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Item Changes in Basal and Bolus Insulin Requirements with Tirzepatide as an Adjunctive Therapy in Adults with Type 1 Diabetes Using Tandem Control-IQ(Springer, 2024) Karakus, Kagan E.; Klein, Matthew P.; Akturk, Halis K.; Shah, Viral N.; Medicine, School of MedicineIntroduction: This study was aimed at investigating changes in insulin requirements and glycemic outcomes in adults with type 1 diabetes (T1D) using Control IQ (Tandem Diabetes) automated insulin delivery system (AID) over 8 months of tirzepatide treatment. Methods: In this single-center, observational study, we collected demographic, A1c, weight, sensor glucose, and insulin dose data for adults with T1D who were using AID and initiated tirzepatide adjunct therapy for clinical indications (n = 11, median age 37, 64% female and mean body mass index of 39.6 kg/m2). Data were compared from baseline and over 8 months. Results: Within 2 months of tirzepatide treatment, there were significant reductions in total daily insulin [median (IQR) 73.9 (47.6-95.8) to 51.7 (46.7-66.8) units/day, p < 0.001], basal insulin [47 (28.2-51.8) to 32.4 (25.5-46.3) units/day, p < 0.001], and bolus insulin [31.4 (19.9-38.3) to 17.9 (14.9-22.2) units/day, p < 0.001] requirements. Insulin dose reduction from 2 to 8 months was modest. The frequency of user-initiated boluses did not differ throughout the study. Despite reductions in total insulin requirement, time in range (70-180 mg/dl) increased by 7%, A1c reduced by 0.5%, weight reduced by 9%, without increase in time below 70 mg/dl. Conclusions: This pilot study provides clinical guidance on insulin titration for adults with T1D who may initiate tirzepatide therapy. Based on the findings of this study, we recommend reducing 25% of total daily insulin dose at tirzepatide initiation in adults with T1D using AID with baseline A1c of less than 7.5%. Higher doses of tirzepatide were associated with greater weight loss, however, the reduction in insulin requirement was minimal.Item Circulating monocyte chemoattractant protein-1 (MCP-1) is associated with cachexia in treatment-naïve pancreatic cancer patients(Wiley, 2018-04) Talbert, Erin E.; Lewis, Heather L.; Farren, Matthew R.; Ramsey, Mitchell L.; Chakedis, Jeffery M.; Rajasekera, Priyani; Haverick, Ericka; Sarna, Angela; Bloomston, Mark; Pawlik, Timothy M.; Zimmers, Teresa A.; Lesinski, Gregory B.; Hart, Phil A.; Dillhoff, Mary E.; Schmidt, Carl R.; Guttridge, Denis C.; Surgery, School of MedicineCancer-associated wasting, termed cancer cachexia, has a profound effect on the morbidity and mortality of cancer patients but remains difficult to recognize and diagnose. While increases in circulating levels of a number of inflammatory cytokines have been associated with cancer cachexia, these associations were generally made in patients with advanced disease and thus may be associated with disease progression rather than directly with the cachexia syndrome. Thus, we sought to assess potential biomarkers of cancer-induced cachexia in patients with earlier stages of disease. METHODS: A custom multiplex array was used to measure circulating levels of 25 soluble factors from 70 pancreatic cancer patients undergoing attempted tumour resections. A high-sensitivity multiplex was used for increased sensitivity for nine cytokines. RESULTS: Resectable pancreatic cancer patients with cachexia had low levels of canonical pro-inflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β), interferon-γ (IFN-γ), and tumour necrosis factor (TNF). Even in our more sensitive analysis, these cytokines were not associated with cancer cachexia. Of the 25 circulating factors tested, only monocyte chemoattractant protein-1 (MCP-1) was increased in treatment-naïve cachectic patients compared with weight stable patients and identified as a potential biomarker for cancer cachexia. Although circulating levels of leptin and granulocyte-macrophage colony-stimulating factor (GM-CSF) were found to be decreased in the same cohort of treatment-naïve cachectic patients, these factors were closely associated with body mass index, limiting their utility as cancer cachexia biomarkers. CONCLUSIONS: Unlike in advanced disease, it is possible that cachexia in patients with resectable pancreatic cancer is not associated with high levels of classical markers of systemic inflammation. However, cachectic, treatment-naïve patients have higher levels of MCP-1, suggesting that MCP-1 may be useful as a biomarker of cancer cachexia.Item Complications in body contouring stratified according to weight loss method(SAGE Journals, 2016) Chetta, Matthew D.; Aliu, Oluseyi; Tran, Bao Anh Patrick; Abdulghani, Mariam; Kidwell, Kelly M.; Momoh, Adeyiza O.; Surgery, School of MedicineBACKGROUND: Body contouring procedures following