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Hello everyone, my name is Dr. Snage and we are presenting Neurogenic Obesity After Spinal Cord Injury. I'm Gary Farkas. We're both postdocs at the University of Miami Miller School of Medicine in the Miami Project to Cure Paralysis. I only have one disclosure. I'm funded by the Craig H. Nielsen Foundation. These are our learning objectives. First, we'll define neurogenic obesity and what happens after SEI including the demographics and the metabolic comorbidities that are unique to persons with spinal cord injury. We will then discuss energy balance and the unique features of SEI that contribute to over consumption of calories which will then require the unique dietary interventions to manage obesity. Then we will review energy balance and the unique features of spinal cord injury that limits the energy expenditure which then require the intentional exercise prescription for managing obesity. All right, so we're gonna start off talking about neurogenic obesity. Obesity is at epidemic proportions within the spinal cord injured population. And I would almost argue that this is actually a pandemic because when you look at the literature, we see that several different authors in several different countries report that persons with spinal cord injury are living with obesity. And the definition of a pandemic is an epidemic that has crossed international borders. So by that definition, I want you to kind of think about this rather than an epidemic but in a pandemic. So neurogenic obesity, we first introduced in the literature in 2018. It was a paper published in the Journal of Spinal Cord Medicine. And recently, actually as of last year, we had a special issue in topics of SEI rehabilitation focused on neurogenic obesity. So when we talk about neurogenic obesity, it's really, really important for you to understand that we are not referring to traditional measures of obesity like BMI and waist circumference to define the morbidity. We are referring to percent body fat. Traditional measures of obesity used to use body fat and they cut off at 22% in men and 35% in women. So above those values, you are considered obese by percent body fat. So with spinal cord injury, what leads to neurogenic obesity? There's motor paralysis below the level of injury. There's an obligatory sarcopenia that occurs following the injury. So that is a loss of metabolically active tissue below the level of injury such as fat-free mass. We have sympathetic dysfunction due to direct or indirect damage to the thoracolumbar region of the spinal cord. Anabolic insufficiency, so decreases in testosterone and increases in other hormones like cortisol. And then we have blunted satiety. So that means that energy intake is greater than energy expenditure. And we'll focus on that a little later. Now we know within the cord population and outside that obesity mediates metabolic syndrome through several different comorbidities such as insulin resistance, hypertension, dyslipidemia and so on. So adipose tissue for a very long time was thought of as just a storage organ for fat. But within the last 20 years, it's been recognized as much more than a storage organ. It is an active endocrine organ that secretes hormones that have local and peripheral implications throughout for homeostasis. So when we talk about adipose tissue, it is nowhere near homogeneous. There's many different cell types. The most common cell that we think of is the adipocyte. This is the main cell that is going to store our triglycerides. But everything else in the tissue can be kind of lumped together in what we call the stromovascular fraction. This includes preadipocytes, as the name implies. These are the precursors to the adipocytes. There's endothelial cells that are going to help form our blood vessels. There's blood cells, fibroblasts, pericytes, macrophages and monocytes. Now monocytes are the precursors to macrophages. And in healthy adipose tissue, macrophages take on what we call a type one phenotype, meaning that their main job is to secrete anti-inflammatory cytokines that we call adipokines because they're coming from fat. But with obesity, these macrophages take on what we call a type two phenotype and they are pro-inflammatory in nature. And these are very dangerous macrophages that are going to contribute to a lot of the metabolic dysfunction that we are going to talk about. So anatomical location of adipose tissue varies throughout the body. And we like to refer to these locations as depots. So we have subcutaneous tissue, the adipose tissue, which is found deep to the dermal layer of skin. Visceral adipose tissue found around our organs throughout the body. And then intermuscular fat, which is the fat that is found deep to the muscle fascia and around the muscle groups. And then intramuscular adipose tissue is the fat that is found within the muscle fiber itself and adjacent to the muscle fibers. And this is what we typically think of as storing fat for utilizing to exercise, for example. Lastly, there is marrow adipose tissue. And that is, as the name implies, is found in bone. So the pathophysiology of obesity is extremely complex. And we're gonna go through in the subsequent slides how all of these are intertwined. But to paint the picture, with obesity, you have storage of fat, right? So fat is typically going to store in subcutaneous depots. But it eventually reaches a threshold. And once that threshold is reached, free fatty acids start to become secreted from subcutaneous adipose tissue. These free fatty acids are deposited in ectopic locations such as muscle, pancreas, and the liver. But it also is notably transported and deposited into visceral adipose tissue. And visceral adipose tissue is unique in terms of the adipocytes can get really, really large before they start undergoing pathophysiological changes. But they still undergo these pathological changes. So when the adipocytes within visceral adipose tissue become pathologic, what they start doing is they start losing their plasticity. When they lose their plasticity, they themselves start secreting out free fatty acids as well as several other inflammatory molecules called the pro-inflammatory adipokines. These adipokines and the free fatty acids make their way into the circulatory system. And they are then deposited just like the subcutaneous tissue in several organs and organ systems. So when free fatty acids are deposited into muscle, we have an increase in fat in the muscle. And that leads to insulin resistance. At the pancreas, we see that there is beta and alpha cell dysfunction, also leading to insulin resistance. And there's also a decrease in the amount of glucagon produced. At the liver, we have several pathological changes that occur. The free fatty acids will lead