DIABETES EFFECT ON CONNECTIVE TISSUES
(TENDONS / FASCIA / LIGAMENTS)
All blood sugar dysregulation issues (including HYPOGLYCEMIA, which is an early step on the path to diabetes) share a common denominator — INFLAMMATION. The harsh truth is that SUGAR IS ONE OF THE MOST INFLAMMATORY THINGS (I can’t bring myself to call it a food) that you can put in your mouth. Furthermore, diabetes and the issues leading up to it (including INSULIN RESISTANCE) are themselves considered to be inflammatory (they are not only caused by inflammation, but they cause inflammation as well). You already know what blood sugar does to the nerves of those with diabetes (NEUROPATHY), but today I want to look at what current research says sugar does to connective tissues, including FASCIA, LIGAMENTS, and TENDONS (and even bone — yes, bone is a connective tissue as well).
BLOOD SUGAR, GLYCOSYLATION,
A.G.E.’s, & WOUND HEALING
“At least 9% of Americans are living with diabetes. A foot ulcer is the initial event in more than 85% of major amputations that are performed on people with diabetes. In the United States, every year about 73,000 amputations of the lower limb not related to trauma are performed on people with diabetes. Of non-traumatic amputations in the United States, 60% are performed on people with diabetes.” From 25 Must Know Statistics About Amputation Due to Diabetes on the Azura Vascular Care website
“Diabetes is characterized by chronic hyperglycemia and an altered cellular homeostasis, which lead to diffuse vascular damage and multi-organ dysfunction. Diabetic patients risk both micro- and macro-vascular complications: the former result from damage to retinal, renal, and neural tissues, which is the cause of blindness, end-stage renal failure, and non-traumatic lower limb amputation. Reactive oxygen species (ROS) are the unifying mechanism behind the main pathological pathways triggered by hyperglycemia, one of which leads to the formation of advanced glycation end products (AGEs).” From the October 2016 issue of Intech (A Potential Mechanism for Diabetic Wound Healing: Cutaneous Environmental Disorders)
This creates a situation I’ve spoken of numerous times in regards to a whole host of tissues — THE LEAKIES. Only in this case, the AGES attack the tight cellular junctions in the walls of your arteries, causing the vessels to leak. The body cannot tolerate excess fluid leaking out of its blood vascular system so it patches it with — you guessed it — CHOLESTEROL. This process also leads to an inability to clear HOMOCYSTEINE, a molecule associated with HYPERTENSION and HEART DISEASE, from an increasingly toxic body. On top of everything else, the process leads to the formation of FREE RADICALS / OXIDATIVE STRESS.
Lots of sugar, lots of inflammation, lots of AGES, lots of homocysteine and ROS formation, and you’ll have lots of cholesterol building up in your arteries (which is why 99% of you who were told that your cholesterol issue is due to “BAD GENES” were lied to). This buildup of arterial plaques not only leads to all the things we typically think of (heart attacks, strokes, a lifetime of STATIN DRUGS), it leads to problems with vision (Diabetic Retinopathy) as well as an array of Diabetic Wounds and Ulcers, which tend to get worse in body parts that are farther away from the heart. AGES in your blood can actually be measured by a simple blood test known as the A1C (the HbA1C measures glycosylated hemoglobin). While a fasting blood sugar test measures what you blood sugar is here and now, the A1C provides a longer-term view because it measures the amount of glucose that has attached to the oxygen-carrying protein hemoglobin, over the lifespan of the RBC — about 90 days.
Blood vessels are made up of many layers of both connective tissues and smooth muscles. Attack the connective tissues in arteries and as you will see throughout this post, the arteries will become stiff and inelastic — not a good property for arteries as, among other issues, it always results in high BP. Furthermore, because these AGES block angiogenisis (the production of new blood vessels), your body will have a tough time healing wounds. Take a look at some of the cherry-picked conclusions from a 2006 issue of Diabetes (Receptor for Advanced Glycation End Products Is Involved in Impaired Angiogenic Response in Diabetes).
“One consequence of long-term hyperglycemia is the formation of advanced glycation end products (AGEs); the accumulation of AGEs in the vessel wall has been implicated in the pathogenesis of diabetes complications. Among a variety of AGE receptor or AGE-binding proteins that have been described, the receptor for AGEs (RAGE) is probably the best-characterized molecule. RAGE belongs to the immunoglobulin superfamily of cell surface molecules to which AGEs bind. Recently, RAGE has been shown to be involved in both microdiabetic and macrodiabetic vascular complications. In this study, we showed for the first time that RAGE is involved in impaired angiogenic response in diabetes. Moreover, our results implicate esRAGE as a therapeutic factor to protect impaired angiogenic response in diabetes. In addition to the vaso-degenerative changes, several observations indicated that angiogenic response or development of new vessels in response to local ischemia/inflammation is significantly reduced in diabetic patients and animals.”
Here is how this scenario plays out. Not only does jacked blood sugar cause major issues with the RBC’s themselves, it stiffens the connective tissue in arteries, while causing them to be filled with thick, waxy, plaques that eventually harden to the consistency of stone. When I was doing cadaver dissections at both Kansas State University and Logan College of Chiropractic, it was easy to tell which arteries had “hardened”. Tap them with your scalpel and many would not only feel like you were tapping on a rock, it would actually sound like it as well. The obvious result is a starvation of blood / oxygen / nutrients to all cells and tissues, but particularly those farthest from the heart. It’s not hard to see why this is such an important issue.
According to the American Podiatric Medical Association (Diabetic Wound Care) as many as a quarter, “of patients with diabetes who develop foot ulcers will require an amputation.” A decade old issue of the Journal of Clinical Investigation (Cellular and Molecular Basis of Wound Healing in Diabetes) has a list of, “Over 100 known physiologic factors that contribute to wound healing deficiencies in individuals with diabetes.” I’m going to leave you with a few of them that affect connective tissues.
- DECREASED OR IMPAIRED GROWTH FACTOR PRODUCTION: Many of these are similar to HGH (human growth hormone), and when they are not present, connective tissue cannot grow / repair properly.
- DECREASED ANGIOGENIC RESPONSE: Although this was previously mentioned, it goes along with the previous point. Any tissue or wound healing requires a blood supply in the form of new capillary beds. So not only is blood sugar screwing up the vessels that are already there, it’s preventing new ones from forming.
- DECREASED MACROPHAGE FORMATION: Macrophages are like mini Pac Man units running around and eating cellular debris. As you might imagine, there is an abundance of cellular debris in degenerative diseases like diabetes. A failure to clean this garbage up leaves you both TOXIC and prone to CHRONIC INFECTIONS (macrophages also present antigens such as germs to the T-CELLS so they can be destroyed).
- DECREASED COLLAGEN ACCUMULATION: Without COLLAGEN — nature’s protein building block — how would you ever hope to heal a wound?
- DECREASED EPIDERMAL BARRIER FUNCTION: This is a no-brainer. Diminished quality of the tissues that make up the skin, and it won’t be the barrier is was meant to be.
- DECREASED QUANTITY OF GRANULATION TISSUE: Granulation Tissue is simply the name for new connective tissue and it’s capillary bed that forms on wound surfaces during the healing process. You could have deduced this from what we’ve already seen.
- DECREASED KERATINOCYTE AND FIBROBLAST MIGRATION & PROLIFERATION: FIBROBLASTS are the cells that create Collagen. Keratinocytes are the cells that create keratin — a fibrous structural protein that not only makes up hair and fingernails, but is the tougher outermost layer of the skin.
- DECREASED NUMBER OF EPIDERMAL NERVES: This is a hallmark of NEUROPATHY. Just today I talked to a patient who had a relative who dropped a huge chunk of wood on their foot, and never felt it or knew it had been broken because they can no longer feel their feet. This person was under forty.
- DECREASED BONE HEALING: For those not in the know, bone is a connective tissue.
- FOULED UP BALANCE BETWEEN ECM COMPONENTS AND THEIR REMODELING: Although in some connective tissues the process is slow, while in others it’s very rapid, they are always being remodeled (broken down and built back up) by the body. Higher blood sugar skews this process towards the catabolic (breaking down) side of the equation, while moving it away from the anabolic side (building up). ECM is an important part of all connective tissues, including fascia.
MORE ON DIABETES & CONNECTIVE TISSUE
One of the things I talk about at length to my patients is the importance of full and unrestricted Ranges of Motion (ROM). Lose ROM and it not only tends to cause pain, but is a huge factor in developing DEGENERATIVE ARTHRITIC CONDITIONS. We see this occurring in something known as Diabetes Induced Limited Joint Mobility (LJM). In fact, a 2011 study from the Journal of Musculoskeletal Medicine talked about this in regards to it’s ability to mimic several common issues associated with adhesed fascia (DUPUYTREN’S & PALMAR FASCIITIS were discussed). “Limited joint mobility (LJM) is a common complication of diabetes mellitus (DM). LJM often is characterized by hand stiffness, but other joints may be involved. The prayer and tabletop signs is a condition characterized by hand stiffness resulting from flexion contractures of the fingers and by thickened, tight, waxy skin. “LJM” is the newer, preferred term used in describing the condition because joints other than those in the hands (eg, in the wrists and elbows, feet, and spine) also may be involved.“
The problem with diabetes attacking connective tissues is so large that Dr. Frits Holleman (MD / Ph.D), Professor of Medicine at the Academic Medical Center in Amsterdam, wrote an article for Diapedia called Connective Tissue Disorders, noting how AGES particularly attack collagen. “In the pathogenesis of diabetes complications various processes play a part. One of these is the formation of Advanced Glycation Endproducts (AGEs) in blood and tissues by irreversible binding of glucose degradation products to proteins such as albumin, myelin and collagen.” Some of the problems he associated with diabetes included, “Limited Joint Mobility (LJM), Dupuytren´s disease, Flexor tenosynovitis (Trigger finger), Carpal Tunnel Syndrome, Shoulder capsulitis (Frozen shoulder), Stiff hand syndrome, Scleredema diabeticorum (also known as Scleroderma diabeticorum), and Necrobiosis lipoidica (diabeticorum.” None of this is new information as Holleman’s statement was virtually identical to the conclusions of a 1996 issue of Endocrinology & Metabolism Clinics of North America (Connective Tissue and Joint Disease in Diabetes Mellitus).
In 2006, The Journal of the CCA (The Musculoskeletal Effects of Diabetes Mellitus) contained a list of the various side effects seen when diabetes attacks various collagen-based connective tissues (although muscles are not officially a connective tissue, I’ll include them here).
- MUSCLE CRAMPS: These authors gave many metabolic pathways that this occurs, including loss of electrolytes. After concluding that, “electrolyte imbalances are common in people with Type II diabetes,” the authors of a 2015 New England Journal of Medicine study (Electrolyte and Acid–Base Disturbances in Patients with Diabetes Mellitus) discussed the ways that this disease adversely affects your body’s intricate ACID / ALKALI balance. Why? Because all of these electrolytes are ions that have either a positive or negative charge. Too much positive charge (H+) and you’ll be acidic. Not enough negative charges (OH-) and you’ll be acidic as well. It’s why uncontrolled diabetes leads to ketoacidosis (not to be confused with KETOSIS that occurs purposefully as the result of a Ketogenic Diet).
- DIABETIC MUSCLE INFARCTION: Also known as Spontaneous Diabetic Myonecrosis, this is when a muscle, due to a non-blood clot related occlusion, dies because it can’t get enough oxygen. Not super common, but admittedly “under-diagnosed” by numerous studies.
- CRPS: Although it used to be called Reflex Sympathetic Dystrophy (RSD), Complex Regional Pain Syndrome (CRPS) is what happens when the nervous system gets tipped way beyond standard, run-of-the-mill SYMPATHETIC DOMINANCE that is so common in today’s pedal-to-the-metal society. A study from one of last year’s issues of the Annals of Rehabilitation Medicine (Relationship Between HbA1c and Complex Regional Pain Syndrome in Stroke Patients With Type 2 Diabetes Mellitus) concluded plainly that, “Diabetes is considered highly related to CRPS occurrence.” BTW, one of the visible manifestations of CRPS is that the skin and fascia of the affected areas thickens.
- HYDROXYAPATITE DEPOSITION DISEASE (HADD): A year ago in September, the journal Radiology Research and Practice (Calcium Apatite Deposition Disease: Diagnosis and Treatment) concluded that, “Calcium apatite deposition disease (CADD) is a common entity characterized by deposition of calcium crystals within and around connective tissues. An association has also been found between adult onset diabetes and calcific tendinitis.” That association is that diabetics are about 300% more likely to have this issue than non-diabetics.
