Open Access Original
Article
DOI: 10.7759/cureus.13844
Association Between Diabetes Mellitus and Carpal
Tunnel Syndrome: Results From the United
States National Ambulatory Medical Care Survey
Jason Low 1 , Adrian Kong 2 , Grettel Castro 1 , Pura Rodriguez de la Vega 1 , Juan Lozano 1 , Marcia Varella 1
1. Department of Translational Medicine, Florida International University Herbert Wertheim College of Medicine,
Miami, USA 2. Department of Orthopedics, Florida International University Herbert Wertheim College of Medicine,
Miami, USA
Corresponding author: Jason Low, jlow004@fiu.edu
Abstract
Background
Carpal tunnel syndrome (CTS) is the most common compression neuropathy in the upper limb. While
various risk factors have been linked to CTS, the role of diabetes mellitus (DM) in the development of CTS
remains unclear. Previous studies have failed to consistently demonstrate a clear association between DM
and CTS due to variations based on the geographic setting and differences in the study design. The objective
of this study was to assess if there is an association between DM and CTS using population-based data from
the United States.
Methodology
We used data from patients ≥18 years old who contributed to the National Ambulatory Medical Care Survey
between 2006 and 2015. The outcome was CTS identified by the International Classification of Diseases-9Clinical Modification codes (354.0 and 354.1), and the main independent variable was physician-reported
diabetes status. Multivariable logistic regression was used to adjust for confounding variables. Odds ratios
(ORs) and 95% confidence intervals (CIs) were reported. Stata v15 was used for all analyses.
Results
Among the patients included in this study (n = 322,092), 13.5% were reported to have diabetes while 0.55%
reported CTS. The unadjusted odds of having CTS among patients with diabetes was 0.92 (95% CI: 0.74-1.14;
p = 0.447). After adjusting for confounding variables, the association remained not statistically significant
(adjusted odds ratio [aOR]: 0.84; 95% CI: 0.65-1.09; p = 0.203). Other variables independently associated
with CTS included age 50-59 (aOR: 1.91; 95% CI: 1.49-2.45; p < 0.001), female gender (aOR: 1.31; 95% CI:
1.09-1.58; p < 0.004), and current tobacco users (aOR: 1.32; 95% CI: 1.07-1.63; p < 0.01).
Conclusions
Received 02/22/2021
Review began 02/28/2021
No association was found between DM and CTS in adult ambulatory patients in the United States, but results
should be considered in light of potential outcome misclassification.
Review ended 03/10/2021
Published 03/12/2021
© Copyright 2021
Low et al. This is an open access article
distributed under the terms of the
Creative Commons Attribution License
CC-BY 4.0., which permits unrestricted
Categories: Endocrinology/Diabetes/Metabolism, Orthopedics, Epidemiology/Public Health
Keywords: carpal tunnel syndrome, diabetes mellitus, association, national ambulatory medical care survey
use, distribution, and reproduction in any
medium, provided the original author and
source are credited.
Introduction
Carpal tunnel syndrome (CTS) is the most common compression neuropathy in the upper limb [1]. In the
general population, the prevalence of CTS is approximately 2.1% for men and 3.0% for women [2]. CTS is
characterized clinically by numbness, tingling, and pain in the median nerve distribution [3]. While the exact
etiology of CTS is not fully understood, researchers agree that the condition is caused by a compression of
the median nerve as it passes through the carpal tunnel of the wrist, leading to ischemia and subsequent
segmental demyelination [4].
Diabetes mellitus (DM) has been proposed as a risk factor for CTS. DM is one of the leading causes of
disability (affecting 9% of the global population and 10.5% of the US adult population) [1], and is a rapidly
growing global health issue affecting 420 million people worldwide. Although the pathogenesis linking DM
to CTS is not well understood, studies propose that the cause is multifactorial [4,5]. In the hyperglycemic
state, excess metabolism of glucose leads to intracellular sorbitol accumulation in the neuron and the
adjacent Schwann cells. Ultimately, this leads to axonal degeneration and segmental demyelination of the
nerve, making it more vulnerable to compression with a lower threshold to develop CTS [4].
