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Background: Obstructive Sleep Apnea (OSA) is a chronic breathing disorder that is estimated to affect 20% of the US adult population. Intermittent hypoxia and sleep fragmentation caused by OSA likely affects cardiometabolic function. Individuals with OSA might be at risk of developing hypertension and type 2 diabetes (T2DM), with a dose-response relationship related to OSA severity. The objective of this study was to estimate the association between severity of OSA at diagnosis with 1) incidence of hypertension incidence of hypertension and 2) incidence of T2DM. Methods: We conducted a retrospective cohort study of Kaiser Permanente members diagnosed with OSA during 2000-2005. Adults without baseline hypertension or T2DM were eligible. Patients were excluded if hypertension or T2DM was diagnosed within one year prior to OSA diagnosis, and right censored at the end of follow-up or at the time Kaiser Permanente membership ended. Kaplan-Meier curves and Cox Proportional Hazard models were used to estimate the association between OSA severity and incident hypertension and incident diabetes. Results: Overall 719 patients were diagnosed with OSA during the study periods; 614 were included as those at risk of developing either hypertension (N=265) or T2DM (N=489). Overall, 261 had severe OSA at diagnosis. Those with severe OSA were more likely to be middle aged, overweight, and have prevalent hypertension or T2DM. Among those without prevalent hypertension at OSA diagnosis, 47.4% (126/266) were subsequently diagnosed with hypertension. Among those without prevalent T2DM at OSA diagnosis, 16.3% (80/491) were subsequently diagnosed with T2DM. After adjusting for BMI and prevalent T2DM, the hazard rate of incident hypertension among patients with severe OSA was 1.35 (95%CI: 0.88-2.06) compared to the rate among patients with mild OSA. The hazard rate of incident T2DM among patients with severe OSA was 1.49 (95%CI: 0.83-2.67) compared to the rate among patients with mild OSA after adjusting for BMI and prevalent hypertension. Discussion: We found high incidence rates of hypertension and T2DM among adults diagnosed with OSA. Severe OSA at diagnosis was associated with increased risk of either incident hypertension or T2DM, but not significantly (for p≤0.05).

African-American women (AAW) have had the largest increase in diagnosed diabetes in the US. Few studies have focused solely on dietary changes (one of the foundations for diabetes self-care), particularly in the context of family and the role of AAW. The purpose of this descriptive ethnographic study was to explicate cultural influences on food practices of AAW with type 2 diabetes (T2DM) in order to inform the health care community as well as future development of culturally-tailored interventions. Specific aims were to describe typical daily food practices and identify cultural influences on food practices of AAW with T2DM. Symbolic Interactionism, a sensitizing framework for viewing AAW with T2DM as a subculture, guided this study. Purposeful sampling was used to recruit 20 AAW who: were between 35 and 70 years of age, had been diagnosed with T2DM, shopped and prepared meals for their families, and attended church functions where food was served . Data collection consisted of one-one-one interviews and participant observation of church fellowship dinners, grocery shopping, and food preparation. A social anthropological approach to content analysis was used to describe behavioral regularities in food practices. Trustworthiness was maintained by an audit trail. Findings indicate that for informants in this study, who had diabetes ranging from 2 to 30+ years, there is a constant struggle between cultural food practices and eating healthier because of diabetes, particularly within the home setting where a majority of daily food practices take place. Difficulties in making dietary modifications result from conflicts between the need to change dietary practices to control diabetes and personal food preferences, as well as the preferences of people within the participants' social network. In addition, difficulties derive from AAW's emotional dedication to the symbolism of food and traditional cultural food practices. AAW are the gatekeepers for family food practices and are the keys to healthy dietary practices. This study begins to fill the research gap regarding cultural dietary food practices of this population. With increased knowledge, researchers and health care providers will be better able to improve AAW food practices, and ultimately improve diabetes control in this high-risk population. / text

