Research - 2006
Complementary / Nutrition Research
Pilot Trial of Chromium-Metformin Combination in Type 2 Diabetes: Impact on Blood Sugar Control and Insulin Resistance
Ryan Bradley, MD
Postdoctoral Research Fellow, National Center for Complementary and Alternative Medicine, Bastyr University
Irl Hirsch, MD
Director: Diabetes Care Center, University of Washington Seattle, Washington
Metformin is the most commonly prescribed oral medication for type 2 diabetes in the world. In previous trials a commonly used nutritional supplement, chromium, also improved glycemic control and/or lipid profile. Research at the Bastyr Center for Natural Health, the largest naturopathic health clinic in the country, suggest 69% of patients get chromium as part of their treatment and 45% are on oral medications. The combination of chromium and metformin has NEVER been studied in a clinical trial, despite frequent use in combination. This study will clinically investigate combination therapy to determine possible synergistic effects and see if supplemental chromium can improve health outcomes in combination with traditional therapy.
Efficacy of blueberry, Vaccinium angustifolium, extracts in treating diabetes-induced metabolic complications
Amy J. Davidoff, Ph.D.
Assoc. Professor and Assoc. Chair of Research
Univ. of New England, College of Osteopathic Medicine
The use of natural products and dietary supplements is extremely attractive to the general population, but the effectiveness of many supplements is not well documented. The purpose of this study is to evaluate the effects of extracts from blueberries to improve the metabolic (glucose, lipids) and inflammatory status in insulin resistant rats. The Co-Investigator of this project has a unique perspective, being both a Native American Indian healer and a physician trained in conventional medicine. Dr. Deanna Francis has found blueberry supplementation to effectively reduce blood sugar levels in some of her diabetic patients, so this study will also document the treatment effectiveness of natural therapies in two Native American Indian populations in Maine and Michigan.
Lower Carbohydrate Diet Effects in Type 2 Diabetes Mellitus
Joel S. Edman, D.Sc, FACN, CNS
Director of Integrative Nutrition
Center for Integrative Medicine
Thomas Jefferson University & Hospital
Low Carbohydrate diets have become increasingly popular for weight loss and blood sugar control, even though there is little evidence supporting their effectiveness, and there are concerns about health consequences and long-term compliance. While there are published studies examining very low carbohydrate diets for weight loss, there are few investigations of these diets related to type 2 diabetes. The purpose of this pilot study is to examine the effects and feasibility of a lower carbohydrate diet of 50 to 100 grams per day. In addition to evaluating blood sugar control, kidney function will also be evaluated by measuring microalbumin and transforming growth factor beta (TGF-B) to determine the impact of higher dietary protein content on kidney function. This pilot study and related future research will help to determine optimal dietary protein and carbohydrate levels, as well the appropriate circumstances in which they may be recommended.
Mechanism of Soy isoflavone genistein in prevention of diabetic vascular complications
Dongmin Liu, Ph.D.
Asst. Professor of Molecular Nutrition and Vascular Physiology
Virginia Polytechnic Institute and State University
Elevated blood sugar levels in diabetic patients cause blood vessel damage causing vascular disease which is the major complication of diabetes. Vascular endothelial cells which lie on the vessel wall to separate circulating blood and peripheral tissues play an important role in maintaining vascular function by releasing various molecules such as cyclic adenosine monophoshate (cAMP). Dr. Liu’s project plans to determine the potential use of the iso-flavone, genistein, as an inhibitor of the vascular complications of high blood sugar. Results of this project could facilitate the development of novel nutritional strategies for prevention and treatment of diabetic complications.
Longitudinal Follow-up of Arterial Stiffness and Endothelial Dysfunction in Children with Type 1 Diabetes
Michael J. Haller, MD
Pediatric Endocrinology Fellow
University of Florida
Studies have shown that atherosclerotic lesions begin in childhood and that some children have evidence of aortic fatty streaks and raised fibrous plaques as early as 3 years of age. Endothelial dysfunction is one of the earliest signs of increased risk for cardiovascular disease, and has been shown to occur more often and at an earlier age in patients with type 1 diabetes compared to the non-diabetic population. This study is a follow-up to Dr. Haller’s original study which demonstrated that arterial stiffness, as measured by radial tonometry, was higher in 10-18 year old children with diabetes than controls, but no correlation was found between arterial stiffness and traditional cardiovascular risk factors. Thus, this study is needed to determine the natural history of arterial stiffness and endothelial dysfunction in children with type 1 diabetes.
Role of Mitochondria on the Development of Diabetic Cardiomyopathy
Mohammed A. Matlib, Ph.D.
Professor, Dept. of Pharmacology and Cell Biophysics
Univ. of Cincinnati College of Medicine
Heart failure is a common cause of death in diabetic patients. The failed hearts show fatty acid metabolite deposits postmortem. Since high levels of fatty acid metabolites are toxic, their accumulation is a major cause of heart failure. A fuller understanding of failure of the metabolic pathway leading to fatty acid metabolite deposits is needed to design better prevention and therapy for diabetic heart failure. Dr. Matlib’s lab has recently discovered a new metabolic pathway which exports fatty acid metabolites from mitochondria and prevents their accumulation in the normal heart. Dr.Matlib plans to measure fatty acid metabolites deposition and export from hearts of mice lacking the genes involved in the generation and in the export of fatty acid metabolites. This study is important because it will generate information crucial for designing drugs and other therapies for prevention and treatment of heart failure in diabetic patients.
Intravenous Insulin in Critically Ill Patients
Jane Eileen Weinreb, MD
Chief, Diabetes Program
VA Greater Los Angeles Healthcare System at West LA
Los Angeles, CA
High blood sugar is often overlooked in critically ill patients in the Intensive Care Unit, where hospital deaths are significantly higher in patients with hyperglycemia compared with those who have normal blood sugars. Correction of hyperglycemia using a continuous insulin infusion into the vein has been shown to improve outcomes (morbidity and mortality) in patients with heart attacks or after heart bypass surgery, but tight control of blood sugar with intensive intravenous insulin therapy has not been studied in Medical Intensive Care Unit patients. The goal of this study is to determine whether tight blood sugar control with the medical ICU patients would have similar positive benefits as seen with the surgical patients.
Beta Cell Function
Ingested Interferon-alpha in type 1 Diabetes
Staley A. Brod, M.D.
Associate Professor of Neurology/Immunology
University of Texas Health Science Center
The goal of intervention in type 1 diabetes (T1DM) should be a non-toxic oral agent that prevents additional loss of residual beta cell function. In a phase I clinical trial with 10 T1DM patients, 8 of the 10 patients demonstrated a 30% increase of stimulated C-peptide levels for 12 months after initiation of ingested Interferon-alpha (IFN-a) with no discernible chemical or clinical toxicity. This new study will be a phase II trial examining biochemical outcomes in T1DM using ingested IFN-a. 80 out of 120 newly diagnosed T1DM patients will be on active treatment with IFN-a, and 40 patients will be on placebo with saline treatment. If ingested IFN-a can preserve residual beta cell function in T1DM, then a much longer phase III clinical trial will be initiated. Ingested IFN-a may potentially provide a continuous, convenient, non-toxic, and effective therapy for T1DM administered during vulnerable periods in populations such as high risk children, adolescents, and young adults.
Matrix and Adhesive Influences During Pancreatic Islet Development in Zebrafish
Phillip Dilorio, Ph.D.
Instructor Dept.of Medicine
Univ. of Massachusetts Medical School
Type 1 Diabetes occurs as a patient’s immune system destroys their own insulin-producing B-cells. A critically important question for the initiation of Type 1 diabetes is “where do the first B-cell specific antigens come from that are misidentified by the immune system as foreign?” Recent evidence suggests that these antigens are provided by B-cells that die pre- or perinatally normally or because of defects in development. Dr. Dilorio’s study will explore the role of extracellular matrix in determining the fate of pancreatic beta cells in zebra fish.
Role of HNF1B in B cell development
David B. Rhoads, Ph.D.
Asst. Professor of Pediatrics, Harvard Medical School
Massachusetts General Hospital, Boston, MA
MODY5 is a special form of diabetes with an onset age around 25 that is caused by mutations in the gene for HNF1B transcription factor. This HNF1B factor is necessary for normal islet development and beta cell function. Although it has been shown that removing HNF1B from beta cells changes islet gene expression and prevents normal insulin release, it is not known what HNF1B does during development. Dr. Rhoad’s research will attempt to characterize the role of HNF1B in both the developing and mature beta cell. Results of this project will lead to improved strategies to restore beta cell function and to engineer stem cells for regulated secretion for type 1 diabetes therapy.
Perfusion pressures and distal oxygenation in the limbs of individuals with diabetes undergoing chronic hemodialysis
Nairmeen Awad Haller, Ph.D.
Akron General Medical Center
Long term complications of diabetes include disorders of the small blood vessels. These disorders put patients at greater risk of developing chronic foot wounds leading to amputation. Patients on hemodialysis are especially at risk for wound infection because of reduced blood flow to the feet during dialysis. By using laser Doppler measurements, Dr. Haller’s study will provide a better understanding of how dialysis affects blood flow to the feet in diabetic and nondiabetic patients during dialysis. Hopefully, results of this study will make it possible to modify the hemodialysis process in order to minimize any effects on blood flow.
Susceptibility Gene Search for Albuminuria in Mexican Americans with Diabetes
Farook Thameem, Ph.D.
Research Asst. Professor
The Univ. of Texas Health Science Center at San Antonio
San Antonio, Texas
Kidney disease, secondary to diabetes, is the most common complication of diabetes, and as kidney disease develops, cardiovascular risk increases progressively. Diabetic nephropathy affects about 30% of Type 1 and 25-40% of Type 2 diabetic patients with substantial racial variation in prevalence, which suggests genetic causes. Population-based studies of Mexican Americans with Type 2 diabetes have shown that these patients are 2 times more likely to develop microalbuminuria, a marker for diabetic kidney disease, and 4 times more likely to develop clinical proteinuria compared to non-Hispanic white diabetic subjects. By identifying the genes responsible for diabetic nephropathy in the Mexican American population Dr. Thameem hopes this will enable earlier detection and treatment.
Gene Research / Islet Cell
Regulation of Osteopontin in the Pancreatic Islets and Beta cells: An Endogenous Feedback Mechanism to Protect Against Cytokine-Induced Islet Dysfunction
Hwyda Arafat, Ph.D.
Asst. Professor Thomas Jefferson University
Transplantation of the pancreatic islets has long been considered a potential curative treatment for diabetes. However, the results of several clinical trials showed that most transplant recipients failed to achieve complete insulin independence. Transplanted islets are extremely sensitive to the injurious effect of substances called cytokines that are released by the recipient immune cells. This results in early islet cell dysfunction and possibly death of the transplanted tissue. Dr. Arafat’s project plans to evaluate the role of the osteopontin gene in modulating this cytokine-induced islet cell dysfunction following pancreatic islet transplantation.
Enhancing Pancreatic Islet Cell Survival after Isolation and Transplantation
Melissa L. Brown, Ph.D., RD/LD, CNSD
Research Instructor of Surgery
Univ. of Mass. Medical Center
In the attempt to establish a cure for diabetes, much research is focused on ways to improve pancreatic islet transplantation. The success of islet transplantation is limited by the death of islet cells following their separation (isolation) from the donor pancreas and transplantation into the recipient. Free radicals are involved in the death of the islet cells and antioxidants can neutralize this damage. In preliminary studies, Dr. Brown has found that a compound known as pyruvate (an energy compound as well as an antioxidant) is successful in protecting rodent islet cells from death. In this study Dr. Brown plans to further verify the protection of islet cells by pyruvate, identify potential mechanisms of action, and then continue the studies in human islets. Since it is important to make it possible for a greater number of diabetics to benefit from islet transplantation and enjoy a better quality of life, this project can help improve the success of this procedure and give new hope for a diabetes cure.