massive weight loss have become increasingly common and, unfortunately, continue to be associated with a high complication rate. OBJECTIVE: To evaluate how weight loss method affects complications following abdominally based body contouring procedures. METHODS: Patients undergoing abdominally based contouring procedures were retrospectively evaluated over an 11-year period and stratified into two groups based on method of weight loss: diet and exercise; or bariatric surgery. Complications, including seroma, wound dehiscence, skin necrosis, infection, hematoma and venous thromboembolism, were included if they required intervention. An adjusted logistic model was used to examine the effect of weight loss method on aggregate complication rates. RESULTS: A total of 307 patients were included: 77 (25%) lost weight through diet and exercise; and 230 (75%) through bariatric surgery. Results from the logistic model showed no difference in complication rates between weight loss methods (OR 1.01 [95% CI 0.51 to 2.02]). However, there was a strong correlation between body mass index at the time of surgery and complication rates (OR 1.05 [95% CI 1.02 to 1.08]; P<0.01). CONCLUSIONS: The findings reveal no difference in complication rates following abdominal body contouring procedures attributable to method of weight loss. Rather, there was a proportional rise in complication rates in patients with a higher body mass index at the time of surgery. Surgeons and patients should be aware of this trend, and it should be part of any discussion of abdominal body contouring procedures and informing patients of their risk profile.Item Effects of Dietary Protein Source and Quantity on Bone Morphology and Body Composition Following a High-Protein Weight-Loss Diet in a Rat Model for Postmenopausal Obesity(MDPI, 2022-05-28) Wright, Christian S.; Hill, Erica R.; Reyes Fernandez, Perla C.; Thompson, William R.; Gallant, Maxime A.; Campbell, Wayne W.; Main, Russell P.; Physical Therapy, School of Health and Human SciencesHigher protein (>30% of total energy, HP)-energy restriction (HP-ER) diets are an effective means to improve body composition and metabolic health. However, weight loss (WL) is associated with bone loss, and the impact of HP-ER diets on bone is mixed and controversial. Recent evidence suggests conflicting outcomes may stem from differences in age, hormonal status, and the predominant source of dietary protein consumed. Therefore, this study investigated the effect of four 12-week energy restriction (ER) diets varying in predominate protein source (beef, milk, soy, casein) and protein quantity (normal protein, NP 15% vs. high, 35%) on bone and body composition outcomes in 32-week-old obese, ovariectomized female rats. Overall, ER decreased body weight, bone quantity (aBMD, aBMC), bone microarchitecture, and body composition parameters. WL was greater with the NP vs. HP-beef and HP-soy diets, and muscle area decreased only with the NP diet. The HP-beef diet exacerbated WL-induced bone loss (increased trabecular separation and endocortical bone formation rates, lower bone retention and trabecular BMC, and more rod-like trabeculae) compared to the HP-soy diet. The HP-milk diet did not augment WL-induced bone loss. Results suggest that specific protein source recommendations may be needed to attenuate the adverse alterations in bone quality following an HP-ER diet in a model of postmenopausal obesity.Item Environments and situations as correlates of eating and drinking among women living with obesity and urban poverty(Wiley, 2021-09-01) Clark, Daniel O.; Keith, NiCole R.; Ofner, Susan; Hackett, Jason; Li, Ruohong; Agarwal, Neeta; Tu, Wanzhu; Medicine, School of MedicineObjective: One path to improving weight management may be to lessen the self-control burden of physical activity and healthier food choices. Opportunities to lessen the self-control burden might be uncovered by assessing the spatiotemporal experiences of individuals in daily context. This report aims to describe the time, place, and social context of eating and drinking and 6-month weight change among 209 midlife women (n = 113 African-American) with obesity receiving safety-net primary care. Methods: Participants completed baseline and 6-month weight measures, observations and interviews regarding obesogenic cues in the home environment, and up to 12 ecological momentary assessments (EMA) per day for 30 days inquiring about location, social context, and eating and drinking. Results: Home was the most common location (62%) at times of EMA notifications. Participants reported "yes" to eating or drinking at the time of nearly one in three (31.1% ± 13.2%) EMA notifications. Regarding social situations, being alone was significantly associated with less frequent eating and drinking (OR = 0.75) unless