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English: insulin resistance model

English: insulin resistance model (Photo credit: Wikipedia)

In two earlier blog posts (I and II), I outlined a fairly common extra articular complication of rheumatoid arthritis called metabolic syndrome which is associated with increases in insulin resistance, type II diabetes and cardiovascular disease. Although all of the connections are not fully understood, it is clear to researchers that the systemic inflammation brought about by RA can contribute to metabolic malfunctioning (see this scientific review).

Since I was writing about these topics, it should come as no surprise that metabolic syndrome has become an issue for me. This originally came to the surface when I was receiving Actemra infusions every month. One of the listed side effects of Actemra is an increase in blood pressure and lipids. My rheumy began regularly checking these parameters and we began to see an increase in hypertension and the lipid test results were high and rising over time. I already knew that my cholesterol was borderline going into the use of Actemra. But the dramatic changes, coupled with the lack of efficacy of Actemra in treating RA, were enough to cease using it after five months. But even after stopping Actemra and going on a low fat diet to try to lower cholesterol, the test results kept coming back high. At their peaks over the past few months, my total cholesterol was 293 (target is below 200), high density lipoproteins (HDL) or “good” cholesterol was 33 (target is above 40), low density lipoproteins (LDL) or “bad” cholesterol was 226 (target is below 100), and triglycerides was 469 (target is below 150). The fact that triglycerides were high points to the fact that sugars were going unused and were being converted into long term storage molecules. Insulin resistance was occurring and I was headed towards type II diabetes as my general practitioner pointed out.

My rheumatologist and general practitioner both agreed that metabolic syndrome was a real danger and we developed a comprehensive plan to treat it. I did not want to develop type II diabetes and I felt like a ticking time bomb for a heart attack or stroke. This all seemed surreal as these issues don’t run in my family and I was not really overweight. My body mass index (BMI) was 24.4 which is still in the low category – albeit at the high end (see this simple online BMI calculator). The major culprit must have been the systemic inflammation caused by RA.

My general practitioner commented that eating a low fat diet does not do much to lower cholesterol and that since my triglycerides were high and insulin resistance a real threat, he suggested cutting back on sugars and starches. After much investigation, I found an excellent book on insulin resistance diets. I began to analyze my eating habits and found out that I was eating far too many processed sugars and starches. I’ve learned to keep total carbohydrates to about 30 grams per meal, balance quality carbs with low fat proteins (about a 2 to 1 ratio of carbs to proteins), and snack regularly when hungry. I’ve learned that American diets are full of processed sugars and starches that can wreak havoc on someone with metabolic syndrome. There’s been a complete change in mindset in how I eat. I avoided Atkins, South Beach, and Paleo diets as they are not necessarily designed for insulin resistance and may be difficult to follow long term. A balance in macronutrients – quality carbs from whole grains, proteins, and fats – seems to be the best approach. Of course, I can eat all the green vegetables I want. 🙂

Exercise is another way to stave off insulin resistance as muscles can burn through large amounts of unused glucose in the bloodstream (see this article). RA patients often have trouble remaining physically active that was the case with me over the past few years. While RA is currently active and not under control, I have attempted to go on walks several times a week and started doing some fairly light resistance band exercises when my joints and energy levels permitted. The only medication that was used was a daily dose of the cholesterol lowering statin drug atorvastatin (Lipitor).

At my most recent blood tests last week, the cholesterol and triglycerides are finally within normal parameters – total cholesterol = 136 (target below 200), HDL = 46 (target above 40), LDL = 70 (target below 100), and triglycerides = 99 (target below 150). Cholesterol was down and insulin resistance was no longer an issue! In addition to the dramatic decreases in lipids, my blood pressure has decreased and I’ve lost 10-12 pounds in two months. The spare tire from my waistline is disappearing and my BMI is decreasing. My general practitioner wanted to make sure that I was not prediabetic so he ran a fasting blood glucose test and it came back within the normal range. Thyroid function was also tested since it has so much to do with metabolism and everything came back normal. While it’s impossible to pin the improved metabolic markers on any one treatment or prevention, the systematic and aggressive approaches are probably acting in concert with one another.

