Browsing by Subject "Type 2 Diabetes"
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Item Barriers to Insulin Initiation The Translating Research Into Action for Diabetes Insulin Starts Project(2010-04) Karter, Andrew J.; Subramanian, Usha; Saha, Chandan; Crosson, Jesse C.; Parker, Melissa M.; Swain, Bix E.; Moffet, Howard H.; Marrero, David G.OBJECTIVE Reasons for failing to initiate prescribed insulin (primary nonadherence) are poorly understood. We investigated barriers to insulin initiation following a new prescription. RESEARCH DESIGN AND METHODS We surveyed insulin-naïve patients with poorly controlled type 2 diabetes, already treated with two or more oral agents who were recently prescribed insulin. We compared responses for respondents prescribed, but never initiating, insulin (n = 69) with those dispensed insulin (n = 100). RESULTS Subjects failing to initiate prescribed insulin commonly reported misconceptions regarding insulin risk (35% believed that insulin causes blindness, renal failure, amputations, heart attacks, strokes, or early death), plans to instead work harder on behavioral goals, sense of personal failure, low self-efficacy, injection phobia, hypoglycemia concerns, negative impact on social life and job, inadequate health literacy, health care provider inadequately explaining risks/benefits, and limited insulin self-management training. CONCLUSIONS Primary adherence for insulin may be improved through better provider communication regarding risks, shared decision making, and insulin self-management training.Item Bone Fragility in High Fat Diet-induced Obesity is Partially Independent of Type 2 Diabetes in Mice(Springer, 2024) Uppuganti, Sasidhar; Creecy, Amy; Fernandes, Daniel; Garrett, Kate; Donovan, Kara; Ahmed, Rafay; Voziyan, Paul; Rendina‑Ruedy, Elizabeth; Nyman, Jeffry S.; Orthopaedic Surgery, School of MedicineObesity and type 2 diabetes (T2D) are risk factors for fragility fractures. It is unknown whether this elevated risk is due to a diet favoring obesity or the diabetes that often occurs with obesity. Therefore, we hypothesized that the fracture resistance of bone is lower in mice fed with a high fat diet (45% kcal; HFD) than in mice that fed on a similar, control diet (10% kcal; LFD), regardless of whether the mice developed overt T2D. Sixteen-week-old, male NON/ShiLtJ mice (resistant to T2D) and age-matched, male NONcNZO10/LtJ (prone to T2D) received a control LFD or HFD for 21 weeks. HFD increased the bodyweight to a greater extent in the ShiLtJ mice compared to the NZO10 mice, while blood glucose levels were significantly higher in NZO10 than in ShiLtJ mice. As such, the glycated hemoglobin A1c (HbA1c) levels exceeded 10% in NZO10 mice, but it remained below 6% in ShiLtJ mice. Diet did not affect HbA1c. HFD lowered trabecular number and bone volume fraction of the distal femur metaphysis (micro-computed tomography or μCT) in both strains. For the femur mid-diaphysis, HFD significantly reduced the yield moment (mechanical testing by three-point bending) in both strains but did not affect cross-sectional bone area, cortical thickness, nor cortical tissue mineral density (μCT). Furthermore, the effect of diet on yield moment was independent of the structural resistance of the femur mid-diaphysis suggesting a negative effect of HFD on characteristics of the bone matrix. However, neither Raman spectroscopy nor assays of advanced glycation end-products identified how HFD affected the matrix. HFD also lowered the resistance of cortical bone to crack growth in only the diabetic NZO10 mice (fracture toughness testing of other femur), while HFD reduced the ultimate force of the L6 vertebra in both strains (compression testing). In conclusion, the HFD-related decrease in bone strength can occur in mice resistant and prone to diabetes indicating that a diet high in fat deleteriously affects bone without necessarily causing hyperglycemia.Item Effects of diet, BMP-2 treatment, and femoral skeletal injury on endothelial cells derived from the ipsilateral and contralateral limbs(Wiley, 2022) Dadwal, Ushashi C.; Staut, Caio de Andrade; Tewari, Nikhil P.; Awosanya, Olatundun D.; Mendenhall, Stephen K.; Valuch, Conner R.; Nagaraj, Rohit U.; Blosser, Rachel J.; Li, Jiliang; Kacena, Melissa Ann; Orthopaedic Surgery, School of MedicineType 2 diabetes (T2D) results in physiological and