Erythropoietin (EPO) gene transfer for diabetic neuropathy
Munmun Chattopadhyay, Ph.D.
Research Investigator Univ. of Michigan
Dept. of Neurology Ann Arbor, Michigan
Approximately 18 million Americans with either type 1 or type 2 diabetes are affected by peripheral neuropathy, which leads to the increased likelihood of foot ulcerations and gangrenous infections that lead to a 15% risk of amputation. Dr. Chattopadhyay is using a gene transfer vector that efficiently carries genes from the skin to the sensory nerves. In the current study she will use a novel gene transfer vector to deliver the gene for erythropoietin, a potent neuroprotective agent to sensory nerves. The major aim is to determine whether erythropoietin gene transfer will be effective in preventing or reversing diabetic neuropathy in animals. A successful study could lead to the development of novel therapy for what has been to now an untreatable complication of diabetes.
Defining biochemical and physiological parameters of insulin secretion by adult pancreas derived mouse and human progenitor cells
Vijay Ramiya, Ph.D.
Asst. Professor, Univ. of Florida
A clinical method to replace insulin-producing islet cells is intra-portal islet implantation, also called the “Edmonton Protocol”. Although this protocol has been used successfully to establish normal glucose levels in diabetic patients, a severe shortage of human islets prevents a widespread use of this procedure. Dr. Ramiya’s research will attempt to obtain insulin secreting “islet cells” from adult pancreatic stem/progenitor cells and determine if the derived cells functionally mimic normal islet pancreatic tissue, and thus provide important comparisons between stem cell derivatives and freshly explanted islet cells. If Dr. Ramiya’s research can successfully develop techniques to allow for the creation of large numbers of insulin secreting cell lines, these cells could then be useful for treating insulin deficient diabetes.
Chlamydia pneumoniae Infection and Progression towards Insulin Resistance in an Obese Mouse Model
Bernhard Kaltenboeck, DVM, Ph.D.
Auburn University, Auburn, AL
Scientists searching for causes of insulin resistance and type 2 diabetes have begun to focus on chronic inflammation, and it has become increasingly clear that there is an important inflammatory component to this disease. Dr. Kaltenboeck’s study will examine the role of chronic infection with C. Pneumoniae in the development of insulin resistance in a mouse model of obesity. This project will analyze the mechanisms by which infection enhances progression of insulin resistance and determine whether treatment of the infection blocks insulin resistance development. This study is important in providing clues to the molecular link between inflammatory conditions and insulin resistance.
Effects of Adiponectin on striated muscle cells
Silvia Mora, Ph.D.
Kansas State University
In people affected by type 2 diabetes, the tissues, and particularly the muscle, are unable to take the glucose from the circulation and the glucose accumulates in the blood. Glucose enters the muscle through a gate that is specifically activated by insulin. This gate is a glucose transporter named GLUT4. In the presence of insulin this transporter is activated and glucose can enter the cells. However, this activation does not occur in people with type 2 diabetes. Fat cells produce and release into the blood types of hormones that affect how the body utilizes glucose. One of these hormones, adiponectin, helps the muscle to respond to insulin. In this project Dr. Mora will study the molecular basis of how the hormone works to stimulate glucose transport into muscular and cardiac cells. The results of this study will improve our understanding on how this hormone works to regulate glucose utilization and will identify future molecules for therapeutic intervention focused on ameliorating glucose blood levels in type 2 diabetes.
Fasting and Blood Glucose Regulation in STZ-Induced Diabetic Rats Treated with Leptin
B. Douglas White, Ph.D.
Associate Professor and Head
Department of Nutrition and Food Science
To investigate the association of type 2 diabetes with obesity, Dr. White is examining the effect of leptin in the brain on insulin sensitivity. Dr. White has shown that administration of leptin into the brain of diabetic rats greatly enhances insulin sensitivity and normalizes blood glucose concentrations. However, these rats cannot tolerate a relatively short-term fast without developing hypoglycemia. This study will examine the reason fasting causes hypoglycemia in these animals, providing a better understanding of the relationship between leptin signaling in the brain and insulin sensitivity in the body. Now that leptin has been suggested as an adjunct therapy with insulin in the treatment of diabetes, this research is especially important and aims to promote the development of better treatment therapies and methods of prevention.
Maximizing Adherence to Diabetes Treatment Utilizing the Diabetes Weigh Program
Arnaud Bastien, MD
Assoc. Professor of Medicine, Univ. of Medicine & Dentistry of NJ
Robert Wood Johnson Medical School at Camden
Cooper Univ. Hospital, Camden, New Jersey
Lifestyle change is the key to successful management of diabetes. Effective self-management heavily depends on diet and proper lifestyle practices. Given the very high levels of failure (50%) to achieve ADA target goals, and lack of acceptance of the necessity for lifestyle changes in most patients with uncontrolled diabetes, Dr. Bastien will test the effectiveness of a new tool, Diabetes Weigh, which offers promise in reducing goal failure significantly.
Understanding the Goal Setting Process in Diabetes Dietary Self-Care in Latinos and Caucasians with Type 2 Diabetes
Jill Armstrong Shultz, Ph.D.
Professor of Nutrition
Washington State University
Goal setting, the joint process between patient and diabetes educator to set patient behaviors or “goals” to manage diabetes, is an important component of diabetes self-management education among non-Hispanic Caucasians. It is not known if goal setting education needs to be conducted differently with Latinos as opposed to Caucasians. Because of high rates of type 2 diabetes among Latinos, and the high incidence of diabetic complications in this group, developing effective diabetes self-management education is imperative. In addition to assessing dietary goal setting, Dr. Shultz will also identify personal, family, and social issues that may affect Latino patients in carrying out dietary goals. By identifying effective education techniques for dietary management, this study will be useful to clinics serving Latino and Caucasian patients.
Relationship between Physician Expertise Indicators and Quality of Care of Patients with Diabetes Mellitus
Alexander Turchin, MD
Clinical Fellow in Endocrinology
Brigham and Women’s Hospital
As the number of diabetic patients has increased dramatically over the last decade, a large percentage of these patients have suboptimal treatment results. Dr. Turchin will examine the possible influence of clinical experience (as defined by patient numbers, dates of specialty training, generalist vs. specialist status, and elapsed time since completion of generalist formal training) on the quality of care given diabetic patients. Records of 80,000 to 100,000 diabetic patients will be analyzed for levels of quality care and outcomes. Results of this study could lead to significant changes in public health policies, more training for certain groups of physicians, and ultimately to improvement in diabetes care.
Educational Intervention for Supervisors of Employees with Diabetes
Felecia Wood, DSN, RN
Assistant Professor Sharol Jacobson, PhD,RN,FAAN
Professor and Assoc. Dean for Research & Practice
The University of Alabama,Capstone College of Nursing Tuscaloosa, AL
The worksite presents special challenges for people with diabetes, such as finding time and privacy for checking blood sugar and giving insulin, being able to eat within certain time periods, dealing with fluctuations in job stress and physical activity, and deciding whether or not to tell one’s diagnosis and special needs to one’s supervisor. The purpose of this project is to conduct, refine, and evaluate an innovative educational program for supervisors of employees with diabetes. Two innovative teaching strategies will involve living the life of a person with diabetes for two days and using case studies to practice correct decision making. The results of this study will hopefully enable supervisors to perform their diabetes-related duties better, lead to improved work life for employees with diabetes, and decrease employers’ healthcare costs.