Unfortunately, these metabolic syndrome treatments and lifestyle changes have not had a dramatic impact on RA symptoms as they remain uncontrolled. In fact, I predict that if systemic inflammation from RA gets under control, it will help with metabolic issues. But that is another battle that my rheumy and I are systematically tackling right now.

If you have RA, it is critical that you and your doctor regularly monitor your blood pressure, lipids, body weight, and glucose levels to make sure that metabolic syndrome is not running amok. If problems persist, then please be proactive by treating and preventing these extra articular symptoms from having a serious impact on your health and life span.

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Although not publicly well known, scientists and doctors have known for sometime that rheumatoid arthritis is linked to an increased risk for cardiovascular disease (CVD) including heart attack and stroke. The first person I knew with RA some 20 years ago succumbed to heart problems at the age of 62. When I was informed of his death by his family, they immediately attributed his heart problems to the RA.

My doctors have been tracking some of the variables typically connected with CVD including blood pressure, lipids, and insulin. This came about when a sharp increase in these markers were noted while I was taking Actemra infusions (a listed side effect of Actemra). Even though I’m not on Actemra anymore, we continue to track these variables as the increase may be attributed to active RA.

According to a study at the Mayo Clinic, traditional forms of documenting CVD risk don’t necessarily apply to RA patients, particularly those who are seropositive for rheumatoid factor (RF). Traditional predictors of CVD are helpful with RA patients but not sufficient as in general populations. Systemic inflammation inherent in rheumatoid arthritis may play a role in the increased CVD risk (see this review). Some researchers have called for the development of specific CVD predictors for RA patients as a special population with unique characteristics.

My rheumatologist recently mentioned something called “metabolic syndrome” and it’s relationship to RA. Metabolic syndrome involves a set of interconnected risk factors which are related to cardiovascular disease and diabetes (see this excellent overview from the U.S. National Institutes of Health). All of these complex biochemical processes are connected and involve metabolism of food for energy, sugar processing, insulin, insulin resistance, fat/lipids including cholesterols and triglycerides, liver health, food types, excess weight, exercise, and systemic inflammatory responses. Whenever one of the interconnected systems gets out of normal parameters, a cascade of problems may occur which may impact cardiovascular health. In a study published in 2013, it was found that 18-49% of RA patients also had metabolic syndrome which was significantly higher than general populations. These researchers also found that RA patients with higher inflammatory blood markers and those who used corticosteroids were more likely to show signs of metabolic syndrome. Anti-inflammatory treatments for RA including DMARDS and many of the biologicals like anti-TNFs may impact the biochemical pathways involved in metabolism (see this recent study).

Cardiovascular risk is one extra-articular manifestation of RA that can have serious and fatal consequences. All RA patients and their doctors should be aware of the risk factors, closely monitor CVD related factors, and treat as needed. Ultimately, control of RA and it’s underlying systemic inflammation should help lower CVD risk.

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Three cities in three days…that’s been my recent experience as I’ve rambled across the country. Last Thursday, I got up at 4:30 in the morning to catch a 7:00 flight to Spokane for a board meeting and professional conference. After two busy days, I got home to Seattle Friday evening around 10:00 p.m. The following day I drove my daughter over the Cascade Mountains to a soccer game in Ellensburg, Washington. It was a glorious autumn day full of sunshine, sports competition, and turning leaves (at least on the non-evergreen trees). After church Sunday morning, I caught a five hour flight to Alexandria, Virginia for another work-related meeting. And it’s from Virginia on the other side of the country that I sit preparing this post pondering how RA affects travels.

Traveling can be stressful enough without battling RA. Getting out of routine, waiting in lines, sitting cramped in small spaces with crowds, changes in diet, and time zone differences can wear on anyone. But it can wreck havoc on someone with an autoimmune disease that increases fatigue. During these busy few days I’ve made a special effort to take time to relax and allocate energy and resources carefully. Not wanting to have a loss of sleep exacerbate things, I find that the judicious use of a safe sleep medication such as Ambien can work wonders.