to a decrease in the amount of HGL that is produced and an increase in other types of cholesterol. And then we also see that there is hepatic insulin resistance and glucagon resistance that takes place. So to understand what happens with insulin resistance, we need to understand what happens with normal glucose transport. You eat a meal, right? Beta cells secrete insulin, right? And then the glucose is going to be near your cells for uptake, right? Insulin is going to bind to the insulin kinase receptor. That's going to autophosphorylate. The autophosphorylation will trigger the insulin receptor substrate one and two. That then triggers a downward cascade of the PI3 kinase, AKT cascade, thus activating our glute transporters. The glute transporters will then migrate up to the plasma membrane of the cell. In the case of muscle, this is the sarcolemma. And then glucose is taken up and it's brought into the cell for use. But what goes wrong with obesity? Our pro-inflammatory molecules are going to trigger a transcription factor called NF-kappa-beta, right? This is a protein that is essentially going to interfere with normal signaling cascades throughout our body. Particularly, there are four notable inflammatory molecules that we see with obesity. Interleukin-1-beta, tumor necrosis factor alpha, interleukin-6, and monocyte chemoattractant protein. These are released from adipose tissue in some way, shape, or form. And interleukin-1-beta is going to cause upregulation of NF-kappa-beta and lead to beta cell apoptosis. Interleukin-6 and tumor necrosis factor alpha are both going to prevent the PI3 kinase cascade, leading to insulin resistance. And lastly, monocyte chemoattractant protein is very unique in the sense that even though it is released from adipocytes and doesn't have a direct role in insulin resistance, what it does is it attracts monocytes to the vascular tree. The monocytes in the vascular tree will differentiate into type II macrophages. Those are the bad macrophages. They then recruit more monocytes. But these macrophages are now going to basically eat up fat within the blood cell and they become foam cells. And that contributes to atherogenic dyslipidemia. So adipose tissue-induced insulin resistance is also mediated by non-esterified free fatty acids, specifically their metabolites. And they activate protein kinase C, junk kinase, NF-kappa-beta inhibitor kinase, and again interfere with our signaling cascade for insulin and glucose. And those pro-inflammatory cytokines we spoke about earlier are going to have a similar mechanism as the metabolites from the NIFA. So insulin resistance is closely tied to dyslipidemia. And that is because these pro-inflammatory cytokines, when they are upregulated, cause the upregulation of NF-kappa-beta, inducing insulin resistance. And that leads to an increase in adipose tissue lipolysis, hypertriglycerinemia, as well as non-esterified free fatty acids. These free fatty acids are deposited into the liver. At the liver, they are going to reduce the amount of apolipoprotein A, and that subsequently reduces the amount of HDL cholesterol that is produced. Apolipoprotein B, on the other hand, is the bad type of apolipoprotein. And that is going to increase, resulting in an increase in LDL and VLDL cholesterol. Now cholesterol esterol transfer protein, it's a mouthful to say, ultimately what that's going to do is in the circulatory system, that is going to cause any type of good HDL cholesterol that is circulating through your system to come dysfunctional, thereby taking that out of the equation. You know, the HDL cholesterol is kind of like a scavenger. And therefore, you're allowing for more buildup of cholesterol. Now adipose tissue-mediated hypertension. There's five mechanisms that are involved in hypertension. They're not really well understood. But in the literature, there's five hypotheses that contribute to this mechanism of hypertension. There's obesity-induced leptin resistance. So with increasing leptin, we see an increase in aldosterone synthase. That causes an increase in blood pressure through the secretion of aldosterone and its action on sodium. Leptin also has central mechanisms that lead to the activation of the sympathetic nervous system leading to an increase in blood pressure. With increases in fat, we see that muscular and renal sources of sympathetics are also activated. This leads to, again, increase in blood pressure. And then we have the renal angiotensin-aldosterone system. So adipose tissue secretes angiotensinogen. Angiotensinogen is converted to angiotensin 1 and 2. And subsequently, angiotensin 2 activates aldosterone. Aldosterone is then going to cause an increase in sodium absorption, which retains fluid, thus increasing blood volume and then blood pressure. But angiotensin 2 also causes vasoconstriction itself. And it reduces low-level nitric oxide production. So natriuretic peptides normally decrease the amount of blood pressure. And we see that with obesity, endopeptidase nephrolisin is going to cause those natriuretic peptides to decrease. And then lastly, there's mechanical stimulus. So with increases amount of fat, you're going to compress kidneys and associated tissue. And that causes the tissues, the blood vessels, to constrict and increase blood pressure. Okay, so ultimately, this leads to metabolic syndrome. And metabolic syndrome is a cluster of metabolic risk factors that increases your risk for cardiovascular disease, cardiovascular disease mortality, diabetes, stroke, and eventually mortality. And there are several definitions in the literature that are used to define metabolic syndrome. We historically have used the International Diabetes Federation definition. And that is because it focuses on obesity as the driver of metabolic syndrome. So the IDF defines metabolic syndrome in men as a waist circumference greater than 102 centimeters and in women above 88 centimeters, plus any two of the following criteria. So for triglycerides, you have triglycerides above 150 milligrams per deciliter, or you're on treatment for dyslipidemia. HDL cholesterol below 40 in men, or below 50 in women, or on treatment for dyslipidemia. Hypertension is a systolic blood pressure above 130, or a diastolic blood pressure above 85, or on treatment for hypertension. And then dysglycemia is defined as blood glucose above 100, or being treated for diabetes. So if you have obesity, as defined by a waist circumference measurement, plus any two of those other criteria, you are said to have metabolic syndrome. But within the spinal cord population, we cannot use waist circumference. It's not a validated tool to measure obesity. So we use surrogate markers. So we use the SCI-specific BMI cutoff of 22, and then we use percent body fat, which is technically the most accurate way you can measure obesity. 22 and above for men, and 35 and above for females. In 2019, we published a paper looking at about 500 veterans who were about 56 years of age, evenly split between paras and tetras. And we saw that when using the traditional definition of obesity, according to the World Health Organization and the CDC, we saw that 27% had obesity. But when we use the SCI-specific BMI, we see that 77% had obesity. We also saw that nearly 70% had reduced HDL cholesterol, 37% had elevated triglycerides, 50% were classified as having dysglycemia, and then 55% had hypertension. And then using the definition from the IDF for metabolic syndrome, we saw that nearly 60% had metabolic syndrome. Last year, we published another paper looking at civilians with spinal cord injury using the IDF criteria, which is in 72 persons, mean age about 44, and a mean BMI of 27. And we saw that using that BMI cutoff of 22, 82% were classified as obese, and 97% were obese when using percent body fat. 97%. That's in a staggering number, okay? Dyslipidemia was found in 83% of our folks, and then dysglycemia was found in 32%, and hypertension was in 43%. Now, when we use the SCI-specific BMI cutoff, we saw that 56% had metabolic syndrome, and 59% had metabolic syndrome when using percent body fat. So what's that telling us? Percent body fat, unsurprisingly, is a more sensitive marker for metabolic syndrome in those with a cord injury. So now we're gonna be talking about energy balance. Energy balance is a dynamic relationship between energy intake into a system and the energy that's exiting a system. For our purposes, we're gonna be talking about the system as our body. Therefore, the energy that's coming into our bodies in food in the form of calories is the energy in, and the energy that's exiting our bodies is through three main components. They are basal and resting metabolic rates, the thermic effect of food, and the thermic effect of physical activity. We'll be diving deeper into each of these different components. Energy balance is a very complex relationship. There are many factors that influence it, many hormones, different biomarkers in the body, as well as the environment. However, it all boils down to the energy intake as well as the energy output. And when one equally offsets the other, we've achieved a state of maintenance. Energy in that's coming into our bodies is in the form of macronutrients, including carbohydrates, protein, fat, and alcohol. Carbohydrates and protein both contribute to four calories per gram of energy. Fat is more energy dense and contributes about nine calories per gram. Alcohol, even though it's non-essential macronutrients, still contributes to the overall energy intake at seven calories per gram. Fiber falls under the macronutrients of carbohydrates, and even though providing energy is not a main role for fiber, however, it does contribute slightly at two calories per gram. I do wanna mention that even though micronutrients, including vitamins and minerals, are important for the body and proper physiological functioning, they do not contribute to the overall energy intake. Moving on to energy output, there are three main different components, which are the resting and basal metabolic rate, the thermic effect of food, and the thermic effect of physical activity. It's the sum of all three components that equates to the total daily energy expenditure. So we have, if you see in the top left-hand corner, there is the equation that I just mentioned. And we're gonna be moving down the different components. We are missing one slide, it's the BMR. I'm just gonna talk about it briefly. In persons with spinal cord injury, it's lower than the general population. It's a major contributor to the total daily energy expenditure. It contributes about 60 to 70% in the general population. However, it's higher in persons with spinal cord injury. And so now we're gonna move on to the next components, is the thermoeffective food. So this contributes about 10% to the total daily energy expenditure in the general population. However, in persons with spinal cord injury, the literature is mixed. We do know that the thermoeffective food is lower in obesity. And given the shifts in body composition towards obesity in our folks with spinal cord injury, it leads us to believe that it's also gonna be lower in persons with spinal cord injury. Lastly, it's the thermoeffective physical activity. This contributes about 25 to 30% to the total daily energy expenditure in the general population. This is also the most variable component of the total daily energy expenditure, particularly due to the fact that it's highly dependent on the body composition, as well as the frequency and intensity of the physical activities that are being performed. The thermoeffective physical activity is lower in persons with spinal cord injury compared to the general population by about 27%. And this is particularly due to the fact that the movement is restricted to the upper extremities, which then lowers energy cost for exercise, as well as activities of daily living. Okay, so now we're going back into our relationship. We know that when the energy intake equally offsets energy output, then we've achieved energy balance. However, if we are expending more energy than we are consuming, then we are in a negative energy balance and fat loss is expected. And if we're consuming more energy than we are expending, then we're in a positive energy balance, and therefore fat gain will occur. Excess energy that's consumed but not expended will then be stored as fat, also known as adipose tissue, which Dr. Parkes went into detail about. There is strong evidence that suggests that persons with spinal cord injury are indeed consuming more energy than they are expending. This is particularly due to the fact that their BMR and RMR is substantially reduced, potentially reduced thermic effect of food, and also a reduced thermic effect of physical activity, which all contribute to the total daily energy expenditure. We do know that if there's a positive energy balance of between 10 and 100 calories per day, this will eventually lead to obesity. And in SEI, there has been a reported positive energy balance of more than 85 calories. However, this was calculated using a rather old equation called the Long Equation, where they determined the total daily energy expenditure by multiplying the RMR by 1.2. This, however, may be overestimating the energy needs. A more recent publication that's provided by Parkes is called the Parkes Equation. It is the, we determine the total daily energy expenditure by multiplying the RMR by 1.15. These are the, if you do the math, you can see on the left-hand side, the equation for the Long Equation, and you can see that there's a positive energy balance of 85, more than 85 calories per day. On the right-hand side is the Parkes Equation, and you will see it's actually almost double that. And they're in positive energy balance of 160 calories per day. And if you can see on the bottom, with the Long Equation, we'll be having about 0.7 pounds of fat gain per month. And with the Parkes Equation, they're expected to have more than a pound of fat gain per month. This may not seem a lot. We're talking about one pound a month. However, if you look in the context of a year, we're talking about between eight and almost 16 pounds per year. And if you don't change anything, it's just gonna accumulate year after year and year. This is what's driving the neurogenic obesity that we see in persons with spinal cord injury. So what are they eating? If you can see on the right-hand side, the right column is the USDA recommendations for dietary. And then in the middle is what people in the general population are consuming. And in the left-hand column is what our folks with spinal cord injury are consuming. And what we can see is that they're not eating very different than the general population. They are consuming a little bit more carbohydrates than general population. However, it's still within the USDA guidelines. And we also see that they are consuming less calories than the general population, but they're still consuming more than they're expending. In 2019, we looked at energy intake by level of injury and by body weight in persons with SCI. So on the left-hand side are persons with paraplegia and on the right-hand side are persons with tetraplegia. So what we did is we took their energy intake as well as their macronutrients and we adjusted it to their body weight. And what we saw was that total caloric intake in persons with tetraplegia was significantly greater than those with paraplegia. And we also noticed that same phenomenon when it came to fat and protein consumption that our folks with tetra were consuming more than that with para. When we looked at body composition, we saw that body fat in our folks with tetraplegia was significantly greater than that with paraplegia. And that has been relatively mixed in the literature throughout the years. So ultimately, you can kind of conclude from this data that the consumption that is occurring in those persons with tetraplegia could be driving the increase in body fat in that cohort of persons with SCI. So the next couple of slides are some work that I'm really excited about. This is some unpublished data. The paper's about halfway done. And what we're doing is we are looking at actual energy intake in about 41 persons with spinal cord injury and comparing it to the equations that are used to estimate total daily energy intake. So as Dr. Snage mentioned, energy intake should be equivalent to energy expenditure. So that's how these equations often work, okay? So you'll see that on the right-hand side in the B-SWARM plot, we've graphed out energy intake on the far left. See if this works, yeah, is the actual intake for our folks. And then these three B-SWARMS are the different equations. So we use the Farkas equation, which multiplies resting metabolic rate by 1.15. That's the correction factor. We use the long equation that multiplies resting metabolic rate by 1.2. And then we use the Academy of Nutrition and Dietetics SCI guidelines for persons with paraplegia and tetraplegia. These guidelines are quite old, they're from 2009. They have yet to be updated, but I'm not passing judgment. And what they do is they use weight as a factor to determine intake. So there's an equation for para and there's an equation for tetra. And just by looking at this B-SWARM, you can see there's a slope upward from left to right, indicating that these equations are slightly overestimating intake. Well, guess what? They are, except for one. So what we did is we took the delta, so the difference between the estimated intake and the actual intake, and we graphed that. So on this figure, you'll see we have zero on the y-axis and then the different equations on the x-axis. So this is the difference in intake. If they are at zero, that means that the estimated intake and the actual intake are exactly the same, so they're dead on correct. But what we're finding is we see that each of the equations are overestimating. But when we apply our statistics to that, we use the Wilcoxon signed weight exact test. What we saw is the Farkas equation here on the left did not overestimate energy intake. However, the long equation and the Academy's equation both significantly overestimated energy intake for our folks with SCI. What we also did is we looked at the root mean square error. That's just a fancy name for a type of statistical error test and we saw that the least amount of error, as we expect, was in the Farkas equation and that the Academy's equations were well overestimating and there was a lot of error, over 1,000. So to confirm these results, we use Bland-Altman plots and we don't need to go in detail about these, but the big idea here is that the top and bottom bar tells you the 95% confidence agreement with the two measures and the differences in the middle. So what we saw is the narrower the lines, the more agreement that was occurring and we saw that the Farkas equation had the most agreement to the actual intake compared to the long and the Academy. So what we're also doing is we're looking at protein consumption in our folks and the Academy, that same 2009 publication, suggests that for persons with SCI, they need to consume .821 gram of protein per kilogram of body weight per day. So what we did is we graphed on the x-axis. You see all the participants. They are increasing order. It's kind of hard to see from my angle and then the y-axis is protein intake. So the lines, the gray lines correspond to the ranges of protein intake. So the bottom is that .8 measurement and the one is going to be the higher measurement for protein intake and what we saw is that 16% of our folks were meeting recommendations and then we see this weird relationship where those who have lower body weights are consuming more protein with those with higher body weights are consuming more protein. So what we did next is we regressed protein intake on body weight. So we looked at the association. So the triangles are those who are overeating protein, the circles are those within the range and then the squares are those who are under eating. These two gray lines right here correspond to the .821 recommendations for protein intakes and for those of you who know regression lines, this is by far one of the worst regression lines I have ever seen but this is really, really important because we're not seeing a significant association here. So this is contrary to the recommendations. The academy says that with increasing body weight, you need increasing amounts of protein but we don't see that right here. So what we did next is we looked at the difference in protein intake. So the recommended amount compared to what they're actually eating. So it's the delta again. And what we saw is a negative relationship. So we saw for every one unit increase in body weight in kilogram, there was a .8 decrease in protein intake in our folks and that's illustrated by this regression, the best fit line right over here. So the same values correspond, I mean the shapes. So triangles are those who are overeating, the circles are those who are within range and the squares are under eating. And what we also saw is that there's a threshold for this occurs. So persons who have a body weight at 72 kilograms, at that level, we see those who are under that are over consuming and those who are over that are under consuming protein. Okay, so we've established that they are overeating the amount of calories and they are expending. So what do we do about it? We need to target their diets and we can use the help of established guidelines for that. Our goal is to achieve a low energy yet a nutrient dense diet. And we can start with a dietary guidance for Americans. We're using the MyPlate Consumer Guide, which you can see on the right hand side. Some of the key recommendations are to focus on the five MyPlate groups, which will naturally increase the nutritionally dense foods. So for example, half the plate should be loaded with fruits and vegetables. Grains should be at least 50% whole grains. The protein should be lean and dairy should be low fat, all reducing the energy content while maintaining the nutrient density. There are dietary recommendations from the Paralyzed Veterans of America from the clinical practice guidelines on the cardiometabolic disease. They have similar guidelines, but these are what they are focusing on. For example, fruits and vegetables, whole grains, low fat dairy, poultry, fish, nuts, legumes, and non-tropical vegetable oils. They recommend limiting sweets, sugar-sweetened beverages, red meats, also limiting saturated fats to no more than five to 6% of total caloric intake, which is also endorsed by the American Heart Association. And they also recommend restricting your sodium intake to no more than 2,400 milligrams per day, only for individuals with hypertension. This is a good start to improve the diet quality of our folks with spinal cord injury, but we needed more. We needed something more practical, more tangible to be able to implement this into practice. So last year we published a comprehensive review on the specific dietary recommendations for persons with spinal cord injury. We published it in the British Journal of Nutrition, and we just provided more practical recommendations. Some specific instructions were portion sizes, their frequency of consumption, food variations. We also recommended a shift away from the macronutrient distribution and focusing more on the overall healthy eating patterns. This is also promoted in the 2020 to 2025 Dietary Guidelines for Americans. We recommended in the comprehensive review that food intake should be two to three servings per day, with an emphasis on whole fruits over juice, which tends to be high sugar with low fiber content. We also recommended vegetable intake should be between three and four servings per day from the five different vegetable subgroups, including the dark green, red and orange, legumes, starchy, and other vegetables, which are outlined in more further detail in the Dietary Guidelines for Americans. We recommend that all persons with spinal cord injury with and without hypertension will consume less than 2,400 milligrams of sodium per day. Also that poultry should be lean at three to four ounce portions and they would consume fish twice a week. So these are just more specific recommendations. Dairy should be low-fat milk, yogurt and cheese. Sugar-sweetened beverages including soda, Kool-Aid, sweetened iced tea, everything with sugar should be replaced with a zero calorie water. High-fat, sugary sweets should be replaced with naturally sweet, fresh fruits. And that red meats and sweets should be consumed on special occasions and not on a regular basis. So how does this help us to achieve a low-energy yet nutrient-dense diet? Well, fruits and vegetables are naturally low-energy density, meaning that they provide minimal calories with respect to their weight. They're also nutrient-dense. They're abundant in vitamins and minerals and fiber, especially those vitamins that are important for wound healing, especially vitamins A, C, D, zinc, iron and copper. And this is particularly important for persons with spinal cord injury due to the fact that they are prone to pressure injuries. Whole grains, in addition to the carbs that they naturally will provide, they also provide fiber, iron and B vitamins, which is stripped away from refined grains. Protein, we recommend it to be lean to lower the energy density by trimming off the fat, removing the skin off of poultry. And then we also recommend preparation methods that require minimal fat being added. For example, grilling, baking, roasting versus deep frying. And dairy should be low-fat, so we recommend skim or reduced fat. It will lower the energy density whilst still retaining the calcium content as well as being a good source of protein. So this illustration was published in our comprehensive review. It's basically an outline of everything we just talked about. So we can see on the left-hand side, we want to determine what the BMR and the RMR is, either by indirect calorimetry, which is a gold standard, or if that's not available, then we can use prediction equations. We will then plug it into the Farkas et al equation where we multiply it by the 1.15 SDI-specific correction factor. We will then determine the total daily energy needs. And then we want to offset it with the amount of calories that we're consuming, equally offset it so that we're in energy balance. And ideally, there'd be an oversight by a registered dietitian for all folks with a spinal cord injury to ensure that they're at energy balance. All right, so we're gonna switch gears and look at physical activity and exercise. So there's really two main goals when we talk about exercise, all right? And I think most of us are familiar with one of those goals. We want to create energy expenditure to create an energy deficit, right? So you want to burn calories. The other aspect that us exercise physiologists are concerned with are substrate utilization or partitioning. We want to burn fat. Fat is very nutrient-dense, and we get a lot of bang for our bucks when we use it, all right? And we'll talk why that's important in the cord population. Okay, so what modalities are out there