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The protein Poly was first discovered in Drosophila melanogaster, during a screening for third chromosome lethal mutations. Drosophila poly mutant larvae exhibit a slower rate of development. However, they reach the third instar larval stage and remain at that stage for 21 days before they die without reaching pupation. This phenotype is attributed to developmental impairment of the imaginal discs, therefore suggesting defects in cell growth and/or proliferation. During that stage, the mutant larvae develop melanotic masses. Poly is conserved and its homolog, Elp6, is one of the small subunits of the Elongator Complex, a complex involved in many cellular functions including transcription and translation. Drosophila larvae mutated at the Elp3 gene, the gene encoding the catalytic subunit of the Elongator complex, develop melanotic masses, a phenotype very similar to that of poly. The Heck laboratory published that Poly is a positive mediator of the Insulin Receptor/TOR (InR/TOR) pathway, which leads to protein, glycogen and fatty acid synthesis, regulates cell growth and apoptosis. It was shown that Poly interacts with InR, at least in some cases, therefore promoting cell growth and metabolism (Bolukbasi et al., 2012). The Drosophila genome shares 60% similarity to the human, with 77% of the genes attributed to a human disease having a Drosophila counterpart (Chien et al., 2002). In 2011, an intriguing study by Musselman et al. reported that feeding wild type Drosophila larvae with excessive amounts of sucrose led to the development of an insulin resistance phenotype similar to that of Type 2 Diabetes (T2D), thus rendering Drosophila an easily accessible T2D model. The phenotype included impaired metabolism, slower rate of development, and excessive accumulation of triglycerides (TAG) in the larval fat body. In my thesis research, I examined the involvement of Poly in insulin resistance - T2D using Drosophila as a model. The understanding of the connection between the protein and the disease came upon the discovery of a new form of Poly, Poly14. Poly14 is enriched in the Drosophila fat body, the equivalent of the human fat tissue and liver and its protein levels are significantly decreased when larvae are fed a high sucrose diet, compared to other types of diets – potentially linking the protein to the onset of T2D. Poly mRNA levels were also lower. To examine whether the overexpression of poly might be able to rescue the insulin resistance phenotype, two new Drosophila transgenes were generated with the ability to express the gene in a tissue of interest. In these two new transgenes, Poly is tagged with tRFP (Red Fluorescence Protein) at the N’- (UAS_N’RFPpoly) or the C’-terminus (UAS_polyC’RFP). Overexpression of Poly rescued the insulin resistance phenotype, therefore implicating Poly as a possible important regulator in the development of the insulin resistance phenotype. All of the above findings suggest a vital role of Poly in metabolism and the development of the insulin resistance/diabetic phenotype in Drosophila, providing us the opportunity for new tools in this very medically-relevant field of research.

Thesis (M Med (Family Medicine))--University of Limpopo (Medunsa Campus), 2010. / Introduction: Diabetes Mellitus still remains an important non- communicable disease globally. The burden of the disease continues to rise even in the sub-Saharan Africa. Aim: The study aimed to assess and describe the dietary practices and the prevalence of obesity among type 2 diabetic patients seen at Scott Hospital. Methods: A descriptive cross- sectional study was conducted among type 2 diabetic patients at Scott Hospital, Morija, Lesotho. A simple random sample of 50 participants was selected and each completed an interviewer administered questionnaire. The administration of the questionnaire was done by the researcher and a research assistant. Socio- demographic characteristics of the participants were obtained, anthropometric measurements were height and weight of each participant with subsequent determination of the BMI. Dietary intake was assessed using questions from a modified food frequency questionnaire of 16 food groups that reflect the commonest food items available. Results: The results showed that 86% (43/50) of the participants were females and 14% (7/50) were males with a female: male ratio of 6:1. The majority (72%) were above age 50 years and with regards to educational status, 62% had primary school education as the highest level attained. Four percent (4%) had no formal education. Fifty percent (50%) of the participants were unemployed. The mean weight of the participants was 84.22 ± 13.51 kg and the mean height was 157.76 ± 6.10 cm. The mean BMI was 33.97 ± 4.99 kg/m². Seventy-eight percent (38/50) of the participants were obese, and 14% (7/50) of the participants who were females, were morbidly obese with BMIs ≥ 40kg/m². The prevalence of obesity when stratified by gender showed that 57% (4/7) of male participants and 81% (35/43) of female participants were obese. According to the dietary assessments, food groups with the highest reported consumption per unit per month were; maize meals, breakfast-cereals and bread respectively. Conclusion: The study showed a predominantly female and elderly population of type 2 diabetics at Scott Hospital, Morija, Lesotho. The prevalence of obesity was high (78%) among the participants and this further supports the view that obesity is a major risk factor for type 2 diabetes. Reported dietary intake showed a higher consumption of carbohydrates and a very low intake of dietary fibre as represented by legumes. Keywords: Type 2 diabetes mellitus, dietary habits and obesity.

