How diet, Type II diabetes and obesity compromise tendon healing

Ross Hauser, MD., Danielle Matias, PA-C., Marion Hauser, MS, RD

In this article we will examine the research surrounding the problems of a broken tendon healing cycle caused by problems of diabetes and obesity.

If you are having concerns about your diabetes and obesity hindering your healing ability, you can get help and information from our Caring Medical staff.

High HbA1c levels cause a higher risk of re-tear following tendon surgery

A February 2023 paper in the journal Arthroscopy (1) assessed whether increased levels of HbA1c levels, impacted the repair and rehabilitation of rotator cuffs three to six months after rotator cuff surgery. Further, did these high HbA1c levels cause a higher risk of re-tear?

A total of 103 patients were analyzed
- The patients were then divided into two groups
  - 47 patients (increased postoperative HbA1c) in Group 1
  - 56 patients in Group D (same or decreased postoperative HbA1c).
The patients with increased postoperative HbA1c re-tear was significantly higher 51.1% (24/47 patients) then those in the Group D (same or decreased postoperative HbA1c) 14.3% (8/56 patients).
The researchers suggested: “glycemic control within 3-6 months after surgery when the healing process of the tendon was in progress had a significant effect on re-tear rate. In particular, the re-tear rate was higher when the HbA1c level increased at postoperative 3-6 months compared to before surgery.”

This research was furthered by doctors at the University of Utah who wrote in the same journal Arthroscopy, (6) “Retear rates after arthroscopic rotator cuff repair continue to be unacceptably high. Of the known risk factors for failure of rotator cuff repair, many are nonmodifiable. Poor glycemic control in patients with diabetes in the first 3 to 6 months after arthroscopic rotator cuff repair is associated with a lower healing rate.”

Preliminary evidence suggests that various nutrients such as proteins, amino acids (leucine, arginine, glutamine), vitamins C and D, manganese, copper, zinc, and phytochemicals may be useful in improving tendon growth and healing.

Doctors at Washington University School of Medicine wrote in a January 2023 paper (2): “Diabetes mellitus (DM) is associated with musculoskeletal complications-including tendon dysfunction and injury. Patients with Diabetes mellitus show altered foot and ankle mechanics that have been attributed to tendon dysfunction as well as impaired recovery post-tendon injury. Despite the problem of Diabetes mellitus -related tendon complications, treatment guidelines specific to this population of individuals are lacking. ”

In the medical publication Nutrition, researcher Luke Curtis wrote that tendon injures cause a great deal of disability and pain, and increase medical costs. However, relatively little is known about tendon biology and healing.

Many tendon-related surgical procedures are not very successful and leave the patient with essentially a chronic injury.
Preliminary evidence suggests that various nutrients such as proteins, amino acids (leucine, arginine, glutamine), vitamins C and D, manganese, copper, zinc, and phytochemicals may be useful in improving tendon growth and healing.

Obese/diabetic tendons healed with increased scar formation and impaired mechanical properties.

In a July 2017 study from the University of Rochester Medical Center, Rochester, New York and the Mayo Clinic wrote in the online scientific journal PLos One (Public Library of Science one) (3) that:

Type II Diabetes dramatically impairs the tendon’s ability to heal resulting in decreased collagen organization and mechanics relative to non-diabetic tendons.
- In other words Type II Diabetes prevents the full production of the collagen building blocks that are needed for any soft tissue healing.
Despite this problem, there is little research or information regarding the mechanisms that govern impaired healing of diabetic tendons.

To bring light to this problem, the researchers placed mice on either a high fat diet or low fat diet and underwent flexor tendon transection and repair surgery to simulate tendon injury and repair.

