Chicago June 17, 1998
The meeting came into conclusion in Chicago yesterday. During the four days, 1300 scientific papers were presented to a large audience.
Among some of the interesting findings on Tuesday were the results finding MUSE, a VIVUS, Inc. product 60 per cent effective among diabetic men. MUSE is dosed intrameatally (to the mouth of urethra) with an applicator. The drug is currently marketed in the USA, and has been approved in a number of other countries, including Sweden.
Chicago June 16, 1998 10 am. GMT
FIRST REPORT OF SUCCESSFUL WEIGHT LOSS IN HUMANS WITH LEPTIN
Daily Hormone Injections Yield Substantial Weight Loss Compared to Diet Alone
An early phase 1 clinical trial with humans using leptin, the so-called anti-obesity hormone, to achieve weight loss was reported here. A related study suggests leptin also may help lower blood sugar levels.
"Obese participants taking the highest dose of the daily leptin injection lost an average of nearly 16 pounds over six months," explained Andrew S. Greenberg, MD, Director of the Program in Obesity and Metabolism, Jean Mayer USDA Human Nutrition Center at Tufts University, and Director of Research at the Obesity Consultation Center at the New England Medical Center in Boston.
"Our preliminary results demonstrate that recombinant methionyl human leptin causes weight loss and has an acceptable safety profile, suggesting further study is warranted," said Dr. Greenberg.
Obesity is a major concern for the nearly 15 million Americans who have type 2 diabetes, (formerly called non-insulin-dependent diabetes). Type 2 diabetes usually arises due to insulin resistance, in which the body fails to use insulin properly, combined with relative (rather than absolute) insulin deficiency. In other cases, it primarily involves an insulin secretory defect, combined with some insulin resistance. Obesity is believed to play a critical role in type 2 diabetes because the disease occurs most commonly in people who are over 45 and overweight. Diabetes can lead to severely debilitating or fatal complications, such as blindness, kidney disease, heart disease and amputations. It is the sixth-leading cause of death by disease in the United States.
Understanding Leptin
Leptin is a hormone, first discovered in mice, that is made in fat cells and circulates in the body. It is believed to be involved in food intake and body weight regulation. In laboratory studies, mice genetically deficient in leptin became obese and, subsequently, got thinner when given extra leptin.
However, both mice and humans make more leptin as they gain weight, but a genetic problem handling leptin has very rarely been found in humans. Thus, it was unclear whether giving humans extra leptin would promote weight loss.
Impact of Synthetic Leptin
Recombinant methionyl human leptin is a synthesized form of the natural human hormone, created by Amgen, Inc. using the DNA of leptin.
In the multicenter study, daily subcutaneous injections were given to 53 lean subjects and 70 moderately obese subjects for one month at one of four leptin doses or placebo, with doses ranging 0.01 to 0.30 mg/kg/day randomly assigned. The obese participants had a body mass index (BMI) of at least 27.5 kg/m2, a level of overweight known to place people at risk for developing such problems as diabetes and heart disease.
All participants also were placed on a weight reduction diet. Based on age, body weight, and activity levels, diets were tailored to provide 500 calories less than each individual's basic energy needs. Dietary compliance was monitored by self-report mechanisms.
A statistically significant dose response for weight loss was seen in all participants at the end of the first month. Average weight losses ranged from .04 kg (0.09 lbs) for those on placebo to 1.9 kg (4.18 lbs) for those on the highest leptin dose.
Subsequently, 60 of the obese patients continued participation, and 76% completed the study. At the end of six months, average weight losses ranged from 0.7 kg (1.54 lbs) to 7.1 kg (15.6 lbs), the latter loss averaged by the eight patients on the highest leptin dose.
Leptin did not appear to cause any significant adverse effects, based on laboratory monitoring of blood values, liver and kidney function, electrocardiograms, and physical examinations. The most common side effect seen was moderate skin reactions (redness, itching and/or swelling) at the injection site, a common occurrence when human proteins are injected.
Potential Impact on Diabetes
Although people with diabetes were intentionally excluded from the multicenter study, preliminary data suggest that a positive trend in the impact on blood sugar levels occurred. It is not known whether that trend is a direct result of the leptin itself or a side effect due to weight loss, which is known to lower blood glucose levels.