- LIMITED JOINT MOBILTY (LJM): We discussed this earlier.
- DIABETIC STIFF HANDS SYNDROME (DSHS) / CHEIROARTHROPATHY: This is the part of LMJ above that affects the hands and wrists. How common is it? A study from a 2013 issue of the Annals of Medical and Health Sciences Research (Prevalence of Hand Disorders in Type 2 Diabetes Mellitus and its Correlation with Microvascular Complications) concluded that, “Physicians have long recognized the association between diabetes mellitus and several pathologic conditions of the hand. Diabetic foot has always been a point of worry for treating physicians but complications like diabetic hand syndrome might not have gained enough recognition. Diabetes is complicated by musculoskeletal problems of upper extremity and particularly the hand, collectively referred as “the diabetic hand.” This study found that the hand disorders were present in two third of the patients of type 2 diabetes.” Re-read that last sentence if you didn’t quite grasp (no pun intended) its implications.
- NEUROPATHIC JOINTS: We already know that the neurology of diabetics is affected severely. We also know that many, maybe most, neurological diseases have their origins in blood sugar dysregulation. Thus, it can’t be a surprise to see that joints are affected neurologically as well. And if joints are affected, we see that not only is bone affected, but cartilage also — yes, cartilage is the last of the main connective tissues we had not yet mentioned. Also called Charcot Arthropathy or Diabetic Osteoarthrothapy, Medscape says, “Charcot arthropathy results in progressive destruction of bone and soft tissues at weightbearing joints; in its most severe form, it may cause significant disruption of the bony architecture. Charcot arthropathy can occur at any joint; however, it occurs most commonly in the lower extremity, at the foot and ankle.” Just last year the journal Diabetes Research shed even more light (Charcot Neuropathic Arthropathy of the Foot: A Literature Review and Single-Center Experience) by concluding that, “Charcot neuropathic osteoarthropathy of the foot is a relatively common complication of diabetic neuropathy. Incorrect diagnosis and improper treatment often result in the extremity having to be amputated.” This happens because when DIABETIC NEUROPATHY is present, people can’t feel their joints (particularly their feet) due to a massive loss of PROPRIOCEPTION (abnormal joint function always causes joint degeneration).
- CARPAL TUNNEL SYNDROME: Once you realize that this diabetes-induced thickening or “DENSIFICATION” of the tissues of the hand and wrist occurs at the FLEXOR RETINACULUM (a cross between a fascia and a ligament), it’s easy to see why diabetes would be associated with CARPAL TUNNEL SYNDROME.
- ADHESIVE CAPSULITIS / FROZEN SHOULDER SYNDROME: There are dozens upon dozens of articles linking Frozen Shoulder to type II diabetes. Just last month, an article in Very Well called Adhesive Capsulitis and Diabetes: Diabetes and Frozen Shoulder stated, “The shoulder joint capsule actually adheres (or sticks) to the head of the humerus bone. The humerus is the long bone that extends from your shoulder to your elbow. The joint capsule is a protective sleeve of connective tissue that surrounds the joint.” Last year, researchers from England published a study in the journal MLTJ called Adhesive Capsulitis of the Shoulder and Diabetes: A Meta-Analysis of Prevalence, that looked at over 5,400 studies and determined that “A high prevalence of adhesive capsulitis exists in diabetes, and an equally high prevalence of diabetes is present in adhesive capsulitis.” How high? Depending on the study, incidence was anywhere from 3 to 8 times higher than the non-diabetic population.
- TENOSYNOVITIS: Tenosynovitis is an inflammation of the fluid-filled membrane that surrounds certain tendons — particular those in the hands — usually manifesting in the form of trigger fingers or a thumb issue known as DeQUERVAIN’S SYNDROME. In a study from Diabetes Care (HbA1c Values Determine the Outcome of Intrasheath Injection of Triamcinolone for Diabetic Flexor Tenosynovitis), the worse the blood sugar values, the greater the chance that treatment would not be effective. Furthermore, “Tenosynovitis has a reported incidence ranging from 1.7 to 2.6% in the general population. However, the incidence of tenosynovitis in diabetes is reported to be between 10 and 20%.“
- DUPUYTREN’S CONTRACTURE: This is a thickening of the palmar surface of the hand (see earlier link).
- OSTEOPOROSIS: Both OSTEOPOROSIS and diabetes are in the “inflammatory” family of diseases. Our government’s own NIH talks about this link in an article called What People With Diabetes Need to Know About Osteoporosis. As far as peer-review, the studies are numerous. One of the best can be found in a 2014 issue of the International Journal of Endocrinology (Osteoporosis, Fractures, and Diabetes). “It is well established that osteoporosis and diabetes are prevalent diseases with significant associated morbidity and mortality. Patients with diabetes have an increased risk of bone fractures. In type 1 diabetes, the risk is increased by 6 times and is due to low bone mass. Diabetes itself is associated with increased risk of fracture, although T2DM is often characterized by normal or high bone mineral density (BMD). Thus, diabetes may be associated with a reduction of bone strength, that is, not reflected in the measurement of BMD.” In other words, a bone density examination (DEXA Scan) not likely to give you anything helpful as far as osteoporosis is concerned.
- OSTEOMYELITIS / SEPTIC ARTHRITIS: These pertain to infections of the bone. And while not particularly common, diabetics are at far greater risk simply because they are at far greater risk of infections period. Why? Because in the same way that SUGAR FEEDS CANCER, sugar also happens to be ROCKET FUEL FOR INFECTIONS (this included DYSBIOSIS).
- DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS (DISH): I’ve seen plenty of DISH in my day, and I cannot recall one that was in a person that was not either diabetic, or functionally a diabetic (obese, sedentary, poor diet, etc). On x-ray, DISH looks like someone poured wax down the spine (huge amounts of calcification). The authors of this list trotted out twenty year old research showing that possibly over a quarter of diabetics will develop DISH.
- OSSIFICATION OF THE POSTERIOR LONGITUDINAL LIGAMENT: The PLL is a long ligament that runs the length of the back of the vertebral body (which puts it inside the spinal canal acting almost like a lining for the spinal cord). As I have written before pertaining to SPINAL STENOSIS, when this ligament thickens or calcifies (ossifies), it crowds the spinal cord. The result is spinal stenosis or a shrinking of the spinal canal. It’s a miserable problem that can affect either the neck or the low back, and is often accompanied by RADICULOPATHY or SCIATICA.
Much of what you see on this list this boils down to what are known as crosslinks. Connective Tissues — particularly fascia — look somewhat like netting under a microscope. There are, of course, the main fibers that run parallel to each other, but there are the cross-links that keep these main fibers in line. While having more cross-links tends to make tissue stronger and more stable, it also makes it stiff and inelastic. Listen to what renowned podiatrist, Dr. Emily Splichal, says in her book called Barefoot Strong: Unlock the Secrets to Movement Longevity.
“Although crosslinks provide strength and stability, excessive or what are called non-specific crosslinks create stiffness and a lack of elastic recoil in the connective tissue. It is these non-specific crosslinks we call fascial adhesions. These non-specific crosslinks are formed through a process of glycation, which occurs in the presence of excess glucose. These AGES are responsible for forming non-specific crosslinks in collagen, resulting in stiffer and non-elastic fascia and tendons. The stiffer the connective tissue, the increased risk of tearing during dynamic movement.”
this is why there are others that could be added to the list above. For starters an article in Everyday Health (The Role of Fascia in Rheumatoid Arthritis) talked about the link between RHEUMATOID ARTHRITIS and problems in the fascia. WebMD upped the ante earlier this year in an article called Rheumatoid Arthritis and Diabetes: Are They Linked? In it they said, “research shows that RA raises your risk for diabetes by about 50%. And diabetes raises your risk of having arthritis, including RA and arthritis-related issues, by about 20%. Nearly half of American adults who have diabetes also have arthritis.” And how about PF.
