Initial Combination Therapy for Type 2 Diabetes: Is It Ready for Prime Time?

Cancer, HIV, tuberculosis and asthma are complex diseases that are routinely, and immediately upon diagnosis, treated with medication cocktails. Diabetes is complex, too, so clinicians should strongly consider a combination therapy approach for this disease, according to Bernard Zinman, a clinician-scientist at Mount Sinai Hospital in Toronto, Ontario, Canada.

Zinman borrowed from a point made in a journal article about how cellular pathways operate more like webs than like superhighways – meaning there are multiple routes that could be activated in response to inhibition of one pathway.

“If you get blocked one way going to Cleveland from Columbus, there are other ways to get there. The same is true in cellular pathways,” Zinman told attendees at the 2012 Global Diabetes Summit hosted by Ohio State’s Diabetes Research Center at Wexner Medical Center.

That article was pointing to the need for combination therapies for tumors and infectious diseases. “I believe the same principles apply to metabolic pathways and the use of pharmacological interventions,” he said, adding that there are a lot of pathways that lead to excess blood glucose and that the disease is progressive, getting worse over time as beta cells disappear.

This being the case, he said, why wait? Why “treat to failure,” as is the current standard of care for new diabetes cases?

Zinman published a 2011 article in the American Journal of Medicine detailing his rationale for the cocktail approach. His reasoning is that starting with combination therapy could: more rapidly lower hemoglobin A1c, a measure of blood glucose levels in the previous two to three months; avoid clinical inertia associated with the current stepwise approach to therapy; potentially improve beta cell function; set off multiple mechanisms of action that work well together; and allow for less than maximal doses, which could reduce side effects.

“We should start with combination therapy right from the get-go,” he said, also acknowledging, “It’s a major paradigm shift.”

Studies of combination therapies for diabetes have produced mixed results, and often show quick improvements in health measures that disappear over time. Acknowledging that the best evidence doesn’t yet exist to support his argument in favor of early combination treatments, Zinman said the most effective study would be a randomized clinical trial of monotherapy with the existing stepwise approach compared to initial combination therapy.

Current guidelines tend to recommend this stepwise approach, meaning that they recommend clinicians begin treatment with lifestyle interventions and a single drug to combat hyperglycemia. The addition of new therapies is typically recommended when A1c levels reach 9 – though the normal A1c level is 5.6 and 7 or above triggers a diabetes diagnosis. That A1c threshold is too high in Zinman’s estimation.

“Combination therapies with complementary mechanisms of action should be used early in the disease process. The earlier we achieve the target, the better off patients will be,” he concluded.

-Emily Caldwell

It’s ‘All Hands on Deck’ or Bust in National Diabetes Prevention Effort

The staggering numbers associated with Type 2 diabetes in the United States are enough to get any health professional down: 26 million currently diagnosed, 79 million with high enough blood sugar to be at highest risk for the disease.

If the trajectory of new diagnoses doesn’t change, says Ann Albright, director of the Division of Diabetes Translation for the Centers for Disease Control and Prevention (and Ohio State alumna), experts predict that one in three Americans will have diabetes by 2050.

“That is not sustainable,” Albright told attendees at the 2012 Global Diabetes Summit hosted by Ohio State’s Diabetes Research Center at Wexner Medical Center. “If we think prevention is difficult now, we ain’t seen nothing yet if we don’t get it together.”

But one intervention does not fit all at risk for diabetes, she noted, referring repeatedly to a “risk continuum.” People at low or moderate risk for diabetes cannot be cast aside in prevention efforts, but they are not the focus of the most ambitious prevention effort that the CDC is responsible for implementing.

The Diabetes Prevention Program (DPP) trial was an important milestone in national prevention efforts.

“It was vital for us to know whether or not we can say that you can prevent Type 2 diabetes in high-risk people,” Albright said. The trial showed that a lifestyle intervention aimed at dietary changes and increased physical activity was more effective than medicine at delaying or preventing high-risk individuals from developing diabetes.

As experts work to translate the program to communities in which high-risk people live, they note that one element of the DPP cannot practically be scaled to a national level: the one-on-one counseling each participant experienced.

Instead, the intervention now is offered in group settings, and an analysis of 28 studies of the effectiveness of group counseling suggested that average weight loss among participants was 4 percent – a bit shy of the goal of 5-7 percent weight loss.

An interesting finding: The weight loss was similar no matter which kind of leader hosted the counseling – a health professional or a lay educator. And this is why it’s an “all-hands-on-deck” situation, Albright said.

“If we build this on the backs of health professionals, we’ll never get where we need to go.”

The Affordable Care Act of 2010 authorized the CDC to lead a national DPP, “but this is not a CDC program. This belongs to the US and around the world,” she said. CDC is responsible for providing organizing infrastructure so a national DPP can be implemented in the United States.

Elements of that infrastructure include training to increase the work force; assuring quality; delivering the program at identified intervention sites; and marketing to increase referrals so the program is put to use on the scale required.

