16th World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease :

Diabetes Prevention Possible If All Available Clinical Tools Employed

With W. Timothy Garvey, MD, and J. Michael Gonzalez-Campoy, MD, PhD

As diabetes prevalence rises, so does the financial burden on our patients and the healthcare system, making it clear that more assertive measures are needed, 1 said W. Timothy Garvey, MD, Butterworth Professor of Nutritional Sciences and director of the UAB Diabetes Research Center at the University of Alabama at Birmingham at the 16th World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease in Los Angeles, California, particularly in the those most at risk for type 2 diabetes (T2D).


 

For that assertion to take hold, a major change in mindset must occur among both physicians and patients, said Dr. Garvey. "Right now, we wait until people develop type 2 diabetes, and then we decide to treat but if we don't start addressing patients proactively and earlier, we are going to be in deep difficulty as time goes on. And we know how to do this."

Are You Assessing Your Patients for Diabetes Risk Early Enough?

After presenting some sobering statistics about the prevalence of prediabetes, T2D, and obesity, Dr. Garvey went on to give concrete suggestions to advance the current clinical approach to care, key points are summarized below.

But first—some perspective. In 1958, barely 1% of the US population had a diagnosis of diabetes, Dr. Garvey said, while more than 7% of the adults had been diagnosed with T2D in 2015,according to data compiled by the Centers for Disease Control and Prevention more than 7%. Paralleling the rise in diabetes is an equally distressing rise in the rates of obesity—In 2008, age-standardized prevalence of obesity in US adults was estimated at 33.7%, yet less than 10 years later (2016), the prevalence rose to 39.6%.3

Anticipation is key, Dr. Garvey said, followed by action, referring to both arresting prediabetes and focusing on necessary weight loss.1

Results from the often cited Diabetes Prevention Program provide ample proof that we have the necessary tools to address T2D now,4 he said. When the Diabetes Prevention Program researchers compared three groups: those receiving a placebo, people who were given metformin, and another group who received lifestyle intervention, the risk of the patients progressing to diabetes over four years of follow-up was 31% lower for those taking metformin and 58% less among those who changed their lifestyle.4

Getting Ahead By Focusing on P-R-E-V-E-N-T-I-O-N

While it may be obvious, Dr. Garvey urged clinicians to redouble their efforts to guide patients who are overweight and obese to achieve even a little weight loss. “After all, promoting just a 10% weight loss is sufficient to prevent 80% of the anticipated complications of diabetes,” he said.

What’s more heartening is that achieving a 10% reduction in weight is achievable by lifestyle changes alone,1 he said. “However, the pool of people that must be reached to meet the risk reduction needed in at-risk patients is about 40% of the population," he said. Needless to say, many of these individuals will need help in meeting that weight loss goal and may be best served with medical or surgical interventions, he told EndocrineWeb.

Among the medical and surgical interventions that can delay or prevent type 2 diabetes are antihyperglycemic agents, weight loss medications, and for those with morbid obesity, strong evidence points to bariatric surgery.

A look at the benefits achieved by the range of therapeutic options include:1

  •  Metformin reduced the risk by 31% over 2.8 years of follow up
  • Acarbose reduced the risk by 25% over 3.3 years of follow up
  •  Pioglitazone reduced the risk by 72% over 2.4 years of follow up
  • Rosiglitazone reduced the risk by 60% over 3 years of follow up
  • Orlistat reduced the risk by 37% over 4 years of follow up
  • Phentermine/topiramate reduced the risk by 79% over 2 years
  • Liraglutide 3 mg/day reduced the risk by 80% over 3 years
  • Bariatric surgery reduced the risk by 75% over 10 years

Taking characteristics of the metabolic syndrome into account, each of which has an opportunity for preventive effect on diabetes risk, as well as patient’s sex, race, and level of insulin resistance, Dr. Garvey together with Fangjian Guo, MD, PhD, assistant professor at the University of Texas Medical Brank in Galveston, developed an algorithm— Cardiometabolic Disease Staging (CMDS)—to guide clinicians in effectively assess which patients may be most responsive to the array of therapeutics available.5,6

