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Interviewer: How exercise is key for managing prediabetes and diabetes by improving the body's ability to use sugar. We'll talk more about that next on The Scope.

Announcer: Medical news and research from University of Utah physicians and specialists you can use for a happier and healthier life. You're listening to The Scope.

Interviewer: Dr. Tim Graham is a diabetes expert. He's also an assistant professor of medicine, biochemistry and nutrition at University of Utah and is the medical director for the diabetes, obesity, and metabolism programs here at University of Utah Health Care.

I want to drill down a little bit into the importance of exercise for prediabetes, those who have been diagnosed with it, and diabetes, almost more important than nutrition, is what I've heard. Is that accurate?

Dr. Graham: Yeah, it's at least as important. We tend to, in our society, focus so much on body weight, and partly because we look at skinny people and they're the people that we see in Hollywood.

Interviewer: They look so healthy.

Dr. Graham: Yeah, they look so healthy, and yet without activity you're not so healthy. So it's not just about body weight, but it's also about keeping your body moving.

Really, prediabetes and diabetes are diseases of glucose metabolism. Normally, when you take a meal, your body produces insulin from the pancreas. Insulin circulates through the blood and tells the muscle to take up glucose so that right after a meal you might have a rise in glucose, but then when insulin kicks in, it causes the blood sugars to go down pretty quickly, because it tucks it away into muscle where you can use it later as glycogen when you're exercising.

The problem with diabetes is not necessarily that people don't make enough insulin, although in the case of Type 1 diabetes, we do see that. We can talk about that as a separate issue, but Type 2 diabetes, which is by far the most common type of diabetes, is a problem where people don't respond normally to insulin.

You make the insulin, in fact, you tend to make more insulin than the average person, but your body just doesn't respond normally. The skeletal muscle won't take up glucose in response to insulin. We call that condition insulin resistance, and that's really the classic Type 2 diabetes type problem.

One of the beauties of exercise is that it bypasses that defect by directly stimulating glucose uptake by muscle, so even if your insulin isn't working great, you can get your skeletal muscle to take up glucose more avidly or more efficiently just by exercising on a regular basis.

Interviewer: Can that condition be fixed by exercise, or is it just a workaround?

Dr. Graham: It's both. If you are exercising regularly and you have diabetes, you'll notice your blood sugars are more well-controlled with less and less insulin. Ultimately, if you have prediabetes and you can exercise regularly, you very likely will prevent yourself from developing the worsening condition of diabetes.

Interviewer: So it's a condition that can be taken care of.

Dr. Graham: By all means, yeah.

Interviewer: What kind of exercise are we talking about? People are busy; people don't like to be in pain.

Dr. Graham: There's been a lot of work done to figure out exactly what is enough exercise to have an effect. Frankly, as little as 150 minutes per week, now, that sounds awful, 150 minutes, but you break that down . . .

Interviewer: Sounds like a lot.

Dr. Graham: We're not talking about going to the gym and working out to the point where you're exhausted, we're talking about some brisk walking five times a week.

Interviewer: Or getting out in the garden or some house . . . I was vacuuming the house this weekend and I was sweating moving the furniture and bending down.

Dr. Graham: Yeah, truly. Anything that causes your heart rate to go up for a sustained period of time, causes you to sweat, most likely is having a good benefit from the standpoint of diabetes prevention.

Interviewer: So exercise, key for managing diabetes, for reducing your chance of getting it. If you have been diagnosed with prediabetes, to backing that off.

Dr. Graham: Absolutely.

Interviewer: Anything else that I need to know about exercise?

Dr. Graham: If you already have diabetes and you've had it for a sustained period of time, we do recommend that people get evaluated by their physician before they undertake a more rigorous exercise program. That's only because when you've had diabetes for a while, there's an increased risk that you might develop some heart problems, so we do recommend that people go out and at least get some evaluation to make sure that that's not a risk factor that they have before they undertake more rigorous exercise.

But the vast majority of people don't fit into that category who are contemplating starting exercise. Many people will have prediabetes, and frankly, they should feel comfortable just going out and getting it done.

Interviewer: If a little bit of exercise is good, is a lot of exercise even better? Do the benefits increase linearly?

Dr. Graham: They actually do. There are always people who we can see that develop syndromes of over exercise and sometimes that's associated with bulimia and other problems. But in most cases, people exercising more intensely for longer periods of time will be beneficial for people overall.