Participant engagement is vital, and the culture needs to shift so that community-based programs are “the thing to do, the place to be for diabetes prevention,” she said.

So far, the national program has served or is serving 9,000 people and is being run by more than 1,000 lifestyle coaches serving citizens in this country. Early data suggest weight loss achievement is about 4.9 percent, and that goes up to 5.1 percent among programs that have been running the longest. Retention is best after participants get through the first four sessions.

Planners are heartened by the results, but Albright warned that health gains being made in people currently diagnosed with diabetes are being overtaken by new cases, driving home now critical prevention of diabetes will be to the country’s economic and public health future.

“If we don’t do this,” she said, “one in three, one in three, one in three.”

-Emily Caldwell

National Research Battling Diabetes On Multiple Fronts

Federally funding basic and clinical research isn’t enough to stem the tide of Type 2 diabetes, says Griffin Rodgers, director of the National Institute of Diabetes and Digestive and Kidney Diseases. The federal government also must – and does – support efforts to get the results into public hands.

Speaking at the 2012 Global Diabetes Summit hosted by the Ohio State’s Diabetes Research Center at Wexner Medical Center, Rodgers outlined the research efforts of the federal agency responsible for diabetes as well as numerous related conditions, including kidney disease and obesity.

Because of those multiple areas of research, Rodgers said the agency’s approach is integrated, recognizing that in the United States, Type 2 diabetes is the leading cause of kidney disease, which can have an amplifying effect on cardiovascular complications.

“These diseases are common, costly and consequential,” he said.

Prevention of diabetes is a significant national effort. While about 26 million Americans have diabetes, 79 million have prediabetes – meaning their blood sugar is higher than normal but not high enough to trigger the diabetes diagnosis. They are considered at highest risk for developing diabetes.

The decade-old Diabetes Prevention trial showed that a lifestyle intervention emphasizing dietary changes and 150 minutes of physical activity per week was highly effective at delaying or preventing the onset of diabetes in high-risk individuals compared to a drug, metformin, or no intervention at all. The lifestyle intervention showed a 58 percent reduction in diabetes onset, compared to a 31 percent reduction for those on metformin. A follow-up showed that the results can be sustained in the long term. Among participants who were 65 or older, the reduction was 71 percent.

Women who develop gestational diabetes during pregnancy are also considered a high-risk group under study for the most effective interventions. Research suggests that children born to these women are at higher risk, as well, for developing Type 2 diabetes.

In addition, children are being watched closely as experts grow increasingly concerned about weight issues in youths. Researchers are seeing an increase in the prevalence of Type 2 diabetes in the pediatric population, Rodgers noted, which indicates that the need for prevention interventions must start earlier in life. A middle-school-based program helped children lower weight, but not any more than could be attributed to chance.

“Not only does one have to intervene in schools, but also in other settings,” Rodgers said.

Perhaps the biggest challenge is engaging potential intervention participants – which is why sharing information about research results is so vital.

“Fundamentally, if one is funding studies that develop the acquisition of knowledge and subsequently transformation of that data into knowledge that can affect patients, if one doesn’t also invest in dissemination, one is in a sense leaving at the table discoveries as well as efficiencies,” he said. “Not only is it important to fund clinical research, but also the dissemination of information to individuals so that we might make a substantial public health impact.”

-Emily Caldwell

Evidenced-based, Personalized, and Lifestyle Approaches to Diabetes

The following highlights some of the sessions at the 2012 Global Diabetes Summit, hosted by Ohio State’s Diabetes Research Center at Wexner Medical Center.

Look AHEAD — what were the takeaways?

We have had much pharmaceutical successes in working towards a cure for diabetes — every year or two we have one or two new drugs for treatment. But researchers hypothesized intensive lifestyle interventions might be the key for the management of diabetes specifically for preventing cardiovascular disease.

Samuel Dagogo-Jack, MD, DM, FRCP, discussed the recent study which sought to prove just that, called “Look AHEAD. ” This trial implimented lifestyle-intervention programs which were focused on helping patients with Type 2 diabetes lose weight.

While there were many benefits, the study did not show that weight loss lowers heart disease risk in type 2 diabetes management as predicted, which examined this topic for 11 years — the longest diabetes study that looked specifically at weight management to help prevent cardiovascular disease in patients with Type 2 diabetes.

What they did find was improvements in glycemic control, blood pressure, HDL cholestorol (or good cholestrol), sleep apnea, and many other health benefits by participating in a management program.

Dagogo-Jack says that interventions may have started too late or that it ended too early. In the future, they also want to consider how statin use affected the weight management and other risk-factors which may not have been considered. Dagogo-Jack  says the jury is still out and the importance of weight loss should not be dismissed. Stay tuned for additional data and in the meantime, “keep your health in check.”

Lifestyle Intervention Changes in Arab-Americans

Linda Jaber, PharmaD, presented on lifestyle changes which effectively helped Arab-Americas in her study with weight loss/management which is a key risk factor for Type 2 Diabetes. The educational intervention in an Arab-American population focused on educating around lifestyle intervention that was cultural sensitive and scalabile.

The education was group-delivered, family-centered and the strategies offered were culturally-specific and sensitive to the needs of the population. Another successful strategy was involving participants to act as coaches by sharing success stories with the group. Since a majority of the participants were Muslim, the education had specific strategies for fasting during Ramadan.

Many people met a 7 percent weight loss goal set by the study. By encouraging participants to reduce fat intake, they were able to reduce calories with simple modification of ethnic foods and portion control for participants. They also found that family support was a significant predictor of weight-loss support, 70 percent of people who achieved the weight-loss goal had family support.

In summary, a culturally-appropriate, group lifestyle intervention implemented in a community setting was feasible and effective in helping to prevent diabetes risk factors in Arab-American patients.

Incorporate Healthy Meals

Thanks to @OSUWexMed’s nutrition services for providing these tips.
Whether you already live a healthy lifestyle or are trying to be healthier, reminders about how you can improve your overall health and wellness are helpful.
Planning ahead for meals can help you meet nutrition goals and not rely on “fast food” options at the end of a long day. When planning menus, try to ensure that five of the 14 (lunch and dinner) meals per week are “healthy.” By healthy this means meals 600 calories or less with no more than 1,000 milligrams of sodium.
If your usual meal averages 800-1,000 calories, you can save 4,000-8,000 calories over a month by doing the above, which equals to one to two pounds.
A healthy and balanced meal should include a starch, vegetables, protein, fruit and dairy. If this seems like too much food for one meal, try to get your daily dairy or fruit in as a snack. Here are examples of healthy meals that are all about 600 calories:
  • Grilled salmon – 3- to 4-ounce grilled salmon, a small baked sweet potato, 5 sprigs of asparagus, 1 cup of  1% milk, and a small apple.
  • Chicken sandwich – 2 slices of whole wheat bread, 3 ounces of baked chicken, 1 tablespoon of light mayo, lettuce, onion, tomato, 4 ounces of lite yogurt, 1 cup of strawberries.
  • Turkey cheese burger – 1 whole grain hamburger bun, 3- to 4-ounce turkey patty, lettuce, onion, tomato, a slice of low-fat cheese, and a small banana.
  • Spaghetti – 1 cup of whole wheat pasta, 3 ounces of ground turkey, 1/2 cup of spaghetti sauce, small side salad with some shredded cheese and light dressing, 3/4 cup of cantaloupe.

Okay – now you tell us. What are you favorite healthy meals?

Ohio State’s Wexner Medical Center a Hub for Diabetes Experts Around the World

The Second Global Diabetes Summit will be held Nov. 14 – 16 at the Ohio Union presented by Ohio State’s Diabetes Research Center. The summit theme is, “New Horizons in Diabetes: Genetic to Personalized Health Care,” and will be led by a variety of diabetes physicians, researchers and advocates regarding the latest research on prevention, diabetes technology, cellular and tissue therapies, islet cell therapy, pharmacology, pregnancy and cardiovascular disease and other relevant topics.  Notable speakers include:

  • Ann Albright, PhD, RD – Director of Diabetes Translation, Centers for Disease Control and Prevention who will discuss the research behind The U.S. National Diabetes Prevention Program
  • Jean–Claude Mbanya, MD, PhD, FRCP –  President, International Diabetes Federation will focus on the global pandemic of obesity and diabetes in adults, include epidemiological solutions and challenges, and the global economic impact of diabetes
  • Vivian Fonseca, MD, FRCP – President, American Diabetes Association, who will discuss future oral anti-diabetic medications
  • Griffin Rodgers, MD, MBA, MACP –  Director, The National Institute of Diabetes and Digestive and Kidney Diseases will present on genomics and diabetes

To view a complete agenda and register, visit http://go.osu.edu/diabetessummit.

In addition, on the final day of the summit, Saturday, November 17, a Community Event themed “Focus on Health and Wellness: Life Choices”, will be held at Veterans Memorial Auditorium located at 300 W. Broad St. This event will give community members the opportunity to ask one-on-one questions, view exercise and cooking demonstrations, experience hands on workshops and listen to panel discussions featuring diabetes experts.

Celebrity guests includeNBA Hall of Fame legend and vice president of Basketball for Atlanta Hawks, Dominique Wilkins; and Oscar Joyner, president and Chief Operating Officer of REACH Media, Inc. and son of Tom Joyner, who will speak on their personal battles with diabetes and successful management of this disease.

The community event, is FREE and open to the public, but pre-registration is required. Lunch will be served to all registered attendees.

To register for the community event, visit http://go.osu.edu/GDSCommunity or call 614-273-1400.

If you would like to donate your time as a clinical or non-clinical volunteer for the Global Diabetes Summit, contact Dorian Harriston, senior marketing manager, at Dorian.Harriston@osumc.edu.

Ohio State’s P4 Medicine Update, Oct. 23, 2012: http://conta.cc/X8bd05

Captured by Sherri Kirk