The global rise in the prevalence of obesity has been labeled a pandemic. The increasing rates of overweight and obese persons across the world is discerning, as obesity is a risk factor for many life-threatening and debilitating diseases including type two diabetes mellitus (T2DM), a disease that decreases insulin sensitivity of skeletal muscle, adipose tissue and liver, and insulin secretion in pancreatic beta cells. Despite its pervasiveness, the mechanism by which obesity causes T2DM remains elusive. Adipose tissue is known to contribute to whole body glucose metabolism and as a result has been implicated in T2DM. Obesity causes changes in the physiology of adipose tissue, including hypertrophy of adipocytes, rendering them stressed and dysfunctional. The result is an increase in free fatty acids in the blood, due to increased lipolysis and decreased triglyceride storage. Free fatty acids have been shown to cause insulin resistance in insulin sensitive tissues. It has also been observed that in some patients, obesity results in inflammation of adipose tissue. As adipocytes enlarge, they not only secrete increasing amounts of free fatty acids, they also secrete chemoattractant proteins like MCP-1, which attract macrophages. These macrophages secrete inflammatory cytokines such as Tumor Necrosis Factor- alpha, Interleukin-1beta and Interleukin-6, among others, which have been shown to alter adipose tissue metabolism by increasing lipolysis and decreasing triglyceride storage. In addition, inflammatory cytokines have been suspected to play a role in insulin resistance, although the exact mechanisms remain elusive. The present study explored the possibility that Interleukin-1beta and Interleukin-6 affect insulin signaling in human adipocytes by increasing lipolysis, thus increasing free fatty acids in the blood. Recent studies have emphasized the role of fat specific protein 27 (FSP27) in the regulation of lipolysis in adipocytes whereby, FSP27 controls lipolysis by regulating the lipolytic capacity as well as transcription of the primary lipase ATGL. In the present study we used FSP27 as a tool to investigate if managing lipolysis could protect human adipocytes from the impairment of insulin signaling caused by the presence of inflammatory cytokines. We found that Interleukin-1beta and Interleukin-6 increase lipolysis in human adipocytes by depression of endogenous FSP27 protein levels and that the rate of lipolysis can be rescued by adenoviral expression of FSP27. In addition, we found that interleukin-1beta decreased insulin signaling by decreasing phosphorylation of AKT and that adenoviral expression of FSP27 has a protective effect over Interleukin-1beta - induced impairment of insulin signaling in human adipocytes. Our experiments regarding the effect of Interleukin-6 on insulin signaling were inconclusive and need further experimentation. These results suggest that the inflammatory cytokine Interleukin-1beta indirectly suppresses insulin signaling, by increasing lipolysis and that maintenance of FSP27 protein levels in obese patients could prevent patients from developing insulin resistance and T2DM.

