Immigrants are at elevated risk for not having their diabetes treatment appropriately intensified, likely resulting in poorly-controlled diabetes and increased morbidity and mortality. Immigrant status is a powerful sociodemographic cue, yet its influence on providers' diabetes treatment decisions remains unknown. The study objective was to determine the effect of patient immigrant status on provider decisions to (1) take no action, (2) add an oral hypoglycemic agent (OHA), (3) add/switch to insulin, or (4) refer the patient to an endocrinologist. Participants were 140 medical students/professionals ('providers'). Providers viewed profiles (videos+vignettes) for virtual patients different in immigrant status (born in Mexico or U.S.; other characteristics held constant). Analyses were completed at the group and individual levels. Group levels indicated providers were less likely to refer foreign-born patients to endocrinology than U.S.-born patients (p=0.03). No differences were detected for the other three treatment likelihood ratings. Individual results indicated that about half of provider decisions were influenced by patient immigrant status (i.e., Cohen's d≥0.50) across all four decisions. Effect size data show an almost even split between higher treatment ratings for foreign-born vs. U.S.-born patients for three decisions (take no action, add an OHA, add/switch to insulin), explaining why group-level differences for these ratings did not emerge. This study found that providers are less likely to refer foreign-born patients to endocrinology, potentially leading to therapeutic inertia. In addition, half of individual-level provider decisions were meaningfully influenced by patient immigrant status. However, traditional group-level analyses mask these important individual-level differences. These systematic differences in treatment based on non-relevant factors could lead to unintended adverse outcomes for the foreign-born population.

Obesity, a major risk factor in the development of Type 2 Diabetes (T2D), is commonly associated with insulin resistance and hyperinsulinemia. The long accepted view has been that insulin resistance drives hyperinsulinemia; however, there are multiple lines of evidence that hyperinsulinemia can precede and drive insulin resistance. The signals and mechanisms by which chronic excess nutrients promote pancreatic β-cell dysfunction remain poorly understood. This prompted us to define the signaling events that contribute to basal insulin hypersecretion induced by excess glucose. Of particular interest is signaling through mechanistic target of rapamycin complex 1 (mTORC1), a nutrient sensitive kinase complex whose hyperactivation has been shown to promote hyperinsulinemia. Clonal ß-cells (INS-1 cells) with and without mTORC1 inhibition were pre-exposed to physiological (5mM) or excess (11mM) glucose for 4 to 24 hrs. Basal insulin secretion, respiration and metabolites were measured. Pre-exposure to excess glucose resulted in sustained mTORC1 hyperactivation, basal insulin secretion, higher basal respiration and increased maximal respiratory capacity, due to accelerated mitochondrial pyruvate metabolism. Inhibition of mTORC1 reduced basal insulin secretion, basal respiration and maximal respiratory capacity. Moreover, cells challenged with excess glucose had increased levels of glycolysis and TCA cycle intermediates. Our results suggest that hyperactivation of mTORC1 induced by excess glucose results in increased energy demand and in the generation of metabolic factors that can lead to basal insulin hypersecretion. Therefore, targeting mitochondrial pyruvate metabolism and /or mTORC1 signaling could potentially lead to specific therapies to control hyperinsulinemia and diabetes progression.

archives@tulane.edu / Gestational diabetes mellitus (GDM) increases the lifetime risk of developing type 2 diabetes mellitus (T2DM) in the mother; however, biological mechanisms remain relatively unknown, and known risk factors have shown to be incomplete. Both epidemiological and experimental research suggest that environmental exposure to particulate matter (PM2.5) may initiate and further progress chronic diseases such as T2DM. This study investigates the association between PM2.5 exposure and the risk of T2DM among women with a history of GDM. Associations between prevalent and incident T2DM with PM2.5 utilized two PM2.5 metrics: 1) annual average PM2.5 concentration and 2) annual average modeled PM2.5 exposure, calculated from daily PM2.5 concentration levels provided by the USRA/NASA Marshal Space Flight Center. Data from the Southern Community Cohort Study, who at recruitment reported a previous diagnosis of GDM, for whom T2DM, risk factor, and follow-up information were available, was provided. In total, 2403 participants were included in the analysis of prevalent T2DM, and 1036 participants were included in the analysis of incident T2DM. Associations between proximity to roadways and race with PM2.5 metrics were also conducted. Participants that live close to roadways were exposed to higher annual average PM2.5 concentrations and annual average modeled PM2.5 exposures. When stratified by race, non-Black participants were exposed to higher averages. After adjustment, a significant association was observed between annual average PM2.5 concentration and incident T2DM (hazards ratio (HR)= 1.022, 95% confidence interval (CI): 1.003, 1.040). No association was observed between annual average PM2.5 concentrations and prevalent T2DM. Annual average modeled PM2.5 exposure was not associated with either prevalent or incident T2DM. Results were partly consistent with previous literature. Additional studies with a greater range of air pollution exposures, including higher levels, additional pollutants, and more tailored exposure models, are warranted to investigate hypothesized associations. / 0 / Ashley Bell

