Patients with type 2 diabetes mellitus (T2DM) are more likely to die from cardiovascular diseases (CVD) than people without diabetes. Furthermore, patients with diabetes have not benefited from the advances in the management of CVD and/or its risk factors that have resulted in a decrease in mortality for CVD patients without diabetes. Short-term studies have demonstrated that weight loss in overweight or obese subjects with T2DM is associated with decreased insulin resistance, substantial improvements in glycemic and lipoprotein profile, and reduction in blood pressure. However, long-term data substantiating that these improvements can be maintained are limited. Obesity, and susceptibility to weight gain, is a chronic condition. Continuous care is required to avoid weight regain especially after intensive weight loss. Morbidly obese patients with body mass index (BMI) over 35 kg/m2 have significant difficulty maintaining weight loss adequate to resolve obesity-related medical conditions by changes in lifestyle or pharmacologic strategies. Currently, surgical treatment of morbid obesity, termed bariatric surgery, appears to be the only modality that results in significant and sustained weight loss along with reversal of diabetes and improvements in cholesterol biosynthesis, and lipoprotein metabolism in morbidly obese patients. Given these observations, we question if patients with T2DM who undergo gastric bypass surgery will significantly reduce levels of abnormalities in vascular structure and function that are central to the development of atherosclerosis.
In Specific Aim 1, we will determine whether surgically induced weight loss decreases the risk of CVD in morbidly obese subjects with T2DM.
In Specific Aim 2, we will elucidate the mechanisms by which surgically induced weight loss reduces over time the risk of CVD in morbidly obese subjects with T2DM. The proposed study is a prospective cohort clinical trial aimed to evaluate changes over time in cardiovascular structure and function of morbidly obese subjects with T2DM undergoing gastric bypass surgery compared to a matched control group who do not undergo gastric bypass surgery. The results of the proposed studies will provide the foundation for a new clinical strategy aimed to prevent the development of CVD in obese patients with T2DM. Furthermore, they will serve as the baseline for future large scale longitudinal studies based on aggregate occurrence of severe cardiovascular events.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
7K23DK075907-03
Application #
7492632
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Podskalny, Judith M,
Project Start
2006-09-01
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
3
Fiscal Year
2008
Total Cost
$149,202
Indirect Cost
Name
Duke University
Department
Surgery
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Omotosho, Philip; Mor, Alessandro; Shantavasinkul, Prapimporn Chattranukulchai et al. (2016) Gastric bypass significantly improves quality of life in morbidly obese patients with type 2 diabetes. Surg Endosc 30:2857-64
Khoo, Chin Meng; Muehlbauer, Michael J; Stevens, Robert D et al. (2014) Postprandial metabolite profiles reveal differential nutrient handling after bariatric surgery compared with matched caloric restriction. Ann Surg 259:687-93
Mor, Alessandro; Omotosho, Philip; Torquati, Alfonso (2014) Cardiovascular risk in obese diabetic patients is significantly reduced one year after gastric bypass compared to one year of diabetes support and education. Surg Endosc 28:2815-20
Khoo, Chin Meng; Chen, Jiegen; Pamuklar, Zehra et al. (2014) Effects of Roux-en-Y gastric bypass or diabetes support and education on insulin sensitivity and insulin secretion in morbidly obese patients with type 2 diabetes. Ann Surg 259:494-501
Mor, Alessandro; Tabone, Lawrence; Omotosho, Philip et al. (2014) Improved insulin sensitivity after gastric bypass correlates with decreased total body fat, but not with changes in free fatty acids. Surg Endosc 28:1489-1493
Pamuklar, Zehra N; Chen, Jiegen; Muehlbauer, Michael et al. (2013) Necdin-E2F4 interaction provides insulin-sensitizing effect after weight loss induced by gastric bypass surgery. Surg Obes Relat Dis 9:94-9
Chen, Jie-Gen; Spagnoli, Anna; Torquati, Alfonso (2012) Adipogenic differentiation of adipose tissue-derived human mesenchymal stem cells: effect of gastric bypass surgery. Surg Endosc 26:3449-56
Chen, Jiegen; Spagnoli, Anna; Torquati, Alfonso (2012) Omental gene expression of adiponectin correlates with degree of insulin sensitivity before and after gastric bypass surgery. Obes Surg 22:472-7
Evans, Sarah; Pamuklar, Zehra; Rosko, Jonathan et al. (2012) Gastric bypass surgery restores meal stimulation of the anorexigenic gut hormones glucagon-like peptide-1 and peptide YY independently of caloric restriction. Surg Endosc 26:1086-94
Mor, Alessandro; Sharp, Lindsey; Portenier, Dana et al. (2012) Weight loss at first postoperative visit predicts long-term outcome of Roux-en-Y gastric bypass using Duke weight loss surgery chart. Surg Obes Relat Dis 8:556-60

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