Approximately 25.8 million people, 8.3% of the population in the United States have diabetes mellitus (DM), which makes this disease one of the biggest public health problems facing this country. Type 2 diabetes (T2DM) is a heterogeneous disease characterized by variable degrees of insulin resistance, impaired insulin secretion, and increased glucose production. Currently, the insulin secretagogues known as sulfonylureas represent the major mainline drug class for long-term treatment. However, serious side effects, such as hypoglycemia and loss of potency with long-term use necessitate the development of novel insulin secretagogues. Transient receptor potential (TRP) channels have been reported to be involved in pancreatic insulin secretion. TRPA1 is a Ca2+-permeable nonselective cation channel. TRPA1 can be activated by molecules produced during oxidative glycolysis. TRPA1 may be an attractive candidate for drug development because of its involvement in the mechanism of insulin secretion. Previous studies have shown TRPA1 is expressed in rat pancreatic islets and that its activation promotes insulin release. This study was designed to determine if TRPA1 is expressed in mouse and human pancreatic β cells and whether it can promote insulin secretion. I demonstrated that TRPA1 is expressed in mouse and human pancreatic islets. I measured TRPA1-induced membrane currents using patch-clamp and used Ca2+ imaging to demonstrate that TRPA1 agonists induce Ca2+ influx in rat β cell-derived RINm5F cells. I confirmed that TRPA1 KO mice have no TRPA1 mRNA or protein in pancreatic β cells. I used isolated islet cells to demonstrate TRPA1-induced Ca2+ influx using Ca2+ imaging. By using pancreatic islets obtained from wild-type and TRPA1 KO mice, I determined that TRPA1 is important for insulin secretion. Finally, I determined that intraperitoneal administration of a TRPA1 agonist and antagonist affected blood glucose levels and plasma insulin levels in a manner consistent with the TRPA1 acting to increase insulin secretion. Furthermore, glucose tolerance was impaired in TRPA1 KO mice upon intraperitoneal glucose tolerance test (IPGTT) challenge compared to wild-type mice. In summary, I have shown TRPA1 is expressed not only in rat pancreatic islets but also in mouse and human pancreatic islets. I confirmed the localization of TRPA1 in pancreatic β cells. All of the experimental results are consistent with the concept that TRPA1 acts as to increase the insulin-secreting capacity of pancreatic β cells. According to my data, TRPA1 may play a role in promoting insulin secretion in patients with T2DM. Therefore, pharmacological activation of TRPA1 may be a novel therapeutic method for the treatment of diabetes.

Background Within the last century, Type 2 diabetes mellitus has become one of the major health concerns both in the US and globally. Overall prevalence and incidence of the disease within younger populations including adolescents and young adults has sharply increased since 1990 and is estimated to increase further if no actions are taken. It is estimated that 5.7 million people have a form of diabetes. Of the total estimated prevalence of T2DM, 25% of persons with diabetes are unaware they have the disease. This study aims to identify populations most at risk as well as to label important risk factors associated with the rise of T2DM within the young adult population. Objectives This study aimed to measure the prevalence of diagnosed and undiagnosed T2DM among different populations based on ethnicity, socioeconomic status, and weight classification among a representative sample of young adults within the United States. This study also aims to identify and quantify associated risk factors of T2DM among young adults, and address current preventative and treatment measures. Methods Six two-year samples of the National Health and Nutrition Examination Survey (NHANES) containing a total of 62,160 individuals were compiled into one dataset. Of these, 11,874 young adults aged 20-40 were selected into the study. Prevalence of diagnosed and undiagnosed T2DM was calculated for specific populations. The study also aimed to identify important risk factors through univariate and multivariate binomial logistic regression analysis. Results Among young adults aged 20-40, overall prevalence of T2DM was found to be 1.4% (CI: 1.2-1.6%). Of observed diabetes cases, an alarming 20.1% (N = 68) were categorized as undiagnosed. Significant increases in risk were observed within older age groups, overweight and obese weight categories, individuals living below poverty and within minority racial/ethnic groups. Weight, measured by both BMI (OR: 10.7; CI:5.88-19.44) and waist circumference (OR: 5.29; CI: 3.18-8.79), was identified as the most influential risk factor, and should be a main area of focus in development of interventions. Increases in activity levels, both at work and during leisure-time, were found to decrease one’s risk of having T2DM. Discussion Type 2 diabetes has become a major health concern within the past decades, and will continue to be an area of focus in the future. If current trends of diabetes among the young continue, significant burden will be placed on both health facilities as well as on the economy. Based on the findings from this study, further research should be place on prevention methods aimed at altering life-style behaviors such as diet and exercise early in one’s life. Based on the alarming prevalence of undiagnosed cases, continued research and support should also be place on access to care for minorities, especially persons of Latin American decent.