for our folks with SCI? So there's aerobic training and resistance training. So upper arm exercise for aerobics is wheeling around a park. Arm cycling, there's sports activities, rugby, hockey, et cetera. There's lower extremity exercise, body weight-supported treadmill training, passive cycling, whole-body exercise, recumbent stepper, water exercise, et cetera. Resistance training, there's free weights, there's elastic bands, cable pull, these weight machines, and our friend, FAS, functional optical simulation. There's a little asterisk next to that because I would argue that it's both aerobic and anaerobic, and I don't have enough time to talk about that, so happy to speak later about that. And then there's really both, the circuit resistance training, Mark Nash, published in the early 2000s, a circuit training regimen that's used for spinal cord injury. It incorporates resistance training as well as arm cranks, so that's the aerobic component. All right, I know this slide is microscopically small. It's intentional because I'm trying to illustrate a point here. These are just some of the guidelines that are currently out there for our able-bodied folks for exercise and activity, physical activity guidelines, all right? There are a ton of different authoritative organizations that come out with guidelines, but guess what? They say the exact same thing. 150 minutes, at least 150 minutes per week of moderate to vigorous intensity exercise. That should be between 30 to 60 minutes, three to five days per week, or you could do what we call little snack bouts where you do 10 minutes of activity at least three times a day. For resistance training, strength training, you want to train major muscle groups, right? That's two times per week, three sets, eight to 10 reps, start off with higher reps when you first start off the activity, and then you can kind of move down to the lower reps. This should be anywhere from 30 to 60 minutes with one to two minutes of rest in between with more rest starting off in the very beginning. All right, and then flexibility, range of motion. Most people, and when I say most people, this is universal, forget to do flexibility and range of motion. It is so important, and especially for our folks with spinal cord injury. You want to do this daily, all right? So you want two sets of 30 to 60 second stretches, sometimes with hold, sometimes without, depending on your capability, and you want to do this for five to 15 minutes, all right? It's important that these are gentle, slow stretches and that they are pain-free. If it elicits pain, that's a sign. Okay, now guess what? These are our recommendations for our folks with SCI. There are several different authoritative guidelines out there that provide recommendations for our folks, but guess what? They say the exact same thing, but that is an issue and we will see why in a minute. So what do we know about how the amount of time that you spend in a week exercising, how does that compare to calorie burn? So there was a somewhat of an old paper, 2009, that was published that quantified that and what they said is that 150 to 250 minutes a week of moderate intensity exercise is energy equivalent to 1,200 to 2,000 kcal per week. This is ultimately going to prevent weight gain greater than 3%. Caveat is in most adults. Okay, why do we see that as an issue? So when we talk about energy expenditure, we can quantify it many, many different ways, but when you look at the kcal expenditure, it ultimately comes down to how many calories as energy are you burning in one minute. Those are not equal in our folks with spinal cord injury and able-bodied folks. So if you want them to burn calories to reduce obesity and you tell them they need to do at least 150, that is not enough. We need higher volumes. Okay, so this is important because the guidelines that we use, you know, they're implemented hopefully in practice amongst all the physiatrists, it's not enough. You know, you really need to go to the upper limit 250 and we also know that exercise is not the only thing that needs to be done. The diet component is very important. So in 2020, we published a paper looking at persons with spinal cord injury compared to controls during a sub-max exercise test and the real focus of this slide is the figure on the right and we divided our folks by mid paraplegia and low paraplegia using a marker of T9 to define mid versus low and we had controls and we saw that persons with mid paraplegia had significantly lower kcals per minute energy expenditure than our neurologically intact controls. That was significant. But however, you see that regardless of significance, there is a lower trend in energy expenditure regardless of level of injury. Many, many others have reported the same phenomenon, right? So on the left, we see various modalities for our folks with SCI. So you can burn anywhere from 5 to 10 kcals per minute with FES cycling and rowing, all right? And then FES and arm cranks, this is called hybrid exercise, below 6 calories. When you start incorporating upper extremity exercise, it's anywhere from 2 to 4 calories and when it comes to motor complete exercise, it's even lower, right? It's about 1 to 4 and in some cases, very rare cases, one paper does report 8. But it is a lot lower and our folks with tetraplegia, it's 0.9, not 1 calories burned on arm cycling on our folks with tetraplegia. When we look at our able-bodied folks through different modalities, those numbers are significantly higher, right? It's 8, 9, 10, 11 and those who are aerobically fit, it's above 11 in some cases, all right? So let's do some math. I know it's later in the day and we don't have to get too complex. So what we did here is we determined in one week how many calories are you expending, all right? So we took 4 kcals per minute. This is corresponding to upper extremity exercise. Let's say somebody with paraplegia, all right? And we plugged in some numbers. So we used our values from the meta-analysis that said caloric intake was about 1,900 calories per day and their measured resting metabolic rate was about 1,500 calories. So using the total daily energy expenditure equation, we plugged in some values. We saw, so RMR, we plugged in thermic effect of food and then we put in the thermic effect of physical activity. They are expending about 1,700 calories per day, a person with paraplegia, okay? So they're exercising, this is what they're expending. Now when we take a look at what they are consuming, they're consuming about, we said 1,900 calories down over here. We take the difference, all right? And we see that's about 147 calories per day in excess and over the course of the year that is going to come out to be about 15 pounds of fat gain. So even when they are exercising, it's still not enough. So during