No abstract available. / Thesis (DPhil)--University of Pretoria, 2010. / Biokinetics, Sport and Leisure Sciences / unrestricted

Background: Self-monitoring of blood glucose (SMBG) can inform on the timing of hyperglycaemia; however there is currently no standardised approach to utilise these data to improve glycaemic control in type 2 diabetes patients. Aims: To assess the efficacy of structured blood glucose testing in guiding an insulin titration algorithm in poorly controlled, insulin-treated type 2 diabetes patients. The secondary aim was to compare change in HbA1c between the study subjects and matched controls receiving standard treatment. Methods: This six-month prospective intervention recruited 39 poorly controlled (HbA1C ≥ 8.5% or 69.4 mmol/mol), type 2 diabetes subjects using twice-daily biphasic insulin from two public hospitals in Tshwane, South Africa. Patients were asked to perform structured SMBG over 4 weeks and return monthly for consultations where physicians titrated insulin doses using a standardised algorithm guided by the data collected. Post-hoc analysis was performed to assess glycaemic control of study participants compared to those receiving standard treatment. Results: It was found that mean HbA1c decreased over the study period by 1.89% (95% CI: -2.46 to -1.33, p-value<0.001). Mean SMBG and mean fasting plasma glucose (FPG) decreased by 1.6 mmol/L (95% CI: -2.5 to -0.6 mmol/L, p-value: 0.002) and 1.5 mmol/L (95% CI: -2.2 to -0.2 mmol/L, p-value: 0.024), respectively. Hypoglycaemic event rate (≤3.9 mmol/L) was 33.08 events per patient-year. Total daily insulin use increased by a mean 40.12 units.day-1 (SE: 7.7, p-value<0.001); weight increased by an average 3.98 kg (95% CI: 2.56 to 5.41, p-value <0.001) over the study period. Study participants were found to have a greater mean (SE) reduction of 0.777% (0.404) in HbA1c compared to patients receiving standard care, which fell short of statistical significance (95% CI: -1.569 to 0.015%, p-value: 0.054) due to lack of power (56.5%) in the post-hoc comparison. Conclusion: A structured SMBG programme that advises monthly algorithmic insulin titration can improve glucose control in type 2 diabetes patients using insulin, with moderate hypoglycaemic events and weight gain. / Dissertation (MSc)--University of Pretoria, 2016. / National Research Foundation (NRF) / Roche Products (South Africa) / School of Health Systems and Public Health, University of Pretoria / School of Medicine, University of Pretoria / School of Health Systems and Public Health (SHSPH) / MSc / Unrestricted

Periodontitis (PD) and type 2 diabetes mellitus (T2D) are chronic inflammatory diseases in which the host immune system encounters changes in its T and B cell distribution and function. Both disorders are increasingly prevalent in the U.S. and while T2D is a risk factor for periodontal disease, PD can exacerbate diabetes. Previous studies have unsuccessfully attempted to determine the underlying molecular mechanism for the relationships between T2D and periodontitis. To test directly the effect of T2D on periodontitis, I quantified cytokine production by gingival immune cells from three types of subjects: healthy, periodontal disease and T2D with periodontal disease, using single cells purified via flow cytometry and assessed for function with an enzyme-linked immunospot (ELISPOT) assay. The cells were sorted into subtypes according to CD45+, CD4+, CD8+, CD11b+, CD19+ and/or CD56+ expression, were stimulated by PMA, ionomycin or LPS, and were aliquoted into a well of a 96-well ELISPOT plate for 36 hours. Outcomes showed that CD4+ is the predominant cell population in lymphocytes and that gingiva tissues from periodontitis/T2D group produced higher concentrations of cytokines characteristic of the Th1 T cell subset, namely IL-2, IL-10, TNF-α and IFN-γ (p<0.05, <0.001, <0.001, <0.01, respectively) compared to tissues from either healthy or periodontitis group. This work illustrates that T2D increases inflammation in periodontitis through an increase in Th1 T helper cell function.