Hispanics are the largest minority group in the United States. They are disproportionately affected by diabetes and are twice as likely to develop diabetes then are non-Hispanic white adults. Mexican Americans are the largest subpopulation of Hispanics in the United States and one out of ten has diabetes. The purpose of this qualitative descriptive study was to explore the experiences of adults of Mexican origin who were newly informed of having elevated glucose levels in the diabetes range. This qualitative inquiry was conducted by means of in-depth semi-structured interviews with eight individuals of Mexican origin who had been recently informed of having hyperglycemic values exceeding the threshold of diabetes. A modified version of Kleinman's explanatory model of illness was used to elicit the EM of high blood sugar of the study participants. Qualitative content analysis was utilized to analyze the data. Domains, categories and subcategories were elicited through the immersion and crystallization of thematic units attained through the in-depth, semi-structured interviews. Three overarching domains emerged describing the experience and perception the participants had of being newly informed of having high blood sugar: 1) EM of High Blood Sugar 2) Response to Being Informed of High Blood Sugar 3) Facilitators and Barriers to Seeking Care. The participants describe a Temporal Order of how they responded to being informed of having high blood sugar. Facilitators, barriers and gaps to seeking care was also discussed. This study provides valuable insight that can influence the development of culturally relevant interventions that may promote behavior changes to reduce blood glucose levels and promote healthy outcomes for this population.

AN ABSTRACT OF THE THESIS OF Cassidy Scoggins, for the Masters of Science degree in Food and Nutrition, presented on November 19, 2009, at Southern Illinois University Carbondale. TITLE: THE EFFECTS OF A COMMUNITY-BASED LIFESTYLE INTERVENTION ON SNACKING PATTERNS, SCREEN TIME PATTERNS, AND PHYSICAL ACTIVITY LEVELS AMONG ADOLESCENTS WHO ARE AT-RISK FOR TYPE 2 DIABETES MAJOR PROFESSOR: Dr. Sharon Peterson Previous research has shown that overweight and obesity in adolescents is one of the leading risk factors for developing Type 2 Diabetes Mellitus (T2DM). There are several risk factors for obesity that are modifiable in adolescents. Of these, snacking patterns, screen time, and lack of physical activity have an impact on the body weight and overall health of adolescents. The design of this "R.U.A. Healthy Kid?" study was a prospective cohort of 16 free-living adolescents at-risk for T2DM. Each participant was previously screened and found to have two or more risk factors for T2DM. The intervention targeted several components, however snacking patterns, physical activity levels and screen time levels mold the foundation for the current study. An overall "snacking score" was developed to measure the frequency and quality of snacking patterns of participants. After three months of intervention, participants' overall snacking score increased. Many significant relationships were found between the overall snack score, physical activity, and screen time questions, such as negative relationships between: "time on TV" and total snacking score and "time spent walking, biking, or jogging" and "unhealthy" snacking score. These results show how community-based lifestyle interventions that address adolescents' snacking patterns, screen time levels, and physical activity levels are crucial in the fight to overcome the T2DM epidemic now prevalent in adolescents.

Background: T2DM patients can be treated with both Insulin or/and non-insulin antidiabetic drugs. Biguanide-derivate is the first-line antidiabetic that is cost-effective and safe. DPP-4Is are antidiabetic drugs that can be used to treat old patients and those with kidney failure. While SGLT2-inhibitors and GLP-1analogues can be used by T2DM patients with cardiovascular problems and those with overweight. The initiation of antidiabetic drug is influenced by several factors such as patient characteristic, physician’s knowledge and guidelines. Aim: The aim of this study was to study the type of antidiabetic medication initiated to naïve T2DM patients, how age and sex affect the choice of medication and difference in prescribing between Primary healthcare centers in Region Uppsala. Methods: The study was a cross-sectional based on health record data from Region Uppsala. The study included 2473 T2DM patients that were initiated antidiabetic medication between January 2019 and December 2020. Results: Non-insulins accounted for 88 % and insulins for 21.1% of the prescriptions. The proportion of men that received both insulin and non-insulins were higher than women. The proportion of patients that received insulins was higher for the age group 80 years and older. The proportion of men that received SGLT2- inhibitors was higher than for women, while women received more GLP-1- analogues. There was a variation between PHCs, but non-insulins were mostly prescribed at all PHCs. Conclusions: Initiation of antidiabetic drugs to naïve T2DM patients in region Uppsala fallowed the guidelines. There are some differences in prescription pattern between the two sexes and the age groups.