exercise you burn calories, but even after exercise, as a result of the exercise, you're burning calories. And this is referred to as post-exercise oxygen consumption. We call it EPOC. And this represents an increase in energy demand that is manifested through an increase in oxygen consumption. You're breathing heavier to intake more oxygen. And that is because you have an increase in metabolism at this point. So during this time, the body's going through a recovery phase. It's repairing the damage you did to your muscles during the exercise. And it brings your body back to a pre-exercise state. And during exercise recovery, there is not only an increase in energy expenditure, but we also see in able-bodied folks that there is an increased amount of lipid oxidation. So fat burning that is occurring following the exercise. Some studies report this lasting for hours and some even say days. But we don't really understand EPOC following spinal cord injury. The study on the right was published in 2016 by Astrid Porgy. And he did a single bout of FES in folks with motor complete SCI. And they used two surrogate markers to measure EPOC. So that was ventilation, so ventilatory rate, and VCO2. Both you could use as surrogate markers for oxygen consumption and energy expenditure. And they saw that after exercise, so in the recovery phase here and here, VCO2 was above resting as well as ventilation was above resting. So that's telling us that the post-exercise oxygen consumption in our folks is elevated relative to the resting state. In 2004, there was another paper that was published that used iso-intensive arm crank exercise in six recreational active folks with SCI with paraplegia. And they matched them to six controls that were matched based on VCO2 peaks. They didn't see any difference. And part of that reason was the study wasn't really designed to look at that. And they only assessed EPOC 40 minutes following the activity. So it's somewhat inconclusive what is going on with EPOC following spinal cord injury. So in the population without SCI, lipid oxidation, as I mentioned, is upregulated following exercise. But in spinal cord injury, we really don't know what's happening. We think it is limited, and that has to do in part with the damage to the sympathetic nervous system. So they're not really able to harvest fat through sympathetic activation. But the other aspect to this too is that upper extremity exercise is not really the best for lipid oxidation. Upper extremity exercise relies more on carbohydrate utilization than it does fat utilization. So these limitations collectively are going to limit our folks with SCI from burning fat. So in the same paper from Ashraf, he saw that fat utilization was significantly lower than carbs in the recovery phase of that FES bout. And it also was a lot higher during the exercise session that they were performing in those 10 persons with spinal cord injury. So I know this slide, these figures are a lot. So I'll walk you through the study. So there's three graphs. They correspond on the top left to our controls, neurologically intact. On the top right, it's our persons with tetraplegia. And the bottom is our persons with paraplegia. This study had eight people in each group, and there was two conditions. There was a control condition, and then there was a exercise condition. The exercise condition, they did arm circuit training. It was an acute bout of exercise, about an hour. In that control condition, the person just sat there for an hour for the same length of time. So they matched the time in the control vesting condition to that of the exercise condition, and they compared it between folks with and without the injury, as well as within the individual. So what I want you to note on this busy slide is that before the exercise bout and during the exercise bout, there are no differences in energy expenditure. Energy expenditure here is the entire bar, and then the black corresponds to utilization of carbs, and the white corresponds to utilization of fats. We'll talk about those results in a minute. I have a summary slide. So in the last 120 minutes of the exercise, or excuse me, of the post-exercise EPOC session, we saw that our folks with and without an injury were using more fat during their vesting phase of the injury than they were using carbs. What does this all mean? Okay, what is the summary takeaway? Carbohydrates were the main substrate used during exercise, and that energy expenditure and lipid utilization increased similarly between both groups after the exercise. So that corresponds to EPOC in persons with and without spinal cord injury, independent of level of injury. Okay, so while this study was well done, one limitation is that it was underpowered to really show between group differences between persons with and without spinal cord injury. So this is a colleague of mine, so I could say this. I would argue that this is an incomplete study to show inter-group differences between persons with and without spinal cord injury. So EPOC is really not understood in our folks, and it requires further research. So, why does this matter? What is the two most important questions in research, right? So what? Who cares? Why does this matter? Dysregulation of lipid metabolism after SCI is going to contribute to increased morbidity and mortality from cardiometabolic disease in spinal cord injury, right? So cardiometabolic disease is a silent killer, and we believe it is predominantly driven by the obesity pandemic in this population. So we need interventions that target not only the energy expenditure, but we also need interventions that target lipid metabolism in this population. So the PVA cardiometabolic guidelines and the AGREE guidelines are both evidence-based guidelines that are somewhat recently published, and neither of those guidelines provided any sort of recommendation on exercise intensity to treat cardiometabolic syndrome in this population. This is despite the fact that we know in able-bodied folks high intensity exercise has more benefits than low intensity exercise. This is supported also, or not supported, but in 2019 there was a meta-analysis that was published, and they said that low-volume, high-intensity interval training therefore appears to be time-efficient to treatment for increasing fitness, specifically cardio-respiratory fitness, but not for improvement in body composition, right? So it doesn't help to decrease obesity. And meta-analysis in 2016 stated that monotherapies are insufficient to modify component risks of cardiometabolic disease. So what does this mean? We need a joint approach. Exercise and diet must be used collectively together. And I always like to say, even though there's really no data to back this up, it's 25% exercise and 75% what you eat, right? Those are