New Hope for Ending Complications
Working together to protect your body from diabetes damage
Elevated blood glucose is sneaky. You may feel just fine, while slowly and imperceptibly the extra glucose in your blood may be damaging the blood vessels that nourish the heart, eyes, kidneys, and nerves. Fear not, though. There are already effective strategies for safeguarding your health against diabetic complications, plus scientists and providers are busily pushing toward better treatments.
Stopping complications before they start is the strategy of choice for achieving a long, healthy life with diabetes. "It's pretty clear that primary prevention makes a difference," says John Harold, MD, vice president of the American College of Cardiology and a cardiologist at the Cedars-Sinai Medical Institute. Studies have shown that people with diabetes can stave off heart attacks and strokes by keeping their blood pressure, cholesterol, and blood glucose within target ranges and not smoking.
Doctors are developing methods to detect heart disease at an earlier stage, when prevention measures may be at their most effective. "We have newer ways of detecting premature atherosclerosis," says Harold. The new methods allow doctors to see the plaque that forms on blood vessel walls when fat, cholesterol, and other cellular debris build up. However, whether these techniques will improve treatment is unclear.
Repairing damaged heart tissue after a heart attack remains a challenge. Advances in stem cell research may change that. In one study, published in the November 2011 issue of The Lancet, researchers harvested stem cells from the hearts of people with heart failure, cultivated them in a laboratory, and then injected them back into the patients' hearts. Stem cell recipients increased their heart function by almost 10 percent, while a control group didn't improve at all. Stem cell therapies have yet to reach prime time, but according to Harold, "this is likely to be a promising methodology in the future."
|Take a moment to honor Limb Loss Awareness Month in April and decrease the risk of amputation—check your feet. The amputation rate in people with diabetes dropped 65 percent between 1996 and 2008, thanks to better care. Continue the improvement with your own sole searching.|
|> Visually inspect feet every day (using a mirror or the help of an assistant, if necessary) for cuts, sores, blisters, redness, or other problems.|
|> Wash feet every day in warm water and dry thoroughly.|
|> If feet are dry, apply lotion (but not between the toes).|
|> Always wear socks or stockings.|
|> Wear cushiony shoes with good support and fit.|
|> Trim toenails straight across weekly.|
|> Gently file corns or calluses with an emery board or pumice stone.|
|Seek the care of a podiatrist if you have lessened sensation or tingling or pain, poor circulation, or the inability to reach your feet.|
Another developing area, according to Harold, is surgery. There is a move toward making procedures as minimally invasive as possible. For example, there's now a way to repair a heart valve without open-heart surgery; the valve is replaced through an incision in the groin. The focus on making fewer cuts may be particularly important for people with diabetes, who are at a heightened risk of infections after surgery.
Foremost in many doctors' minds is the upcoming revolution of personalized medicine. It's now possible to sequence a person's genome, a complete genetic blueprint, in just a day and for about $1,000. Doctors could use this information to both predict disease and come up with individualized treatments. "As we go into the future, we'll probably be able to figure out, based on a person's genetic profile, what drugs they are likely to respond to," says Harold. Even now, researchers know that clopidogrel (Plavix), a common anticoagulant, works best in people with a particular gene.
Multiple studies have shown that maintaining blood glucose and blood pressure control can protect the eyes from diabetic retinopathy, damage to the retina. Long-term and uncontrolled diabetes can cause retinopathy, which may not have any obvious symptoms until it degenerates into vision-threatening proliferative retinopathy or macular edema. This is why the American Diabetes Association (ADA) recommends annual dilated eye exams to catch retinopathy early.
Proliferative retinopathy is actually triggered by the eyes' attempts to heal themselves after diabetes does damage. "They grow new blood vessels to try to get around blockages," says Stephen Schwartz, MD, of the Bascom Palmer Eye Institute in Naples, Fla. The problem is that these new blood vessels are leaky and weak. "It's extraordinarily dangerous to have unchecked blood vessel growth," he says. Macular edema, swelling in the center of the eye that compromises fine-detail vision, is less well understood but may also be related to blood vessel growth and leakage.