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

No description available.

Background: A cross-sectional design was employed to ascertain the relationship between dairy consumption and insulin resistance (IR) in 272 middle-aged, nondiabetic women. Methods: Participants kept a seven-day weighed food record to report their diets, including consumption of dairy foods. IR was assessed using the homeostatic model assessment (HOMA), using the following formula: fasting plasma insulin (µU/ml) x fasting plasma glucose (mg/dL)/405. The Bod Pod was used to examine body fat percentage, and accelerometry over a seven-day period was used to assess physical activity. HOMA values were log-transformed and regression analysis and the General Linear Model procedure were used to determine how mean HOMA differed across low, moderate, and high dairy intake groups. Results: (Mean ± SD) age: 40.1 ± 3.0 years, physical activity (average activity counts for one week, divided by 1,000): 2700.1 ± 781.9, body fat percentage: 31.7 ± 6.9, weight (kg): 66.1 ± 10.0, fasting glucose (mg/dL): 86.7 ± 5.9, fasting insulin (µU/mL): 7.0 ± 4.2, energy intake (kcal/day): 2051.9 ± 319.1, kcal from carbohydrate (%): 55.7 ± 6.2, kcal from protein (%): 13.8 ± 2.5, kcal from fat (%): 30.5 ± 5.8, soluble fiber (g per 1,000 kcal): 1.7 ± 0.9, insoluble fiber (g per 1,000 kcal): 3.8 ± 1.9, dairy intake (servings/day): 1.1 ± 1.0, HOMA: 1.5 ± 1.0, log-transformed HOMA: 0.3 ± 0.6. Those in the highest quartile for dairy consumption had significantly higher log-transformed HOMA (0.41 ± 0.53) than those in the moderate (0.22 ± 0.55) or low (0.19 ± 0.58) consumption categories (F = 6.90, p = 0.0091). This relationship remained significant after controlling for all covariates (F = 4.71, p = 0.030). Controlling for physical activity strengthened the relationship between dairy consumption and IR by 7%. Adjusting for body weight, percent of kcal from fat, and insoluble and soluble fiber intake also strengthened the relationship. Controlling for energy intake and body fat percentage weakened the relationship by 32% and 13%, respectively, though it remained significant. Conclusion: High dairy consumption is significantly associated with IR in middle-aged, nondiabetic women.

Bakgrund: Typ 2 diabetes mellitus (T2DM) är en globalt växande sjukdom och är nationellt en av de vanligaste folksjukdomarna. Behandlingen baseras på egenvård, vilket omfattar kosthantering, regelbunden fysisk aktivitet, blodglukoskontroller och i många fall strävan efter viktnedgång. Detta ställer stora krav på individens eget ansvar och förmåga att ta beslut gällande sin vård i vardagen. Syfte: Syftet med litteraturstudien var att beskriva erfarenheter som inverkade på genomförandet av egenvården hos personer diagnostiserade med typ 2 diabetes mellitus. Metod: Litteraturöversikten baserades på åtta kvalitativa studier. Databassökningar genomfördes i Cinahl och PubMed. Analysprocessen genomfördes med insipiration av Popenoes beskrivning av innehållsanalys vid litteraturstudie.  Resultat: I analysarbetet framkom sju subkategorier och tre övergripande kategorier. De framtagna kategorierna var: Egen kapacitet och förståelse för egenvårdens betydelse, Stödjande relationer och samspelande omständigheter för egenvården samt Egenvårdens inverkan på självbilden.  Konklusion: Litteraturstudiens resultat visar på behovet av en helhetssyn när det gäller egenvården, som integrerar individuellt stöd, anpassad kunskap och positiv förstärkning, för att främja hälsa och välbefinnande hos personer med T2DM.