structural changes in bone, contributing to poor fracture healing. T2D compromises microvascular performance, which can negatively impact bone regeneration as angiogenesis is required for new bone formation. We examined the effects of bone morphogenetic protein-2 (BMP-2) administered locally at the time of femoral segmental bone defect (SBD) surgery, and its angiogenic impacts on endothelial cells (ECs) isolated from the ipsilateral or contralateral tibia in T2D mice. Male C57BL/6 mice were fed either a low fat diet (LFD) or high fat diet (HFD) starting at 8 weeks. After 12 weeks, the T2D phenotype in HFD mice was confirmed via glucose and insulin tolerance testing and echoMRI, and all mice underwent SBD surgery. Mice were treated with BMP-2 (5μg) or saline at the time of surgery. Three weeks post-surgery, bone marrow ECs were isolated from ipsilateral and contralateral tibias, and proliferation, angiogenic potential, and gene expression of the cells was analyzed. BMP-2 treatment increased EC proliferation by 2 fold compared to saline in LFD contralateral tibia ECs, but no changes were seen in surgical tibia EC proliferation. BMP-2 treatment enhanced vessel-like structure formation in HFD mice whereas, the opposite was observed in LFD mice. Still, in BMP-2 treated LFD mice, ipsilateral tibia ECs increased expression of CD31, FLT-1, ANGPT1, and ANGPT2. These data suggest that the modulating effects of T2D and BMP-2 on the microenvironment of bone marrow ECs may differentially influence angiogenic properties at the fractured limb versus the contralateral limb.Item From Program to Policy: Expanding the Role of Community Coalitions(Centers for Disease Control and Prevention, 2007) Hill, Anne; De Zapien, Jill Guernsey; Staten, Lisa K.; McClelland, Deborah Jean; Garza, Rebecca; Moore-Monroy, Martha; Elenes, JoJean; Steinfelt, Victoria; Tittelbaugh, Ila; Whitmer, Evelyn; Meister, Joel S.Background Diabetes mortality at the United States–Mexico border is twice the national average. Type 2 diabetes mellitus is increasingly diagnosed among children and adolescents. Fragmented services and scarce resources further restrict access to health care. Increased awareness of the incidence of disease and poor health outcomes became a catalyst for creating community-based coalitions and partnerships with the University of Arizona that focused on diabetes. Context Five partnerships between the communities and the University of Arizona were formed to address these health issues. They began with health promotion as their goal and were challenged to add policy and environmental change to their objectives. Understanding the meaning of policy in the community context is the first step in the transition from program to policy. Policy participation brings different groups together, strengthening ties and building trust among community members and community organizations. Methods Data on progress and outcomes were collected from multiple sources. We used the Centers for Disease Control and Prevention’s Racial and Ethnic Approaches to Community Health (REACH) 2010 Community Change Model as the capacity-building and analytic framework for supporting and documenting the transition of coalitions from program to policy. Consequences Over 5 years, the coalitions made the transition, in varying degrees, from a programmatic focus to a policy planning and advocacy focus. The coalitions raised community awareness, built community capacity, encouraged a process of “change in change agents,” and advocated for community environmental and policy shifts to improve health behaviors. Interpretation The five coalitions made environmental and policy impacts by engaging in policy advocacy. These outcomes indicate the successful, if not consistently sustained, transition from program to policy. Whether and how these “changes in change agents” are transferable to the larger community over the long term remains to be seen.Item Lifetime Duration of Depressive Disorders in Patients With Type 2 Diabetes(American Diabetes Association, 2016-12) de Groot, Mary; Crick, Kent A.; Long, Molly; Saha, Chandan; Shubrook, Jay H.; Medicine, School of MedicineOBJECTIVE Depression in patients with type 2 diabetes (T2D) is associated with long-term complications, disability, and early mortality. No studies have systematically examined the length of episodes and remission in adults