However, researchers at the Indiana University School of Medicine reported findings from laboratory studies that suggest leptin may play a regulatory role in glucose metabolism directly within human fat tissue, independent of centrally mediated metabolic effects, according to Robert Considine, PhD, an assistant professor in medicine at the Indianapolis school.
Thus, leptin may have the potential to help lower blood sugar levels in people with type 2 diabetes in two ways: through a direct impact on glucose metabolism and an indirect impact via weight loss.
Larger Studies Underway
Larger phase 2 multicenter clinical trials have already begun with about 500 obese participants. In addition, two phase 2 clinical trials are underway to study leptin's effects in controlling blood sugar in overweight adults with type 2 diabetes. People interested in participating in future studies can volunteer by calling 1-800-77-AMGEN.
Symposia on weight management and impotence
Two corporate -sponsored symposia will be held today at ADA Annual Meeting in Chicago: one on "New Directions for Weight Management in Diabetes", and another on "Cardiovascular and/or Metabolic Disease: Diabetes and the Patient with Erectile Dysfunction".
The symposium "New Directions for Weight Management in Diabetes" explores the strong relationship between type-2 diabetes and obesity. Current, effective strategies to help patients lose weight, maintain weight loss, and improve health and risk factors are discussed. For further information: Contact us or Ed Heinz, tel. 1-973-785 8500
The other program "Cardiovascular and/or Metabolic Disease: Diabetes and the Patient with Erectile Dysfunction" will address the prevalence, diagnosis, and medical management of erectile dysfunction (ED) in male patients. Patient management will be discussed using actual case studies, i.e., diabetes and cardiovascular disease, and interactive keypad technology. For further information, contact us or Alice Haynes, tel. 1-212-366-0440
Chicago June 15, 1998 1 pm. GMT
Sessions on obesity
Two sessions of today's program in Chicago will deal with obesity -related issues:
Regulation of Energy Expenditure: Clinical/Molecular Aspects consists of four presentations: "Partitioning and Expenditure of Energy and Weight Gain" by Dr. Ravussin; "The Novel Uncoupling Proteins" by Dr. Ricquier; "Beta-3-Adrenergic Receptors, Brown Fat, and Thermogenesis in Energy Regulation" by Dr. Collins; and "Genetic Forms of Obesity in Man" by Dr. O'Rahilly.
Prevention and Management of Obesity in Children in Remembrance of Dr. Julio V. Santiago will have three papers: Epidemiology and Natural History of Obesity in Children" by Dr. Whitaker; "Energy Balance in Obese Children: Too much Food or Too Little Exercise?"; and "Treatment of Obese Children: Efficacy of Behavioral and Nutritional Interventions" by Dr. Dietz.
Chicago June 14, 1998 9 pm. GMT
Olefsky Receives Banting Medal
The Banting Medal for Scientific Achievement is the Association's most prestigious award for scientific excellence, and recognizes significant, long-term contributions to the understanding, treatment, or prevention of diabetes. This year's award goes to Jerrold M. Olefsky, MD. Dr. Olefsky presented the Banting Lecture, entitled, "Insulin Action, Insulin Resistance, and Type 2 Diabetes: Where Have We Been, and Where Are We Heading?" on Sunday, June 14, 1998.
Dr. Olefsky has been a pioneer in the area of insulin resistance. His view that many human insulin resistant states were because of post-receptor binding defects generated a field of study on post-binding insulin signaling in human insulin resistant states, which has now flourished. In the mid-1980s, incorporating molecular biologic approaches into his work, he led a series of studies showing that the insulin receptor is a multifunctional protein, with specific functions ascribed to discrete linear receptor domains, often encoded by specific exons. This area of research has ramifications far beyond insulin resistance and diabetes.
In the past several years, his research has focused on understanding the intracellular signaling cascades that mediate insulin's biologic actions. Toward this end, he has adapted single-cell microinjection techniques, adenoviral-mediated gene transfer, as well as other molecular and cell biological approaches, allowing him to elucidate the role of recently discovered molecules, as well as older well-recognized proteins that are involved in insulin's pleotrophic actions.