Obesity is a significant health care problem, affecting more than one third of the United States population and is an important risk factor for Type 2 Diabetes Mellitus (T2D). Adipose tissue expansion results in the recruitment and accumulation of macrophages, which secrete proinflammatory cytokines that impair insulin signaling. Adenosine regulates inflammation by signaling through G-protein coupled receptors (GPCRs), such as the A2b adenosine receptor (A2bAR). Recently a role for adenosine receptors has been described in the differentiation of osteoblasts and adipocytes. This thesis tests the hypothesis that the A2bAR regulates adipose tissue dynamics at the level of preadipocyte differentiation and macrophage inflammation. This thesis showed that activation of the A2bAR inhibited preadipocyte differentiation. A2bAR-induced adipocyte inhibition was dependent on the expression of Krüppel-like factor 4 (KLF4), which is important for stem cell maintenance and renewal. A2bAR knockdown enhanced adipogenesis in vitro and A2bAR knockout (KO) mice had more adipocytes as compared to wild type (WT) mice, suggesting enhanced adipogenesis in the absence of the A2bAR. The translational potential of this work is strengthened by the previous finding of elevated A2bAR expression in adipose tissue of obese individuals as well as our new finding of a close correlation between the expression of A2bAR and KLF4 in adipose tissue of obese individuals. A2bAR KO mice have impaired insulin resistance, in part due to reduced levels of insulin receptor substrate-2 (IRS-2). Proinflammatory cytokines have been shown to reduce IRS-2 levels. Given the role of the A2bAR in regulating inflammation, the contribution of A2bAR signaling in macrophages to insulin resistance was elucidated. Transgenic mice that express A2bAR only in macrophages were generated. Intriguingly, restoration of A2bAR signaling in macrophages ameliorated insulin resistance, glucose tolerance, and fat and liver tissue insulin signaling. As expected, tissue and plasma proinflammatory cytokine levels were reduced to that of WT mice. This suggested that the protective effect of A2bAR signaling on insulin resistance was due in large part to A2bAR control of macrophage cytokine expression. This thesis highlights the importance of A2bAR signaling in adipogenesis and in regulating inflammation in the setting of obesity and T2D.

Diabetes, a major public health challenge in St. Kitts, has been a focus of international public health community research. Although researchers have demonstrated that diabetes self-management education is a cost-effective strategy for the prevention of diabetes-related complications, they have yet to establish whether there is adequate education occurring in treatment settings with diabetic patients. The purpose of the study was to implement and evaluate the short-term effectiveness of a diabetes self-management education intervention on diabetes-related knowledge and accepted behavioral changes to decrease risk for complications. Based on a self-care approach, this education intervention was designed to improve diabetes-related knowledge and self-management behaviors. To test and evaluate the pre and post intervention effect, a convenience sample of 15 patients diagnosed with Type 2 diabetes attending a scheduled diabetic clinic completed the Diabetes Knowledge Test and a researcher-designed sociodemographic survey, which included self-report of blood glucose self-monitoring and foot care behaviors. The results of these analyses indicated that the participants’ knowledge level increased (p = < .001). However, Chisquare and Fisher’s exact tests determined no significant changes in the participants’ self management behaviors. The results may be attributed to the short time frame of the intervention. The implications for positive social change include opportunities to improve inter-professional collaboration in programs that will create positive effects on diabetic self care and reduce the incidence of negative health outcomes. Furthermore, the use of a self-care approach by health care professionals could be a key factor in strengthening diabetes knowledge, engagement, and self-management for Type 2 diabetic patients.

Indiana University-Purdue University Indianapolis (IUPUI) / Immigrants are at elevated risk for not having their diabetes treatment appropriately intensified, likely resulting in poorly-controlled diabetes and increased morbidity and mortality. Immigrant status is a powerful sociodemographic cue, yet its influence on providers’ diabetes treatment decisions is unknown. The study objective was to determine the effect of patient immigrant status on providers’ decisions to (1) take no action, (2) add an oral hypoglycemic agent (OHA), (3) add/switch to insulin, or (4) refer the patient to an endocrinologist. Participants were 140 medical students/professionals (‘providers’). Providers viewed profiles (videos + vignettes) for virtual patients differing in immigrant status (born in Mexico or U.S.; other characteristics held constant). Analyses were completed at the group (‘nomothetic’) and individual (‘idiographic’) levels. Nomothetic results indicated providers were less likely to refer foreign-born patients to endocrinology than U.S.-born patients (p=0.03). No differences were detected for the other three treatment likelihood ratings. Idiographic results indicated that about half of provider decisions were influenced by patient immigrant status (i.e., Cohen’s d≥0.50) across all four treatment decisions. Effect size data show an almost even split between higher treatment ratings for foreign-born vs. U.S.-born patients for three decisions (take no action, add an OHA, add/switch to insulin), explaining why group-level differences for these ratings did not emerge (i.e., they were cancelled out). This study found that providers are less likely to refer foreign-born patients to endocrinology, potentially leading to therapeutic inertia. In addition, half of individual-level provider decisions were meaningfully influenced by patient immigrant status. However, traditional group-level analyses mask these important individual-level differences. These systematic differences in treatment based on non-relevant factors could lead to unintended adverse outcomes for the foreign-born population.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20568号 / 医博第4253号 / 新制||医||1022(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 原田 浩, 教授 武藤 学, 教授 戸井 雅和 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM