Exercise has long been considered a core component of conservative treatment for osteoarthritis (OA).1 Health organizations — including the Arthritis Foundation,2,3 Centers for Disease Control and Prevention,4 American College of Sports Medicine (ACSM),5,6 and the Osteoarthritis Action Alliance7 — have strongly encouraged individuals with OA and those at risk of developing OA to stay regularly active, advertising the many benefits of exercise for people with this condition.
How exactly does exercise benefit people with OA? What exactly is happening at the joint and molecular level to achieve these benefits?
Exercise Increases Joint Range of Motion
As mentioned in a previous Rheumatology Advisor article, OA results in neuronally-mediated pain responses that promote natural behaviors, such as aversion to and avoidance of pain-inducing activities and self-imposed immobilization in an attempt to thwart further pain exacerbation. Though counterintuitive, immobilization can further promote joint stiffness and changes in viscosity of the synovial fluid inside the joint.
Normal joint synovial fluid contains high concentrations of hyaluronan,8,9 which plays a key role in cartilage biomechanics. Hyaluronan is a polysaccharide that increases joint lubrication and synovial viscosity into the synovial cavity.8 The presence of sufficient amounts of hyaluronan in the synovial fluid reduces the coefficient of friction between the articular cartilages during motion of the joint.10,11
"
Though counterintuitive, immobilization can further promote joint stiffness and changes in viscosity of the synovial fluid inside the joint.
Results of an animal study conducted by Ingram et al discovered that synoviocytes synthesize and secrete hyaluronan in response to cyclic movement of the joint.8 Joint immobilization reduced the concentration of hyaluronan in the synovial fluid,9 decreasing joint lubrication and synovial viscosity and increasing the coefficient of friction between articular cartilages of the synovial joints. Immobilization also decreased the activity and presence of synovial intimal cells compared with active controls, suggesting the existence of mechanosensitive homeostatic mechanisms.9
Synovial fluid exhibits non-Newtonian flow characteristics, meaning fluid viscosity either increases as the fluid is subjected to a low shear rate over time (rheopectic effect) or the fluid viscosity decreases with exposure to a high shear rate (shear-thinning effect).The viscous dissipation effect refers to heat generation from irreversible work done by fluid motion to overcome layers of shear forces in the flow. This viscous dissipation effect manifests as an increase in synovial fluid temperature.10
A case study conducted by Hor et al demonstrated this viscous dissipation effect occurring in the synovial fluid, following oscillations of an artificial hip joint — a finding quite pertinent to patients with OA who have undergone joint replacements.10 This also explains the concept of injections of shear-thinning, hyaluronan-based fluid hydrogels into the synovium of patients with OA to delay the need for arthroplasty.12
Repetitive oscillating movements that occur during walking or daily joint movement increase the joint temperature as heat is generated, both from muscle contractions and the viscous dissipation effect in the synovial fluid. Movement also stimulates the production of hyaluronan, which lubricates the joint and increases ease of motion with a lowered coefficient of friction at the articular surfaces.
These findings explain one of the cardinal symptoms reported by patients with OA: joint stiffness that is typically worse first thing in the morning or after prolonged periods of inactivity. However, they often report that this stiffness and the accompanying pain improves gradually after repeatedly moving the joint.
Flexibility and stretching exercises also help to restore the length-tension balance of the muscles surrounding joints affected by OA. Individuals with OA are prone to developing contractures. However, routine stretching and flexibility training have been found to improve joint range of motion and functional mobility, as well as reduce OA-related contractures and pain with moderate-quality evidence, according to a systematic review and meta-analysis of the literature conducted by Campbell et al.13
Targeted flexibility exercises may also benefit patients with OA prior to arthroplasty.14 Orthopedic surgeons often refer patients with OA to a physical therapist for preoperative assessment of functional impairments, customized exercise recommendations, and a preoperative physical therapy program for the purpose of optimizing surgical outcomes.
