New Studies Examine Potential Genetic Markers For Diabetes

By Brian McCurdy, Associate Editor

Two new international studies reveal intriguing findings in the realm of diabetes research. In the Finland-United States Investigation of NIDDM Genetics (FUSION) study, which involved over 1,200 patients, researchers identified 10 single nucleotide polymorphisms (SNPs) that are associated with type 2 diabetes in the Finnish population. According to the study, which was published in a recent issue of Diabetes, these SNPs were located within or close to the hepatocyte nuclear factor 4 alpha (HNF4A) gene, which influences the expression of glucose metabolic genes. In a separate study, which was also published in the same issue of Diabetes, researchers focused on 600 Ashkenazi Jewish patients. Two hundred seventy-five of these patients had type 2 diabetes. These researchers also “found diabetes-related associations for SNPs in the same region of the HNF4A gene,” according to an article on Gerit Mulder, DPM, cautions against reading too much into the studies as they do not clearly establish “a direct correlation” between genetic markers and the clinical progression of diabetes. However, he praises research efforts that recognize the importance of genetic predisposition for diseases such as diabetes. “Determining a genetic marker that leads to the subsequent expression and development of a disease may significantly contribute to disease prevention through gene therapy or related treatment,” says Dr. Mulder, Director of the Wound Treatment and Research Center at the University of California-San Diego. “Preventing a disease through genetic manipulation could lead to a significant reduction in the prevalence of diabetes and its associated problems.” Identifying patients who may be genetically predisposed to developing type 2 diabetes can go a long way toward more targeted patient education on reducing risk factors and making appropriate lifestyle changes, points out Dr. Mulder, who is an Associate Professor of Surgery and Orthopedics at the University of California-San Diego. He says that this can also help facilitate prevention of sequelae related to a disease such as diabetes. Dr. Mulder adds that continued research in the area of genetic mapping may eventually have even more significant benefits in the future. “As our knowledge of genetic mapping and marker identification increases, I anticipate reaching a point in medical care where the genome is manipulated or altered to reduce or eliminate select diseases,” says Dr. Mulder. Is Antibiotic Approval On The Wane? By Brian McCurdy, Associate Editor Given the increasing prevalence of antibiotic-resistant infections such as methicillin-resistant Staph aureus (MRSA), there appears to be a need for new antibiotics. However, are drug companies meeting the need? While there are 506 new drugs currently in the pipeline for approval, just six are antibiotics, according to a recent study in Clinical Infectious Diseases. Specifically, the study notes FDA approval of new antibacterial agents decreased by 56 percent in the last 20 years. Both Benjamin Lipsky, MD, and David G. Armstrong, DPM, suggest that among the major causes of the decrease in approval for antibiotics are economic reasons, saying drug companies would have higher profits for drugs prescribed over a long period of time than for antibiotics taken for several days. “If it costs a few hundred million dollars to bring a drug to market in 2004, then the drug company will want to put that toward an agent that is used for the life of the patient, not just for seven to 10 days,” says Dr. Armstrong, Professor of Surgery, Chair of Research and Assistant Dean at Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine. Authors of the study emphasize that there is a critical need for new antimicrobial agents, citing the resistance of common pathogens to antibiotics, emerging new infections and the potential use of multidrug-resistant agents as bioweapons. Dr. Lipsky, a Professor of Medicine at the University of Washington School of Medicine, notes that 10 years ago, many clinicians, researchers and pharmaceutical companies believed that all the antibiotics needed were available and “we’re now paying the price” as few drugs are under development. Unfortunately, resistance to approved agents is growing, according to Dr. Lipsky, the Director of the General Internal Medicine Clinic and Head of the Antibiotic Research Clinic of the VA Puget Sound Health Care System in Seattle. He says that while the concern in the 1970s and ‘80s was mostly about gram-negative rods, a major concern in the last decade has been gram-positive cocci such as MRSA and vancomycin-resistant enterococci (VRE). Although more anti-MRSA agents are being developed, “it remains to be seen which will be optimal in various settings,” concludes Dr. Lipsky. “The trouble is, that as superbugs divide and multiply, the life of our patients will be curtailed,” says Dr. Armstrong, a member of the National Board of Directors of the American Diabetes Association. Editor’s Note: For a related article, see the April 2004 supplement, “Treating MRSA Infections” or check out the “Supplements” tag at Can Minimally Invasive External Fixation Have An Impact For Heel Fractures? By Brian McCurdy, Associate Editor Would a less invasive surgery be successful for intraarticular calcaneal fractures? The authors of a recent study in the Journal of Foot and Ankle Surgery found that combining external ring fixation and minimally invasive open reduction via a lateral approach helped facilitate immediate weightbearing and a quicker return to activity than previous treatments. Over a seven-year period, the authors treated 23 patients with 25 intraarticular calcaneus fractures. According to the study, the average period of treatment with the fixator was 6.6 weeks. George Vito, DPM, one of the authors of the study, says they encouraged patients to bear weight the first day after surgery. “The ability of the patient to bear weight is due to the fact that the patient’s weight is directed through the foot to the frame,” explains Dr. Vito, a Fellow of the American College of Foot and Ankle Surgeons. “The calcaneal fracture is distracted and one applies the frame with 30 pounds of distraction. This aligns the fragments of the fracture.” Dr. Vito adds that, at times, the team placed a small incision laterally below the lateral malleolus and also placed a small elevator to raise the posterior facet. Then they would apply the frame. Twenty-three of the patients rated the results of the procedures as either “excellent” or “good,” according to the study. The authors noted that no one required further surgery and all of the patients are “ambulating in normal shoe gear and are able to perform daily activities.” They added that there were few complications and no infections other than a superficial skin infection at the site of the wire insertion. Citing the immediate full weightbearing and the fact that the frame is only left on for six weeks, Dr. Vito says this procedure is “a viable alternative” to highly invasive traditional methods for treating fractures of the heel. Dr. Vito, a faculty member of the Podiatry Institute, adds that perhaps the biggest advantage of using external fixation in such cases is it allows one to distract the calcaneus at the subtalar joint. “Distraction of the subtalar joint with weightbearing allows for regeneration of the articulation surface,” explains Dr. Vito. In Brief Pedinol Pharmacal Inc. has launched its renovated Web site, The site will provide information and news on Pedinol products and commonly treated podiatric conditions. The site also features patient education brochures, and ordering and contact information, according to the company. Over 800 residents have heard 76 lectures since PRESENT Courseware began last September and 24 additional lectures will be available in the next few months, according to the company. The program, which delivers online podiatric lectures at more than half of the 295 residency programs nationwide, features more than 60 authors and 40 corporate sponsors. New lectures include a vascular series and a surgery/wound care program. For more info, see

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