By: Daniel Trecroci
Diabetes professionals from all over the world descended on San Diego, California, this past June for the 65th Annual American Diabetes Association Scientific Sessions. Some brought with them the latest drugs, meters, pumps and software. Others came armed with research.
Each year, the Scientific Sessions gives the ‘independent’ as well as the pharmaceutical-sponsored researcher the opportunity to showcase his or her hypotheses, study designs, results and conclusions. We share with you here a sampling of that research.
Dual-Action Muraglitazar—Is It the Next Big Type 2 Med?
Every year at the ADA Scientific Sessions, new research is presentedthat puts a drug or technology “on the radar” and suggests it is the “next big thing.” This year, that drug was muraglitazar, a novel dual PPAR alpha/gamma agonist, a member of the new class of type 2oral medications called the glitazars with action to improve bothinsulin resistance and diabetic lipid disorders.
Researchers say that long-term (two-year) monotherapy withmuraglitazar at doses of 1.5 mg and 5 mg effectively reducedtriglycerides while also reducing non-HDL-C (total cholesterol minusHDL cholesterol) and increasing HDL cholesterol in participants withtype 2 diabetes. This study focused on the lipid-regulating effects ofmuraglitazar rather than the drug’s action potential in decreasinginsulin resistance and improving blood glucose control in type 2diabetes.
In this multicenter study, 985 patients with type 2 were givendoses of either 1 mg or 5 mg of muraglitazar or 15 mg of Actos(pioglitazone, a PPAR gamma agonist). At the study’s outset, allparticipants had inadequate blood glucose control on a regimen of justdiet and exercise alone.
For participants on 5-mg doses of muraglitazar, there was a 22.4percent reduction in triglycerides, 28.9 percent increase in HDL cholesterol and an 11.3 percent decrease in non-HDL cholesterol.Participants on 15 mg of Actos had a 12.3 percent reductionin triglycerides, a 17.7 percent increase in HDL cholesterol andan 8.8 percent decrease in non-HDL cholesterol. Muraglitazarwas generally well tolerated and no safety concerns were observed.
Clinical adviser’s note: Thecurrent class of type 2 oral meds known as “glitazones” that includes Actos (pioglitazone) and Avandia (rosiglitazone) are PPAR gammaagonists, which primarily improve insulin sensitivity but also havesome lipid-regulating action. Some studies indicate glitazones alsohave anti-inflammatory action and possibly have the potential toprevent the loss of beta cell insulin-producing action in type 2s.
Pargluva (muraglitazar) will probably be the first of the newglitazar class of medications with dual PPAR gamma and alpha actionto be approved by the FDA to help control both glucose and cholesterollevels in type 2 diabetes. Pargluva is a product of Bristol-Meyers, Squibband Merck.
At the ADA Scientific Sessions, there was an oral presentation of aclinical study of another promising glitazar called Galida (tesaglitazar)in development by AstraZeneca.
Both Pargluva and Galida show possible side effects of edema (fluidretention) and some degree of weight gain as is seen with the glitazonesActos and Avandia.
Lantus May Be Better Twice Daily for Type 1s
Although its indication is as a once-daily basal insulin,researchers suggest that twice-daily administration of Lantus(insulin glargine) with a mealtime bolus of NovoLog (insulin aspart)may improve blood glucose although nighttime blood glucoseconcentration was higher with the twice-daily regimen.
In an eight-week study, 20 type 1s were randomized to once-dailyLantus injection at dinnertime or twice-daily Lantus injection atbreakfast and dinnertime. Mealtime insulin was NovoLog.
Post-breakfast, post-lunch and pre-dinner blood glucose levels werelower with twice-daily compared with once-daily Lantus.
Early Intensive Insulin Therapy May Improve Beta Cell Functionin Type 2s
Type 2s who utilize intensive insulin therapy at the outset of theirdiagnosis can significantly improve beta cell function and facilitatefurther long-term blood glucose control.
Sixteen newly diagnosed type 2 diabetic patients with A1Cs over8.5% were treated with multiple daily injections or twice-dailyinjections for an average of 11.3 weeks. Average insulin intake was0.5 units/kg/day.
A1C fell from an average of 10.1% to 6%. During the periods of intensiveinsulin therapy, body weight remained unchanged and there wereno critical hypoglycemic episodes.
Researchers suggest that if long-term controlled studies are performedto establish the mechanism and effectiveness, “intensive insulintherapy may [be] considered as [an] initial approach in new-onset type 2diabetes.”
Avandia/Metformin Combo Improves Kidney Function
Adding Avandia (rosiglitazone) to an oral medication regimen ofmetformin demonstrated beneficial effects on urinary albumin/creatinine ratio in people with type 2 with elevated microalbuminuria(protein in the urine).
Participants were randomized to the addition of 4 mg per day of Avandiaor 5 mg per day of glyburide for eight months. With the Avandia/metformin combo, urinary albumin/creatinine ratio decreased 22.8 percent compared to 7.1 percent in the glyburide/metformin group.
Diabetics Sweat Differently Than Nondiabetics
In a pilot study, researchers found that abnormalities in perspirationfunction in patients with diabetes are location-specific rather thangeneralized during isometric exercise.
Seven participants with type 2 were matched against a controlgroup. Before exercise, sweat level was lower in all areas in subjectswith diabetes. But during exercise, sweat was significantly higher in theforehead of subjects with diabetes than in the controls. It was the samein the chest and lower in the arms and legs.
Aspirin May Slow Development of Retinopathy
Nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin mayinhibit the development of early stages of diabetic retinopathy,according to researchers.
In a study on diabetic rats, 25 mg of buffered aspirin, 25 mg of salicylateor 150 mg of sulfasalazine was given in either food or water.
“Administration of each of these salicylate derivatives significantlyinhibited the diabetes-induced increase in retinal capillary celldeath and formation of acellular capillaries,” write the researchers
Fructose-Sweetened Beverages Make Things Worse for OverweightPeople
In overweight people who drink fructose-sweetened beverages,circulating insulin and leptin levels are lower and plasma triglyceridesare higher than when glucose-sweetened drinks are consumed.
Researchers speculate that this may lead to increased caloric intake andthereby contribute to further weight gain as well as atherosclerosis.
Insulin Resistance Peaks at Breakfast
Type 2s who are not treated with insulin have exaggerated plasmaglucose excursions for the first meal of the day despite increasedpancreatic beta cell secretory products. This promoted researchersin the United Kingdom to speculate that increased morning highblood glucose in the patient group may be primarily due to changesin insulin sensitivity rather than beta cell dysfunction.
Fish Oil Supplementation Benefits Obese Pediatric Patients on Low GI Diets
Inflammation markers decreased in obese pediatric patients who supplemented their low glycemic index (GI) diets with long-chainomega-3 fatty acids.
Researchers enrolled 30 overweight pediatric patients (10 to 18 yearsin age) in an intervention program that emphasized exercise and a lowglycemic load diet supplemented with fish oil. After six weeks, the fish-oil group saw a 19 percent decrease in the C-reactive proteininflammatory marker while the ratio of arachidonic acid toeicosapentaenoic acid decreased 73 percent.
Fiber Supplements Improve Metabolic Profile in Type 2s
Type 2s looking for an improvement in blood glucose levels and plasmalipid concentrations may want to consider upping their intake ofdietary fiber—particularly of the soluble variety.
Researchers measured the effects of supplementing a diet with the fiber drink BiosLife 2. Seventy-eight patients with an average age of 59were given 5 grams of soluble fiber in a drink two to three times daily 5to 10 minutes prior to a meal.
After 90 days, before-meal blood glucose levels decreased 9.8percent, while after-meal BGs decreased 14.7 percent. In addition,total cholesterol decreased 14.4 percent, and LDL (bad) cholesteroldecreased 28.7 percent. HDL (good) cholesterol increased 21.8 percentand A1C decreased by 0.9 percent points.
Chromium Supplementation May Improve Control
A small, randomized study of 27 type 2s, average age 59 years, treatedwith a sulfonylurea plus chromium picolinate or a sulfonylurea plusplacebo found that chromium supplementation improved insulinsensitivity and blood glucose control. In addition, chromiumimproved body-weight gain and visceral fat accumulation whencompared to the placebo group.
Type 1 Kids With Good Parental Communication Have Better Control
Researchers emphasize that parent-child communication regardingdiabetes care responsibility is important “to promote self-carebehaviors and prevent elements of care without clearly assignedresponsibility.”
Boston researchers assessed 42 adolescents, looking at measures ofproblem-solving ability, self-care behavior, delegation of diabetesresponsibility between parent and child and hypoglycemia frequency.
Adolescents with poor parental communication regardingresponsibility for diabetes care had lower problem-solving ability andtrends suggesting poorer adherence to self-care. Hypoglycemicepisodes, however, were lower in the group that had poor parentalcommunication, which the researchers attribute to “underlyingadolescent desire to avoid hypoglycemia in order to minimizeembarrassment.”