Exercise Improves Muscle Strength and Activation
Exercises that progressively strengthen muscles can have numerous benefits for individuals with OA. Arthrogenic muscle inhibition and motor weakness are neurally-mediated consequence of OA disease processes that cause pain, swelling, and inflammation, which in turn activate nociceptor and mechanoreceptor discharges that prevent full activation and contraction of muscles surrounding the affected joints. This neural inhibition can contribute to muscle weakness and atrophy15 and presents as a significant challenge to effective rehabilitation in patients with OA, even after surgery.16
In one study, Rice et al reported that individuals with OA demonstrated γ-loop dysfunction compared against those without OA.15 This finding may explain the marked quadriceps weakness and atrophy seen with arthrogenic muscle inhibition. Muscles around the joints affected by OA do not demonstrate normal motor unit recruitment secondary to dysfunctional spinal reflex pathways, such as the gamma-loop spindle system,16,17 the flexion reflex,16 and the group I nonreciprocal inhibitory pathway.16 Neuromuscular electrical stimulation, transcutaneous electrical nerve stimulation, and cryotherapy in conjunction with pain-relievers and anti-inflammatory therapies may help patients with OA overcome this barrier to muscle activation.16
Other aspects that may accelerate the progression of OA are joint instability18 and impaired neuromuscular control around the joint, as evidenced by impaired varus-valgus proprioception in individuals with medial knee OA.19 Some patients may be at greater risk of developing OA due to ligamentous laxity and proprioceptive impairment, either from previous joint injuries18 or genetic comorbidities, such as connective tissue disorders.20 Other individuals with OA may demonstrate impaired neuromuscular stabilization of the affected joint.19
Muscle strengthening can restore proprioceptive awareness and increase neuromuscular stabilization of the joint by balancing the strength of the periarticular muscles and offloading stress on the articular cartilage.18 Results of a randomized controlled trial (RCT) by Mikesky et al demonstrated that strength training for 30 months compared with range of motion exercises alone resulted in a decreased mean rate of joint space narrowing, implying that increased muscle strength delayed the progression of OA.21
In terms of exercise frequency, duration, and intensity, 3 or more exercise therapy sessions per week demonstrated increased effectiveness for addressing OA-related symptoms and impairments, compared with sessions occurring less than twice per week; although, exercising twice per week may be more acceptable for individuals who are new to exercise or who have more comorbid conditions.22 The ACSM currently recommends the following exercise prescription for individuals with hip and knee OA: 2 sessions per week with 2 to 4 sets of 8 to 12 repetitions at an intensity between 60% to 80% of the individuals 1-repetition maximum for exercises customized to address muscle strength deficits.22
Therapeutic Exercise and Manual Therapy Provide OA Pain Relief and Improve Functional Mobility
Current evidence suggests that muscle strengthening, flexibility exercises, and manual therapy effectively reduce OA-related pain and disability.23-26 If land-based exercises with full loading of the joint are too painful, water-based exercises may allow individuals with OA to stay physically active, while offloading the painful joint.27
Physical therapists prescribe home exercises so that individuals can independently maintain and progress the gains made during therapy sessions. Continuation of these exercises is critical to prevent loss of function, optimize outcomes, and prevent the return of OA symptoms among this population.27
Proprioception/Balance/Kinesiophobia
In a comparative study, Mani et al found that individuals in the earliest stages of knee OA demonstrated loss of proprioception in the hip and ankle joints.28 Lack of neuromuscular and proprioceptive control over adjacent joints can increase stress at the knee joint, potentially accelerating OA disease progression. Studies have also indicated that OA itself can contribute to reduced proprioceptive capabilities due to dysfunctional articular mechanoreceptors, particularly in severe cases of OA.29
Loss of proprioception, arthrogenic muscle inhibition, and avoidance of painful exercise fuels kinesiophobia — the fear of moving. Individuals with OA report a significant fear of falling and injury related to loss of proprioception and decreased range of motion.30 Kinesiophobia, in turn, accelerates disuse atrophy and muscle weakness by discouraging functional mobility, allowing OA to progress.
Weight Loss Through Exercise May Slow OA Progression
Decreased desire or ability to move due to OA-related pain or symptoms may result in increased sedentary lifestyles and weight gain. Weight gain increases joint compressive forces from external reaction forces due to increased load and the larger muscle contractions that are generated.31
Messier et al reported that knee joint compressive forces increase 4-fold for every pound increase in body weight.32 According to another study by Felson et al, the effect of body weight on the progression of knee OA depends on limb alignment. Moderate degrees of knee joint malalignment (genu valgus or varus) together with excess loading due to increased body weight elevated compartmental pressure in the knee joint. This elevated pressure amplified the risk for structural progression of knee OA, resulting in increased articular cartilage and meniscal degradation in compartments with decreased joint space.33
Disease-Modifying Effects of Exercise on OA
Interestingly, both overuse34,35 and disuse34,36,37 of joints contribute to the physiological degradation of the cartilage by upregulating matrix metalloproteinases in articular cartilage, resulting in tissue degradation.34 Excessive mechanical loading activates the gremlin-1-NF-κB pathway, contributing to OA pathogenesis via cartilage degeneration.35 Similarly, mechanical unloading and immobilization induce thinning of the articular cartilage by accelerating aggrecan catabolism and matrix mineralization in chrondrocytes, as well as cartilage matrix degradation and resorption via subchondral osteoclasts.36 Immobilization also alters proteoglycan synthesis.37
Located in the extracellular matrix of cartilage, proteoglycans retain water, giving cartilage the biomechanical ability to absorb high compressive loads. Proteoglycans also protect and regulate the activity of proinflammatory chemicals, growth factors, and morphogens during remodeling and repair of cartilage following tissue injury. Both OA disease processes and joint immobilization trigger proteoglycan degradation and loss of the extracellular matrix, resulting in severe changes to cartilage homeostasis.38
To combat these degenerative changes seen in OA, moderate loading of the joints promotes and maintains integrity of the articular cartilage.34 Results of an RCT conducted by Roos et al revealed that individuals at risk for knee OA who participated in moderate exercise demonstrated increased proteoglycan content in their knee cartilage, as seen on gadolinium-enhanced magnetic resonance images taken after completing supervised exercise 3 times per week for 4 months.39
Moderate loading of the joints is essential to prevent OA progression. Exercise itself can have disease-modifying effects with less likelihood of harmful side effects or unsustainable outcomes, compared with the long-term pharmacological management of symptoms.40-42
Low Impact Exercises
Both excessive joint loading and immobilization contribute to the progression of OA. Healthcare professionals who specialize in movement rehabilitation and exercise prescription, such as physical therapists, can guide individuals with OA by developing a customized therapeutic exercise program to optimize outcomes. This can simultaneously minimize pain, weight gain, and other negative effects while improving strength, range of motion, balance, and functional mobility.39
It is important to educate individuals with OA about the need to avoid exercises that may cause further harm to the joint integrity, encouraging avoidance of repetitive, high impact activities such as running and jumping.43 Walking, cycling, swimming, and water aerobics are low impact activities that reduce stress on the affected joints while also providing moderate amounts of joint loading, movement, and strengthening.4
In short, motion is lotion for osteoarthritic joints. And exercise really is medicine.
