre l’adhésion passée et l’intention. Pour répondre aux objectifs 2 et 3, deux revues systématiques et méta-analyses ont été effectuées et rapportées selon les lignes directrices de PRISMA. Un modèle à effets aléatoires a été utilisé pour estimer l’efficacité globale (g d’Hedges) des interventions et son intervalle de confiance à 95 % (IC95%) dans chacune des revues. Nous avons également quantifié l’hétérogénéité (I2 d’Higgins) entre les études, et avons fait des analyses de sous-groupe et des analyses de sensibilité. Résultats : Objectif 1 : Il y avait une interaction statistiquement significative entre l’adhésion passée et l’intention (valeur-p= 0,03). L’intention n’était pas statistiquement associée à l’adhésion future au TADNI, mais son effet était plus fort chez les non-adhérents que chez les adhérents avant l’enquête web. En revanche, l’intention était principalement prédite par le contrôle comportemental perçu à la fois chez les adhérents [β= 0,90, IC95%= (0,80; 1,00)] et chez les non-adhérents passés [β= 0,76, IC95%= (0,56; 0,97)]. Objectif 2 : L’efficacité globale des interventions sur l’adhésion au TADO était de 0,21 [IC95%= (-0,05; 0,47); I2= 82 %]. L’efficacité globale des interventions dans lesquelles les intervenants aidaient les patients et/ou les cliniciens à être proactifs dans la gestion des effets indésirables était de 0,64 [IC95%= (0,31; 0,96); I2= 56 %]. Objectif 3 : L’efficacité globale des interventions (basées sur l’entretien motivationnel) sur l’adhésion au traitement médicamenteux était de 0,12 [IC95%= (0,05; 0,20); I2= 1 %. Les interventions basées uniquement sur l’entretien motivationnel [β= 0,18, IC95%= (0,00; 0,36)] et celles dans lesquelles les intervenants ont été coachés [β= 0,47, IC95%= (0,03; 0,90)] étaient les plus efficaces. Aussi, les interventions administrées en face-à-face étaient plus efficaces que celles administrées par téléphone [β= 0,27, IC95%=(0,04; 0,50)]. Conclusion : Il existe un écart entre l’intention et l’adhésion future au TADNI, qui est partiellement expliqué par le niveau d’adhésion passée. Toutefois, il n’y avait pas assez de puissance statistique pour démontrer une association statistiquement significative entre l’intention et l’adhésion future chez les non-adhérents passés. D’un autre côté, quelques solutions au problème de l’adhésion sous-optimale au TADO ont été identifiées. En effet, le fait d’aider les patients et/ou les cliniciens à être proactifs dans la gestion des effets indésirables contribue efficacement à l’amélioration de l’adhésion au TADO chez les adultes atteints de diabète de type 2. Aussi, les interventions basées sur l’entretien motivationnel améliorent efficacement l’adhésion au traitement médicamenteux chez les adultes atteints de maladie chronique. L’entretien motivationnel pourrait donc être utilisé comme un outil clinique pour soutenir les patients dans l’autogestion de leur TADO.

Analyse des facteurs pouvant contribuer à l’augmentation de la prévalence du diabète de type 2 au Nouveau-Brunswick

Résumé : Problématique : Une augmentation importante de la prévalence du diabète a été observée au Nouveau-Brunswick au cours de la dernière décennie. Sachant que le diabète est associé à des complications de santé nombreuses et à des coûts élevés infligés au système de soins de santé, il devient important d’identifier les facteurs pouvant expliquer l’augmentation de la prévalence du diabète. L’étude a pour objectif de décrire l’évolution de ces facteurs afin de prioriser les interventions en lien avec cette maladie. Méthodes : Une revue critique de la littérature a permis l’identification de l’ensemble des facteurs pouvant expliquer l’augmentation de la prévalence du diabète. Des données administratives disponibles au Nouveau-Brunswick et des données tirées d’enquêtes de Statistique Canada ont été utilisées afin de décrire l’évolution de plusieurs des facteurs tirés de la revue critique de la littérature. Résultats : Une augmentation de 120% de la prévalence du diabète de type 2 au Nouveau-Brunswick a été observée entre 2001 et 2014. Cette augmentation pourrait être explicable par l’ensemble des cinq catégories de facteurs pouvant expliquer une augmentation de la prévalence dont plusieurs facteurs de risque individuels (dont l’obésité, le prédiabète et l’hypertension), de facteurs de risque environnementaux (dont l’urbanisation), de l’évolution de la maladie (exprimée par une diminution du taux de mortalité et une augmentation de l’incidence), de l’effet de détection (augmentation du nombre de personnes testées, diminution de la valeur d’HbA1c et de l’âge à la détection) et d’un effet du changement dans l’environnement (exprimé par un effet de période et de cohorte). Conclusion: L’augmentation de la prévalence du diabète notée au Nouveau-Brunswick pourrait s’expliquer par plusieurs facteurs de risque individuels, environnementaux, de l’évolution de la maladie, de l’effet de détection et d’un effet du changement dans l’environnement. Cette étude permettra de guider les actions sur le diabète au Nouveau-Brunswick et d’inspirer les autres provinces et pays à identifier les facteurs pouvant contribuer à l’augmentation de la prévalence du diabète grâce à la liste de l’ensemble des facteurs potentiellement explicatifs.

Impact of weight loss on oxidative stress and inflammatory cytokines in obese type 2 diabetic patients.

Background: Type 2 diabetes mellitus is associated with abnormal markers of inflammatory cytokines and oxidative stress markers. Although, these abnormalities could be modulated with weight reduction; there is limitation in clinical studies that have addressed the beneficial effects of weight reduction in modulating biomarkers of inflammatory cytokines and oxidative stress for obesity associated with type 2 diabetes mellitus. Objective: This study was designed to detect the effects of weight loss on the inflammatory cytokines, oxidative stress markers in obese type 2 diabetic patients. Material and Methods: Eighty obese patients with type 2 diabetes mellitus, their age ranged from 35-57 years and their body mass index ranged from 31-35 kg/m2 were equally assigned into 2 groups: the weight reduction group received aerobic exercises, diet regimen, where as the control group received medical treatment only for 12 weeks. Results: The mean values of body mass index (BMI), tumor necrosis factor–alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (sCRP), conjugated dienes (CD) and malondialdehyde (MDA) were significantly decreased, while the mean values of glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione (GSH) were significantly increased in patients of group (A), while changes were not significant in group (B). Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) at the end of the study. Conclusion: Weight loss ameliorates inflammatory cytokines and oxidative stress markers in obese type 2 diabetic patients.

Le partenariat intersectoriel : une stratégie gagnante pour la prévention et la gestion du diabète de type 2 dans un contexte de diversité.

Rapport de stage présenté à la Faculté des sciences infirmières en vue de l'obtention du grade de Maître ès sciences (M.Sc.) en sciences infirmières option expertise-conseil en soins infirmiers