How to cite this article
Low J, Kong A, Castro G, et al. (March 12, 2021) Association Between Diabetes Mellitus and Carpal Tunnel Syndrome: Results From the United
States National Ambulatory Medical Care Survey. Cureus 13(3): e13844. DOI 10.7759/cureus.13844
Studies reporting on the association between DM and CTS vary greatly on the magnitude based on the
geographic location where the study took place; the association was reported to be lower in populationbased studies than in hospital-based studies [4,6-8]. A study from a university hospital in Turkey found that
the odds of CTS was 60 times higher in the DM group compared to the control group (odds ratio [OR]: 60;
95% confidence interval [CI]: 13-246) [6]. Population-based studies in Sweden and Taiwan reported a
moderate association between diabetes and CTS [4,7,8] (hazard ratio [HR]: 2.10; 95% CI: 1.65-2.70 for the
Swedish study [4]; HR: 1.31; 95% CI: 1.28-1.34 for the Taiwan study [8]). Furthermore, different approaches
to address confounders may have contributed to variations in the associations assessed, as several studies
assessing type 2 DM and CTS did not find associations once age, gender, and body mass index (BMI) were
adjusted for [3,9].
Whether the source of heterogeneity among research findings was due to differences in the target
population or unmeasured confounding variables is yet to be assessed. In the present study, we aimed to
assess if diabetes status is associated with CTS diagnosis using data from a national sample of adults under
ambulatory care in the United States to improve the generalizability of results for community-dwelling US
adults.
Materials And Methods
We conducted a secondary analysis of data from the National Ambulatory Medical Care Survey (NAMCS).
The NAMCS is a sample of visits to non-federally employed office-based physicians, community health
centers, and advanced practice providers (nurse practitioners, physician assistants, and certified nurse
midwives) who were primarily engaged in direct patient care. Data were collected by assigning each
physician randomly to a one-week reporting period. During this period, data from a systematic random
sample of visits were recorded using a computerized patient record form [10].
The study sample consisted of all adults >18 years old who participated in the NAMCS from 2006 to 2015. We
chose to study the adult population because pediatric CTS is rare and has a unique etiology [11]. We excluded
patients with cervical radiculopathy, brachial plexopathy, and peripheral nerve trauma as these conditions
can cause peripheral neuropathy and potentially mask the symptoms of CTS. These conditions were
identified based on the International Classification of Diseases-9 (ICD-9) code recorded as other diagnoses
related to the visit, including chronic conditions. Lastly, patients with missing or incomplete age, gender,
smoking status, and BMI data were excluded from analyses.
The primary independent variable was current diabetes status on record, collected systematically by the
NAMCS. The dependent variable was patient-reported diagnosis of CTS listed as a chronic condition or
diagnosis related to the visit (noted as ICD-9-Clinical Modification code 354.0). Other variables known to
influence the risk of carpal tunnel such as age, sex, BMI, obesity, smoking status, race, ethnicity, and history
of hypothyroidism, chronic kidney disease, rheumatoid arthritis, psoriatic arthropathy, and asthma were
assessed for their potential role as confounders.
Descriptive analysis was performed to assess the characteristics of the sample, followed by bivariate analysis
to assess the distribution of the selected characteristics according to diabetes and CTS status. Multivariable
logistic regression models were finally used to determine the association between diabetes and CTS. Results
were presented as OR and the corresponding 95% CI. P-values less than 0.05 were considered statistically
significant. Statistical analyses were performed using Stata version 15 software (StataCorp LLC, College
Station, Texas, USA).
This study was based on a secondary analysis of data obtained from the NAMCS database, a publicly
available, de-identified dataset. Approval by an internal review board (IRB) and informed consent were not
required as the study constituted non-human subject research.
Results
Approximately 403,703 adults >18 years old participated in the NAMCS from 2006 to 2015 and were eligible
for inclusion in the study. Of those individuals, 81,611 were excluded due to missing or incomplete age,
gender, smoking status, and BMI data. In the remaining sample, an additional 865 patients with a diagnosis
of cervical radiculopathy, brachial plexopathy, and peripheral nerve trauma were excluded. The final sample
size consisted of 322,092 individuals. Of these individuals, the prevalence of diabetes was 13.5% (Table 1).
Patients who had diabetes were older, more frequently males, non-white, non-current tobacco users, obese,
and with chronic kidney disease, hypertension, and asthma. Of note, approximately 17.7% of the group with
diabetes were obese, while only 6.7% of the group without diabetes were obese.
