Distribution of Highly Prevalent Musculoskeletal Disorders and Their Association With Diabetes Complications in a Population of 140 Individuals With Type 1 Diabetes: A Retrospective Study in a French Diabetes Center

Discussion

In this real-life retrospective study, we confirm the high prevalence of MSKDs in a population of individuals with type 1 diabetes. We also highlight for the first time the distribution of MSKDs and show the frequent association of MSKDs with other diabetes complications.

The prevalence of MSKDs in our population was about half that reported by the DCCT/EDIC research group (5), whose population had been selected initially in a randomized controlled trial, was older (mean age 52.2 ± 6.9 years), and had a longer diabetes duration (mean duration 31.1 ± 4.9 years) compared with ours (43.4 ± 15.4 and 22.5 ± 12.7 years, respectively). On the other hand, the MSKD prevalence in the T1D Exchange registry (31%) (6) was quite similar to the one we report (29%). Although the methodology differed among those three studies (5–7), all observed that half of patients with both type 1 diabetes and MSKDs had at least 2 MSKDs.

To our knowledge, this is the first report of the distribution of the main MSKDs in patients with type 1 diabetes. We observed that more than two-thirds of our patients with either tendinitis, CTS, or TF had other MSKDs, including FS for more than one-third of the patients. FS was present in almost half of the patients with MSKDs and was often bilateral. This condition can have specific consequences in patients with type 1 diabetes in that it can severely interfere with diabetes care and especially with the use of FGM because each sensor insertion and each scan requires shoulder motion. Although sensor insertion has to be performed only every other week, the recommended scan frequency is >10 times daily, and much higher if possible (10). So far, the manufacturer of FGM devices has not validated the accuracy of sensors inserted anywhere except the back of the upper arm. Thus, bilateral FS could prevent adequate use of FGM for a long period of time.

Furthermore, FS and DD are often associated, and DD with contracture can reduce the ability to perform fingersticks for self-monitoring of blood glucose in patients who already cannot perform adequately FGM because of FS. Patients with FS could have an eightfold increased risk of DD (11). In our population, four patients had DD, including three with FS. It should be emphasized that all our patients with DD were women. This condition is usually more frequent in men (∼80% of cases), and it could have an especially aggressive course in women (12).

The pathogenesis of retractile disorders and the reasons for the higher incidence among people with diabetes remain uncertain. Genetic predisposition was reported in DD, which has been associated, like type 1 diabetes and other autoimmune diseases, with the HLA DR3 and DR4 alleles (13).

The mechanisms of entrapment syndromes involving nerves or tendons are also complex. Entrapment syndromes occur where there is only a tiny space for the tendon to glide or for the nerve to go, such as in TF or CTS. However, the thickening of the sheath around the nerve or the tendon could also play an important role. For example, in nerve entrapment syndromes, the entrapment is partly the result of the accumulation of sorbitol, which leads, by osmotic effect, to an accumulation of fluids into the sheath (14).

The accumulation of advanced glycation end products (AGEs), especially in pericytes, could also play an important role. Although entrapment syndromes occur even in patients with good blood glucose control, their prevalence increases with rising A1C levels (5), and it can be supposed that sustained high blood glucose levels lead to AGE deposits into the collagen and to joint stiffness (15).

The excess of AGEs also leads to a thickening of the vascular wall and secondary excessive production of growth factors (16), inducing fibrosis (17). AGE accumulation is associated with other diabetes complications such as retinopathy (18) and CVD (19). This link could explain the association we observed between the presence of several MSKDs and having diabetic retinopathy or taking a CV treatment (7). We previously reported in the same study population that diabetic retinopathy was associated with the presence of MSKDs (odds ratio [OR] 4.8 [95% CI 1.2–18.9] for 1 MSKD and OR 18.0 [95% CI 3.1–104.4] for 2+ MSKDs) and that taking a CV treatment was independently associated with the presence of several MSKDs (OR 6.7 [95% CI 1.05–43.3]).

In this study, the mean A1C values of the different subgroups appear not to be associated with the presence or the number of MSKDs. However, because A1C does not reflect glucose variability, further studies should be designed to look at possible associations of CGM/FGM parameters and MSKD status.

Initial nerve or tendon abnormality, combined with entrapment, has been called “double crush syndrome” (20). In this syndrome, the nerve or tendon, which is enlarged because of the accumulation of sorbitol and AGEs in the sheath, is trapped in a tiny space. Ultrasound examination and macroscopic observations during surgery of yellow-colored, thickened nerves (21) confirm this hypothesis.

Because these mechanisms do not respond to corticosteroids, surgery appears to be the treatment of choice for entrapment syndrome in patients with diabetes (22). Moreover, corticosteroid injections can deteriorate blood glucose control—although it can be managed—and are less efficient in patients with either type 1 or type 2 diabetes, having only a 9% success rate at 1 year (23). Finally, it is mandatory for orthopedic surgeons operating on patients with type 1 diabetes to be skilled at using surgical approaches that do not require tourniquets to avoid additional tourniquet-induced neuropathy in patients with damaged nerves (24). All of these considerations and precautions are also valid for patients with type 2 diabetes.

There are limitations to our study. First, it was a real-life retrospective single-center study. However, the retrospective design should not have had any impact on our results regarding the distribution of MSKDs. The size of the population was limited, but this did not prevent us from observing the same prevalence of MSKDs as in the T1D Exchange registry (6). That study included a much larger population, with 1,911 of the 6,199 individuals in the T1D Exchange registry answering an Internet survey. Our study is, by design, representative of the people a diabetologist typically sees in clinical practice. Furthermore, we report the same proportion of patients with 2+ MSKDs as in the two published landmark studies (5,6).

Second, it is possible that some people did not spontaneously report MSKDs. However, because MSKDs interfere with daily life and diabetes treatment, it is likely that participants did report MSKDs in most cases. Moreover, with the exception of tendinitis, which could have been under-reported, entrapment syndromes usually lead to surgery, and it can be assumed that retractile MSKDs (FS and DD with contracture) pose such a heavy burden that they would have been reported. We did not have a control group, but the prevalence of MSKDs in a same-age general population was reported much lower than in our study (at 5.0%) (25). Additionally, the fact that only one diabetologist saw all of the subjects led to homogeneity in MSKD assessment.

Third, regarding the various components of MSKDs, we chose to include Morton’s neuroma even though it has not been strictly associated with diabetes. Nevertheless, Morton’s neuroma is considered to be a type of nerve entrapment (26), and, in our population, the three patients with Morton’s neuroma also had at least CTS.

Finally, many patients in our population were treated with statins. Because toxic side effects of statins on tendons have been described (27), it could be argued that tendinitis was related to a statin side effect. However, only one of the 44 patients on a statin had isolated tendinitis (data not shown), making this hypothesis unlikely.