Robert Frykberg, DPM, MPH presents the current knowledge behind diabetic foot disorders and its relevance to the podiatric profession. Dr Frykberg reviews the different types disorders, their costs to society, and their impact on the health care system. Along with citing relevant literature, he discusses the mortality rates for those with diabetic foot disorders and the value to society to detect and treat these patients.
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Robert Frykberg, DPM, MPH,
PRESENT Editor - Diabetic Limb Salvage
Carl T Hayden VA Medical Center
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Male Speaker: I like to usually start off our sessions with an overview of the major problem of wounds, and especially diabetic foot ulcers since this is where we spend the majority of our time. I think as resident is imperative upon yourselves to understand the underlying risk factors, the scope of the problems, the frequency of the problems. Because as you know, the frequency is only getting higher as our population, ages and diversifies. So we know that in the United States there are about, this is an estimate, about 26 million people comprising 8.3% of the population with this disease. That becomes important when we think of the magnitude of the complications in this rather small population and recognize many of these diabetic patients are undiagnosed until they have one of the major complications of diabetes. We know there are one and a half million new or incident cases per year. This cost is actually old. There was a new paper. Unfortunately I haven’t put it in here yet, where the total cost of diabetes in the United States is over 200 and somewhat billion dollars. This is only an 8% of our population, both direct and indirect cost over 200 billion dollars. Huge cost to our society and still remains the seventh leading cause of death in the United States very, very important. Many of the deaths, let’s say of MI or renal failure also going to be diabetes related. So this is a huge problem for us. And we know of course there are many major complications in the lower extremity of diabetes. Neuropathy is always first and foremost on your list. It must be first and foremost because that is the predisposing risk factor that leads to many of the other complications, obviously ulceration but also infection. In some degrees PAD, certainly amputation and certainly Charcot foot which we’ll talk about this afternoon. If we look at hospitalizations from the diabetes surveillance system, when we look at diabetes related hospitalization discharge diagnoses, you see ulcer is high, followed by PAD, followed by neuropathy. But doesn’t that seem strange? Discharge data is not always reliable. Do you really think that these 111,000 people don’t have neuropathy or some degree of neuropathy or PAD? So we know that this data is not really accurate but it really portends the magnitude of the problems that we are talking about. We see in some years we had spikes and hopefully as we’ll see that the amputation rate is actually going down in time with more of our prevention efforts because of all the focus that we have now on diabetes. Unfortunately, we know that diabetic patients are at risk for premature death and we’ve even found from several papers that those patients with ulceration have a higher death rate or shorter life expectancy than those diabetic patients without ulcers and compared to all sorts of those patients without diabetes. This is first brought to light by Ed Boyko from Seattle. I’m sure Dr. Hati knows Ed Boyko, who reported a twofold increase risk of death in persons with ulcers after adjustment for age duration and smoking which always should be done, so twofold risk of deaths adjusted for these other important factors. You’ve often heard people talk about the Moulik Study from 2003 where the 5-year mortality rate was 44%. As we’ll see, that’s equivalent or higher than some types of cancer. We know that it’s highest in ischemic ulcers. Do they die at the ischemic ulcer? No. The ischemic ulcer also a mark the first ischemic or heart disease. Then in 2009, Iverson reported a 10-year mortality rate. I believe this is from Finland or Norway; 10 year mortality rate of 49% which is probably lower than many other centers. They probably eat more fish than we do in the United States, but 47% increase mortality versus those patients without foot ulcer. So here, foot ulcer is a predictor for earlier mortality. These are important markers. Sometimes they die of infection. We’ve all seen this kind of a graph. Just showing the relative mortality, 5-year mortality rates of various complications of diabetes compared to very common cancers.
Obviously we know pancreatic cancer, 95% 5-year mortality rate. Lung cancer, 86%. But look right here for amputation. This is from an old paper by Larsson and Appelquist in Sweden, 68% 5-year mortality rate for an amputation. These are all amputations combined. Then we look here, the Moulik paper, 44%. A Charcot foot. We’ll talk about later. Charcot foot from one paper, 41% 5-year mortality rate. These are higher even in colorectal cancer, breast cancer, Hodgkin’s disease, etcetera, and PAD is down here. We used to say this patient has like malignant type of diabetes. Well this really brings it home. These complications are markers for early death. These are sick people that you’re dealing with. Even though they can look for a robust, they are sick people and you must appreciate that. Hence you don’t just be cavaliering your approach to these patients. With major reconstructions because they have a little deformity in their foot, you have to think about the underlying comorbidities as you approach the care of these patients. It’s critical. This paper came out of the Hines VA here in Chicago several years ago where they looked at the 5-year mortality rate in actually the nationwide veteran population. I think it was from the year 2003 if I’m not mistaken where they’re looking at patients with diabetes, Charcot foot, and diabetic foot ulcers. And you can see in their population, the patients with diabetic foot ulcers had a 37% 5-year mortality rate which was higher than Charcot. And yet in patients with diabetes alone without these complications had a significant way lower death rate than the Charcot patients. But even here, just take note obviously; patients with Charcot foot have a higher 5-year mortality than do patients with diabetes without that complication. Very, very important attribute. This is a similar paper from Nottingham in the UK from Van Baal and William Jeffcoate. And here they’re looking at 1, 3 and 5-year mortality rates for patients with Charcot foot as well as with diabetic foot ulcers. Look at the 5-year mortality rate for Charcot foot compared to diabetic foot ulcers in this well-controlled population. The same. No difference. Over the first time we’re seeing even Charcot foot now. There’s good healthcare system. Same 5-year mortality rate as diabetic foot ulcers which we already knew predicted an earlier mortality. Very, very important. Here if you look at the survival curve of diabetic foot ulcer and Charcot, no difference. But the acute Charcot foot median survival was just under eight years. This curve here is the non-diabetic population. So we’re seeing some very interesting data about this major complication of diabetes that you really need to appreciate as you’re dealing with your patients. We know that diabetic foot ulcers have a 15% lifetime risk for ulcers, multifactorial ideology. But the easiest way to classify them would be neuropathic, ischemic, or neuroischemic which is probably more common now than it was 30 years ago. Of course we recognize that it’s a precursor to amputation about 85% of cases. The incidents of foot ulcer varies depend upon your study in the population but generally about 2% of the population understudy per year will develop an ulceration. If you look at just a neuropathic population, of course the frequency is going to be much higher. There are many risk factors for diabetic foot ulcerations. We break them into intrinsic factors versus extrinsic. Intrinsic factors are obviously due to the metabolic deficits of the patient themselves and neuropathy should always be the top of the list. Not just sensory or motor but also autonomic. We can’t forget the importance of autonomic neuropathy and what it does systemically. Of course vascular disease, both macrovascular and microvascular immunopathy and immunologic impairment that makes these people more susceptible to infection has been shown by [Shawn Hopps] [09:38] in 2003, significant difference in rate of infection in these patients. You can go down the line here of course. Extrinsic factors, minor trauma, very common, callus, walking barefoot, minor trauma, blunt trauma, burns. We are in Phoenix. Second and third degree burns, very common in the summer as people walk out barefooted or in a stocking feet to get to the car, to the mailbox or the pool.
Very common and many people can lose their limbs especially if they have a superimposed peripheral arterial disease. So we have to be aware of these various risk factors. We look another important paper out of the Seattle VA by Ge Reiber in 1999, Diabetes Care. They look at these seven possible risk factors called component causes. They found that in 63% of the causal pathways in these 150 so patients that they studied in two centers, this triad was present, most trauma obviously neuropathy but also deformity and trauma. And you put these components together to form a sufficient cause that always leads to the outcome. We can see how these are biologically plausible. Neuropathy, deformity, like a Charcot foot, deformity like a hammer toe, trauma, like shoe pressure on that deformity causes ulceration. So very insightful using the Rothman model that had been previously published in May of 1990 in Diabetes Care, addressing causal pathways leading to amputation. So remember the risk factors and the component causes for ulceration are almost always the same as amputation for the two are so closely related. It gets more complicated. But you need to keep all these in mind. I’ve used this figure for many, many years, and it still remains the same. This represents the underlying complicating factors within a diabetic patients and how they can relate to cause these major problems. We see on this side a neuropathy, motor sensory autonomic. On this side vascular disease, critically important both microvascular as well as macrovascular, leading to a high risk foot as we call it with an impaired response of infection. You applied trauma to that high risk foot. Trauma in the form of tight shoes, walking barefoot or punctured wound or blister or what have you that can develop foot ulceration. As they continue to walk on that patient it gets worst and can get infected, turn gangrenous, then requiring amputation. Not all patients have all these underlying metabolic perturbations but you must be aware of them so that you can appropriately intervene in your management. These are sick patients and you must appreciate that. As I said, foot ulcers are major risk factors for subsequent amputations. About 85% of diabetes related amputations there is an ulcer that went unhealed in that pathway leading to an amputation. So we recognize for many years and more than 60% of non-traumatic lower extremity amputations in the United States are in diabetic patients. Just that 8% of the population sustain 60% of the amputations. Obviously hit rates are all greater in men and elderly, minorities, and those with renal insufficiency. And of course it impacts their survival, depending upon the level of amputation; the more proximal the level of amputation, there, the earlier the death rate. Of course the average cost of amputation depends on the acuity of the patient, the level of the amputation. But probably $40,000 is probably a very low figure. When you start adding on indirect cause such as rehab, prosthesis, the costs go up much higher. Of course the risk factors here, very much similar to the risk factors that we saw for a diabetic foot ulcer. The two are very, very closely related. My former student and colleague, Lee Rogers, published this in the Journal of Vascular Surgery in 2010, the stairway to amputation. Just like Stairway to Heaven but you guys are probably too young to remember Stairway to Heaven. You have the high risk foot with neuropathy with or without PAD, but we recognize the increasing role of PAD in our patients now compared to 30 years as I said. Sustained an injury; a callus, step on a tack, what have you, a burn as we see in Phoenix all the time. That breaks the skin envelope. Then we develop a chronic wound. The chronic wound becomes infected and the infection turns into gangrene when treated inappropriately or not treated. So there are many steps along this stairway in which you have the opportunity to intervene to arrest the progress. It’s your job to arrest the progress through appropriate management of foot ulcerations. If this could have been prevented or if this step could have been prevented, gangrene could have been prevented. Of course, once we have gangrene, we know we must perform amputation.
Our goal is to prevent the progression to gangrene whenever possible and prevent that amputation which is sometimes the only realistic treatment for these patients. In summary, recognize a diabetic foot complication is a leading cause for diabetes-related hospitalizations, neuropathy, PAD, ulceration, and infection are major risk factors for amputation. And both ulceration and amputation adversely affects survival. We know for years that amputation affected survival. Now I’ve shown you the data that supports the fact that just a foot ulcer has an adverse effect on survival. And knowledge of risk factors for complications provides you the opportunity for early intervention and prevention of these very important risk factors. You also need to recognize the important role for multidisciplinary management. This has been established for the last 30 years. This is nothing new. In fact, if you go back to The Menace of Diabetic Gangrene, a paper in 1934 from Elliott P. Joslin, he talked about the need for multidisciplinary management. It just took us 60 years to catch on to realize that’s the way it needs to go. We have the podiatrist here as the gate keeper and my center for podiatrist sees these patients far more frequently than any other specialty and we get all referrals from primary care as well as hospital. But we work very closely with vascular surgeons or internist or medical people, our various consultants, infectious disease, ortho, nephrology, etcetera, and wound nurses, as well as other ancillary services. And by working as a team dedicated to taking care of these patients and preventing amputation, you’re going to be far more effective in your amputation prevention strategies. Okay. So with that I thank you from one of our typical patients here in the VA and it took a long time to get this picture but I finally got it. It’s classic, classic, classic VA patient. Right. [Dr. Hati’s] [17:08] here laughing because she knows how true it really is. Okay.