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Interviewer: When do you need to see a diabetes specialist? We'll talk about that next on The Scope.

Announcer: Medical news and research from University of Utah physicians and specialists you can use for a happier and healthier life. You're listening to The Scope.

Interviewer: Dr. Tim Graham is a diabetes expert. He's also the medical director of the diabetes, obesity, and metabolism programs for University of Utah Health Care. When do you need to see a diabetes specialist? When is it beyond something that your primary care physician can help you with?

Dr. Graham: That's a great question, and it's actually somewhat debated even in the medical community.

Interviewer: A hot topic.

Dr. Graham: Yeah, it is. It is. It's important because every time you escalate care it costs more for the patient, and it may or may not benefit them in the long run. So we do take seriously when to escalate care and when we get the most out of that extra bang for the buck when we send someone to a specialist.

Basically, we tend to look at diabetes as a general medicine problem, and it really is. It's a chronic condition that can generally be managed with the knowledge of a good internist, or a good family physician or generalist.

However, sometimes some patients don't fit into the usual protocols that we use in general medicine. So when patients start to develop recurrent low blood sugars or if they've been hanging out at a high blood sugar for more than six months and working with their primary care physician they're not really achieving the target blood sugar that they would like to get to, or the one that they need to get to to be more healthy, then I would recommend that they consider seeing a diabetologist.

Diabetology is just a fancy name for something we do in endocrinology. So it's always been endocrinologists or hormone doctors who tend to oversee the specialty care of diabetic patients.

Interviewer: So the primary care physician in how many cases would you say is able to handle through exercise, maybe medications, helping them with nutrition?

Dr. Graham: I would say at least 80% to 90% could be easily handled by the primary care physician. However, there are these patients that their physiology just doesn't fit into the normal sort of mold, the normal care protocols that we use. So really there's no reason to hesitate to take it outside the primary care setting to see the specialist physician at some point to get some additional input into the care plan.

Interviewer: Are there some specific indicators that a patient would see that would indicate that maybe they would want to request to be elevated to the next level?

Dr. Graham: Well, a couple things. If your primary physician isn't helping you set goals and telling you where you should be in terms of your hemoglobin A1C, which is the number . . . It's a blood test that we often follow to tell us where a diabetic patient is on a three-month basis for their blood sugars. If that goal isn't being set, then you need to address that with your primary physician. Say, "Hey, let's set a goal and let's make sure I'm getting there, and I'd like to talk about how to get there."

Now, maybe you have a goal that's been set, and maybe it's been communicated to you. But it's been six months and you're still not there. I think that's time to bring up the discussion with your primary physician, "Do you think we should escalate care a little bit and see a diabetologist?"

Now we've, at the University of Utah, taken a new approach to this. We want diabetic patients to be seen in their medical home with their primary care provider. So what we're actually doing is bringing diabetes specialty services to each of the community clinics in the University of Utah healthcare system. That way we don't have to have patients making this uncomfortable discussion with their primary care physician about whether they need to be referred out for something that the primary care physician may not be able to achieve easily in the primary care setting.

So instead, the primary care physician can literally just, at the click of a button, have the patient seen by one of our diabetes care teams right there in their own clinic where we've integrated into their practice. So we think that's easier for both the primary physician to deal with and easier for the patient to deal with.

Interviewer: That's something that primary care physicians kind of like. It's a checklist meaning, "If it's to this point, I'm just going to go ahead and refer."

Dr. Graham: Yeah. In fact, we're working with our primary care colleagues to decide really where exactly to activate the referral. At what point do we identify a patient who's been, say, lingering with a high blood sugar for six months or has had multiple episodes of low blood sugar? At what point do we pull the trigger, if you will, to get them hooked into one of these community care teams?

Interviewer: Then at that point, what would that expert do?

Dr. Graham: So typically what happens is, when they see the community care team, they get a lot more face time. They'll either see a specialist nurse practitioner or an M.D. physician such as myself, who's a diabetologist endocrinologist, and we'll sit down and do some problem-solving. We'll look at their medication list and we'll try to figure out what they aren't getting or what they might be able to get, from a medical standpoint or pharmaceutical standpoint, that would improve their blood sugar better.

Or maybe sometimes it's the timing of the dosing. Or maybe it's the types of foods that are being eaten. So we also tend to have them see a dietician nutritionist no matter what at those visits, as well. We'll often bring in our colleagues in pharmacy who are very good at helping adjust complex insulin regimens.