That brings up another set of issues – traveling with medications. It just so happens that my scheduled injection of Humira is due while away. As a delicate genetically engineered protein, Humira must stay refrigerated. I carefully packed my auto-injector pen in a portable cooler and threw in three ice packs. I also made sure I had an alcohol wipe and bandage. I placed this in the middle of my clothes for added insulation and checked my bag figuring that it would last the seven some hours of total travel time. When I opened my luggage in my hotel room, it was still a perfect temperature. I quickly placed the medicine in the small fridge in my hotel room and it’s all ready for tomorrow’s injection. In addition to Humira, there’s the assorted other medications that must be brought along and I use a pill organizer keep in my carry-one bag.

With careful planning and preparation, things went swimmingly well. That was until late this afternoon when I decided to get some fresh air and go for a walk around Alexandria. As I returned to the hotel, I noticed my right Achilles getting painful and tight. By the time I got ready to meet colleagues for dinner, I could barely walk on it. Not able to take NSAIDS, I don’t have many treatment choices other than ice and rest. But I will likely blow off the ice since I don’t feel like tracking down the ice machine and finding a bag in which to put it. Based on prior experience and surgeries, I suspect that the tendon is tearing again. I’ll make adjustments and try to stay off it as much as possible knowing that this will be the first topic of discussion when I see my rheumatologist next week.

Thus far it’s been a productive and pleasurable set of excursions away from the comforts and routine of home. Prior planning and careful use of time and energy makes the difference between a miserable trip and an enjoyable one.

Photo Credit Creative Commons License http://www.flickr.com/photos/booleansplit/

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A work colleague made a statement yesterday that many would consider a compliment…”You’ve lost weight.” True enough, I’ve lost about 15 pounds over the past few months. The problem is, I was not purposefully trying to lose weight. There have been no dramatic changes to my diet. On the other hand, exercise had not been much of a possibility due to knee and ankle problems. One would suspect that weight gain would be in order given the lack of exercise. The topic was raised with my rheumatologist in early August and he immediately tested for thyroid problems and diabetes – two common causes of quick weight loss. But both of those tests came back negative. I’ve always been considered skinny. I weighed 129 pounds my senior year of high school (and that was probably soaking wet). Of course, age and changes in metabolism set in but I’ve remained at or below average for weight. So the mystery of the quick weight loss remains unsolved. But I’m beginning to wonder if RA is the culprit.

According to the Johns Hopkins Medical School arthritis website,

“Patients with RA are considered to be at nutritional risk for many reasons. One cause of poor nutritional status in this patient population is thought to be the result of the weight loss and cachexia linked to cytokine production. In patients experiencing chronic inflammation, the production of cytokines, such as interleukin-1 and tumor necrosis factor, increases resting metabolic rate and protein breakdown.” [i]

Interestingly, this statement is under the heading Malnutrition. The medical definition of cachexia is Physical wasting with loss of weight and muscle mass caused by disease.”[ii] Muscle wasting is the most common cause of weight loss in RA patients. [iii] [iv] The only real proposed treatment is physical activity to keep muscle mass as increasing protein intake has no effect. [v] [vi] Treatment with a TNF blocker like Enbrel or Humira may help but studies comparing their use to methotrexate demonstrated no differences. [vii]

Perhaps my metabolism has increased as a result of RA. I’m currently on Humira, a TNF blocker and yet the weight loss continues. In the meantime, I’ll keep stepping on the scale and discuss it again with my rheumy at my next appointment. I guess I should go sign up for a membership at the local pool because no other exercise regimen seems possible at this time.

photo credit Creative Commons License http://www.flickr.com/photos/oter/

 

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This post concludes the series on Weapons in the War Against RA Inflammation. The focus on inflammation is due to the fact that RA is a disease of chronic inflammation. Thus far we’ve  examined Conventional Weapons – NSAIDs, Nuclear Weapons – Steroids, Chemical Weapons– Methotrexate and others, and Biochemical Weapons – biological drugs. The arsenal in the war is vast but comes with pros and cons. 

The historical medical approach to treating RA seems to center on the use of drugs. Out of frustration with the lack of success of treatments, RA sufferers often look for other cures on their own. Indeed, some natural approaches to reducing inflammation may be worth trying. 