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This physician forum is the second part of a 2-part feature on health care for transgender and gender-divergent youth in the United States. The first part outlines the current legislative climate surrounding pediatric gender-affirming care and the health consequences of anti-trans laws.
The following transcription of our physician forum has been edited for clarity and length.
Matthew Eck: Welcome to today's virtual forum in which we will be discussing gender-affirming hormone therapy for transgender and gender-diverse children. My name is Matthew and I will be your moderator today. Before we dive into our questions, I would like to go around and invite each of our brilliant guests to introduce themselves and share a brief description of their current appointments. Let's start with you, Dr Forcier.
Michelle Forcier, MD, MPH: My name is Michelle Forcier. I use “she” and “they” pronouns. I am a pediatrician, but I've been providing gender, sex, and reproductive health care for over 25 years. I am located on the East Coast, and I am a clinician for Folx Health, and I consult across a lot of different agencies.
ME: Thank you, Dr Forcier. How about you, Dr Bethin?
Kathleen Bethin, MD, PhD: Hi, I am Kathy Bethin. I am a pediatric endocrinologist at University of Buffalo, and I've been a pediatric endocrinologist for, like, 25 years. I do all of endocrine, but I'm the lead for our gender health clinic.
ME: Amazing. Thank you, Dr Bethin. And finally, Dr Shumer.
Daniel Shumer, MD: Hi, I am Dan Shumer, I use “he/him” pronouns. I'm also a pediatric endocrinologist and I work at the University of Michigan as the Clinical Director for the Child and Adolescent Gender Clinic. And I've been involved in gender care since the beginning of my career.
ME: All right, thank you, Dr Shumer. I'm going to go ahead and jump into our first question.
What factors do you consider when initiating a pediatric patient on hormone therapy? Do any patient-specific factors influence your opinion on the risk-benefit ratio of hormone therapy?
MF: I think the way I look at gender care and initiating hormone therapy is [that] gender care is a part of human development, it's a part of primary care. It really is a part of understanding how people grow…their hormones, pre-puberty and puberty, adulthood, into their elder years. It's also a way of understanding where people are in terms of their social, emotional, and cognitive development.
Starting people on gender hormones or gender care is really a matter of where they are in the process of knowing who they are, what their gender identity is, and where they are in their gender identity development. And then [determining] if they require anything that is medical, or if they just require more conversation, support, and resources.
So the sort of primary care approach is, first of all, just finding out who the patient is, listening to their gender narrative, and looking at their support and family and resources. And from there coming up with a strategic plan that is developmentally appropriate.
ME: Thank you for sharing, Dr Forcier. Dr Bethin, would you like to add anything to that?
KB: Yeah, I like to get their story of when this began and try to see where they are and have a discussion. I encourage people to refer even the young kids, just so we can talk and let them know what to expect in the future. And then I ask them to come back once a year, just so we can touch base and see if they're still thinking that way.
And most of the time people come to me and they want hormone therapy, but there are even teenagers that are like, “I'm still thinking about this.” And so we just have a conversation and decide when they're ready.
ME: Thank you, Dr Bethin. How about you, Dr Shumer? Would you like to add anything to that?
DS: Sure. I think the first thing I wanted to say is that having a difference in gender identity, itself, is not a medical problem. It's not a mental health problem. But if someone has a difference in their gender identity, and that difference is causing them distress in their life or impairment in certain social or school activities, making it harder for them to function, contributing to poor mental health — there’s a term for that, and it's called gender dysphoria.