with major depressive disorder (MDD) and T2D. This study examined the course of depressive disorders in patients with T2D and MDD. RESEARCH DESIGN AND METHODS Participants (N = 50) enrolled in a behavioral intervention for adults with T2D and MDD were interviewed using the Structured Clinical Interview for DSM-IV-TR to assess history of depressive disorders at baseline (lifetime history), postintervention, and 3-month follow-up. Onset and remission dates were recorded for all Axis I depressive disorders from birth to final interview. RESULTS Average number of MDD episodes was 1.8 with a mean duration of 23.4 months (SD 31.9; range 0.5–231.3). Over the life course, mean exposure to MDD was 43.1 months (SD 46.5; range 0.5–231.3). Kaplan-Meier survival curve analysis indicated median episode duration decreased with subsequent episodes (14 months, first episode; 9 months, second episode; P < 0.002). In patients with multiple depressive episodes, recovery time was shorter with each subsequent episode (P = 0.002). No differences in length of episode or remission were observed based on chronology of T2D diagnosis. CONCLUSIONS The overall exposure to depression in this sample of adults with T2D represents a substantial period of time that can contribute to negative medical and psychiatric outcomes. Recurrent episodes decrease in duration as do recovery periods, resulting in a waxing and waning pattern. Findings from this study underscore the need to effectively diagnose and treat depression in patients with T2D to minimize risk of future depressive episodes.Item Mechanisms of spinophilin-dependent pancreas dysregulation underlying diabesity(Cold Spring Harbor Laboratory, 2023-02-08) Stickel, Kaitlyn C.; Mosley, Amber L.; Doud, Emma H.; Belecky-Adams, Teri L.; Baucum, Anthony J., II; Biology, School of ScienceObjective: Spinophilin is an F-actin binding and protein phosphatase 1 (PP1) targeting protein that acts as a scaffold of PP1 to its substrates. Spinophilin knockout (Spino-/-) mice have decreased fat mass, increased lean mass, and improved glucose tolerance, with no difference in feeding behaviors. While spinophilin is enriched in neurons, its roles in non-neuronal tissues, such as beta cells of the pancreatic islets, are unclear. Methods & results: We have corroborated and expanded upon previous studies to determine that Spino-/- mice have decreased weight gain and improved glucose tolerance in two different models of obesity. Using proteomics and immunoblotting-based approaches we identified multiple putative spinophilin interacting proteins isolated from intact pancreas and observed increased interactions of spinophilin with exocrine, ribosomal, and cytoskeletal protein classes that mediate peptide hormone production, processing, and/or release in Leprdb/db and/or high fat-fed (HFF) models of obesity. Moreover, loss of spinophilin specifically in pancreatic beta cells improved glucose tolerance without impacting body weight. Conclusion: Our data further support a role for spinophilin in mediating pathophysiological changes in body weight and whole-body metabolism associated with obesity and provide the first evidence that spinophilin mediates obesity-dependent pancreatic dysfunction that leads to deficits in glucose homeostasis or diabesity.Item Predictors and Impact of Intensification of Antihyperglycemic Therapy in Type 2 Diabetes(American Diabetes Association, 2009-02-19) McEwen, Laura N.; Bilik, Dori; Johnson, Susan L.; Halter, Jeffrey B.; Karter, Andrew J.; Mangione, Carol M.; Subramanian, Usha; Waitzfelder, Beth; Crosson, Jesse C.; Herman, William H.; Medicine, School of MedicineOBJECTIVE The purpose of this study was to examine the predictors of intensification of antihyperglycemic therapy in patients with type 2 diabetes; its impact on A1C, body weight, symptoms of anxiety/depression, and health status; and patient characteristics associated with improvement in A1C. RESEARCH DESIGN AND METHODS We analyzed survey, medical record, and health plan administrative data collected in Translating Research into Action for Diabetes (TRIAD). We examined patients who were using diet/exercise or oral antihyperglycemic medications at baseline, had A1C >7.2%, and stayed with the same therapy or intensified therapy (initiated or increased the number of classes of oral antihyperglycemic medications or began insulin) over 