two really important kind of non-evidence-based things you want to remember. So for our folks with SCI, I personally believe that that highly applies. So in summary, we see that our folks with SCI have a limited ability to acutely increase energy expenditure. As a result, we need to do two things. We need to use exercise interventions that will increase their basal resting metabolic rate. So muscle mass is directly proportional to resting metabolic rate. The more muscle mass you have, the more energy you burn at rest, the higher the resting metabolic rate. FES, electrical stimulation, I don't get any kind of kickback from them, but I'm a firm believer in using that for our folks, is really important in increasing basal metabolic rates and resting metabolic rate in our folks. But at the same time we do that, we also have to modify their diets. We need to decrease their energy intake to get below, at least initially, their total daily energy expenditure. And we also want to make sure that they are following a dietary pattern, right? It sounds cliche, but it is extremely important because when you follow a healthy dietary pattern, you know, you naturally eat fruits and vegetables, you have low fat, you automatically decrease your intake of high caloric dense foods. You increase the amount of vitamins and minerals you're eating, you decrease the amount of saturated fat you're intaking, and you decrease the amount of sodium that you intake as well. So it's a double whammy when you do that. These are our references. I want to take a moment and acknowledge Dr. David Gator. This is a crowd that we don't typically, I don't, Dr. Schnage, don't typically present to. I've worked with Dr. Gator for almost 10 years. He was my PhD mentor at Penn State. I did my postdoc with him and Mark Nash at UMiami. He was a mentor, a colleague, a dear friend, and somebody that is going to be greatly missed. And I know for this crowd, he was somebody who was really impactful in the association. And I want to take a moment and just acknowledge his work, his legacy, and that his legacy will live on through his trainees and those he has touched. Thank you. Questions, comments? I want to first thank you all for a wonderful and very detailed explanation towards SEI and obesity. I think a comment I have, though, that exists is practicality. So when you implement any of these strategies, you have to look at the concept of compliance and sustainability. And the biggest factor that I find is when you look at socioeconomic factors is what is their access to these types of nutrition and what is their access to the relative exercise that, you know, you're prescribing here. And I think going beyond just saying physical therapy, what have you, that's a very real problem that we run into. And I appreciate the detail that you go into, but I think we need to also look at how we afford our energies into getting the sustainability and compliance factor so you can make a difference in terms of implementing these changes. The other point I wanted to ask you, when you're saying 0.8 to 1 gram of protein per kilogram of body weight, so you express that there's already a high incidence of obesity and fat there. So is it lean body mass that you mean in terms of that calculation rather than their total body weight? So that calculation uses body weight. They don't differentiate between lean mass or fat-free mass. Because then I would argue then you might be going over their caloric needs. Absolutely. Yep. So body weight is a horrible metric for everybody, not just spinal cord injury, but it's especially bad for spinal cord injury. So a smarter, more efficient way to do it would use lean mass, but I would actually say fat-free mass because that includes the metabolism of the organs as well. Currently there are no estimation equations for fat-free mass and the way you measure that is with DEXA. And that, as we know, is not readily available. I mean we have one in our lab, but for most people they don't have that unless they're getting a bone scan, but you don't see that in your report. So it would make more sense to use metabolically active tissue, but it's not and they use body weight for that. A comment in terms of the socioeconomic status. You know, there is a psychological component, a behavioral component, an education component involved in everything we're talking about. It's lifestyle medicine. So it's extremely true. But if you are interacting with your patients, have them change one thing. It can be as simple as cutting out a 200 calorie can of pop. I'm from the Midwest, so I say pop. So you know, and seeing from one visit to the next, are they maintaining that? Having them easily swap out a bag of chips for something else. Small, small changes have large impacts. They'll notice they're going to feel better. They're not going to feel, you know, it's going to have impacts on bowel, bladder, not just the obesity component that we see. So we know of the dangers of excess body fat, hypertension, dyslipidemia, etc. Your patients, our subjects, might not necessarily see that. But having them in your office and have them make a small change is one way that you can do that. The other thing, to be very blunt, is refer them out to specialists. Exercise physiologists, to dietitians. A lot of our folks with SCI are diabetic. Diabetes is covered for RDs, for insurances. And have them start that way. And then a lot of centers, SCI centers, you know, that we interact with, do have sort of gyms that our folks can come in and use the equipment. Our center, the Miami Project to Cure Paralysis, we have a lifestyle center where they sign up to be part of research studies and they get to use the gym. Other institutions have modeled something similar to that. And it's one way to get fitness into the community. But even something where you are limited, going to a park, doing, wheeling around, you know, is important. Grabbing some light resistance, you know, milk, you know, taking a gallon of milk and lifting that. Not for too long because it might go bad. But that, those are home-based, easily implemented activities that you can do. And if you provide structure to them, rigid structure, and you tell them to do it, do it two days a week. Cut the cans of Coke out, do it, and then do, you know, a little come wheeling around the park two days a week. And then the next session you see them, see if they keep to it. So I think that's some easy, implementable ways to do it. The people who are going to work, it will work for. And the people who it won't work for. But it's a way to start. Any other questions? All right. We have a flight to catch. So thank you.

neurogenic obesity

spinal cord injury

body fat

sarcopenia

metabolic syndrome

adipose tissue

energy balance

weight gain

dietary interventions

exercise