Diabetes
Characteristics
Number
Age
2021 Low et al. Cureus 13(3): e13844. DOI 10.7759/cureus.13844
No diabetes
%
Number
P-Value
%
<0.001
2 of 8
18-29
832
1.86
35,147
13.1
30-39
1,891
4.26
35,997
13.3
40-49
4,284
9.77
43,538
15.9
50-59
8,840
20.3
52,120
18.6
60+
27,674
63.8
111,769
39.1
Sex
<0.001
Female
23,018
53.1
168,379
62.1
Male
20,503
46.9
110,192
37.9
Race
<0.001
White
35,154
79.7
239,856
84.8
Black
5,786
14.2
25,969
9.96
Other
2,581
6.15
12,746
5.2
Tobacco
<0.001
Not current
26,777
84.3
156,964
82.8
Current
5,711
15.7
34,692
17.2
Obesity
<0.001
No
36,072
82.3
261,042
93.3
Yes
17,529
17.7
7,449
6.72
Hypothyroidism
0.007
No
42,749
97.9
274,727
98.3
Yes
772
2.09
3,844
1.74
CKD
<0.001
No
43,066
99
277,818
99.7
Yes
455
1.01
753
0.28
Rheumatoid arthritis
0.273
No
43,375
99.5
277,370
99.4
Yes
146
0.46
1,201
0.56
Psoriatic arthritis
0.261
No
43,506
100
278,442
99.9
Yes
15
0.04
129
0.06
Hypertension
<0.001
No
15,093
34
206,258
72.6
Yes
28,428
66
72,313
27.4
Asthma
<0.001
No
40,344
93.1
262,882
94.4
Yes
3,177
6.91
15,689
5.61
TABLE 1: Baseline characteristics of patients with diabetes versus without diabetes.
CKD, chronic kidney disease
“Other” is defined as Asian, Native Hawaiian, or other Pacific Islander, American Indian, or Alaska native
2021 Low et al. Cureus 13(3): e13844. DOI 10.7759/cureus.13844
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“Not current” is defined as never, former, or unknown prior tobacco use
The prevalence of CTS was 0.55%. As age increased, there was an increasing trend in the frequency of CTS as
0.18% of young adults aged 18-29 had CTS compared to 0.80% of older adults aged 50-59. The proportion of
patients with CTS was statistically significantly higher among females (0.57% compared to 0.43% in males),
tobacco users (0.68% compared to non-smokers 0.50%), and among those not reporting a diagnosis of
hypothyroidism or chronic kidney disease (Table 2).
CTS
Number
No CTS
%
Number
P-Value
%
Diabetes
0.446
No
1,521
0.52
277,050
99.5
Yes
254
0.48
43,267
99.5
Age
<0.001
18-29
90
0.18
35,889
99.8
30-39
212
0.53
37,676
99.5
40-49
351
0.65
47,471
99.4
50-59
464
0.80
60,496
99.2
60+
658
0.43
138,785
99.6
Sex
<0.001
Female
1,177
0.57
190,220
99.4
Male
598
0.43
130,097
99.6
Race
0.693
White
1,533
0.51
273,477
99.5
Black
193
0.57
31,562
99.4
Other
49
0.45
15,278
99.6
Tobacco
0.005
Not current
910
0.50
182,831
99.5
Current
292
0.68
40,111
99.3
Obesity
0.54
No
1,655
0.51
295,459
99.5
Yes
120
0.57
24,858
99.4
Hypothyroidism
0.002
No
1,768
0.52
315,708
99.5
Yes
7
0.13
4,609
99.9
CKD
0.018
No
1,773
0.52
319,111
99.5
Yes
2
0.10
1,206
99.9
Rheumatoid arthritis
0.797
No
1,767
0.52
318,978
99.5
Yes
8
0.58
1,339
99.4
2021 Low et al. Cureus 13(3): e13844. DOI 10.7759/cureus.13844
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Psoriatic arthritis
0.114
No
1,772
0.52
320,176
99.5
Yes
3
1.46
141
98.5
Hypertension
0.234
No
1,259
0.54
220,092
99.5
Yes
516
0.48
100,225
99.5
Asthma
0.824
No
1,684
0.52
301,542
99.5
Yes
91
0.50
18,775
99.5
TABLE 2: Characteristics of patients by diagnosed CTS status.
CKD = chronic kidney disease; CTS = carpal tunnel status
“Other” is defined as Asian, Native Hawaiian, or other Pacific Islander, American Indian, or Alaska native
“Not current” is defined as never, former, or unknown prior tobacco use
The odds of CTS in both the unadjusted and adjusted models did not differ by diabetes status. Incidentally,
patients aged 50-59, females, and current tobacco users had higher odds of CTS (Table 3).