18 months. RESULTS Of 1,093 patients, 520 intensified therapy with oral medications or insulin. Patients intensifying therapy were aged 58 ± 12 years, had diabetes duration of 11 ± 9 years, and had A1C of 9.1 ± 1.5%. Younger age and higher A1C were associated with therapy intensification. Compared with patients who did not intensify therapy, those who intensified therapy experienced a 0.49% reduction in A1C (P < 0.0001), a 3-pound increase in weight (P = 0.003), and no change in anxiety/depression (P = 0.5) or health status (P = 0.2). Among those who intensified therapy, improvement in A1C was associated with higher baseline A1C, older age, black race/ethnicity, lower income, and more physician visits. CONCLUSIONS Treatment intensification improved glycemic control with no worsening of anxiety/depression or health status, especially in elderly, lower-income, and minority patients with type 2 diabetes. Interventions are needed to overcome clinical inertia when patients might benefit from treatment intensification and improved glycemic control.Item Real and Perceived Discordance in Physicians and U.S. Adults’ Beliefs Regarding the Causes and Controllability of Type 2 Diabetes(Taylor & Francis, 2021) Derricks, Veronica; Mosher, Jeremy; Earl, Allison; Jayaratne, Toby E.; Shubrook, Jay H.Discordance between physicians and patients’ health beliefs can impede health communication efforts. However, little research considers physicians’ perceptions of patient beliefs, despite the importance of perceptions in shaping communication. In the current work, we examine instances of actual and perceived discordance between physicians and U.S. adults’ beliefs regarding the causes and controllability of type 2 diabetes. 229 family physicians completed an online survey measuring their health beliefs and perceptions of their patients’ beliefs. Physicians’ responses were contrasted against beliefs from a national survey sample of 1,168 U.S. adults. T-tests assessed whether (a) physicians’ beliefs diverged from the national sample’s beliefs (actual discordance), (b) physicians perceived that their health beliefs diverged from their patients’ beliefs (perceived discordance), and (c) physicians’ perceptions of patient beliefs diverged from the national sample’s beliefs (accuracy of perceived discordance). Findings revealed evidence of actual discordance; compared to the national sample, physicians were more likely to attribute type 2 diabetes to genes (versus lifestyle factors) and perceived greater control over developing diabetes. Moreover, although physicians perceived discordance between their own and their patients’ beliefs, data from the national sample suggested that these gaps were less substantial than physicians expected. In particular, findings showed that physicians generally overestimated discordance, expecting that people would be less likely to (1) attribute the development of diabetes to lifestyle factors (versus genes), and (2) perceive control over developing diabetes, than was actually reported. Implications of actual and perceived discordance for effective health communication and patient education are discussed.Item The Skeletal Phenotype Of The Kk/Ay Murine Model Of Type 2 Diabetes(2022-08) Chowdhury, Nusaiba Nahola; Wallace, Joseph; Allen, Matthew; Bone, Robert; Na, SungsooType-2-diabetes (T2D) is a progressive metabolic disease characterized by insulin resistance and β-cell dysfunction leading to persistent hyperglycemia. It is a multisystem disease that causes deterioration of multiple organ systems and obesity. Of interest, T2D affects the urinary system and is the leading cause of kidney disease. Both T2D and chronic kidney negatively impacts the skeletal system and increases fracture incidence in patients. Therefore, it is important to establish an animal model that captures the complex multiorgan effects that is common in T2D. In this study, we characterized the metabolic phenotype of the KK/Ay mouse model, a polygenic mutation model of T2D. We concluded that KK/Ay mice closely mimic T2D and are hyperglycemic, hyperinsulinemic and insulin resistant. KK/Ay mice have also had worsened kidney function as supported by elevated levels of blood urea nitrogen, phosphorous, creatinine, and calcium in plasma exhibiting the kidney’s inefficiency in clearing waste from the body. Even though we were able to confirm