PLANTAR FASCIITIS (PF) affects millions of Americans each year, and if not dealt with properly can be debilitating. In a study led by Dr. Maria Craig of Sydney’s Institute of Endocrinology and Diabetes in Australia (Plantar Fascia Thickness, a Measure of Tissue Glycation, Predicts the Development of Complications in Adolescents With Type 1 Diabetes) her team concluded exactly what the title said, that the thickness of the PF is an “alternative index of tissue glycation and a marker of microvascular disease.” Granted, this was for Type 1 diabetics, but I’ll bet you a dime to a dollar that the same would be true for Type 2’s. By the way, you see the same thing for something known as plantar fibromatosis, which is essentially Dypyertyns of the bottom of the foot instead of the palm of the hand.
Before we cover our last topic of the day (tendons), I want to take a moment to discuss the relationship between diabetes and the odds of developing POST-SURGICAL ADHESIONS. Not only is it easy to find studies discussing the increased risk of diabetics developing post-surgical SCAR TISSUE, but having this disease dramatically increases their chances of the incision site not holding (HERE). An August study published in the journal Hernia (Advanced Glycation End Products as a Biomarker for Incisional Hernia) concluded…
“Incisional hernia is one of the most frequent complications after abdominal surgery, with incidences up to 30%. Advanced glycosylation end products (AGEs), also known as non-enzymatic collagen crosslinks, are correlated with aging, smoking, hyperglycemia, hyperlipidemia and oxidative stress. Due to the auto-fluorescent properties of AGEs, measurements can be carried out on the skin using auto-fluorescent readers (AF readers). The levels of accumulated AGEs measured in the skin correlate with systemic AGE levels. A preoperative screening tool or biomarker for postoperative surgical complications may be helpful to select patients who are fit for surgery. This could lead to prevention of major complications like wound complications or anastomotic leakage. AGE accumulation measured in the skin indirectly with autofluorescence might be associated with incisional hernia.”
I do want to briefly mention one more problem before we move on; something called Necrotizing Fasciitis. Although NF is not common, it’s an increasingly bigger issue thanks in part to diabetes. Less than two weeks ago, Medscape said of this problem: “The frequency of necrotizing fasciitis has been on the rise because of an increase in immuno-compromised patients with diabetes…. Necrotizing fasciitis is a rapidly progressive inflammatory infection of the fascia, with secondary necrosis of the subcutaneous tissues. The speed of spread is directly proportional to the thickness of the subcutaneous layer. Necrotizing fasciitis moves along the fascial plane.“
BLOOD SUGAR’S EFFECTS ON TENDONS
“The tendons connect muscle to bone or to specific structures or organs—for example, the eye. Tendons are flexible but non-elastic cords made up of a specific type of protein, collagen. In Type 2 Diabetes, there are a number of tendon conditions that can be relatively common. These conditions are usually associated with poor blood sugar control as well as by how long someone has been diagnosed. Diabetic patients are at higher risk for these tendon conditions, likely because of the inflammation that is consistent with high blood sugar levels. Poor glycemic control— chronic high levels of blood sugar—cause the formation of advanced glycation end products or AGEs. The critical characteristic of AGEs that can cause tendon (and other) damage is that they can form chemical cross-links between proteins. Think of it as ropes that are tangled with each other and all knotted up—these ropes aren’t useful anymore. When proteins and other molecules become cross-linked—they lose their function. The risk of tendon disorders also increases in diabetic patients who also have diabetic neuropathy.”
This last sentence is a huge deal because I am not only seeing tons of younger Type II diabetics in my clinic (it’s no longer uncommon to see teens with Type II), but increasingly younger patients with Diabetic Neuropathy. In fact, I’ve previously shown you that as many as half of those with neuropathy don’t know it because even though it would be detected on a test, they have not had major loss of sensory or motor function (OR SEXUAL FUNCTION) —- yet. This is why there are studies showing that by the time people are actually diagnosed with T2D, half will have some degree of neuropathy. And if you have neuropathy, you will have tendon issues (HERE). Much of this has to do with the fact that tendinosis is both an inflammatory and a degenerative problem (HERE).
What’s my best advice to you? The first point would be to realize that while sugar is heavily associated with Type II diabetes, T2D is not so much a sugar issue as it is an inflammation issue. In other words, there are a myriad of drivers of inflammation other than sugar that could be the chief culprit in diabetes. It’s is why reading THIS POST is important, and helps explain why some people go on strict low carb diets but cannot control their blood sugar. I not only show you what diets typically work to combat diabetes, but how to potentially rid your body of diabetes-inducing inflammation as well.