Interviewer: So a lot of tools that you have if the standard treatments don't work.

Dr. Graham: That's exactly right. I would emphasize, I like the term, it takes a village to care for a diabetic.

Interviewer: Yeah. Okay.

Dr. Graham: There are a lot of aspects of diabetes care, including even things like exercise, physiology, physical therapy, and we try to bring all of those to bear on these care teams. So we have people who are experts in behavioral health that work with the care team. We have specialist physical therapists who can work with people who have neuromuscular problems that makes it hard for them to be active.

We have exercise physiologists who can work with just the average person to come up with a good exercise regimen. Then of course, the nutritionists and diabetes educators, and then the pharmacists. All of those, that village of care is what the primary care provider gets when they reach out to one of these teams.

Interviewer: I guess what you're learning is that the old adage of eat better and exercise, you can't just tell a patient to do that because it's a lot more complicated than maybe a lot of us get.

Dr. Graham: Oh, yeah. Absolutely right. We've been doing that for years, telling patients to eat better and exercise.

Interviewer: It can be overwhelming.

Dr. Graham: In fact, no one really complies well with that because we all kind of know anyway we should be doing that. Right? So hearing one more person say it doesn't really change anything. However, it's really about strategizing.

So if you have people telling you not just that this is what you ought to do, but exactly how to do it and how to make it work for your life so it's actually personalized to you, we know that the impact is much more substantial. The more times you have people telling you that the better. So the other thing these care teams do is they bring more face time to the patient, basically.

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Interviewer: Pre-diabetes. What is it, what are the symptoms, and what can you do about it? Odds are you have it. We'll talk about that next on The Scope.

Announcer: Medical news and research from University of Utah physicians and specialists you can use for a happier and healthier life. You're listening to The Scope.

Interviewer: Dr. Tim Graham is a diabetes expert at University of Utah Health Care. As a matter of fact, he's the Medical Director of the Diabetes, Obesity, and Metabolism Programs for University of Utah Health Care. Pre-diabetes: epidemic? Is that fair to say?

Dr. Graham: Oh yeah, that's about as fair to say as anything you could ever call an epidemic in all of medicine. So we've got right now about 40% of people in the United States affected with pre-diabetes, and probably less than 10% of those people even know that they have it. So the vast majority have no idea they have this condition. It is asymptomatic so people really don't have symptoms that would prompt them to go see a doctor to get checked out.

Interviewer: And I have to say, I consider myself to be a fairly healthy individual. I walk my dogs a half hour each day. I watch what I eat, for the most part, but I had my glucose done and from what I understand I have pre-diabetes. It was a shock to me.

Dr. Graham: Yeah, yeah. You just shared that with me that your blood sugar was exactly at the level where we call people as having pre-diabetes. The condition is called impaired fasting glucose when you have a blood sugar, a fasting blood sugar of 100 milligrams per deciliter or more. And if you get up to 200 we call it diabetes.

Interviewer: And what does that mean to me? What road am I on?

Dr. Graham: Well, the problem with having been diagnosed with pre-diabetes is you've got roughly, over a five year period, you've got a roughly 30% chance of developing diabetes itself. And so even in the short-term, and to me really five years is a fairly short-term. It's looking out a few years. You've got a good chance of getting diabetes. Now, the important thing is that this can be completely prevented. It can be intervened on, especially by taking on some lifestyle modifications. So if you could do some changes where you lost a few pounds and started increasing your activity, you could prevent it by 50 to 70%.

Interviewer: You're kind of like the ghost of Christmas future right now, aren't you?

Dr. Graham: That's right.

Interviewer: "This is your fate unless you change your ways." So let's talk about pre-diabetes. It means you've got a pretty good chance of having diabetes and that's not fun.

Dr. Graham: No, it's not. I mean, if you haven't had a relative with diabetes, the problem is that the blood sugar elevation that you get with diabetes damages many different tissues. So it causes eye problems. It causes kidney problems, and it causes nerve problems. The nerve problems can lead to amputations. The eye problems can lead to blindness. In fact, diabetes is the number one cause of preventable blindness in the United States. And the kidney problems can lead to dialysis. So it's a really miserable set of things that you can eventually develop if you develop diabetes. Also, it increases your risk of heart attack and stroke dramatically.

Interviewer: So it's such a big deal, as a matter of fact, that here at the University of Utah Health Care that there is a whole program now dedicated to identifying and helping people deal with pre-diabetes.