I classify natural weapons against inflammation into two categories, Ingested Substances and Physical Treatments. Ingested Substances include supplements, diet, and herbs. It stands to reason that one should be careful what you put into your body. Eating unhealthy food is unwise in general and certain foods even increase inflammation.[i] [ii] Some supplements like fish oil may even reduce inflammation.[iii] There may be interactions between supplements and medications so be sure to tell your doctor about everything you take. A few months ago, in response to reading about a possible relationship between diet and autoimmune diseases (see earlier post), I eliminated dairy and gluten for one month. I didn’t notice any difference before, during, or after this elimination diet. I’m glad because a daily latte is a must (maybe caffeine should be included on the supplement list)! I still try to eat as healthy as possible. I also take fish oil and use flaxseed on a regular, but not daily, basis. 

Physical treatments include procedures and substances applied externally and may include heat or cold, massage, lotions, stress management, physical therapy, exercise, and prayer. [iv] [v] Some of these treatments like heat, massage, and lotions have short term effects. There’s nothing better than spending some time in my hot tub each evening. And I’ll apply a topical to a flaring joint periodically. Stress management is a wise life skill for anyone but RA sometimes causes us to slow down. I think that’s our body’s way to speaking to us that it needs rest. I’m still struggling with that exercise thing and there are many conflicting views about it and RA. I regularly receive prayer for my RA symptoms. 

An examination of natural treatments must be tempered with a word of caution. Beware of quick cure schemes and tonics! Books, websites, and TV commercials are used to prey upon those who suffer from chronic diseases. Run a simple internet search for RA and you’ll find all sorts of claims like, “New breakthrough for arthritis discovered!”, “I was cured of arthritis. You can be too!”, and “Diet can send you into remission.” I apologize in advance for any reader who was hoping to find a miracle, natural treatment for RA in this post because it just doesn’t exist. This quote sums up my view on natural therapies… 

Alternative therapies are popular among people with rheumatoid arthritis, however, they should complement, not replace, conventional care.[vi] 

I offer the following words of advice based on the Weapons series: 

  1. There is currently no known cure for RA and anyone who tells you otherwise is wrong.
  2. Take your prescribed medicines. Particularly those that have a long term impact on RA-induced inflammation like methotrexate and biologicals.
  3. Be willing to try various medicines to see what works. When one doesn’t work or stops working, try something else.
  4. Eat a healthy, balanced diet.
  5. Speak with your doctor about any supplement you take.
  6. Live life with moderation.
  7. Use any safe method for short term relief of pain.
  8. Don’t fall for schemes that prey on the chronically ill who are desperate for a cure.
  9. Hold onto to hope as new anti-inflammatory treatments are always in the pipeline.

[i] http://www.webmd.com/diet/guide/anti-inflammatory-diet-road-to-good-health 

[ii] https://livingwithra.wordpress.com/2009/07/19/the-trio-of-triggers-of-autoimmune-diseases/ 

[iii] http://www.mayoclinic.com/health/rheumatoid-arthritis/AN00198 

[iv] http://www.webmd.com/rheumatoid-arthritis/guide/rheumatoid-arthritis-natural-treatments 

[v]http://www.umm.edu/patiented/articles/what_lifestyle_changes_can_help_manage_rheumatoid_arthritis_000048_10.htm 

[vi] http://altmedicine.about.com/od/arthritis/a/rheumatoid.htm

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The causes of rheumatoid arthritis (RA) and most autoimmune diseases are unknown. This includes celiac, type 1 diabetes, lupus, multiple sclerosis, and ulcerative colitis. That’s a sad thing since these diseases are insidious.

Because of the lack of definitive information about these diseases, there are many speculations running wild around the internet and unsuspecting sufferers look for answers from any place they can find it. I was recently eating in a restaurant and the TV on the wall was running a product infomercial and there was a claim at the bottom of the screen…”Arthritis can be cured”. One of my friends pointed and said, “Look, you better check it out!” Of course, at the bottom of the product’s website is this fine print *The statements on this page have not been evaluated by the Food & Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Since being diagnosed with rheumatoid arthritis, my curiosity and scientific training pushed me deep into the research literature. By far the best work I’ve found is from Alessio Fasano from the University of Maryland School of Medicine. He has an excellent article called “Surprises from Celiac Disease” in the August 2009 issue of Scientific American (you have to suscribe to read it but here is a link to story about the article).

