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Treating patients with diabetes means keeping up with a vast body of ever-increasing research. Attendees at the American Diabetes Association's 52nd Annual Advanced Postgraduate Course in New York City in February had an opportunity to bone up on the latest findings on drug therapy, diet comparisons, exercise motivation, and more.
COMBINATION ORAL THERAPY
When should patients with type 2 diabetes move from a single oral agent (monotherapy) to combination oral therapy?
As soon as it's needed to control a patient's blood glucose and before beta-cells fail, according to Janet B. McGill, MD, associate professor of medicine at Washington University School of Medicine in St. Louis. This becomes even more important when diabetes is diagnosed at a young age, allowing more time for retinopathy and other complications to develop.
Although oral agents are useful for controlling glucose excursions, in many cases one is not enough. Patients on a sulfonylurea or metformin alone for more than 20 months are likely to have a glycated hemoglobin (A1C) >8%, McGill says.
Backed by a variety of recent studies, McGill advises low treatment targets that reduce risks but require aggressive medical management. Ideally, she says, practitioners should aim for an A1C <6.5% (ADA recommends <7%), fasting glucose <110 mg/dl, and postprandial glucose <140 mg/dl. Combination therapy may become necessary to reach these targets.
McGill references a 2000 study comparing metformin-rosiglitazone therapy with metformin alone: A1C dropped an additional 1.2%, and fasting glucose levels decreased by 52.9 mg/dl with the combination.1 According to the researchers, "combination therapy with once-daily metformin-rosiglitazone improves glycemic control, insulin sensitivity, and beta-cell function more effectively than treatment with metformin alone."
Other drug combinations have shown similar benefits. In fact, several oral agents are available in combination tablets—including Avandamet (GlaxoSmithKline): rosiglitazone and metformin; Glucovance (Bristol-Myers Squibb): glyburide and metformin; and Metaglip (Bristol-Myers Squibb): glipizide and metformin. The combination tablets simplify patients' pill regimens and may increase adherence to treatment.
In addition, combining drugs can help reduce side effects for patients. Adding one drug and lowering the dose of another can alleviate weight gain, hypoglycemia risk, or gastrointestinal side effects, McGill says.
And there may be other advantages to combination therapy. Because the various classes of oral agents have different mechanisms and metabolic effects, addition of a second oral agent may yield rewards beyond improved glucose control. Thiazolidinediones (TZDs), for example, may reduce several cardiac risk factors and have been found to preserve beta-cell function.
Thus far, negative interactions between classes have not been an issue.
IMPROVEMENTS IN INSULIN
Combination therapy with insulin is another viable treatment option for patients with type 2 diabetes.
Steven V. Edelman, MD, professor of medicine at the University of California, San Diego, gives the following advice for starting insulin with patients:
Edelman says the gold standard for subcutaneous injection treatment is basal-bolus therapy made up of glargine (Lantus, Sanofi-Aventis)—the insulin analog that lasts up to 24 hours—at night combined with a fast-acting analog before meals.
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Pumps are the next step, he says. "I use the same criteria for pumps with type 2 diabetes as with type 1."
One hope for better treatment compliance by patients is inhaled insulin, which is already being used in Europe. Working much like a fast-acting insulin, an inhaled treatment is easier to use than an injectable and causes less weight gain, according to Edelman.
THE RIGHT DOSE OF EXERCISE
The key to preventing and controlling diabetes is to focus on getting patients' weight under control and encouraging exercise, according to John M. Jakicic, PhD, director of the Physical Activity and Weight Management Research Center at the University of Pittsburgh. In his presentation, "Physical Activity and Metabolic Control," Jakicic gave practitioners an idea of what's realistic for persuading sedentary, obese patients to increase their physical activity.
Motivating patients to both exercise and lose weight will be more effective than focusing on exercise alone since patients will be eager to see an immediate improvement, Jakicic advises. Over the long term, however, exercise is more important than weight management in getting metabolic parameters to change.
Encouraging patients to build more activity into their daily routine (such as using stairs instead of elevators) in addition to engaging in moderate-to-vigorous aerobic exercise is the message to convey, says Jakicic, who is principal investigator for the ongoing Active LIFE (Lifestyle Interventions for Exercise) study, funded by the National Institutes of Health (NIH). "Resistance exercise has been oversold for weight loss and... doesn't really change fat-free mass or increase the resting metabolic rate."
Moderately intense activity will result in improved glucose control; for weight loss, patients should be encouraged to increase the volume of exercise, not the intensity, Jakicic advises. Exercising 60 minutes a day, 5 days a week at moderate intensity will benefit both weight loss and glucose control. Patients who are unable to exercise for an hour due to physical limitations can break up the time into 10-minute increments.
DIET: CARBOHYDRATE COUNTERPOINTS
"Dr. [Robert] Atkins was a pioneer or villain, depending on your perspective," says Gary D. Foster, PhD, of the inventor of the famed low-carbohydrate diet. Foster, of the University of Pennsylvania, Philadelphia, urged practitioners to take a more measured look at the controversial diet.
During the postgraduate course, Foster summarized evidence from studies comparing low-carb diets with low-calorie diets and noted that although subjects lost more weight on low-carb diets at 6 months, there was no difference at 12 months.
Similar results were found in participants' blood glucose levels. Data showed a greater reduction with the low-carb diet at 6 months, which evened out by 12 months. Participants on both diets showed improved insulin sensitivity.
What about lipids? In studies so far, low-carb diets do not appear to have a harmful effect on total cholesterol or LDL cholesterol. In fact, HDL cholesterol and triglycerides improved with low-carb diets, according to Foster.
Mild adverse events for people on low-carb diets include constipation, headache, halitosis, muscle cramps, diarrhea, and general weakness.
Why the initial greater weight loss with low-carbohydrate diets? When people count carbohydrates, they eat fewer calories, Foster says. It's tough to eat fewer carbohydrates without eating more protein, which has a satiating effect.
The simplicity of counting carbs may be a strong selling point for the popular diets, in contrast with other plans that involve what Foster calls "the mental gymnastics we put patients through deciding what to eat for lunch."
Safety and long-term adherence and efficacy are still unknowns, however.
The NIH is funding an ongoing, 5-year study of 360 patients comparing
low-calorie and low-carbohydrate diets. Multiple outcomes, including effect on
kidney function, will be measured. 
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