When I'm thinking of gender dysphoria as a medical problem, I'm thinking to myself, that's not too dissimilar to other medical problems, like anxiety, for example. If someone has anxiety, you might say, “Well, what's the goal of treatment?” The goal of treatment would be to reduce the anxiety. “What are the treatment options?” There [are] a lot of non-medical treatment options, like seeing a therapist, or avoiding things that make you anxious, or going for a run. And if those things are helpful, and the anxiety is reduced, then that's terrific. But in the case that it's not, you might also consider a medical intervention, like an anti-anxiety medicine, with the goal of reducing the anxiety and improving well-being. And if you decided to use a medical intervention, then you would re-evaluate that as you used it and re-evaluate that every time you saw the patient for anxiety.
If I'm extrapolating that to gender dysphoria as a medical problem, you say, “Well, there [are] lots of treatment options for gender dysphoria.” There's using a name or pronouns that feel most comfortable for you. There's picking clothes out in the morning that make you feel most confident going out to school. When you pick out your clothes in the morning, you might not be thinking, “I'm treating my gender dysphoria today.” But that's sort of how I think of it. You can talk to a therapist about how to cope with the feelings that you're having related to gender.
And I think it's just really important to say something that I think Dr Forcier touched on, which is that not everyone with a difference in gender identity needs or wants to see a doctor. But it's really when someone is having a difference in gender identity and having challenges with that — because their body is either changing in a way that is not in keeping with their gender identity and that's increasing their distress or making it harder for them to function like other children, or not developing the pubertal changes that other people with that gender are experiencing all around them — that [is when] a medical intervention could be considered.
And just like any other medical decision, just like deciding on an anti-anxiety pill, then you have a conversation with [the patient], including what are their personal factors, their other health concerns, their goals. Talk about the potential benefits of the intervention, talk about the potential risks of the intervention, and then make a decision with them and their family about whether starting that medical intervention could be the right next step for them or not.
ME: Thank you so much, Dr Shumer. That segues nicely into our next question when you brought up gender dysphoria and mental health struggles among transgender and gender-diverse youth.
How do you reconcile the potential clinical challenges of hormone therapy (such as loss of bone mineral density, infertility, and consent) while also considering how trans youth experience disproportionate rates of depression, anxiety, and suicidality?
KB: I talk to them about all of these items. I talk about how important it is for your bone health to get vitamin D and calcium and that any pausing of puberty is not healthy for [your] bones. And I remind them that we can't do this forever. Some patients are non-binary, or gender fluid, and that's great that I can block puberty for them, but at some point you have to allow either male or female hormones because it's not good for your bones.
And I talk about fertility, but that's one thing that is a little problematic because they're all too young to decide for sure that they don't want to have biological children. So, I bring it up every time. I'm like, “Okay, you're still good with adopting if you want children?” And I do talk about [the] research, that there might be new ways to have biological children in the future. But I think it's important to keep bringing it up so that they realize that as long as we continue on this path, there is the possibility that [they] won't have biological children.
ME: Thank you, Dr Bethin. Dr Shumer, do you have anything you would like to add to that?
DS: Yeah, I think there was a lot in your question. You talked about bone health. You talked about fertility… [You talked about] consent. I think that we could spend a whole session talking about all of those topics.
I think that, as Dr Bethin pointed out, you do gain bone density [through] exposure to sex hormones. And that's true, whether it's your endogenous hormones or hormones that are provided during gender transition. If you… measure a 12-year-old’s bone density and it's normal, [then] you take that person and put them on pubertal suppression and you re-measure their bone density at age 13, their [dual energy X-ray absorptiometry] score will be lower because you’re comparing them to other 13-year-olds who are now all going through puberty.
But that person will not be on pubertal suppression forever, and once they come off of their blockers or start hormones, there will be resumption of faster bone density accrual. I think that the takeaway, for me, is not to put someone on blockers for longer than they need to be [and] always thinking about the balance of risks and benefits and having open and candid conversations with them about these things, as Dr Bethin mentioned.
I think fertility is a different conversation, depending on the situation and the age. When you have older adolescents that are presenting to care, there [are] options of fertility preservation prior to starting hormones. When you're using pubertal suppression at the earliest stages of puberty, you're having a conversation about endogenous puberty — that your own puberty is required for fertility to occur, and that endogenous puberty has to happen at some point if you want to achieve fertility.
But these conversations have to be had at an age-appropriate level, and also with the parents. At the end of the day, in the room, the fertility conversation can be more or less meaningful to different patients and families. When we're thinking about what's the risk and what's the benefit, if someone feels that the risk of progressing through an unwanted puberty is, for them, so significant and the fertility question isn't of concern, then they may choose to start on pubertal suppression.
But as was mentioned, this is a conversation that doesn't end at the first visit. It's something that needs to continue over time, and [making sure] that patients and parents are understanding these topics, [in] an age-appropriate way, is an important part of our job as doctors in general, but especially in this area of medicine.