a metabolic phenotype for T2D and diabetic nephropathy, the skeletal effects of the disease were minimal and major differences in bone physiology were driven by sex differences. This study offered valuable insight into preliminary endpoints for the KK/Ay mouse mode that will decide the direction for future use of this model. We plan to use older mice in future studies to allow a longer time for skeletal effects to more prominently manifest.Item Spinophilin Signaling: Impacts on Body Weight, Obesity, and Beta-Cell Function(2023-12) Stickel, Kaitlyn Christine; Cummins, Theodore; Baucum, Anthony, II; Belecky-Adams, Teri; Mastracci, Teresa; Linneman, AmeliaObesity is a worldwide epidemic that is partially linked to changing lifestyles within the modern world, including increased access to calorically dense foods and decreased energy output due to more sedentary jobs. Obesity can lead to many different health complications, such as cardiovascular diseases or Type 2 Diabetes (T2D). Obesity-induced T2D is caused by dysfunction of the insulin-producing beta cells of the pancreas. However, mechanisms that promote obesity and the mechanisms by which obesity leads to beta cell dysfunction are not fully known. Spinophilin is a filamentous (F)-actin binding, protein scaffolding, and protein phosphatase 1 (PP1)-targeting protein that can regulate protein. Spinophilin has multiple actions. Spinophilin can bundle filamentous actin to modulate the cellular cytoskeleton. Spinophilin also mediates substrate phosphorylation by targeting and modulating PP1 activity. In addition, spinophilin interacts with multiple proteins, including certain G-protein coupled receptors and can scaffold them with F-actin and/or PP1. Previous studies established that spinophilin KO mice have decreased fat mass, increased lean mass, and improved glucose tolerance. Yet, how spinophilin modulates the above metabolic parameters is unclear. We found that spinophilin is expressed in hypothalamic tissue and appears to also be expressed in the feeding center of the hypothalamus, as well as in other glucose-sensing cells known as tanycytes that neighbor the arcuate nucleus and the third ventricle. We found that loss of spinophilin limited weight gain observed in both a leptin receptor db/db mouse line (Leprdb/db) and mice fed a high-fat diet. Moreover, we found that the decreased fat mass seen in global spinophilin KO mice, at least in the Leprdb/db mice, was not due to major differences in feeding behaviors, consistent with what was observed by other groups using high-fat diet-fed mice. As spinophilin was not associated with alterations in feeding, we posited that its ability to modulate glucose homeostasis may be linked to non-neuronal actions of the protein. Previous studies have found that spinophilin may regulate adipose tissue function and in vitro pancreatic beta cell function; however, its role in the pancreas and beta cells in vivo is not well characterized. We found that spinophilin is expressed in mouse pancreas. Using proteomics-based approaches we identified multiple putative spinophilin interacting proteins isolated from intact pancreas, including: PP1, the spinophilin homolog neurabin, and myosin-9. KEGG pathway analysis of proteomic proteins identified multiple pathways regulating ER stress, such as the unfolded protein response, and cytoskeletal arrangement. We observed decreased associations of spinophilin with PP1 and neurabin and increased association with myosin-9 in obese, Leprdb/db mice as early as 6 weeks, as well as significant decreases in body weight when spinophilin was knocked out in Leprdb/db mice. Moreover, we confirmed a robust and specific increased interaction of spinophilin with myosin-9, and other cytoskeletal proteins. Additionally, we found specific spinophilin interactions with ribosomal proteins, and exocrine and digestion proteins in high-fat diet-fed mice. Using our recently generated pancreatic beta cell-specific spinophilin KO mice, we found that loss of spinophilin in mice on a high-fat diet significantly reduces weight gain and improves whole- body glucose tolerance, and loss of spinophilin specifically within the beta cells also improves whole-body glucose tolerance, with no effect on body weight, further suggesting cell type-specific and independent roles for spinophilin on body weight and glucose homeostasis.