Dr. Schneider: Dr. Leahy, thanks for joining us this morning. I look forward to understanding where we should be going as a primary care community in thinking about how to best take care of our patients, from a patient-centered approach.  Many of our patients have pre-diabetes or the genetic predisposition to going on to diabetes, and we in primary care have a narrow window to be able to change their course, if you will, or delay at the very least their progression to full-blown diabetes.  What impact does lifestyle modification have with weight loss on beta cell physiology and the progression towards diabetes?

Dr. Leahy: So this is a fundamentally important question and one that I think the average primary care doctor sort of knows in his heart, or her heart, is important, but tends to discount it because it’s so hard to understand what to do with this in a clinical practice and make it affective.  You know, from a scientist point of view diet and exercise should be hugely important especially early in the course of the disease and the simple reason is the following: If you sort of think about what’s happening at that time you’ve got a certain level of insulin demand, i.e., tissue insulin sensitivity or resistance and you’ve got a beta cell that’s able to act at a certain level of function or compensation.  And people who are early in the stage of the disease, it’s not normal, but it certainly is some.  People can compensate some.  And so, if you come in, you can either try and promote better beta cell function and certainly that’s an ongoing issue that we’d like to think about with some of the beta cell specific drugs maybe early in the course of the disease, and I think in the future we’ll have a better idea where they fit, but in today’s world that’s not what we do.  In today’s world we think about trying to lower the demands on the beta cell.  And it could be done pharmacologically so there’s metformin is used some -- clearly many providers know of metformin’s use.  TZDs actually have proven to be incredibly beneficial early in the course of the disease, but they’re complicated because they have side effects and they’re expensive.  So the least expensive, in theory, the most applicable, in theory, and the one which is the safest, in theory, should be promoting healthier lifestyles.  And the problem, I think, for many patients and for many doctors it becomes a complicated conversation that is wrapped up in -- you need to diet, not a terribly attractive word for some patients, and you also need to exercise, i.e., go buy a gym membership and start exercising in a way that is really foreign to many patients.  And so trials that have used diet and exercise in a trial design, meaning more than the average patient would do like the DPP, it worked.  It was the most beneficial at prevention of diabetes in the agents that were in the DPP at least against metformin.  And it lowered the progression of impaired glucose tolerance to Type II diabetes by almost 60 percent over the three years of the study.  At about the same time and in the same journal -- The New England Journal from the same year -- a study was done in Scandinavia that basically showed the same thing -- that diet and exercise can be really effective.  And then if you want to take the most extreme example that probably every doctor has seen -- a patient who has terrible diabetes who’s on every drug known to man, a lot of insulin, gets a gastric bypass.  They come back and see you six months or a year later, they’re 50, 100 or more pounds less and their diabetes drugs are gone or almost totally gone.  I mean, it’s kind of amazing.  So, we have lots of information to say that diet and exercise can work.  We know the physiology that it improves insulin sensitivity and actually improves cardiovascular risk profiles so it’s quote, unquote unloading the beta cell, which should be good for beta cells, and so all of that tells us it should be a great therapy, and I think what’s lacking in our culture and most cultures around the world is finding ways to phrase that and put into practical interventions for patients so they are more effective at it.   One of the amazing things is people can actually do fairly modest dietary changes and fairly modest changes in their level of regular activity and really see large improvements in blood sugars.  It’s actually sort of amazing at times.  But we’re often just not articulate enough to try and help patients to design a program that they actually think they can participate in.

Dr. Schneider: Right, I think you really phrased the lifestyle modification in the context of beta cell failure extremely well, and I would just echo what you have just described as a key cornerstone to primary care and would just make a pitch for primary are doctors to realize that they cannot do this alone and these patients to really achieve the kind of results that you, Dr. Leahy, were just talking about -- they need to be referred out.  They need to be really in a program that is more than just counseling in a primary care office for calorie restriction.  DPP really was a well-organized trial.  In order to duplicate that most primary care offices are not designed to do that.

Dr. Leahy: If I might -- I want to just echo two parts of that  -- two experiences I’ve had.  The first is I learned some years ago in my clinic that I am not good at predicting who are the patients who will be most successful with diet and exercise.  It really comes back to reinforce itself for me almost very frequently.  I’ll see a patient -- they’ll often be there with their spouse – I’ll talk to them for several minutes and they have lots and lots of questions, specific questions about diet changes and activity and what works and what doesn’t work and we’ll have this really interactive, interesting conversation and then they come back and nothing has changed as opposed to I have someone who’s not all that interested, not all that educated, not seemingly a patient you think is going to be very productive, they come back often with the statement that my spouse is really into this -- they’re ten pounds lighter and over the next year they’re just the absolute poster child of using effective lifestyle modification.  So I don’t think we can use one appointment with a patient and make a decision whether this is a good idea or not and I absolutely agree we need to use the professionals -- the dieticians and educators -- who are much better at speaking in language to patients about practical application of these things than I think the average hurried doctor.  The second part to that is we have available at my institution a cardiac rehab program for patients who obviously have cardiac disease, which is based on effective use of the dieticians and also regular exercise and people come actually to the facility and use the gym three times a week under observation.  The thing that’s amazing to me is people really get into it.  It’s like a club for people.  They just really start to adopt healthy lifestyle practices.  And we’re now using that facility for our patients without cardiac disease and it’s really turned out to be a very beneficial program because it’s more than just a doctor saying, “Please go exercise. Please watch your diet. Come back and see me in two months we’ll talk about it.”  I mean there are true goals and guidelines and true sort of milestones along the way that people get positive and negative feedback on and they work with the staff that’s really into it and with other patients that really like it and it’s a fabulous program.  So I think that’s what we have to think about in our own communities -- sort of find a place where people can work on lifestyle around others who are enthusiastic and really trying to put it into practice for their own life.

Dr. Schneider: I concur one hundred percent and I think you phrased it perfectly by saying that lifestyle changes will improve insulin sensitivity and by definition improve beta cell responsivity and beta cell function and will essentially off the beta cell.  I loved that line.

Dr. Leahy, I’d like to thank you for spending time with us today and we appreciate your comments.

Dr. Leahy: So it was a pleasure.  Thank you very much.