I think that when you mentioned the word consent, in the United States, the definition of consent is someone over 18 choosing a medical path. So when we're thinking of children, we use the word assent. And when we're talking with children and their parents about these topics, the parents are proxies for consent. They're consenting to the care that their child is receiving.
I always think [that] the person in the room that's most knowledgeable about the patient [is] the patient. The person that is second most knowledgeable is the parent or guardian, and I'm a distant third — so I really value the input from parents and conversations with parents about what makes the most sense. But we also need the child's assent, and that means that in an age-appropriate way, they're able to understand the medical decision that we're making, that they agree, and that we are continually re-evaluating that assent and understanding at each visit.
ME: Thank you for that, Dr Shumer. Dr Forcier, do you have anything you would like to add to this conversation?
MF: You all put it so well. I think the 2 things I would add are that it really is about 1) risk and perspective and 2) aspects of timing and what we know. And again, you all have addressed that in terms of risk and perspective — the risk of going through the wrong puberty and all the sequelae that we know happens to folks who are not supported in their gender identity over the years vs the risks of either puberty blockers or other gender-affirming hormones, which are usually pretty… safe and effective methods of either temporarily pausing or blocking puberty or starting an affirmation process.
I think the other piece is [that] there are things that we know and things we don't know. We know that support for youth who are wanting to affirm a diverse gender identity is really important. Whether it's family, whether it's community providers, [support is] an important part of their care. What we don't know is we can't predict anybody's fertility. I can't look at a person and say, “You're fertile, and you're not fertile.” There are things that we can't predict. I can't predict that for this 14-year-old, maybe when they're 26 there'll be an aspect of mourning that they don't have their own uterus and they can't carry their own pregnancy. There are things that we can't necessarily predict or know. And we have to act sometimes in the moment of what is the right next best course for this patient, knowing that as pediatric patients and young adult patients, following them over time and adjusting the course of care is really important.
But it comes down to what Daniel was saying, again, listening to that patient. Kids may be minors, but they also know their own experience. They also understand their own lives. And again, parents know their kids, and having those conversations about what's right for them and balancing those risks and benefits and perspective is just so important. Medicine tends to focus on risks, and when we're talking about gender care in the media, the risks are hyperbolized and overdramatized.
That's why the medicine and this type of care should stay [with] the medical provider. It should stay in the patient room with the patient, the parents, and a clinically trained person.
ME: Thank you, Dr Forcier. This next question is particularly for you, Dr Forcier.
All 3 of you have very considerable academic appointments. How would you describe the changes in the medical education system from when you were in medical school to today, regarding health care for trans youth? Are there any current gaps in the education system? What can students and educators do to close these gaps?
MF: Yes! That's an easy way to answer that question — there are lots of gaps. There's lots of opportunities as a pediatrician. I'm all about looking toward the positive and what can we do vs looking at alternatives, and there's a huge potential for change. Gender care is part of human development and we should all [know] about human development as medical providers, gender care, primary care — all of us carry gender hormones.
So, issues of gender and sexuality being a part of being human and development can be integrated into all aspects of medical training. It doesn't have to be a special unit or 3 talks on gender care. It can be integrated into the cardiology case, and it can be integrated into the prenatal care case. It can be integrated into a whole host of normative medical training experiences as we move through. It is important that there [are] times where gender care is especially attended to because it has not traditionally been included in medical curriculum, and because it is a hot topic, in terms of provision of care and in terms of resources and legislation.
Students love gender care. They are ready to go. Medical students want to learn about gender care, they want to be gender affirmative, they want to be gender savvy. And for me, that's one of the most hopeful things about that question — there is a young generation of patients who understand that gender diversity is a normal part of human development and that we are all uniquely gendered because it is a part of individual identity. And there's a whole new group of providers that are ready to go in terms of working with patients and families to provide this care.
ME: Dr Shumer, Dr Bethin, do either of you have anything to add to what Dr Forcier has already touched upon?
DS: One of the joys of my job is [that] I get to be the course director for a medical student elective called “Transgender Health.” And in that elective, our students get to hang out with me, go to the [operating room], go to adult hormone clinics, [and] have some community experiences. We're only able to offer this to 1 student at a time and it's an elective that gets full right away — almost like you're trying to book your Disney trip during spring break and you need to be the first one that logs into the website.
I think that just goes to show that the learners of today are really interested in making care better for gender-diverse populations. And I think a lot of the new initiatives — with regards to including more and more gender training in medical school — have been driven by the medical students themselves because they see that the training is lacking and they know that they need to know this stuff. But the old people — we didn't learn it, and so we don't know how to teach it. So they're trying to find people, like the 3 of us, to step up and be teachers because they want to do better.