Dr. Graham: Yes, that's right. Right now we are working with our community clinic physicians to identify people at highest risk and start screening people across the board. So if you have any concern based on your weight, your lack of activity, or you've got a strong family history of Type II Diabetes, I would really encourage people to talk to their physicians.

Interviewer: Even if you don't, because I have none of those things. I actually had another physician tell me, "I don't understand why this physician's doing this test on you. You look like you're a healthy guy. How old are you? It's pointless," but it wasn't.

Dr. Graham: You know, you're sort of like the poster child of the sort of movement for universal screening. It's exactly patients, like you, who don't even meet the sort of classic risk factors who probably make a good argument for why we should be screening the whole population.

Interviewer: So you go into your physician, you should probably request what type of a test?

Dr. Graham: Typically, we start with two things. One is a fasting glucose and the other is a hemoglobin A1C. Some people call that last one an HBA1C. So the fasting glucose can tell you, basically, when you're not eating what your blood sugar levels look like. The hemoglobin A1C, however, gives you information about what your blood sugars look like over a three-month period. So if you've been high after meals, the hemoglobin A1C may pick that up whereas a fasting glucose won't really give you that information.

Interviewer: So get those tests done. If they come back as they did for me, then exercise, dietary things that you can do to correct that. And there are probably a lot of resources on the web to find.

Dr. Graham: So we really like to start people with a formal lifestyle intervention program. So the old days of the doctor saying, "Hey, you need to exercise more and eat better," and then sending the patient out the door are over. So what we now have are programs that we get people involved with. They're community-based programs. The one that we run here is a version of the National Diabetes Prevention Program. You'll sometimes hear the term "DPP" and we're the first program of this sort in the state of Utah. We're actually backed by the Centers for Disease Control and the NIH in our efforts to do this.

And what it involves is people coming on a weekly basis for about 16 visits where they learn healthy eating approaches, exercise approaches, stress reduction approaches. And then they continue to follow up with the program for a total of one year. And that program alone has been shown to reduce the development of diabetes by about 50% over a three to five year period. And then in older people, over the age of 65, by 71%. So it's pretty dramatic.

We also have medications. One of them is Metformin that can be taken, either in conjunction with that or alone for people who may not be able to adhere to the lifestyle modification. But we really think people should be doing the lifestyle.

Interviewer: As the poster child, I'm going to go ahead and say this. I understand nutrition. I understand how to eat healthy. These are things that I get. I understand exercise. I used to be a trainer at a weight room and never expected that it would happen to me. I don't want to freak people out, but I think it's just a good thing to know so you can start making some lifestyle changes. Like, my job right now I sit a lot. I don't really move around a lot. I get home, I sit more.

Dr. Graham: And that's a really underestimated problem in the United States. So there are people who are not obese or not even overweight who may eat fairly healthily, but at the same time because of their significant amount of inactivity as well as the effects of aging, you can develop pre-diabetes.

Interviewer: Are there any final thoughts that you have, anything that I forgot to ask you that you feel compelled to say, that you feel our listeners should know?

Dr. Graham: Yeah, you know, this is one of those rare things where if you get it, it's not too late. You can actually reverse the disease process. So I think a lot of people fail to take action on their health because they almost dread finding out they've got a problem. This is one of those situations where you want to know if you have this problem because you can really take steps that will make a huge difference.

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Interviewer: There's a pretty good chance that either you or one of your family members is affected by diabetes, obesity and other metabolism issues. We're going to talk about a brand new clinic that can help you. Coming up next on The Scope.

Announcer: Medical news and research from University of Utah physicians and specialists you can use for happier and healthier life. You're listening to The Scope.

Interviewer: Dr. Tim Graham is the Medical Director of the Diabetes, Obesity and Metabolism Programs for University of Utah Health Care. Let's talk about the brand new clinic for diabetes, obesity and metabolism. It's such a big deal that it's become kind of a thing of its own now.

Dr. Graham: Yeah. We basically have what we call a service line that covers multiple clinics throughout University of Utah Healthcare and we've got a couple of very exciting areas that we've brought new services to the people of Salt Lake and Utah. First off, we've got the Utah Diabetes and Endocrinology Clinic itself, which is now providing team-based diabetes care.