Healing was assessed via mechanical testing, histology and changes in gene expression associated with collagen synthesis, matrix remodeling, and macrophage polarization.
- What the researchers were looking for was “gene expression associated with collagen synthesis.” The communication between genes that begin the repair process by creating collagen.
- “Matrix remodeling.” This is a fascinating subject on how the extracellular matrix directs healing damaged areas. The matrix is the “bricks and mortar” of wound repair, we cover this at length in our article Extracellular matrix in osteoarthritis and joint healing.
- “Macrophage polarization.” Macrophages clean up injury debris or dead or dying tissue. When there is increased macrophage infiltration, immune cells are invading the areas causing swelling and edema. For more on this subject as it relates to healing and nutrition, see our article Metabolic syndrome and osteoarthritis joint pain.

The findings?

Obese/diabetic tendons healed with increased scar formation and impaired mechanical properties.
Consistent with this, prolonged and excess expression of extracellular matrix (ECM) components were observed in obese/and type II Diabetes tendons.
- What does this mean? Simply Macrophages are designated as MI (These are macrophages that work on infection, virus, and immune response to illness and M2 Macrophages.
- M2 Macrophages are more designed for wound healing and chronic joint pain. Notice above when I said: “When there is increased macrophage infiltration, immune cells are invading the areas causing swelling and edema.” In chronic joint pain, this mechanism does not shut off leading to the problems of chronic inflammation.
As Macrophages are involved in both inflammatory and matrix deposition processes during healing. Obese/T2DM tendons healed with increased expression of markers of pro-inflammatory M1 macrophages, and elevated and prolonged expression of M2 macrophages markers that are involved in ECM deposition.
- What does this mean? The researchers point out: “tendons from obese/diabetic mice heal with increased scar formation and increased M2 polarization (too much broken inflammation), identifying excess M2 macrophage activity and matrix synthesis as a potential mechanism of the fibrotic healing phenotype observed in type II Diabetes tendons tendons, and as such a potential target to improve tendon healing in type II Diabetes tendons.”
- In other words – Fix the broken healing cycle in this case by management of obesity and Type II diabetes!

Advanced glycation end products (AGEs)

Now let’s look at a 2022 paper that expands on this idea. It comes from researchers at Purdue University, the Hospital for Special Surgery, New York and Weill Cornell Medical College. (4) Here is what they write: “Tendon pathologies affect a large portion of people with diabetes. This high rate of tendon pain, injury, and disease appears to manifest independent of well-controlled HbA1c and fasting blood glucose.” In other words, tendons are not healing as they should because of something beyond HbA1c and fasting blood glucose levels. To these researchers it is Advanced glycation end products (AGEs). Very simply an advanced glycation end product is a fat or protein that combines with sugar (the process is called Glycation). These are harmful end products that are considered suspects in teh cause of a large number of diseases. In the scope of this article, tendinopathy is one of those diseases.

Continuing with the research, “Advanced glycation end products (AGEs) are elevated in the serum of those with diabetes. In vitro (laboratory testing), AGEs severely impact tendon fibroblast proliferation and mitochondrial function.” That is the tendon’s ability to heal. In this paper rat Achilles tendons were exposed to AGEs. The outcomes suggest that “AGEs disrupt the tendon fibroblast transcriptome (the processes of developing collagen to repair and replace damaged connective tissue) on a large scale . . . (and) may contribute to the development and progression of diabetic tendinopathy.”

How diabetes patients walk differently than non-diabetic patients and it has something to do with tendons

Our bodies are very clever when it comes to solving the problems of poor tendon healing in regard to diabetes. In a fascinating study from a combined research team in the United Kingdom, Belgium and the United States (the University of Miami) doctors wrote in the medical journal Gait Posture (5) of how diabetes patients walk differently than non-diabetic patients and it has something to do with tendons.

What the researchers were looking at was why diabetic patients expended more energy in walking than non-diabetic patients. This would obviously be an appealing subject for the easily fatigued diabetic patient.

