Obesity-Related Clinical Research Projects
The following includes examples of obesity-related clinical research currently being conducted at Geisinger; the list is not comprehensive.
Examples of Obesity-related Clinical Research Currently Being Conducted in Geisinger’s Center for Nutrition and Weight Management
- Pre-op Weight loss and Complications: Bariatric surgery has evolved as the preferred treatment for morbidly obese patients who are motivated to improve their health and quality of life. The growing numbers of high-risk patients referred for bariatric surgery has stimulated investigators to expand pre-operative programs in order to attempt to identify surgical risk factors and better prepare patients for surgery. The optimal pre-operative management of high risk bariatric surgery candidates remains controversial. Proposed risk reducing strategies supported by varying degrees of evidence include pre-operative medical weight reduction. These studies will determine the impact and efficacy of weight reduction prior to bariatric surgery.
- Kidney Diseases: Obesity is becoming a wide spread health problem. Extreme obesity (Body Mass Index (BMI) >40) usually does not respond to medical treatment and requires surgery to treat. Extreme obesity is found to be associated with many other medical diseases like hypertension, hyperlipidemia, cardiovascular disease and diabetes mellitus. There has been a reported improvement in above parameters but this has only been studied in a small group patient population. The goal of this longitudinal study is to measure renal function in these patients using a gold standard test (a nuclear scan) and compare it with calculated creatinine clearance [using modification of diet and renal disease (MDRD) equation] and measured creatinine clearance (from 24 hour urine collection). In addition, the effect of bariatric surgery on glomerular filtration rate (GFR) will also be assessed.
- Nephrolithiasis: The purpose of this research study is to evaluate the risk of kidney stone formation in patients undergoing gastric bypass surgery. Currently there is an undetermined risk of kidney stone formation in patients who have gastric bypass surgery. Studies have shown that other types of weight reduction surgery carry a risk of kidney stone development. This study will evaluate stone risk profiles done prior to surgery which are then compared to profiles obtained 6 months after bariatric surgery.
- Polycystic Ovary Syndrome (PCOS): It has been estimated that 229.6 million U.S. adults are overweight or obese based on BMI, including 64.5 million women over the age of twenty. The high incidence of oligomenorrhea and amenorrhea in obese premenopausal women, in part due to Polycystic Ovary Syndrome (PCOS) has great effects on fertility. While weight loss with diet and exercise alone has been shown to improve menstrual dysfunctions and oligoovulation, it is difficult for patients to reach and maintain the desired weight. Weight loss due to bariatric surgery could have an astonishing effect on fertility issues for obese women with irregular menses. The goal is to examine what the change in Body Mass Index (BMI) has on a woman's menstrual cycle with prior history of menstrual abnormalities.
Examples of Translational and Molecular Obesity Research Currently Being Conducted in the Weis Research Center
- Metabolic Syndrome: There appear to be relatively strong genetic influences to both the susceptibility to obesity, and the corresponding obesity-related co-morbidities that constitute the metabolic syndrome. Heritability estimates for individual components of the metabolic syndrome range from 40-90% for insulin resistance/Type II diabetes (T2D), 25-80% for dyslipidemia, and 20-70% for hypertension. The physiological consequences of extreme obesity are likely to be linked to phenotypic expression of genes predisposing to T2D, hypertension, and dyslipidemia. Epidemiologic studies and our own EHR data indicate that some moderate to severe obese individuals appear to be resistant to metabolic syndrome. Genetic factors are likely associated with resistance to these co-morbidities. The goal of these studies is to identify genetic variants that protect morbidly obese patients from the development of T2D, hypertension, and dyslipidemia through genetic studies of those with and without metabolic syndrome.
- Genetic Research on the INSIG2/FTO Genes: We have found that genetic variants in the FTO [the Fat and Obesity Associated Gene] and INSIG2 [Insulin Induced Gene] genes, which previously had been associated with overweight and Class I obesity, are related to body weight in the morbidly obese. We are extending these studies to determine whether they also influence weight loss following bariatric surgery.
- Diabetes: Specific mutations in mitochondrial DNA cause several syndromes in which Type II Diabetes is a prominent clinical feature. Abnormalities in a variety of mitochondrial related functions are present in obesity-related T2D. We are determining whether variants in the mitochondrial DNA of morbidly obese patients predispose them to T2D and related clinical phenotypes. The complete mitochondrial genomes of morbidly obese patients with and without T2D will be sequenced to identify variants that may be associated with T2D susceptibility.
- Iron Overload and Obesity: Approximately 15% of morbidly obese patients manifest hepatic iron overload on liver biopsy. Our long-term objectives are to determine the physiological basis and clinical significance of hepatic iron overload in these patients. We have excluded the most common cause of primary iron overload, due to mutations in the common iron HFE (Hereditary Hemochromatosis) gene that cause characteristic elevations in the serum transferrin saturation and ferritin levels, and are undertaking studies to identify the genetic determinants that underlie the hepatic iron overload in morbidly obese patients.
- NASH: Non-alcoholic steatohepatitis (NASH) is a common but often unrecognized liver disorder in patients with obesity and/or diabetes that can progress to cirrhosis and hepatic failure. An estimated 20% to 30% of adults in the United States have excess fat accumulation in the liver, with about 10% (or 2% to 3% of all adults) that meet current diagnostic criteria for NASH. The pathogenesis of NASH appears to be complex and multi-factorial, although elevated delivery of fatty acids to the liver may be the initiating process that results in accumulation of fat in hepatocytes. How the increase of hepatocyte lipids progresses to encompass the spectrum of abnormalities in NASH, including inflammation and fibrosis, is not known. Liver histology assessed on biopsy is the only definitive and clinically accepted method to make the diagnosis of NASH, which is based upon findings that include steatosis, inflammation, and fibrosis. Less invasive tests, such as liver function studies or radiographic methods, are often measured but lack sufficient sensitivity and/or specificity for diagnosis. Non-invasive markers reflecting histological severity are thus needed. Our long-term objective is to develop clinically useful diagnostic tests for NASH.
Examples of Obesity Research Currently Being Conducted at the Center for Health Research
- Steps to a Healthier PA: This project is being developed in collaboration with Geisinger Wyoming Valley to assist with the implementation of programs to complement the Commonwealth of Pennsylvania Department of Health’s “Steps” grant from the Center for Disease Control (CDC). This federal grant was awarded to specifically develop initiatives that are appropriate for rural areas. Luzerne County is one of three demonstration counties in Pennsylvania. We are proposing to pilot test our school-based obesity prevention health curriculum in the Wilkes-Barre elementary schools as part of this initiative.
- Action for Healthy Kids Evaluation Project (AFHK): Action for Healthy Kids project was formed in response to a call to action from the former U.S. Surgeon General, David Satcher in 2002. It is a public-private partnership of more than 50 national organizations and government agencies representing education, health, fitness and nutrition. AFHK addresses the epidemic of overweight, sedentary, and undernourished youth by focusing on changes in schools. Teams have been established in every state and the District of Columbia. Geisinger is a Pennsylvania State Team member and is helping to evaluate the results gained from implementation of a parent tool kit to educate parents of school age children about nutrition and childhood obesity. This tool kit was developed by Penn State University and the Pennsylvania Department of Education and was tested in 15 school districts across Pennsylvania. Geisinger is developing an in-depth qualitative analysis of the results to complement the quantitative analysis.
- Parent Intervention: This project is an intervention aimed at the parents of infants and preschoolers for the purpose of preventing obesity in early childhood. This work includes secondary analysis of patient data in the Geisinger Electronic Health Record (EHR), Weight Trends Database, and Ob-Gyn Database to support the preliminary development work through statistical model building. These statistical models will help pinpoint the most important risk factors so that the intervention can be most effective. No other institution in the country has the capability to examine such a large electronic database with a decade of patient data. This intervention will be submitted for funding as part of the state’s Commonwealth Universal Research enhancement program and includes faculty research partners at both Susquehanna and Bucknell Universities.??