I often joke it really takes a village to take care of a patient with diabetes because individuals with diabetes have problems with eyes, they have problems with feet, they need special nutrition considerations. We like to have them work with exercise physiologists to improve their activity and to do it in a sustainable way where they don't develop sport-related injuries. They often have physical therapy needs, etcetera. And sometimes behavioral health needs. So we like to bring all those services in a team-based fashion to our patients who come into the diabetes center here at University of Utah.

Interviewer: And that's a kind of new way of thinking for diabetes. Am I correct on that?

Dr. Graham: It is. In the past, it used to be a very much a sub special physician-driven care plan where you would go see a doctor that would make some recommendations, send you back to your primary care provider. What we do is when a patient comes in and sees us, we provide all these services and we provide it in a nice, unified way so that you don't feel you've been juggled between providers. And then we send the patient back eventually to their primary care provider with a much more comprehensive care plan that sort of details all these things and doesn't just pay attention to the insulin dosing or other types of diabetes medication dosing.

Interviewer: What else does the clinic do and how is it helping people?

Dr. Graham: So we've also established a really exciting program in conjunction with bariatric surgery. We now have a pretty tremendous way to reverse diabetes using bariatric surgery. So probably better than any medication we can give people, if we can have them undergo gastric bypass surgery or gastric sleeve surgery, it largely reverses diabetes for a lifetime and longer-term studies are just coming now to bear that shows, this is a very sustainable effect and people do extremely well even a decade out past surgery.

And every decade you don't live diabetes is a decade that will save your body from a lot of damage. So we have partnered with bariatric surgery program to develop a unified approach to obesity. So anyone who has a BMI of 35 or more, and BMI is defined as kilograms per meter square, I use that term because I think more people will know what that is. And if you don't know, just Google BMI and you'll find any number of BMI calculators where you pop in your weight and your height and it will tell you what your BMI is.

But if you've got a BMI of 35 or more and you've got any obesity-related condition, that can be diabetes or it can be high cholesterol or it can be high blood pressure, if you have any of these conditions, then you're candidate for bariatric surgery. So we've recognized this is a really important sort of additional therapy we bring patients. And so we've got a medical bariatric program that's now partnered with the surgical bariatric program to provide what we call a comprehensive weight management program. And this also is not just for people who have very high BMI or who have diabetes. It's for people who just want to lose weight and would like get some medically-supervised nutritional attention and exercise physiology attention to help them.

Interviewer: From what you are telling me, this team-based approach, it seems like somebody might be listening and they're thinking, "I should be a little bit healthy, I should be able to eat better why can I not do this on my own?" But it's really a lot more difficult than that in today's world. And that's why you are bringing all these people, all these experts together?

Dr. Graham: Yeah, that's really one of the myths, I think, that our society sets up. It's like somehow, there is something wrong with you if you can't lose weight. That everyone should be able to have the willpower to do it. And we look at things like "The Biggest Loser." And while I love that sort of program for bringing to attention the problem with obesity, these people have all day of training. They have people preparing their meals for them. Who has the time, the money and the willpower to basically do that on a day-to-day basis?

The idea that it's just something we can easily do on our own without having help is really wrong-headed. And furthermore, I think it's even than the attitude of physicians for many years that the patient should just be able to do it on their own. And yet every time I have ever sent a patient out with just generalistic advice like, "Go lose weight and be healthier," they don't seem to come back having lost weight and eating more healthily. So I think that we really have to come up with personalized strategies to help patients, to support them, to even hold them to their goals. And people do better when they are working in a group like that generally.

Interviewer: Yeah. And I would imagine too that over the past many years we've learned a lot more about these things. And really you need to have those experts to have a better understanding of it?

Dr. Graham: Absolutely. The other side of this is that we now know that obesity is at least 50% genetic in origin. And so the idea that it's just because you're lazy and you don't exercise is completely incorrect. And anything that's genetic in origin has a biological basis so we now understand and very cutting edge research done here, both in Utah and elsewhere, that the brain is wired differently when you become obese and it's very hard to undo that wiring. So the fact that people, when they do lose weight, tend to have what we call recidivism where they gain weight back or very quickly.

Interviewer: We've all heard of that, right?

Dr. Graham: Yeah. That yoyo weight thing is absolutely hardwired in the brain. It's biological. It's not because of lack of will.

Interviewer: So a clinic like this really could help somebody that . . . it's not a magic pill, there is probably some work and some time involved, but it sounds like it would offer hope to somebody that has not had hope before or has failed in the past?