Matching Therapeutic Interventions to the Right Patients

While the traditional approach suggests a body mass index (BMI)-centered approach, Dr. Garvey made a strong case for evaluating patients for responsiveness to a particular modality by considering the patient’s cumulative risk factors.1

“What must be done,” he told EndocrineWeb, “is for clinicians to apply the CMDS risk stratification with each patient to determine the most effective management strategy. CMDS represents a predictive score for type 2 diabetes independent of BMI as demonstrated in the Coronary Artery Risk Development in Young Adults (CARDIA) study,"7 said Dr. Garvey. "The same paradigm can predict cardiovascular mortality and all-cause mortality."

There are five stages in the CMDS scoring system:5

  •  0 indicates patients with “healthy obesity,” for patients with an elevated BMI but no cardiometabolic risk factors.
  • Stage 1 reflects patients with an increased waist circumference, high blood pressure, high triglycerides or low HDL-cholesterol.
  • Stage 2 confirms patients with metabolic syndrome alone or signs of prediabetes.
  • Stage 3 represents a diagnosis of both metabolic syndrome and prediabetes.
  • Stage 4 indicates end-state cardiometabolic disease in someone with type 2 diabetes and/or cardiovascular disease.

In the CARDIA study,7 after adjusting for BMI, the hazard ratio for those at stage 1 as compared to the metabolically healthy, so-called Healthy Obese reference group was 2.38 (1.26-4.50). At stage 2, the HR nearly tripled to 6.10 (3.14-11.9) and at stage 3 it rose to 11.7 (5.69-24.2).

The wide array of medications available to prevent diabetes should be used.

Giving more aggressive therapy—medication, antihyperglycemic agents, bariatric surgery--to those at higher risk makes sense when you consider that 29 million people in the US have diabetes, and 86% of them receive some form of anti-diabetes medication; yet only 2% of the approximately 92 million people who are obese currently receive any anti-obesity therapy.8

"Of course, some patients will need medical or surgical therapy in addition to lifestyle intervention," Dr. Garvey agreed. For that, he refers physicians to the AACE obesity algorithm "for appropriate use of medications or surgical referral,9 and often patients do better when medications are prescribed concomitantly when severe complications such as those associated with cardiometabolic disease, are present. For patients with a BMI of 27 kg/m2 or higher, individualizing medical therapy based on factors such as the clinical profile, and choosing from orlistat, liraglutide, naltrexone/bupropion, or other treatments, whereas in patients with a BMI of 35 kg/m2 or higher, surgical treatment may be advised in addition to lifestyle changes to produce sufficient weight loss."
 

"When to prescribe drugs or surgery in addition to weight management—that's the wrong question," said Michael Gonzalez-Campoy, MD, PhD, FACE, medical director and CEO of the Minnesota Center for Obesity, Metabolism, and Endocrinology in Evans, "Rather, asking how soon these other options should be presented to patients is more appropriate." The goal is to help patients achieve at least a 10% weight loss, 'regardless of how you get there,' he told EndocrineWeb. "So you do not switch to meds or surgery [after lifestyle changes] since for the vast majority of patients we already know that lifestyle changes will not be enough to meet the clinical endpoint of reducing diabetes and CVD risks.''

With today's status quo, he asked: "Are we really engaged in evidence-based medical care?" He responded, suggesting that patients will fair much better if we were to employ the full complement of treatment options, reiterating that physicians have the tools to prevent diabetes and lessen the risks cardiometabolic disease and only need to use them.

"We can stratify [risk] and use that data to treat higher-risk individuals," so it’s time for all of us to act in a more concerted manner to prevent diabetes from developing in our patients from here on in, he said.

Dr. Garvey is on the advisory board for Novo Nordisk, Merck, BOYDSense, Elevian, Gilead, Amgen, and Sanofi. Dr. Gonzalez-Campoy has no conflicts.

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