Metabolic syndrome: A key predictor of diabetes, CVD
The term “metabolic syndrome” has been used to describe a constellation of risk factors that predispose adults to develop diabetes, heart disease or both. These factors, many of which are linked to obesity, inactivity and unhealthy diet, appear to be emerging in younger patients.
Endocrine Today spoke with Peter W.F. Wilson, MD, professor of medicine in the division of cardiology at Emory University School of Medicine, professor of public health in the Rollins School of Public Health at Emory University, and director of epidemiology and genomic medicine at the Atlanta VA Medical Center, about how best to follow and manage patients with metabolic syndrome to avoid progression to disease.
How is metabolic syndrome defined?
Wilson: Metabolic syndrome, as a term, became popular in the 1990s, and it was part of several American and European clinical practice guidelines by about the turn of the century. Metabolic syndrome encompasses five core factors: abdominal girth (BMI is also used as a measure of adiposity), low HDL, high triglycerides, blood pressure that is elevated or being treated, and some sort of glucose abnormality. Different groups have defined these traits through different criteria. The criteria began to be modified after the initial papers were published. In Europe, clinicians always have paid a little more attention to the role of insulin, particularly in people who have moderately elevated, nondiabetic glucose levels but who may have higher insulin levels. The U.S. definition never became overly involved in insulin measurement.
Also, the factors cluster. The syndrome was defined as having three or more of those five factors, but each of these factors has a role, and some of them have an element of variability over time. Each of these factors is considered in terms of how it would increase risk for heart disease, which was one of the initial areas of interest, and also diabetes.
How useful of a concept is metabolic syndrome for health care providers?
Wilson: When the concept originated, physicians started to code for metabolic syndrome, but patients didn’t have a disease diagnosis. Let’s say a patient didn’t have hypertension or had fasting glucose in the nondiabetic range. In endocrinology, we have a term for that: impaired fasting glucose or prediabetes. But internal medicine physicians don’t necessarily pay a lot of attention to fasting glucose that’s not diabetic. So cardiovascular and metabolic scientists thought the concept of metabolic syndrome was going to be really useful, especially for primary care — a way to help non-endocrinologists move forward.
I always tell patients, if you imagine you have watercolors, and each of these factors is a light gray, the more of them you have, the darker it gets. They understand that.
What is the connection between metabolic syndrome and heart disease and diabetes?
Wilson: If you were to pick five factors to predict heart disease, the five factors of metabolic syndrome would not necessarily be the ones. Obesity is important, but is not a critical driver for a 40- to 60-year-old patient to develop heart disease. Also, metabolic syndrome does not address smoking, and smoking is really important for heart disease. And while metabolic syndrome indirectly includes some measure of HDL cholesterol, specifically low HDL, it doesn’t address LDL cholesterol. Those are big-ticket items, so these factors may not predict heart disease in nondiabetic patients very well.
Another point is that it may not be helpful to tell a diabetic patient whether they have metabolic syndrome or not. Generally, it’s sort of extra. Patients know indirectly that if they already have diabetes, they are at very high risk for developing heart disease. When we’re talking with diabetic patients, we often say, ‘Yes, you have diabetes, and you have these other things. You have metabolic syndrome.’ But for research purposes, we’re generally most interested in people with metabolic syndrome who do not have diabetes because they can progress to diabetes, heart disease or both.
What can prevent patients with metabolic syndrome from progressing to these diseases?
Wilson: We’ve had an extensive NIH trial called the Diabetes Prevention Program, the DPP. The researchers did glucose tolerance testing and evaluated three interventions in preventing type 2 diabetes in middle-aged adults. One intervention was lifestyle alone. The second was treatment with the first approved thiazolidinedione, troglitazone. The third arm was standard metformin. The lifestyle program included 16 sessions with trainers, nurses, physical activity counselors and dietitians. After several years of follow-up, there was a favorable effect compared with usual care. Patients in the lifestyle arm reduced their risk for developing diabetes by about 70%. Lifestyle was a big winner.
How did participants in the other intervention arms do?
Wilson: Troglitazone, unfortunately, had a signal of causing liver failure in some patients, and that was enough of a concern that the drug was pulled from the market. Using a TZD was revisited several years later with two other drugs — one was the DREAM trial, led by Hertzel Gerstein, MD, MSc, in Canada, and the other was ACT NOW, led by Ralph DeFronzo, MD. Trials with other TZDs have all generally been good, but they found that TZDs caused fluid accumulation. There’s a concern that, particularly if the person has a heart condition, that fluid accumulation may tip them into heart failure. So, there have been a variety of concerns about TZDs as a class of medicines.
In recent years, we have more and more pills to treat metabolic syndrome-type patients or those with frank diabetes. It’s a different landscape because we only had a few medicines back when the original DPP trial was being done.
The third study arm used metformin, which demonstrated about a 30% reduction in the development of diabetes. So, lifestyle is best, but metformin may also potentially prevent diabetes.
With the medicines, though, you’re just keeping the glucose down. Overall, we’re now winning the heart disease epidemic at all levels. We’re winning for prevention, we’re winning with medicines to prevent heart attacks, and we’re winning with medicines after heart attacks. But, still, we keep seeing more and more diabetes. The medicines are getting better at holding down glucose levels, but we aren’t preventing the development of diabetes very well.
What factors might predispose a patient to developing metabolic syndrome in the first place?
Wilson: Diet and lack of exercise play a significant role. We used to say type 2 diabetes was a disease of older people, and we don’t say that anymore. The disease is occurring in younger and younger people. It’s obesity, it’s the amount of adiposity, and it’s probably that metabolic syndrome burden that cause people to develop diabetes.
When we did analyses of the five factors of the metabolic syndrome, and we considered age as well, we found that age wasn’t very important. The 30- to 40-year-olds were developing diabetes because of the metabolic syndrome burden. It didn’t matter if patients were aged 35 to 55 years vs. 55 to 65 or 70 years and older.
It’s a different world in many ways. When I was in sixth grade to ninth grade, I used to play pickup sports with a basketball hoop and baseball with my friends in the yard — nothing organized, but we were active. I just don’t think that’s the way children are anymore. They come home from school, and they do something passive with a game system or with a computer. They’re not developing habits that are going to keep them moving. If you’re a young adult with a fair amount of obesity, you’ve already set yourself up for diabetes.
Do you think there should be an increased emphasis on lifestyle changes in young patients to prevent metabolic syndrome and diabetes?
Wilson: We encourage everyone to live a more active life, but how many patients actually do it? Once people do become diabetic, and they’re heavy, how many of them really work hard to decrease the obesity? They’ll take the medicines, but how many patients are willing to exercise?
The good news is that we've gotten much better at controlling blood pressure, glucose and lipids. Even though people are still getting diabetes, we have these good BP medications and insulin has become easier and easier to use compared with how much work it was 20 or 30 years ago. We’re doing quite well in preventing complications, if patients keep their appointments and follow instructions. But as far as the actual occurrence of diabetes, we’re losing the battle, and it’s not just the United States, we’re losing worldwide. – Compiled by Jennifer Byrne
For more information:
Peter W.F. Wilson, MD, can be reached at 1462 Clifton Road, Room 530, Atlanta, GA 30322.
Disclosure: Wilson reports no relevant financial disclosures.