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Metabolic syndrome: Key to diabetes, cardiovascular disease

POSTED 13 MARCH 2008


A talk with a biochemist/metabolist
In our effort to nail down the labyrinthine relationships among diabetes, metabolic syndrome and cardiovascular disease, we phoned Stephen Brietzke, an endocrinologist and diabetologist at the University of Missouri-Columbia (see #9 in the bibliography).

Q: Some people think metabolic syndrome is not a helpful term because doctors should already be treating each of its elements anyway. What do you think?
A: From a public-health standpoint,it's important not to lose the forest for the trees. Metabolic syndrome catches people with a family history ofdisease, who have coronary disease, are slightly overweight, have a blood pressure that is high-normal, slightly abnormal bloodchemistry,but aren't reallycandidates for specific drug therapies based on the individual numbers. We know that a healthier lifestyle, 30 to 60 minutes of physical activity on most days of the week, and a small weight reduction are associated with profound health benefits in metabolic syndrome, ifpeople can be motivated to make the changes.Graphic shows abdomen and deposits of fat that lie deep beneath the surface of the skin, among organs

Compounds made by visceral fat seem to play a major role in inflammation, diabetes and cardiovascular disease. Graphic: NIH

Q: Does metabolic syndrome help you understand diabetes and cardiovascular disease?
A: The concept of a syndrome make you think about underlying causes. There are two ways of looking at metabolic syndrome, first as a bunch of linked phenomena: type 2 diabetes, disorders of blood fats, and coronary heart disease, that may have a root cause that would explain them all; or as a group of risk factors for multiple diseases, which have unrelated causes. I'm inclined toward the former analysis. There is evidence that resistance to insulin is central to metabolic syndrome, and in some studies, treating insulin resistance benefits other components of the syndrome. And there is some data that ACE [angiotensin-converting enzyme] inhibitors, which are widely used to treat high blood pressure in diabetes, have some beneficial effects on insulin action and the incidence of diabetes.

Q: Regarding metabolic syndrome, why are people so concerned with visceral adipose tissue (fat inside the abdomen)?
A:
I suspect metabolic syndrome may result from disease or imbalance in this tissue. We used to think of fat as a simple storehouse of energy, but it's much more complicated than that. This visceral adipose tissue plays a yin-yang, good-bad role. It makes beneficial compounds which raise sensitivity to insulin, reduce blood pressure and sustain healthy blood vessels. But it also makes compounds that promote inflammation. When this fat is "healthy," it predominantly makes the beneficial compounds; when it's unhealthy, it shifts toward inflammatory compounds.

Two globules of yellow fat with small slivers of cell organelles and large purple nucleus on left
Fat cells, called adipocytes, store extra fat (energy) in the body, but some of them also release signaling compounds that affect other organs -- and have been implicated in metabolic syndrome and diabetes. Graphic: NIH

Q: I've never heard fat tissue described as "diseased"...
A: Ten years ago, nobody would have said lipid tissue could be diseased; it was seen as storage that was metabolically inert, and the treatment for diabetes was to lose weight. I think some sort of "switch" in the adipose tissue is favoring molecules that stimulate inflammation. Woman dressed in summer running gear runs on a park sidewalkThere is also an emerging concept that people can be fat on the inside. If we look at type 2 patients in Japan, many do not meet our Western eyes as obese, but if you do an imaging study and measure the visceral fat, you see they are fat on the inside.

Hoofing is a good way to stave off metabolic syndrome - and osteoporosis for good measure. Photo: ©David Tenenbaum

Q: We've been taught that diabetes is a disease of high blood sugar, but it's really more complex than that...
A: The complications of diabetes usually fall into two groups. One is damage to the tiny blood vessels in the retina, kidney, and nervous system, largely due to a high level of glucose attaching to structural proteins, gradually altering their function and damaging capillaries. A second complication is atherosclerosis -- hardening of the arteries -- which probably has a different basis. Atherosclerosis may be more related to inflammatory changes to the lining of the blood vessels that accelerate plaque formation and tend to choke off the blood flow. In diabetes, and in metabolic syndrome, the visceral adipose tissue generates inflammatory compounds, and then the balance in the lining of the blood vessels shifts from a healthy condition, rich in antioxidants and compounds that cause relaxation, to an inflammatory condition that leads to high blood pressure and plaque formation. And then cardiovascular disease and diabetes flow from that imbalance.

100% syndromes, 0% fat in our bibliography.

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Megan Anderson, project assistant; Terry Devitt, editor; S.V. Medaris, designer/illustrator; David Tenenbaum, feature writer; Amy Toburen, content development executive

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