Dr. Graham: That's right. And I would say that also includes people who have very significant obesity. We use the term, and I don't like it because it sounds so negative, but morbid obesity, which is a BMI of 40 or more. People who get up that high have a very hard time losing weight and they need additional support, especially physical therapy. Think about many people are starting to get joint problems when you start getting heavier with a BMI of 40-45 range.

And so we need to bring a lot more things to bear to help these people, many of them will be bariatric surgery candidates, some of them won't. But just because they're not doesn't mean that they don't need special health care. And so we really are trying to bring medical bariatrics up to get up to speed with the great advances that have been happening in surgical bariatric. And to give a home for everyone with all these problems so that they don't have to just see the primary care provider who might tell them every time, "You know you need to lose weight. You know you need to . . . "

Interviewer: Every year you hear that, right? And then a year passes and then you come back and you're in the same boat.

Dr. Graham: It takes actually more than that to achieve the results.

Interviewer: Where can I find more information about the Diabetes, Obesity, and Metabolism Program?

Dr. Graham: Well, so we've got on the University of Utah website, we have information about . . . if you go to the Utah Diabetes Center, we've got a web page that will actually branch out all these different programs we've been developing.

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Interviewer: There are nearly 80 million Americans with pre-diabetes, an often unrecognized and dangerous condition that put patients at risk for developing not only diabetes but also heart disease and stroke.

Dr. Timothy Graham, Director of the Utah Cardiometabolic Risk Reduction Clinic treats and researches the condition. Dr. Graham, at your clinic you assess patients for pre- diabetes. Why is this important?

Dr. Timothy Graham: Up to 30 to 40% of the general population has pre-diabetes. And the problem with actually getting to the point of having pre-diabetes is that you are then at a five to 10% risk per year of progressing to diabetes.

And what I try to emphasize to my patients is that by the time your blood sugars have risen to the point where we diagnose you with pre-diabetes, you have already had a process of disease in place that may have lasted for one or more decades. And there are other risks that are attendant with the high glucose levels.

So, for instance, when someone comes into the clinic newly diagnosed with pre-diabetes or even early Type 2 diabetes, many of them will already have signs of congestive heart failure or have damage to their blood vessels that might put them at higher risk for heart disease or strokes. So the earlier we can diagnose and start preventative treatments and medications, the better we think the outcomes will be in the long run.

Interviewer: So what exactly is the difference between pre-diabetes and diabetes?

Dr. Timothy Graham: Now, I think what's important to recognize is that the fundamental aspects of physiology that lead to the sort of less severe elevation of blood glucose and pre- diabetes are the exact same ones that lead to the more severe elevation in diabetes. So it's really just should be looked at the stage of the disease process rather than a distinct identity.

There is no doubt that everything that goes into creating pre- diabetes is exactly what continues and gets worse to create diabetes. It is true that by the time an individual has diabetes the disease process is perhaps more advanced and harder to reverse.

Interviewer: So remind us of one of the basic mechanisms that are in play here about what's the relationship between blood glucose levels and insulin and what goes wrong.

Dr. Timothy Graham: Generally speaking, when we eat a meal we have blood sugar that comes from our gut, from our intestine. It enters by absorption into our bloodstream. And in our bloodstream it is sensed by cells in the pancreas called beta islet cells. These cells are designed to do nothing else but make insulin for the most part, and when glucose floods into the body they know to secrete insulin. The insulin then circulates through the body and acts primarily at two or three places.

Primarily in the liver, insulin acts to turn off glucose production. When we're not eating, the only way we typically get glucose in circulation is by what the liver makes.

The insulin that floods into the system after a meal also induces uptake of glucose into muscle where it's stored as a substance called glycogen. And a certain amount also goes into fat or adipose tissue where it's used to synthesize actually triglycerides which are a storage form of fat.

So insulin kind of acts in these three different places to essentially lower your blood sugar levels after a meal, first by tucking the glucose into muscle and fat, and secondly by turning off the production of glucose by your liver.

Interviewer: What happens if pre-diabetes is not treated?

Dr. Timothy Graham: So one of the defining features of both pre-diabetes and diabetes, and when I talk about diabetes here, I mean Type 2 diabetes. In this country and in most other countries throughout the world 90% of people who have diabetes have Type 2 diabetes. And Type 2 diabetes is specifically defined by the presence of insulin resistance.