I think that, historically, transgender patients have received poor care in our country, [and] people that are transgender are afraid to present to care because they feel like they may be mistreated, or misgendered. In studies of trans folks, [trans people] mentioned that when they go to the doctor, sometimes it feels like they're teaching the doctor, rather than the other way around, about their gender identity; and patients [that are transgender] are sicker before going to the hospital because they wait longer to go because they're afraid of the interactions with the medical community, which had been poor in the past.
In order to do better, we need to teach that youngest generation. But the good news is they're really eager to learn.
KB: And I would have to say that I am so proud of our medical students because they came to us and asked about a trans elective, and we put together something for them and it's a great experience. The young people that have done this rotation are not necessarily going into gender care, but all kinds of different specialties. But they want to learn more about gender health. They formed a group called “OUTpatient,” and at least once a year they have this big get-together where they educate [people] in the community, and it's really nice to see.
ME: Thank you, Dr Bethin. My next question is actually geared toward you specifically.
Some of your presentation and service activities seem to surround helping physicians better understand patients in the context of their community, or where they are in their lives. What do you feel is an overlooked part of the patient-physician discussion surrounding transgender care?
KB: I want to answer a question that I'm not sure that you asked, but I think providers need to ask their patients what they want to be called and how they want to be identified. I think that that's a big missing part of it.
And I'm also answering another question that I don't think you asked, but one of the things I noted was that there [were] a lot of problems because the medical record reflects somebody's dead name if they haven't legally changed it yet. So, I educated our entire Department of Pediatrics, including the registration people and all of the nursing staff and all of the physicians about how important it is to ask people what their preferred name is, what their pronouns are, and to respect that and to look for that in their record.
ME: Dr Shumer, my next question is for you.
How has the current climate surrounding care of trans and gender-divergent youth in the US impacted you or your institution’s approach to working with this population?
DS: I think that the most important tenet that I always think about is that I need to be practicing evidence-based medicine. In this field, we do have evidence to support the notion that patients [who] are struggling with gender dysphoria do better when provided access to gender-affirming care. There [are] longitudinal studies — following patients from before puberty, through pubertal suppression, through hormones, and following outcomes of quality of life and wellbeing — demonstrating improvement in these things. There [are] comparisons of patients that do and do not have access to the care, demonstrating better outcomes for those who do. Retrospective studies of folks that reflect back on whether or not they had access to this care in the past and how they're doing today [are] influenced by that historical access.
And so, when you ask about the climate, I think I always have to go back to keeping the patients front and center in my mind and figuring out with each and every patient what the best course of action may be. While I'm saying that access to gender-affirming care is helpful, it's also not needed for everyone, as I said in the beginning. So really understanding when to apply the care and work with patients about really understanding what they need.
I think that it is hard when there's a lot of misinformation, that patients living in places that are having access problems, I think, are struggling. But what I'll continue to do is point to the evidence and apply appropriate care to the patients that I'm seeing.
"
Yes, do we have lots to learn? Of course, that's just medicine 101. This is patient-centered, consent-based care. That's what we do. We talk to a patient, we figure out what their goals are, what their needs are, how to minimize harm, how to maximize benefit.
Michelle Forcier, MD, MPH
ME: Thank you Dr Shumer. Dr Bethin, Dr Forcier, do either of you have any comments you'd like to add?
KB: I have seen a lot of families moving here from other states where they can't get their treatment any longer. And it's just very heartwarming to see that families are getting up and changing their entire [lives] to help their child affirm their gender.
MF: I think it's also heartbreaking to see persons that don't know medicine, that don't know the evidence — or are outright making misstatements, untruthful statements, for political or personal gain — creating such an atmosphere of distrust, of hatred, of fear. It's not okay to bully children. And a lot of this environment — if we're going to talk about the environment question — is about preventing kids and families from having access to information, from having access to safe and effective therapeutics, from having access to being acknowledged as being an important person as themselves and part of the community. That's an incredible, I think, harm and assault on a particular group of people in our society and our families and lives. And it's wrong.
And I think it's really so scary for kids and families, even if they're not in a state where there's an access problem, they're hearing about it all over the country and all over the world. And even if they have the privilege of being able to move their family, there are people who cannot move. It's always going to be the most disadvantaged that get caught and have the worst end of the deal. And so I think, as a society, as parents, as civic members, as medical providers, that duty to continue to advocate for children, to continue to advocate for particularly vulnerable group[s] of children and [families] is so important.
And like Daniel said, there is evidence. There's evidence that support and listening and authentic self and affirmation have benefits. When people say there's no research and there's no data — that is untrue. And we need to counter it as strongly as the myths and the misinformation that [are] being promoted. Yes, do we have lots to learn? Of course, that's just medicine 101. This is patient-centered, consent-based care. That's what we do. We talk to a patient, we figure out what their goals are, what their needs are, how to minimize harm, how to maximize benefit. It’s nothing shocking or experimental or new. It's taking care of kids and families. It's taking care of patients. And I think it's been waylaid for other purposes.