at work in which case being alone was significantly associated with a greater frequency of eating or drinking (OR = 1.43). At work, eating was most common late at night, whereas at home eating was most frequent in the afternoon and evening hours. However, eating and drinking frequency was not associated with 6-month weight change. Conclusions: Home and work locations, time of day, and whether alone may be important dimensions to consider in the pursuit of more effective weight loss interventions. Opportunities to personalize weight management interventions, whether digital or human, and lessen in-the-moment self-control burden might lie in identifying times and locations most associated with caloric consumption.Item Forever-Fit Summer Camp: The Impact of a 6-Week Summer Healthy Lifestyle Day Camp on Anthropometric, Cardiovascular, and Physical Fitness Measures in Youth With Obesity(SAGE, 2020-01) El Mikati, Hala K.; Boateng, Anthony O.; McKinney, Brett M.; Haberlin-Pittz, Katie; Pike, Julie; Perry, Patrick; Hannon, Tamara S.; Yazel-Smith, Lisa; Medicine, School of MedicinePediatric obesity is a public health concern with lifestyle intervention as the first-line treatment. Forever-Fit Summer Camp (FFSC) is a 6-week summer day program offering physical activity, nutrition education, and well-balanced meals to youth at low cost. The aim of the study was to assess the efficacy of this program that does not emphasize weight loss rather emphasizes healthy behaviors on body mass index, cardiovascular and physical fitness. Methods: The inclusion criteria were adolescents between 8 and 12 years and body mass index (BMI) ≥85th percentile. The data were collected at baseline and week 6 (wk-6) and was analyzed for 2013-2018 using paired-sample t tests. Results: The participants' (N = 179) average age was 10.6 ± 1.6 years with a majority of females (71%) and black race/ethnicity (70%). At wk-6, BMI and waist circumference decreased by 0.8 ± 0.7 kg/m2 and 1.0 ± 1.3 in, respectively. Resting heart rate, diastolic and systolic blood pressure decreased by 8.5 ± 11.0 bpm, 6.3 ± 8.8 mmHg, and 6.4 ± 10.1 mmHg, respectively. The number of pushups, curl-ups, and chair squats were higher by 5.8 ± 7.5, 6.7 ± 9.1, and 7.7 ± 8.5, respectively. Conclusion: The FFSC is efficacious for improving BMI, cardiovascular, and physical fitness in the short term. The effect of similar episodic efforts that implement healthy lifestyle modifications throughout the school year should be investigated.Item Identification of Potential Serum Protein Biomarkers and Pathways for Pancreatic Cancer Cachexia Using an Aptamer-Based Discovery Platform(MDPI, 2020-12-15) Narasimhan, Ashok; Shahda, Safi; Kays, Joshua K.; Perkins, Susan M.; Cheng, Lijun; Schloss, Katheryn N. H.; Schloss, Daniel E. I.; Koniaris, Leonidas G.; Zimmers, Teresa A.; Surgery, School of MedicinePatients with pancreatic ductal adenocarcinoma (PDAC) suffer debilitating and deadly weight loss, known as cachexia. Development of therapies requires biomarkers to diagnose, and monitor cachexia; however, no such markers are in use. Via Somascan, we measured ~1300 plasma proteins in 30 patients with PDAC vs. 11 controls. We found 60 proteins specific to local PDAC, 46 to metastatic, and 67 to presence of >5% cancer weight loss (FC ≥ |1.5|, p ≤ 0.05). Six were common for cancer stage (Up: GDF15, TIMP1, IL1RL1; Down: CCL22, APP, CLEC1B). Four were common for local/cachexia (C1R, PRKCG, ELANE, SOST: all oppositely regulated) and four for metastatic/cachexia (SERPINA6, PDGFRA, PRSS2, PRSS1: all consistently changed), suggesting that stage and cachexia status might be molecularly separable. We found 71 proteins that correlated with cachexia severity via weight loss grade, weight loss, skeletal muscle index and radiodensity (r ≥ |0.50|, p ≤ 0.05), including some known cachexia mediators/markers (LEP, MSTN, ALB) as well as novel proteins (e.g., LYVE1, C7, F2). Pathway, correlation, and upstream regulator analyses identified known (e.g., IL6, proteosome, mitochondrial dysfunction) and novel (e.g., Wnt signaling, NK cells) mechanisms. Overall, this study affords a basis for validation and provides insights into the processes underpinning cancer cachexia.Item Influence of Peri-duodenal Non-constrictive Cuff on the Body Weight of Rats(Springer US, 2015-02) Lu, Xiao; Mattar, Samer G.; Kassab, Ghassan S.; Department of Biomedical Engineering, School of Engineering and TechnologyBackground Weight loss has been found to improve or re- solve cardiovascular comorbidities. There is a significant need for reversible device approaches to weight loss. Methods Non-constrictive cuff (NCC) is made of implantable silicone rubber with an internal diameter greater than the duodenum. Ten or 11 NCC were individually mounted along the duodenum from the pyloric