acase@tulane.edu / Study aim: This study aimed to assess the individualized treatment goals (A1C, Blood Pressure, LDL-C) for patients with type 2 diabetes mellitus (T2DM), which lead to optimal health outcomes by different treatment strategies. Background and significance: The evidences in medical guidelines came from clinical trials with highly selected patients, whereas the treatment goals may differ in some subgroups. Additionally, considerable confusions on treatment target has resulted from recent changes in guidelines. So, there is a critical need to examine heterogeneity in optimal goals that lead to the most efficacious treatment options. Methods: A retrospective longitudinal study was conducted for veterans with T2DM by using US Veterans Affairs (VA) Administrative Database (Jan 2005 and Dec 2015). Longitudinal medical records were prepared for each 6-month cycle and multivariate longitudinal regression was used to estimate the risk of microvascular and macrovascular complication events and mortality. Second-degree polynomial and splines were applied in the model to identify the optimal goals in their associations with lowest risk of clinical outcomes by controlling the demographic characteristics, medical history, and medications. Results: 124,651 patients with T2DM were selected, with 62.68 years old (SD=10.96) and 6.72 (SD=6.68) follow-up years at average. In general population, A1C=6.06, LDL-C=106.10 and BP=137.90/98.00 were associated with lowest mortality risk. As of achieving lowest risk of microvascular and macrovascular complication, the optimal goals were A1C=6.81, LDL-C=109.10; and A1C=6.76, LDL-C=111.65, SBP=130.60 respectively. The optimal goals differed between age and racial subgroups. Lower SBP for younger patients and lower LDL-C for blacks were identified with better health outcomes. Conclusions: Individualized treatment goals were identified and multi-faceted treatment strategies targeting hypertension, hyperglycemia and hyperlipidemia may improve health outcome in veterans with T2DM. In addition to general ADA recommended goals, health system may examine their own large, more diverse patients with T2DM for better quality of care. / 1 / Qian Shi

There is substantial evidence of the elevated risk of cancer among individuals with type 2 diabetes. Very little is known, however, about the role that antidiabetic therapies play in this relationship. The objective of this program of research was to examine whether there is a therapeutic risk associated with antidiabetic therapies that increase circulating insulin levels, such as sulfonylureas and exogenous insulin, or a therapeutic benefit associated with antidiabetic therapies that reduce insulin resistance, such as metformin and the glitazones. This objective was achieved through four related population-based cohort studies using the administrative databases from Saskatchewan Health. The first study looked at the effect of the older antidiabetic therapies metformin and sulfonylureas on cancer mortality. The focus of the second study was to explore more closely the effect of metformin and sulfonylurea by using a time-varying Cox regression to define drug exposures. The third study looked more closely at the effect of exogenous insulin therapy and cancer mortality, and the last study focused on the more recently available antidiabetic therapy the glitazones and cancer mortality. We found that individuals with type 2 diabetes exposed to sulfonylurea monotherapy had a significantly increased risk of cancer-related mortality, compared to patients exposed to metformin. We also observed a dose-response gradient with exogenous insulin therapy and cancer mortality, whereby individuals exposed to higher levels of insulin had a higher risk of cancer mortality. In the last study, we found that the newer class of antidiabetic therapies, the glitazones, were associated with a decreased risk of cancer mortality. These finding add further support that antidiabetic therapies may play a moderating role in the relationship between type 2 diabetes and cancer outcomes. However, it is unclear whether the increased risk of cancer mortality we observed was related to a toxic effect of sulfonylureas and exogenous insulin or a protective effect of metformin and glitazones, or due to some unmeasured effect related to both choice of drug therapy and cancer risk. Future research should incorporate a non-diabetes control cohort for comparison and examine the more proximal outcome measure cancer incidence. / Epidemiology