ME: Thank you all for sharing your experiences and insights today.
Before we wrap up, do any of you have any final thoughts you'd like to share for the group?
DS: I can just share that it's been a privilege to take care of this patient population throughout my career. I think that being a teenager is hard enough by itself, and when you have a difference in your gender identity, that's really hard. So the patients that I'm seeing, especially in light of some of the things we just talked about, are some of the bravest and most courageous people that I've met. And the joy that I get from seeing a patient that was struggling the first time we met, launching out and becoming a happy, healthy, well-adjusted young adult, making their mark on the world — it makes it a pleasure to go to work every single day.
KB: That was so well said and I 100% agree. They come in and they're struggling and after a conversation, you can already see that they're glad that they came. And yes, thank you for saying it so elegantly.
DS: Thank you.
MF: Daniel, you said it very eloquently. It's about being human. It's about being real, and it's about being yourself. We all do better when we're able to be loved and accepted and safe. And gender diverse patients can come see us in these clinical environments to get the medical care and the services they need. But it's also about our community helping kids feel loved and accepted and safe, so every child has the potential to thrive and grow into a super happy, healthy, and wonderful young person and adult.
Disclosures:Michelle Forcier, MD, MPH reported affiliations as a consultant with Folx Health, Planned Parenthood League of Massachusetts, ConferMED, New York University Student Health, and Transhealth.No other speakers declared any potential conflicts of interest.
Recently, telehealth has emerged as a transformative force in health care, effectively overcoming geographic constraints and offering accessible, cost-effective solutions. The role of telehealth is pivotal in elevating adherence among patients with diabetes in rural settings, addressing access challenges, and underscoring the potential for positive outcomes.
Challenges in Rural Diabetes Management
The intricate challenge of diabetes management in rural areas revolves around limited access to health care resources, transportation impediments, a scarcity of health care providers, and insufficient awareness regarding the criticality of regular check-ups. Despite the fact that 20% of the US population resides in rural areas, a meager 10% of physicians currently practice in these regions.1 Consequently, diabetes management in rural communities becomes a formidable hurdle, resulting in suboptimal adherence to treatment plans, and an augmented risk of complications, thereby contributing to unfavorable patient outcomes.
Telehealth as Transformative Solution
Technological progress and the successful adoption of telehealth present an opportunity for health care professionals nationwide to address the longstanding issue of inadequate health care coverage and care barriers. Embracing virtual consultations, remote monitoring, and digital health tools, telehealth emerges as a promising solution to the multifaceted challenges faced by rural populations in managing diabetes. Through the integration of technology, health care providers can establish a virtual bridge, seamlessly connecting patients with diabetes to health care services without the constraints of physical travel.
Benefits of Telehealth in Rural Diabetes Management
The advantages of deploying telehealth technology in rural diabetes management are unequivocal. Telehealth enhances access to care, underscores convenience, facilitates timely intervention, and exemplifies cost-effective, patient-centered care. The utilization of telehealth not only expands access to medical care but also correlates with lower hospitalization rates, reduced readmissions, and decreased emergency department (ED) use. The most robust evidence supporting the positive clinical outcomes of telehealth is found in chronic disease management, breaking geographical barriers, and enabling access to specialized care.2
Overcoming Challenges and Considerations
While the benefits of telehealth are apparent, health care providers must address challenges such as technology literacy, connectivity issues, and regulatory and insurance reimbursement considerations. Acknowledging and proactively addressing these challenges ensures the effective implementation of telehealth in rural diabetes care.
The Future of Telehealth in Rural Diabetes Management
Telehealth stands as a transformative approach to diabetes management in rural health care, providing a lifeline to patients grappling with barriers to regular medical access. As technology advances and health care systems evolve, the seamless integration of telehealth into rural diabetes care holds the promise of heightened compliance, improved health outcomes, and a more inclusive health care landscape.
"
Diabetes management in rural communities becomes a formidable hurdle, resulting in suboptimal adherence to treatment plans and an augmented risk of complications.
Lawmakers, recognizing the impact of telehealth, have expanded access to telehealth services since the COVID-19 pandemic. Continued support from lawmakers and insurance companies is imperative to sustain access to telehealth, coupled with appropriate reimbursement mechanisms. Furthermore, the use of telehealth has demonstrated enhanced compliance and completion of outpatient visits.3,4
By addressing challenges and fostering collaboration among health care providers, policymakers, and technology developers, the full potential of telehealth can be unlocked, empowering rural communities to effectively manage diabetes.
"
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Our easy-to-read fact sheets provide clinicians with reliable information to share with patients and their caregivers.