The doctors looked at 31 non-diabetic control patients
22 diabetes patients without peripheral neuropathy (weakness and pain from diabetic nerve damage)
and 14 patients with moderate/severe diabetic peripheral neuropathy

What the doctors found was not the answer as to why diabetic patients used more energy in walking than non-diabetic patients, but something really incredible. Patients with diabetes and mild diabetic peripheral neuropathy, unknowingly reduced ankle movement during walking to provide stability. How? By redirecting energy towards the ankle.

The body has put the ankle in a reduced motion mode to protect against injury from instability not only in the ankle but the Achilles tendon as well. It did so in part by asking the the plantar flexor muscles to generate less power in walking.
The body recognized how Type II diabetes and obesity compromised healing and tried to prevent injury.

How do we handle problems of diabetes in patients looking to heal damaged tissue?

Our main treatment is Prolotherapy injections. These are injections of simple dextrose, a sugar. We have been doing Prolotherapy for many years now, having started in January 1993. We have treated people with brittle or difficult to treat diabetes, those on insulin pumps, as well as many other diabetics (on oral pills and just one insulin/day). Likewise, we have treated people who are a little overweight to those who were very overweight.

So what happens when these people get Prolotherapy? For many, their pain goes away. Obesity, diabetes, and other medical conditions can slow the effects of Prolotherapy. If this occurs instead of the person needing three to six visits of Prolotherapy they may need six to ten visits.

Over the course of the last almost 30 years and having performed thousands of Prolotherapy sessions on diabetics we have found it very well tolerated. Most of the diabetics tell us that it raises their blood sugar only a mild amount (like 10-30 points). This is also for a short time (perhaps a few hours). In regards to those who are very overweight, they do not need to loose weight for the Prolotherapy to help them. We would encourage them to lose weight because it would mean less stress on their joints. When there is less stress on the joints, they need less Prolotherapy. So if they want to need less Prolotherapy, then loose some weight.

For the person with the complicated medical condition, all we can say is that it would be best to get a comprehensive medical evaluation and treatment. The healthier you are the better you will heal from the Prolotherapy. You can still get Prolotherapy alone, but your healing may be slower.

If you are having concerns about your diabetes and obesity hindering your healing ability, you can get help and information from our Caring Medical staff.

References

1 Kim MS, Rhee SM, Cho NS. Increased HbA1c Levels in Diabetics During the Postoperative 3-6 Months After Rotator Cuff Repair Correlated With Increased Retear Rates. Arthroscopy: the journal of arthroscopic & related surgery: official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.:S0749-8063. [Google Scholar]
2 Vaidya R, Lake SP, Zellers JA. Effect of Diabetes on Tendon Structure and Function: Not Limited to Collagen Crosslinking. Journal of Diabetes Science and Technology. 2022 Jun 2:19322968221100842. [Google Scholar]
3 Ackerman JE, Geary MB, Orner CA, Bawany F, Loiselle A. Obesity/Type II Diabetes Alters Macrophage Polarization Resulting in a Fibrotic Tendon Healing Response. bioRxiv. 2017 Jan 1:131607. [Google Scholar]
4 Patel SH, Mendias CL, Carroll CC. Descriptive transcriptome analysis of tendon derived fibroblasts following in-vitro exposure to advanced glycation end products. Plos one. 2022 Jul 26;17(7):e0271770. [Google Scholar]
5 Petrovic M, Deschamps K, Verschueren SM, Bowling FL, Maganaris CN, Boulton AJ, Reeves ND. Altered leverage around the ankle in people with diabetes: A natural strategy to modify the muscular contribution during walking? Gait & posture. 2017 May 19;57:85. [Google Scholar]
6 Chalmers PN, Joyce CD. Editorial Commentary: Rotator Cuff Repair in Patients With Diabetes: Stricter Glycemic Control for the First 6 Months Is Associated With Better Healing. Arthroscopy: The Journal of Arthroscopic & Related Surgery. 2023 Feb 1;39(2):183-4. [Google Scholar]