The Challenge Area and Topic of this proposal is (05) Comparative Effectiveness Research, and Understanding the Effects of Bariatric Surgery on Type 2 Diabetes and Cardiovascular Risk Factors (05-DK-102*). Patients with T2DM undergoing bariatric surgical procedures demonstrate substantial and sustained weight loss, reductions in diabetes medications in 84%, and remission of hyperglycemia in 77% [2]. Surgical intervention in patients with more recent onset of T2DM appears to result in higher rates of resolution than in patients with longer known duration of disease. Dyslipidemia and hypertension improve, which may translate into substantial clinical cardiovascular benefit. These findings suggest bariatric surgery may represent a potential first-line therapeutic management strategy for T2DM, particularly in those with lesser degrees of obesity or shorter duration of disease. Although this has generated substantial interest in the scientific community, minimal level 1 data is available to guide such an approach. While the laparoscopic adjustable gastric band (LAGB) is the only approach evaluated to date in a randomized clinical trial in less severely overweight T2DM patients, the preponderance of data in the obese population has shown Roux-en-Y gastric bypass (RYGB) offers more substantial metabolic advantages, including greater resolution rates of diabetes compared to LAGB [2, 3]. Differences may be due to mild malabsorption or alterations in gut peptides that regulate appetite and facilitate sustained weight loss, and/or to changes in incretins that may improve ?-cell function with RYGB. Malabsorptive procedures, however, also carry a higher perioperative morbidity rate, were designed to maximize weight loss, and represent substantial life-long alterations to the gastrointestinal tract. Therefore, the optimal surgical procedure for less obese T2DM remains controversial. In addition, concurrent with an expanding experience with bariatric surgery, there have been significant advances in non-surgical treatments of T2DM. Recent advances in pharmacologic and dietary approaches and a greater understanding of optimal medical management for such patients, as practiced in diabetes centers of excellence, have led some investigators to question why surgical options should be considered as primary therapy at the very time that medical, non-surgical treatment is undergoing significant advancement and potentially improved efficacy. In this context, this feasibility trial is designed to begin to directly address the critically important questions that clinicians face in selecting the best approach for a given T2DM patient, as well those confronting health care payers in their decisions regarding covered benefits. We hypothesize either restrictive (LAGB), or combination (restrictive and malabsorptive) (RYGB) surgical interventions will have higher rates of normalization of dysglycemia and more favorable effects on cardiovascular health measures than intensive medical and weight management (IMWM) following an intensive protocol similar to the program used successfully in the NIH Look AHEAD trial [4, 5]. Thus, surgery may represent a primary treatment choice for patients with T2DM in whom operative risks are acceptable. We propose a parallel randomized clinical trial in modestly obese T2DM with BMI 30-42 kg/m2 to compare 1) LAGB to IMWM and 2) Laparoscopic RYGB (LRYGB) to IMWM. The primary endpoint of this 2-year feasibility study will be glycemic control 12 months after randomization, assessed as fasting plasma glucose levels <126 mg/dL and HbA1c <6.5%. Secondary outcome measures include change in fasting glucose and HbA1c and fasting lipid levels;weight;blood pressure;waist circumference;change in concomitant medications, and area under the curve glucose tolerance during MMTT with insulin resistance assessed using the composite insulin sensitivity index (CISI) and insulin secretion assessed by the corrected incremental insulin response (CIR). Gastrointestinal hormones including incretins (GLP-1, GIP) and appetite regulating peptides (ghrelin, PYY, leptin) will be compared. Measures of vascular health will be assessed by blood pressure, lipid profiles and by using fingertip plethysmography (Itamar EndoPat) and by the measure of circulating mediators and markers of endothelial function. As a pilot study, we will also assess the suitability of this trial design, which accounts for inherent patient preference towards surgical procedures, and its potential use in future comparative effectiveness trials. Longitudinal measures of patient reported quality of life outcomes, and cost utility measures, will be collected to generate preliminary data for the design of a more definitive future trial. Finally, as a pilot study we will also determine the feasibility of recruitment for such a trial from surgical as compared to medical clinics and develop standardized materials that can be used at multiple sites in a subsequent study. Importantly, we obtained a commitment from Covidien Surgical Devices (Waltham, MA) to provide $500,000 in matching funds over the two year period of this grant, allowing us to study patients with BMI 30-35 kg/m2 for whom these procedures are not covered by insurance, and for whom the comparative effectiveness of T2DM therapy addressed in this grant is most controversial. In summary, this pilot and feasibility trial will compare the ability to induce glycemic control and improve cardiovascular health markers for each of the two most popular currently available bariatric surgical procedures against IMWM in preparation for a potential more definitive multi-institutional study of longer duration. Adult onset diabetes is now at epidemic proportions in the United States. Surgery for obesity often results in resolution of diabetes. This trial will compare the effectiveness of obesity surgery versus maximal medical management in resolving adult onset diabetes in a less obese population.
Adult onset diabetes is now at epidemic proportions in the United States. Surgery for obesity often results in resolution of diabetes. This trial will compare the effectiveness of obesity surgery versus maximal medical management in resolving adult onset diabetes in a less obese population.
Showing the most recent 10 out of 11 publications