A predominant risk factor for type 2 diabetes is being overweight or obese, so weight loss goals while maintaining normal blood sugar levels are very important for some patients. In addition to lifestyle modifications, medications for type 2 diabetes may aid in losing weight.1,2
Obesity
Obesity is defined as a body mass index (BMI) of 30 kg/m2 or higher and is associated with many major health issues including cardiovascular disease, osteoarthritis, and type 2 diabetes. A weight loss of 5% to 15% can improve obesity-related complications.1,2
There are approved medications to help treat obesity, including phentermine (Lomaira®), orlistat (Alli®), topiramate (Trokendi XR®), and naltrexone/bupropion (Contrave®). However, these are not indicated to treat type 2 diabetes.3
Type 2 Diabetes
Type 2 diabetes is a chronic disease due to a progressive loss of insulin secretion and/or increased insulin resistance. As a result, the body’s naturally produced insulin becomes less effective in reducing the amount of sugar in your blood. Excess weight or excess percentage of body fat can cause some degree of insulin resistance. Most, but not all, patients with type 2 diabetes have overweight or obesity.
Different antidiabetic medications work through different mechanisms to help lower blood sugar. Some of these medications also provide additional benefits for patients, including weight loss. The medications with weight loss benefits include metformin, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists.2
Type 2 Diabetes Medications That Induce Weight Loss
The following is a list of FDA-approved medications for the management of type 2 diabetes that may also result in weight loss. It is important to note that the amount of weight loss can vary depending on the medication, dose, duration of therapy, and lifestyle changes. Speak with your provider to know additional information.
Simulates GLP-1 receptors to increase insulin secretion and decrease glucagon secretion14
Nausea Vomiting Diarrhea Acute kidney injury Injection site reactions24
Weight Loss Differences
Biguanides
In a long-term study, patients who took metformin maintained an average weight loss of 6.2% between 6 and 15 years of treatment. Patients who experienced greater long-term weight loss were those who (1) lost more weight during their first year of treatment, and (2) were older in age.5,6
SGLT2 Inhibitors
Various studies demonstrate long-term weight loss effects among patients taking SGLT2 inhibitors. In an analysis of multiple studies, patients had an average weight loss of between 1.5 kg and 2 kg after 4 years of treatment. These effects increased with increasing doses of these medications. Other studies have revealed average weight loss percentages between 2.2% and 3.3% of patients’ starting weight.5, 10-12
Other studies show improved weight loss among patients combining SGLT2 inhibitors with other drugs, such as metformin or GLP-1 receptor agonists. SGLT2 inhibitors may therefore be the drug of choice for patients also with heart and kidney disease.22,23 However, low blood sugar is more likely to occur when they are used as add-ons rather than used alone.30
GLP-1 Receptor Agonists
Studies report a wide range of weight loss effects associated with GLP-1 receptor agonists, from 1 kg to 15 kg depending on the medication.15-21 Weight loss effects depend on dose and treatment durations.5
Like SLGT2 inhibitors, GLP-1 receptor agonists can be used as add-on therapies for patients with heart and kidney disease, but low blood sugar is more likely to occur. 22, 23, 30
Frequently Asked Questions
Can I eat anything I want while on these medications?
No, food choices still play a significant role in diabetes management.
Different types of diets for patients with diabetes include Mediterranean, low-fat, low-carb, vegetarian, and vegan diets. Additionally, the Dietary Approaches to Stop Hypertension (DASH) approach could prevent more serious complications such as heart or kidney disease among those who have or are at risk for high blood pressure and high cholesterol.22,23
Diet modifications can also enhance natural GLP-1 and insulin production/sensitivity and prevent escalation of antidiabetic therapies while satisfying nutritional needs.24
Do I still have to exercise while on these medications?
Yes, it is recommended to engage in physical activity regularly, even if on medications that can result in weight loss, to prevent development and progression of heart- and kidney-related complications.
Patients with type 2 diabetes are advised to do 150 minutes per week of moderate to vigorous exercise or 75 minutes per week of high intensity exercise over a course of 3 or more days per week.25 Studies report that physical activity can contribute to increased effectiveness of certain medications, including GLP-1 receptor agonists and metformin.25-27
How can I prevent side effects such as nausea, vomiting, diarrhea, bloating, and constipation?
Metformin can cause an upset stomach on initial treatment so it should be taken with food. Note that these side effects should go away over time, so do not skip doses or stop taking metformin without speaking with your provider.7,8
The initial dose of a GLP-1 receptor agonist or SGLT2 inhibitor is typically low to prevent stomach issues but not high enough to help manage your blood sugar. For this reason, your provider may start you on a higher dose, but you should let them know if the stomach side effects become unmanageable for you.28,29
Can I be on multiple of these medications at the same time?
Yes, GLP-1 receptor agonists and/or SGLT2 inhibitors are preferred over other drug classes as add-on treatments to metformin, especially for patients at risk for heart or kidney disease, according to the American Association of Clinical Endocrinology and American Diabetes Association guidelines.
Before adding these medications, your doctor may consider factors such as heart and kidney disease, potential weight loss, and potential adverse effects.22,23 The use of GLP-1 receptor agonists with metformin may also exacerbate diarrhea.29
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