And what that means is your pancreatic beta cells can make insulin just fine, but when that insulin is produced and goes into circulation, it does not act effectively in liver, muscle, and adipose tissue to do what it's supposed to do. And that's because of molecular defect inside the cells that make up those tissues.

What's important to know about insulin resistance is that it varies dramatically from person to person. We have very good quantitative ways of measuring it and that a given individual can be insulin resistant for many years before they develop pre-diabetes or diabetes.

And it's generally been a black box up until fairly recently, that is, we've never really been able to predict among the insulin resistant people who will develop pre-diabetes or diabetes and when they will develop it. But we're changing that now because we're starting to look at the other pieces of the puzzle that go into the actual disease process.

If you think about it, if you're insulin resistant, the response of the body is to make more insulin. So if I have a block to the ability of this hormone to lower my blood glucose levels, the glucose levels stay higher and they keep activating more production of insulin by the pancreas. So the average person with pre-diabetes and most people with early stage Type 2 diabetes will have much higher insulin levels than you or I will.

Interviewer: I believe there's been quite a rise in diabetes in the American population over the last 10 to 20 years. What accounts for that?

Dr. Timothy Graham: So I think it's multi-factorial. There's no doubt as a nation we are more obese. So much so that right now, I believe the most recent 2012 statistics would show that nationwide 60% of the population is either overweight or obese. So it's more common to be overweight or obese than it is to be no which is kind of shocking when you think about it.

Now there's an exceptional line of evidence that supports that excess fat on the body leads to insulin resistance which in turn leads to the development of high blood sugar in diabetes and pre-diabetes. I think what's fascinating is that coupled with this obesity epidemic is an epidemic of inactivity. We probably all see that our kids play outside less than they used to. This time spent not active is, in fact, an independent risk factor even if we control for body weight.

I would say that there's also a less understood transgenerational effect that is fueling the epidemic of diabetes right now. For instance, if your mother was obese or insulin resistant during her pregnancy, even if she didn't have gestational diabetes, you are much higher risk for developing pre-diabetes or diabetes later in life.

And this may be a cumulative effect from generation to generation. Plus finally, there's very good evidence that some of these compounds, like phenol A and others, can have direct effects to sort of program the metabolism of children in utero and in their early childhood so that by the time they're adults they're more prone to diabetes. That's kind of an unspoken about issue, but it really there and it's pretty much acknowledged by people who study environmental health.

Interviewer: There are so many factors that could be influencing the development of diabetes. How do you even begin to approach the problem?

Dr. Timothy Graham: To me there's two ways to react to that. As a clinician, one wants to throw one's arms up in the air and say, "Wow. This is just too big. We can't fix this. All we can do is just sort of hold our head above the water and tread water."

But as a basic scientist I feel like understanding each of these mechanisms as critical because if we can drill down to understand exactly how each of these insults, if you will, leads to the disease. To me if we understand that sort of set of molecular mechanisms, we can actually manipulate them to our benefit.

So, for instance, if we find that a specific environmental toxin activates a certain pathway, it would not at all be inconceivable for us to design a medication that counteracts that, or improve manufacturing processes so that that toxin is eliminated or both.

So the more we understand the molecular level about this process and the various piece of it, which are many, the more opportunities there actually are and the more we understand how we might be able to actually interfere with the process that finally leads to Type 2 diabetes.

Interviewer: What motivates you to look at this problem so carefully?

Dr. Timothy Graham: There really are no approved medications for this. Even the oral medications we have for Type 2 diabetes tend to be somewhat plagued by concerns about their effects on the cardiovascular system. So if you sort of look at the field as a whole, there's an urgent need to develop new approaches to treating the problem.

I think what really excites me is there are so many untapped areas where we can start to come up with new strategies. So, for instance, I mentioned earlier the idea that fat is this major hormonal organ that produces all sorts of substances. Well, if we come back to the basic observation that the strongest association we see in clinical medicine with Type 2 diabetes is with obesity, then it seems like fat is a pretty good place to start.

So I really directed my attention as a basic scientist understanding how fat cells work, what they product, and how they can interfere with that process. I firmly believe that the work we're doing here at the University of Utah in my lab and in other labs like mine here in the Molecular Medicine Program and in the Division of Endocrinology. I believe as a group we're all putting together entirely new ways and approaches to coming up with new treatments for Type 2 diabetes prevention as well as reversal.

updated: November 16, 2021
originally published: January 24, 2014