sphincter toward the distal duodenum to cover ~22 mm in the length. Twelve Wistar rats were implanted with NCC, and six served as sham, and both groups were observed over 4 months. Six rats with implant had their NCC removed and were observed for additional 4weeks. Results The food intake decreased from 40.1 to 28.1 g/day after 4 months of NCC implant. The body weight gain decreased from 1.76 to 0.46 g/day after 4 months of NCC implant. The fasting glucose decreased from 87.7 to 75.3 mg/ dl at terminal day. The duodenal muscle layer covered by the NCC increased from 0.133 to 0.334 mm. After 4 weeks of NCC removal, the food intake, body weight gain, and fasting glucose recovered to 36.2, 2.51 g/day, and 83.9 mg/dl. The duodenal muscle layer covered by the NCC decreased to 0.217 mm. Conclusion The NCC implant placed on the proximal duode- num is safe in rats for a 4-month period. The efficacy of the NCC implant is significant for decrease in food intake, body weight gain, and fasting glucose in a normal rat model. The removal of NCC implant confirmed a cause-effect relation with food intake and hence body weight.Item Integration of the 5A’s Framework in Research on Obesity and Weight Counseling: Systematic Review of Literature(Sage, 2024-12-09) Shieh, Carol; Hardin, Heather K.; Doerstler, Mandelle Dreu; Jacobsen, Anna Liss; School of NursingThe 5A's Framework (Assess, Advise, Assist, Agree, and Arrange) has been recommended as a practice guide for obesity counseling. Its integration in research, however, is not well known. This systematic review was to find how the 5A's Framework was integrated in research on obesity and weight counseling. Methods: A systematic search of four databases was conducted combining two concepts: "5 A's Framework" and "obesity, body size, dieting/eating, exercise, weight loss." Inclusion criteria were quantitative studies with the 5A's Framework as a singular intervention or combined with others to influence patients' healthy eating, physical activity, and weight outcomes or care providers' counseling behaviors. Twenty-two studies were included in the final analysis. Results: Most studies were conducted in the primary care setting. The 5A's Framework was (1) integrated in training interventions as formal medical curricular and on-the-job education workshops to influence obesity/weight counseling skills, (2) utilized to develop assessment tools to evaluate counseling behaviors, and (3) combined with behavior change strategies to impact the patient's weight management behaviors and outcomes. Conclusion: The integration of the 5A's Framework in obesity and weight counseling research is wide-ranging. The findings have implications for clinicians to use the framework to better obesity/weight counseling.Item Intensive Cardiac Rehabilitation Outcomes in Patients with Heart Failure(MDPI, 2023-10-31) Jafri, S. Hammad; Guglin, Maya; Rao, Roopa; Ilonze, Onyedika; Ballut, Kareem; Baloch, Zulfiqar Qutrio; Qintar, Mohammed; Cohn, Joel; Wilcox, Matthew; Freeman, Andrew M.; Kalra, Dinesh K.; Wu, Wen-Chih; Medicine, School of MedicineIntroduction: Cardiac rehabilitation (CR) has proven to be beneficial for patients with heart failure (HF), potentially reducing morbidity and mortality while improving fitness and psychological outcomes. Intensive cardiac rehabilitation (ICR) represents an emerging form of CR that has demonstrated advantages for patients with various cardiovascular diseases. Nevertheless, the specific outcomes of ICR in patients with HF remain unknown. Objectives: The purpose of this study is to assess the effectiveness of ICR in patients with HF. Methods: This retrospective study involved 12,950 patients who participated in ICR at 46 centers from January 2016 to December 2020. Patients were categorized into two groups: the HF group, comprising 1400 patients (11%), and the non-HF group, consisting of 11,550 patients (89%). The primary endpoints included the ICR completion rate, changes in body mass index (BMI), exercise minutes per week (EMW), and depression scores (CESD). A t-test was employed to compare variables between the two groups. Results: The HF group comprises older patients, with 37% being females (compared to 44% in the non-HF group). The ICR completion rate was higher in the non-HF group. After ICR completion, adjusted analyses revealed that patients without HF demonstrated a greater improvement in BMI. There were no differences in fitness, as measured via EMW, or in depression scores, as measured via CESD, between the two groups. Conclusions: Despite the lower baseline functional status and psychosocial scores of HF patients compared to non-HF patients, patients with HF were able to attain similar or even better functional and psychosocial outcomes after ICR.
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