The current gold-standard treatment for vision-threatening retinopathy is photocoagulation, in which a laser is used to cauterize blood vessels in the eye. The procedure lowers the risk of severe vision loss by proliferative retinopathy from 16 to 6 percent and by macular edema from 20 to 8 percent. While the benefits of photocoagulation are impressive, researchers are working to develop pharmaceutical treatments for retinopathy, which could preserve more eye function.
Several drugs in development block the action of a protein called vascular endothelial growth factor (VEGF), which stimulates the growth of new blood vessels. The theory is that VEGF inhibitors can arrest vision-destroying blood vessel growth. It turns out that injecting the inexpensive cancer drug bevacizumab (Avastin)—a VEGF inhibitor that starves tumors by cutting off their blood vessel supply—directly into the eyes of people with retinopathy "is occasionally very helpful," says Schwartz, but it doesn't usually work for very long. Other VEGF inhibitors are being developed. Studies suggest this class of drugs may improve vision, not just stabilize it as lasers do.
There's evidence that steroid injections may also combat diabetic eye disease, though their side effects, glaucoma and cataracts, have given the Food and Drug Administration (FDA) pause. The agency recently failed to approve a treatment for macular edema, Iluvien, a tiny implantable device that continuously delivers steroids (fluocinolone acetonide) into the eye. As researchers learn more about the biological processes behind diabetic retinopathy, they may develop better treatments, including oral medications.
As with retinopathy, the keys to keeping the kidneys healthy are optimizing blood glucose and blood pressure levels. Kidney disease, also called nephropathy, affects between 20 and 40 percent of people with diabetes. Nephropathy is the No. 1 cause of end stage renal disease, when the kidneys can no longer adequately clean the blood and must be treated with dialysis or a kidney transplant.
The ADA recommends that people with diabetes get annual kidney function tests. If kidney problems are detected, treatment may include a special diet as well as specific types of blood pressure medications known as ACE inhibitors and ARBs. "Both have shown benefits in reducing the progression of kidney disease and end stage renal disease," says William Keane, MD, a kidney disease expert in Placida, Fla. Their benefits are greater than what would be expected if the medications worked solely by lowering blood pressure;
the drugs may improve kidney health via an independent mechanism.
Advances in genetics also offer hope. "That's what the next wave will most likely be in the diabetic population," says Keane, pointing to evidence that suggests that certain genes can predict how well a patient will fare on a particular medication. Genes may also help identify those at greatest risk for kidney disease.
Two nephropathy drugs in trial are bardoxolone methyl and pyridoxamine dihydrochloride (Pydorin), which tweak the inflammation and oxidation pathways in the body that are thought to contribute to kidney disease. Both drugs are in phase III clinical trials, the stage right before submission of an approval request to the FDA.
Diabetic neuropathy can affect almost any part of the body, causing foot pain and tingling, and organ dysfunction, such as to the stomach (gastroparesis) and bladder (slow and/or incomplete emptying). There is a wide variety of pain treatment options, including antidepressants such as duloxetine (Cymbalta) and the antiseizure medications gabapentin (Neurontin) and pregabalin (Lyrica). However, there isn't yet an effective way to repair damaged nerves. "They are Band-Aids," says Aaron Vinik, MD, PhD, FCP, MACP, a professor at Eastern Virginia Medical School. "Ultimately, these drugs relieve pain not by fixing the nerves but by helping the brain deal with the pain."
Researchers are actively pursuing several potential nerve-healing medications not yet approved to treat neuropathy. Vinik also says that topiramate (Topamax), an antiepilepsy medication, "helps nerves in the skin regrow." A 2010 study showed that topiramate caused nerves in the legs and arms of people with type 2 diabetes to become longer and thicker.
Further afield, there's evidence that stem cell transplants can stimulate nerve growth, at least in rodents. Other research takes into account that people with neuropathy are deficient in certain nerve growth factors, proteins that maintain nerve cells. So a viable treatment strategy may involve replacing the missing growth factors. One factor that helps nerves grow is VEGF, the same substance that is bad for the diabetic eye. "It gets really tricky," says Vinik, because any treatment for a diabetic complication must benefit the whole person, not just one organ. But he has hope, saying, "I'm looking forward to a lot of things."