While most of Fasano’s research is with celiac disease (a problem digesting the gluten protein in wheat), his work is beginning to shed light on other autoimmune diseases. He notes that a trio of triggers seems to be present. 1. an environmental trigger, 2. a genetic susceptibility, and 3. a “leaky gut”.

With rheumatoid arthritis, scientists has long suspected that an infection of some sort, an environmental trigger, sets off the immune system. That’s why some of the early medicines, like sulphasalazine, were derived from antibiotics. Some still advocate long term antibiotic therapy for RA (check out the Roadback website). But infectious triggers have never been pinpointed nor fully explained the causes of the disease.

Genetics also seem to be connected. Many people suffering from autoimmune diseases show a genetic marker for some type of histocompatibility leukocyte antigen (HLA). HLA proteins bind to objects that they mistakenly recognize as foreign in the body.  This sets off an immune response where T lymphocytes recognize the “foreign object”, call in reinforcements, and the immune system then fights the “invaders.” During this process powerful inflammatory chemicals called cytokines are released. These cause the symptoms of RA. Cytokine receptors, like tumor necrosis factor (TNF), have been the target of RA research for the past 20 years and resulted in powerful drugs like Enbrel. I’m very thankful that scientists figured this much out because I’m a recipient of their hard work. Enbrel seems to be working well for me thus far. A detailed description of the process can be found at Johns Hopkin’s.

This leads us to the third factor in the trio of triggers – the “leaky gut”. This one has been getting airplay in the internet for some time and I was suspicious when I first heard about it. It does sound rather weird. Up to 2/3 of the immune system lies around the intestines. That makes sense because we ingest so many things into our bodies through our mouths. Our defense system must be ready to combat invaders. The intestines normally have a tight wall that keeps particles from leaking into the rest of the body. Fasano’s work with celiacs is shedding light on how increased permeability of the intestines allows proteins to leak out into the body where they are immediately attacked by the immune system. The role of this in RA is speculative at this point but some relief has been found in some people by controlling their diet (milk and wheat proteins being the most common).

Creative Commons License http://www.flickr.com/photos/jkunz/

Creative Commons License http://www.flickr.com/photos/jkunz/

There are many more questions than answers right now. A quote from the editors about Fasano’s article sums it up, “Surprisingly, essentially the same trio …seems to underlie other autoimmune disorders as well. This finding raises the possibility that new treatments for CD (celiacs) may also ameliorate other conditions.” This gives me hope. Perhaps not for me directly since new and complicated medicines take many years to develop, test, and market. But I have hope for the millions of future sufferers of autoimmune disorders.

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I’ve been feeling so good lately that I actually went outside and worked in the garden today (see photos below to prove it). I cut low hanging tree branches, weeded four beds, and edged four beds with the spade. Granted, I only worked a couple of hours (not all at once) and did not shovel mulch (my wife did that). But it felt so awesome to garden once again. I paced myself and knew when to stop. I hope I don’t pay for it tomorrow.

In addition to the physical work, I accomplished so much work for my job in the past two days. I even found myself up at midnight last night pluggin’ away on the computer.

It feels like my medicine, Enbrel, is really working. I’ve had almost “normal” levels of energy. While I’m still feeling stiffness, pain, and swelling in a variety of joints, it’s not to the point of inactivity. So far, so good. I’ve not taken prednisone steroids in a long time.

I’ve also been reading a lot about the role of certain foods in rheumatoid arthritis. The evidence is mixed but there may be a link between food sensitivities and some arthritis symptoms. I”m not sure where that will lead but for now I’m trying to cut out all dairy…so hard because I love milk, cheese, and ice cream. But I’ve grown to enjoy vanilla soy milk from Costco (except in lattes).

I thank God for such a wonderful set of days!

DSCF2386

A weeded and edged garden bed.

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A pile of branches that I cut. I’ll have to haul them tomorrow.

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