Maintaining anutritious diet
and exercise plan is paramount for patients with diabetes in order to reduce the risk of complications from the disease. For pre-diabetic patients, making such lifestyle changes may also be helpful in warding off diabetes. Encouraging pre-diabetic patients to change their habits was a primary focus of discussion recently at the American Diabetes Association (ADA) 65th Annual Scientific Sessions.
Participants in the ADA sessions cited several studies, including the Diabetes Prevention Program and the Finnish Diabetes Prevention Study, that show the positive impact of routine diet and exercise counseling in addressing metabolic issues in patients with pre-diabetes and polyneuropathy.
The ADA also noted the findings of the Impaired Glucose Tolerance Neuropathy Study, in which patients performed 150 minutes of moderate exercise every week. These patients were also asked to decrease fat calories to under 30 percent of their total food intake and lose 7 percent of their body weight over 48 weeks, according to an article in the Doctor’s Guide. The study results showed that diet and exercise improvements led to improved metabolic function and improvements in measures of peripheral neuropathy, according to the ADA.
Although lifestyle changes are effective in slowing the progression of diabetes or preventing the disease, Eric Espensen, DPM, says many patients do not grasp the severity of diabetes. He lauds the ADA’s group encounter meetings as “gold mines” and notes that many hospitals have monthly diabetes meetings to educate patients.
For patients with pre-diabetes or those who are borderline diabetic, controlling diet and exercise is vital, according to Eric Feit, DPM.
He says planning a specific diet plan
for each day is critical and
prefers the Atkins diet as it is easy for patients to remember. The diet stresses cutting back carbohydrates like bread, rice, pasta, cookies and cakes. Dr. Espensen urges patients to keep a journal of the food they eat for a week.
“The patients are amazed at how much they eat and they can start to make simple changes in their diets,” says Dr. Espensen, the Associate Director and Director of Research at the Providence Diabetic Foot Center in Los Angeles.
Having a daily exercise program is also important, notes Dr. Feit, the Past President of the Los Angeles chapter of the ADA. He says patients should start by buying a good pair of running shoes and a soft OTC orthotic like a Spenco Polysorb Cross-Trainer or Sof Sole Athletic Plus. Dr. Feit points out that senior citizens like these orthotics because their feet feel better and they are able to walk more.
Dr. Feit asks his patients to walk 30 minutes each day and suggests settings like the park, the mall or the supermarket. Dr. Espensen concurs, emphasizing that having patients walk 30 minutes a day is “priceless” in facilitating weight loss.
Encouraging Compliance From Difficult Patients
What can podiatrists do to encourage compliance in adult patients who simply do not want to change their habits? Dr. Feit says one can encourage a new diet or exercise program by showing pictures of patients with diabetic wounds, gangrene or amputations. Following that, he enumerates the risks of diabetes and how keeping blood sugar under control can prevent such complications.
“Sometimes a visual stimulus is the best way to get a patient to realize the serious risks involved with being diabetic,” says Dr. Feit of showing non-compliant patients photos of complications. “After scaring the patient a little bit, I like to emphasize that more than 80 percent of diabetic foot complications are preventable with regular podiatric visits, good shoes and insoles, and checking their feet daily.”
Dr. Espensen takes a similar path by having pre-diabetic patients participate in group sessions with diabetic patients who have problems like blindness, gangrene and amputations. When meeting those with complications of diabetes, he says patients may realize what they are facing. He also favors communicating with one’s patients.
“Oftentimes, developing a strong rapport with your patients is essential in helping them,” says Dr. Espensen. “I hate to admit that some patients will not accept help. Just keep trying and don’t give up.”
Are Nonselective NSAIDs Worth Another Look?
By Brian McCurdy, Associate Editor
Given all of the increased scrutiny over the potential negative effects of COX-2 inhibitors, are nonselective nonsteroidal antiinflammatory drugs (NSAIDs) worth another look? Although nonselective NSAIDs have been out of the spotlight for some time, one DPM says there are some benefits to these medications.
“I have had tremendous success with the use of nonselective NSAIDs over the years,” says Bryan Caldwell, DPM, Professor and Assistant Dean of the Ohio College of Podiatric Medicine. “My patients have experienced very few side effects.”
Dr. Caldwell says it is important to understand the differences between COX-1 and COX-2 inhibitors. The COX-1 enzyme blocks production of the vasodilator prostacyclin from endothelial cells and the vasoconstrictor thromboxane from the platelets. Although COX-2 blocks prostacyclin and its inhibitory effect on platelets, Dr. Caldwell points out that it does not block thromboxane, which promotes platelet aggregation. Such an imbalance may allow thromboxane to cause clotting in cardiac or
cerebral vessels, according to Dr. Caldwell.
“Nonselective NSAIDs block both enzymes and accordingly should not predispose patients to cardiac ischemic events,” points out Dr. Caldwell, who holds a master’s degree in molecular biology from the University of Notre Dame.
As Dr. Caldwell emphasizes, while COX-2 inhibitors do not have any better antiinflammatory properties than nonselective NSAIDs, COX-2 inhibitors cause fewer gastrointestinal (GI) ulcers. Nonselective NSAIDs also have the advantage of being cheaper.
What You Should Know About Nonselective NSAIDs
Nonselective NSAIDs can be categorized into five clinically relevant groups: arylpropionic acids, alkanones, heteraryl acetic acids, enolic acids and indole acetic acids (see “A Guide To Non-Selective NSAIDs” below). Dr. Caldwell notes it is useful to know the different categories. If one drug fails in a particular patient, he says clinicians can choose an NSAID from a different group.
When it comes to the arylpropionic acids, Dr. Caldwell notes fenoprofen is a propionic acid that provides relief from mild to moderate pain within 15 to 30 minutes, and sustains this effect for four to six hours. He cites earlier studies that
suggest 100 mg and 200 mg of fenoprofen provide more effective pain relief than 60 mg of codeine, and adds that higher doses can successfully treat acute gout.
Nabumetone, the only NSAID in the alkanone group, is a non-acidic NSAID. While this drug may be of merit for patients with gastrointestinal (GI) upset, Dr. Caldwell says it does not have any protective effect on the stomach. Since nabumetone blocks COX-1, he notes gastric ulcers may still be an occasional problem.
Studies have shown diclofenac, a heteraryl acetic acid, blocks the leukotriene pathway as well as cyclooxygenase enzymes, which Dr. Caldwell says might make diclofenac more appropriate to use in asthmatics. For NSAIDs that do not block this pathway, he says arachidonic acid may be redirected from the COX enzyme to the lipooxygenase enzyme, potentially causing an increase in leukotrienes and exacerbation of an asthma attack in affected individuals. One can use ketorolac intramuscularly but Dr. Caldwell notes it does not bypass the inhibition of COX-1 mediated gastric protection.
Meloxicam, an enolic acid, has less COX-1 activity than the other nonselective NSAIDs, according to Dr. Caldwell. Some have expressed concern about the possible association of thrombotic events with meloxicam but Dr. Caldwell says a previous meta-analysis does not support such a perception. He points out that meloxicam has a long half-life that permits once a day dosing.
Among the indole acetic acids, sulindac may be better suited for geriatric patients due to its lack of effect on renal prostaglandins, according to Dr. Caldwell. He says indomethacin can cause mental confusion so one should not use it in geriatric patients.
Taking Precautions And Combating Misperceptions
What precautions should DPMs take before prescribing NSAIDs? Dr. Caldwell emphasizes obtaining a through patient history to screen for prior GI problems like ulcers. One should take particular care in prescribing NSAIDs in patients with a history of asthma, bleeding disorders or kidney disease, according to Dr. Caldwell. When prescribing nonselective NSAIDs, Dr. Caldwell notes that many podiatrists also prescribe a prostaglandin analogue or proton pump inhibitor in order to protect the stomach.
With all the negative attention NSAIDs have gotten in the media, DPMs may need to combat a perception that such drugs may be harmful. When treating patients who have concerns about NSAIDs, Dr. Caldwell advises reviewing the evidence-based literature with concerned patients and also emphasizing one’s experience with other patients so patients may make informed decisions.
Study Says Gene Therapy Shows Promise In Relieving Neuropathy
By Brian McCurdy, Associate Editor
Can gene therapy unlock the secret of easing painful diabetic neuropathy? A recently published study in the Annals of Neurology studied the transfer of gene coding in mice and concluded that the treatment may have promise in relieving neuropathic pain.
Researchers injected an inactive vector of herpes simplex virus, which contained the gene glutamic acid decarboxylase (GAD), into rats. The antiallodynic, pain-relieving effect in the rats lasted six weeks and additional injections re-established the effect, according to the study.
Gene therapy holds promise for patients with painful diabetic neuropathy, according to Gerit Mulder, DPM, and Stephen Barrett, DPM. Dr. Barrett says researchers delivered “the ideal pharmacologic agent” to the tissue site, which he says will increase efficacy and decrease side effects.
The approach detailed in the study increased GABA, a neurotransmitter in the spinal cord that is proven to inhibit pain, and helped “block the transmission of pain higher within the central nervous system,” explains Dr. Barrett, an Associate Professor of the Arizona Podiatric Medicine Program at the Midwestern University College of Health Sciences. Accordingly, Dr. Barrett says this therapy offers “a great advantage” over simple pharmacologic agents that increase GABA.
As Dr. Mulder notes, researchers are currently in the early phases of studies using an adeno-virus gene activated matrix system in an attempt to assess the use of gene therapy for diabetic foot ulcers.
“I believe that gene therapy is one of the technologies of the future,” says Dr. Mulder, an Associate Professor of Surgery and Orthopedics at the University of California-San Diego. “It offers a more rapid and effective means of gene sequence delivery with potentially expedited therapeutic results.”
What Are The Potential Downsides?
Despite the promise of gene therapy to relieve neuropathy, Drs. Mulder and Barrett concur that DPMs must be aware of the potential downsides. Dr. Barrett warns clinicians to beware of side effects, noting there have been problems in cases in which humans have undergone gene therapy.
Dr. Mulder says there are unanswered questions regarding the effectiveness of gene expression, duration of therapy and the secondary effects associated with the delivery system. Although rapid and persistent delivery of GABA may be advantageous, Dr. Mulder notes the cost and long-term benefits of such therapy may be minimal. Dr. Mulder also emphasizes caution when using any virus, such as herpes simplex, as a vector and stresses the importance of explaining the risk to patients.
How will patients react to such a novel treatment as gene therapy? Dr. Mulder notes patients may be “particularly reluctant” when DPMs mention the herpes simplex virus as part of the treatment. When presenting new treatments such as gene therapy to patients, Dr. Barrett has found patients respond positively when they are educated about a treatment that is based on solid medical principles.
“I see no reason why patients who are educated about the process would be unwilling to undergo this type of therapy, provided it is safe and they know it may offer serious and significant advantages to traditional systemic pharmacotherapy,” says Dr. Barrett.
Avelox Receives FDA Approval For Treating cSSSIs
By Brian McCurdy, Associate Editor
An antibiotic previously approved to treat uncomplicated skin and skin structure infections has received a green light to treat complicated skin and skin structure infections (cSSSIs). The FDA recently approved moxifloxacin HCl (Avelox®
, Schering-Plough) to treat infections including methicillin-susceptible Staph aureus
In clinical studies, researchers compared moxifloxacin with a beta-lactam/beta-lactamase inhibitor compound for the treatment of patients with cSSSIs, according to Schering-Plough, which markets Avelox in the United States for the drug’s manufacturer, Bayer. In the North American study, which involved 335 clinically evaluable patients, moxifloxacin was 82.2 percent effective in eradicating MSSA, compared to the 87.6 percent rate of the beta-lactam/beta-lactamase inhibitor compound, according to Schering-Plough.
Although Avelox is approved to treat cSSSIs, Warren Joseph, DPM, notes the drug is not specifically approved to treat diabetic foot infections. While Avelox has a broad spectrum of activity, it has a relatively narrow spectrum of approval for MSSA, E. coli, Klebsiella pneumonia
and Enterobacter cloacae
, according to Dr. Joseph, a Fellow of the Infectious Diseases Society of America.
However, Dr. Joseph cites a pivotal trial, on which the FDA approval was based, in which researchers compared IV and oral moxifloxacin to piperacillin/tazobactam +/- oral amoxicillin/clavulanate. Out of the 367 evaluable patients, approximately 75 percent had an abscess, cellulitis or a diabetic foot infection. Dr. Joseph says the clinical success rates were 79 percent for moxifloxacin compared to 85 percent for the comparator drugs. He also notes that moxifloxacin is available orally and offers the advantage of once-a-day dosing.
“Given its spectrum of activity and the above study results, (Avelox) should be useful in diabetic foot infections and other severe soft tissue infections,” notes Dr. Joseph.
Dr. Joseph does point out that the overall number of patients with diabetic foot infections was small in the clinical trials and encourages more studies with this specific patient population.
While DPMs can use Avelox in patients who are allergic to the beta-lactam inhibitor compound agent, Dr. Joseph notes a disadvantage in that there is a potential for cross-resistance to other quinolones, including ciprofloxacin, in treating Staph.