Most recently, Dr. Olefsky has taken a new approach aimed at identifying susceptibility genes for type 2 diabetes. His research is exploring whether mitochondrial dysfunction due to mutations in mitochondrial DNA leads to beta-cell dysfunction, causing late-onset insulin deficiency, which, when superimposed on an underlying insulin-resistant state, causes progression to the hyperglycemic type 2 syndrome. Assuming that these mutations exist in beta-cells, this represents a novel and exciting new idea that may provide more insight into the etiology of type 2 diabetes.
Tuomilehto Receives Kelly West Award
The Kelly West Award for Outstanding Achievement in Epidemiology is given in honor of Kelly West, widely regarded as the "father of diabetes epidemiology", to an individual who has made significant contributions to the field of diabetes epidemiology.
A leader in cardiovascular disease and diabetes epidemiology, Jaakko Tuomilehto, MD, MPolSc, PhD, has been involved in numerous major studies. He was a principal investigator in Finland's North Karelia Project, the first community-based study of cardiovascular disease prevention. He participated in and was chief of the Data Centre for the World Health Organization (WHO) MONICA Project, the largest collaborative study of cardiovascular disease, involving 45 populations in 25 countries.
Dr. Tuomilehto was a principal investigator in the Childhood Diabetes in Finland study, an attempt to determine the reasons for the high incidence of type 1 diabetes in Finland; the FUSION study, the largest attempt to date to map type 2 diabetes genes; the Diabetes Epidemiology Research International (DERI) incidence and mortality studies comparing the risk of type 1 diabetes internationally; and the WHO DIAMOND study comparing childhood diabetes incidence with prospective registries in 70 populations worldwide.
Dr. Tuomilehto is a professor in the department of epidemiology at the National Public Health Institute in Helsinki, where he also heads the Diabetes and Genetic Epidemiology Unit. He was president of the Finnish Society of Hypertension from 1995 to 1997, and is now president of the International Diabetes Epidemiology Group.
A strong supporter of physician postgraduate education, Dr. Tuomilehto chaired the steering committee for the 1st World Congress of Prevention of Diabetes and Its Complications in Copenhagen, Denmark (1996), and the 7th International Diabetes Epidemiology Group Symposium in Savonlinna, Finland (1997). He organized the first international symposium on primary prevention of hypertension in Kuopio, Finland (1984), was a member of the WHO Study Group of Prevention of Diabetes in Geneva (1992), and served on the WHO Expert Committee on Physical Status: Uses and Interpretation of Anthropometry in Geneva (1993). Dr. Tuomilehto has written over 600 papers and book chapters, and other articles.
It is with great pleasure that the American Diabetes Association recognizes Dr. Jaakko Tuomilehto with the Kelly West Award for Outstanding Achievement in Epidemiology.
Dr. Tuomilehto presented the Kelly West Lecture on Saturday, His lecture is titled, "Why Is Diabetes Such a Heavy Burden on the Finns?"
For further information, contact us or Prof. Tuomilehto, tel. +358-9-47441
Chicago June 13, 1998 2 pm. GMT
The scientific sessions of the meeting officially started today at the McCormick Place in Chicago. The first plenary lecture "Biology of the Atherosclerosis" is just about to start, and the second plenary of the day in the afternoon will cover "Retroviruses & Human Disease".
The Banting lecture will be given on Sunday by Dr. Jerrold M. Olefsy on "Insulin Action, Insulin Resistance, and Type 2 Diabetes: Where Have We Been and Where are We Heading?"
During four days there will be several presentations on impotence, a medical disorder commonly found in association of diabetes, and on Tuesday, June 16, a session on "Cardiovascular and/or Metabolic Disease: Diabetes and the Patient with Erectile Dysfunction" will take place.
Around 60 presentations during the meeting will deal with obesity -related topics. Today, a session on "Obesity and Type 2 Diabetes: Weight Loss as First-Line Therapy" will be organized, and another session, "New Directions for Weight Management in Diabetes" will be held on Tuesday, June 16, the final day of the meeting.
For further information: