By Nadia Al-Samarrie
I recently interviewed Dr. Paul Zimmet, MD, PhD, an Australian scientist who is acknowledged as one of the world’s experts in diabetes and the metabolic problems associated with it. The subject of our discussion was whether the concept metabolic syndrome should be replaced by “circadian syndrome.” This would refer to the increasing evidence that disturbances in the human body’s biological “clock,” which governs metabolism, can lead to diabetes, heart disease, obesity, high cholesterol, and more.
(See Dr. Zimmet’s bio here: www.monash.edu/medicine/ccs/diabetes/research/zimmet-paul)
Diabetes Health: What is the standard definition of metabolic syndrome (MS)?
Dr. Zimmet: It’s the cluster of important risk factors for heart disease in particular, and includes obesity, type 2 diabetes, high cholesterol, high triglycerides. In that cluster we have a very high risk of heart attacks or strokes.
People with MS also have comorbidities, more likely to have depression, sleep apnea, and also fatty liver. We’ve given the name Circadian Syndrome (CS) to these MS clusters and comorbidities. All of these factors are actually very closely related to our circadian rhythms.
DH: If the circadian rhythm is the body’s way of keeping its functions coordinated, a sort of “body clock,” does staying up late affect it?
Dr. Zimmet: “Body clock” is absolutely right. In every cell there’s a clock that synchronizes to the general body clock. What can disrupt the circadian rhythm? One is staying up late. Or reading or watching TV just before bed. Einstein once asked the question, “Why do we have a body clock?” His answer was, “We have a body clock so that everything doesn’t happen all at once.” That’s why we don’t try to get to sleep, or try to get to the toilet, or try to exercise all at the same time. So we have a very well integrated body clock which makes sure that the body’s functions and the body’s metabolism follow a predictable course every day. Lacking sleep disrupts everything, including digestion.
The main body clock, the pineal gland, which is like a factory producing melatonin, is affected by our behavior, so that going to bed late can reduce the body’s melatonin production—with the result that it is now harder to go to sleep.
Disruptions can have a profound effect on the clocks in our kidneys, livers, hearts, and brains.. COVID-19 is a great example: Our eating has been disrupted, our sleeping has been disrupted, our exercise has been disrupted, we have stress. All these things upset the body clock rhythm and all of the metabolic functions in your body. So we’re looking to get out of this situation and get our system operating again normally so that, as Einstein says, we have a correctly functioning clock that can make that all these different functions operate at the proper time.
DH: Does COVID-19 trigger people at risk for MS and prediabetes?
Dr. Zimmet: In mid-June, my colleagues and I published in the New England Journal of Medicine an article pointing out that we think that the COVID epidemic is triggering new cases of diabetes. So we have proposed and established a global register with contacts worldwide to tabulate actually how many new cases of diabetes have arisen during the epidemic. This includes people who have had prediabetes, but not full-blown diabetes, but who as a result of the COVID-19 epidemic have developed actual diabetes. And we also want to look at whether as things return to normal and their normal diet and exercise habits resume whether they lose the diabetes.
Sleep, but not just sleep, also diet, exercise, and lack of stress are important throughout the immune system, and one of the ways of protecting against a COVID-19 infection is by having all of your body functions properly inline.
DH: Among other things, a high-fat diet, altered sleep patterns, weight gain, and stress are all known to bring on metabolic syndrome. They also induce a marked reduction in brain dopamine activity. There are now drugs called dopamine agonists that can block these environmental factors from inducing metabolic syndrome. Do you think these drugs make sense for treating MS?
Dr. Zimmet: There is this new understanding of the importance of circadian rhythms so that we are taking a look at how and when we administer drugs to treat conditions associated with them. So there’s a very strong move now to a new approach, called circadian medicine, to produce drugs to help get the body aligned and back into its normal rhythm. High blood pressure, for example, has a circadian rhythm, so the timing of high blood pressure drugs is important. Cholesterol metabolism in the body is at its highest just before the evening meal, so we should be taking cholesterol-lowering drugs before meals.
The FDA a couple of years ago actually approved a drug designed to work directly with the circadian rhythm [Cycloset*]. It’s not used all that much yet, but I suspect that with the increasing interest in circadian medicine and this whole new discipline of timing drugs in relation to the body’s rhythm, it’s going to take off very strongly in the future.
DH: So does this mean that MS is now being referred to CS?
Dr. Zimmet: I wish it were. There was a meeting in Los Angeles,† which I think it is one of the best meetings in the world for diabetes and heart disease, where we had a debate as to which one—metabolic syndrome or circadian syndrome—was the better description. Unfortunately, I don’t think the audience understood that MS has certain limitations, because when a doctor sees a patient with it and doesn’t think about the other comorbdities—depression, sleep apnea, etc.—the patient is not getting the right treatment. All they’re getting is a change in medications. CS makes people think much more widely about those factors aligned with those caveated metabolic risk factors.
DH: What about people like shift workers? How are they affected by the circadian rhythm? If they’re taking melatonin to help get to sleep, does their clock still function well? Is it just that they’re on another clock system?
Dr. Zimmet: This is actually one of our society’s major problems. There’s a major Harvard study that shows that nurses, for example, on shift work are much more liable to get diabetes and have heart disease. It’s a very important factor in workplace safety. People who are working overtime, for example, their rhythms get out of balance, especially if they’ve been doing shift work for years. Melatonin may help a little, but what we have to do is work out some more sensible working conditions. In factories, they lose fingers; they have all sorts of injuries which actually relate to working overtime. This also creates a huge problem for modern economies.
DH. Since low brain dopamine and altered brain circadian organization are culprits in the development of depression, do you think that the close association of depression with MS can be attributed to loss of circadian peak dopamine activity?
Dr. Zimmet: I’m not right into the biology and physiology of this, but what I would say, though, is you need a lot more research. One of our problems is that people don’t understand that their lifestyles affect the circadian rhythm, that in fact it is a major factor in the development of diseases like diabetes, heart attacks, and strokes. People have to understand the concept of the circadian rhythm and its importance. We still have a lot to learn about it. But there is a lot of science behind it now. Last year when I attended a symposium on the circadian rhythm at the American Diabetes Association’s annual meeting in San Francisco, all they talked about were rats and mice and not enough about humans.
DH: I’ve heard you use the expression “ideal lifestyle.” What is that?
Dr. Zimmet: A healthy lifestyle is important to immunity and dealing with infections, etc. A lot of it is just regularity. A lot of people wake up at exactly the same time, have lunch at exactly the same time, do their activities throughout the day at the same time, have dinner at the same time, and go to sleep—and getting enough sleep—at the same time. Their body clocks are adjusted to a regularity in their daily activities. COVID-19 has shown the importance of diet and exercise, spending enough time in daylight, and good stress management, especially in the light of job loss. The lack of exercise is crucial: My wife and I go for a walk about an hour each day—we didn’t do that before the pandemic but we will be doing it from now on. These are very simple things people in most situations can do, while acknowledging areas where poverty or necessity make them not so easy to do. Those are the basic things people can do to lead the “ideal lifestyle.” The idea is to have a regular pattern.
An interesting side note: There is some evidence that some people who suffer from depression benefit more from light therapy than they do from medication. This is a very exciting area; I think it is very much untouched. A colleague of mine suggested that it would very interesting to assess the rates of depression and the effects on their health of people who regularly use sun tanning booths. So many of them emerge saying, “Oh, I feel terrific!” That’s an experiment somebody might get a Nobel Prize for someday.
When I worked in a laboratory in London in winter, the only natural light we had was a skylight, and it got dark by 4 in the afternoon. Our mood changed, and we really didn’t feel like working. It just shows you how important light is.
DH: (Dr. Zimmet and I discussed how extensive video gaming has to be disruptive to children’s’ circadian rhythms, especially since it means they don’t go outside as much as they used to in the course of a day. gaming has replaced such traditional youth activities such as biking, hiking, hanging out, swimming, and just hanging out with friends. During COVID-19, it is not unusual for children to game until 2 or 3 or 4 am., then go to bed and sleep in late. I suggested to Dr. Zimmet that it would be interesting to track the gaming group and see the effects CS has had on that demographic.)
DH: Does age play a role in both the circadian organization and metabolic syndrome?
Dr. Zimmet: There is some evidence that disruptions in the circadian rhythm can contribute to cognitive dysfunction and also toward elements of Alzheimer’s disease. This is another area of interest along with all the other aspects of CS.
DH: I have read that some consider Alzheimer’s as a form of diabetes while others disagree with that idea. What’s your position on that?
Dr. Zimmet: Some people do call Alzheimer’s “the third diabetes,” type 1 and type 2 being the other two. A number of people have been trying to get Alzheimer’s pushed in under the category of diabetes. Now one of the pathological findings in Alzheimer’s is the finding of plaques—a substance called amyloid. Also, quite a few people with type 2, based on post-mortem studies, have amyloid in the pancreas. But it’s a different form of amyloid; there are several forms of amyloid. So there’s this belief that because amyloid is in the pancreas and in the brain, it might actually be related. There’s quite a lot of interest in the fact that Alzheimer’s does appear to be more common in people with type 2, but there’s actually in my mind no evidence that in fact there’s an association because of the nature of the amyloid substance that’s found in those pancreatic and brain tissues.
DH: Thank you, Dr. Zimmet.
*See “Cycloset Type 2 Medication – The Happy Hormone” at www.diabeteshealth.com/cycloset-type-2-medication-the-happy-hormone-2/
† 17th World Congress Insulin Resistance Diabetes & Cardiovascular Disease