- School-based Obesity Prevention Program: This project includes the expansion and continued development of a school-based program to prevent obesity in elementary school children. It expands the original program developed by William Cochran, MD, When Every Individual Gets Healthy (W.E.I.G.H.) by adding structure and standardization to the content. It incorporates innovation through adaptation to an online delivery system by taking advantage of Geisinger’s IT capabilities, a core system strength. It has the potential to serve as a national model through its alignment with the CDC’s Coordinated School Health Model and the inclusion of rigorous evaluation tools appropriate for educators and administrators for tracking program performance and effect on federally mandated academic benchmarks. This program has currently generated two grant proposal submissions with two more planned for this year.
- EHR Weight Trends Project: This project uses the information in the Geisinger EHR to explore and describe the nature and extent of obesity in four age groups across the Geisinger service area: preschoolers (ages 2-5 years), children (ages 6 – 11 years), adolescents (ages 12 – 18 years), and adults (greater than 18 years). Due to our sophisticated electronic health record we are able to accurately describe trends across several years and geographic distributions; a capability not possessed anywhere else in the country. Bar graphs have been generated for each age group demonstrating both cross-sectional and longitudinal trends. Construction of prevalence maps by counties in the Geisinger service area is underway. This information has enabled us to report on the extreme severity of obesity in central PA demonstrating rates that far exceed both national and state estimates. It has been useful in the preparation of research and program proposals to demonstrate both the area’s need for resources and potential to serve as a model for other rural areas in generating solutions.
- Obesity and the Built Environment: There is growing recognition that the obesity epidemic is a product of profound changes in our built and social environments over the last 20 years. This project will explore and analyze likely causes through the use of sophisticated Geisinger information system Geographic Information Systems (GIS) technology to describe the geographical and “built” environments where participating adolescents and their families live. The social environments of the families will also be studied to evaluate potential causative effects of selected risk factors, such as family structure, “time squeeze” pressure, eating behaviors, physical activity behaviors, sleep patterns, etc. The purpose of this work is to identify factors beyond the personal level that may be contributing to adolescent obesity so that focused and effective interventions may be designed.
- The Adolescent Weight Management Study: The Adolescent Weight Management study, funded by the PA Department of Health, is a randomized clinical trial comparing two deliveries of a primary care manual guided Family Based Lifestyle Modification (FBM) intervention. This study is being conducted at two sites, The Children's Hospital of Pennsylvania in Philadelphia and Geisinger Clinic in Danville, PA. The primary aim of the study is to assess the relative effectiveness of the group versus self-guided interventions to reduce body mass index (BMI) for the sample as a whole and within the two target groups (urban African-American and rural Caucasians). Participants (N=158) are adolescents (13-17 years of age) with a BMI of 28 or greater kg/m2 and a caregiver. The self-guided intervention consists of six meetings. The group intervention consists of 17 multi-family group meetings plus six adolescent-parent-interventionist sessions. Secondary analyses will evaluate changes in risk factors for cardiovascular disease and diabetes, including lipids (total-, HDL-, LDL-cholesterol and triglycerides), glucose and insulin, waist circumference, blood pressure, diet and activity.
- Garden Gang: Geisinger "Garden Gang" is a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R34 grant to conduct a pediatric overweight/obesity intervention in a two-group randomized clinical trial in primary care. Participants will be 60 children ages 4-8 who are obese or at-risk for obesity (> 85th % BMI for age, sex) and their caregiver. The children will be randomized to one of two conditions: group Family-based Behavioral Modification (FBM; N= 30) sessions or Minimal Nutrition Information (MNI; N=30). FBM includes primary care group meetings where parents receive skills training to reduce sedentary behavior, increase physical activity, reduce energy-dense and increase nutrient-dense food consumption. MNI includes mailed handouts on nutrition and exercise. Primary outcomes measures will be 5-month changes in child weight status, diet and physical activity, and cardiovascular outcomes (for effect size estimation), and measures of treatment acceptability by primary care staff and families. This study will provide investigators pilot data necessary to map a larger-scale multi-site intervention study, via an R18 funding mechanism.