2021 Low et al. Cureus 13(3): e13844. DOI 10.7759/cureus.13844
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Unadjusted
Adjusted
OR (95% CI)
P-Value
OR (95% CI)
P-Value
Yes
0.92 (0.74-1.14)
0.447
0.84 (0.65-1.095)
0.203
No
Reference
Diabetes
Reference
Age
18-29
0.42 (0.30-0.59)
<0.001
0.39 (0.27-0.56)
<0.001
30-39
1.22 (0.89-1.67)
0.21
1.1 (0.73-1.66)
0.637
40-49
1.51 (1.18-1.93)
0.001
1.29 (0.94-1.77)
0.116
50-59
1.86 (1.52-2.27)
<0.001
1.91 (1.49-2.45)
<0.001
60+
Reference
Reference
Sex
Female
1.31 (1.13-1.53)
0.001
1.31 (1.09-1.58)
0.004
Male
Reference
Reference
Not current
Reference
Reference
Current
1.36 (1.09-1.69)
0.006
1.32 (1.07-1.63)
0.01
Yes
1.12 (0.78-1.60)
0.54
1.18 (0.78-1.79)
0.442
No
Reference
Tobacco
Obesity
Reference
Hypothyroid
Yes
0.25 (0.09-0.66)
No
Reference
0.005
0.21 (0.065-0.71)
0.011
Reference
CKD
Yes
0.20 (0.05-0.88)
No
Reference
0.034
0.19 (0.027-1.40)
0.103
Reference
TABLE 3: Unadjusted and adjusted OR for the diagnosis of CTS.
CKD = chronic kidney disease; CI = confidence interval; CTS = carpal tunnel syndrome; OR = odds ratio
Logistic regression was performed to obtain adjusted ORs for the following variables because of association with either the exposure or the
outcome: age, sex, tobacco use, obesity, hypothyroid, CKD
“Not current” is defined as never, former, or unknown prior tobacco use
Discussion
We found no difference in the odds of DM and CTS diagnoses. This result contributes to the growing body of
literature that suggests no association between DM and CTS [3,9]. Examples include a retrospective casecontrol study of patients from a single institution in the Netherlands where type 2 DM was not a significant
predictor for CTS (OR: 0.99; 95% CI: 0.66-1.47) after adjusting for age, gender, and BMI [3]. Similarly, in
patients from a single institution in the United Kingdom, the association between DM and
neurophysiological abnormalities was not significant after adjusting for age, sex, and ethnic origin (OR: 1.6;
95% CI: 0.9-3.1) [9]. Our findings build from previous studies as it used US nationwide data that allow for
better generalizability to adults over 18 years old in the United States.
The pathogenesis of CTS remains complex, and the impact of diabetes on CTS is still unclear and
2021 Low et al. Cureus 13(3): e13844. DOI 10.7759/cureus.13844
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multifactorial. It is thought that diabetes may aggravate ischemia in nerves via glycosylation end products
that are under chronic stress of endoneurial hypoxia [4,5]. Other proposed mechanisms include increased
extracellular fluid, demyelination of Schwann cells, modification of fibroblasts, and proliferation of
cytokines [4]. In the literature, there exist contradicting results regarding DM as a risk factor for CTS.
Previous studies that investigated the relationship suggest that the magnitude of the association is fairly
modest [1]. However, several studies have shown that there was no association between glycemic control
and CTS, with one showing an inverse relationship [12,13]. Gamstedt et al. found that poor metabolic control
yielded less risk than the control group, but the finding was not statistically significant (OR: 0.34; 95% CI:
0.10-1.12; p = 0.08) [13]. This was likely due to the period of time that was used to classify metabolic control.
Therefore, our results do not support the use of diabetes as a clinical predictor of CTS.
The lack of association reported might be because we did not assess whether diabetes was well controlled or
uncontrolled or the effect of medication usage. It is possible that the association between diabetes and CTS
only exists in specific subgroups (e.g., uncontrolled diabetes). Additionally, our study cannot exclude the
possibility of underreporting of CTS, as evidenced by the low prevalence of the condition compared to
previous studies [3,4]. Furthermore, the database only collected ICD-9 information on a maximum of three
chronic conditions or diagnoses related to the visit per patient. Thus, a diagnosis of CTS may have been
excluded if a patient reported other medical conditions or was inaccurately coded. Lastly, the NAMCS is a
national probability sample of physicians that reports on a sample of outpatient visit encounters and not of
patients. Therefore, the database estimates the prevalence of conditions per visit and not per patient. Thus,
patients requiring frequent visits to the same physician could have contributed to data on more than one
visit.
Previous studies that reported the magnitude of effect between DM and CTS varied greatly based on the
geographic location of the study, with a lower effect in population-based studies compared to hospital-based
studies. Our study encountered a similar finding, with far fewer visits for CTS compared to diabetes. This can
partially be explained by sampling bias because patients who experience symptoms of CTS may not seek
ambulatory care. Alternatively, it is possible that surgeons took a more conservative approach with nondiabetic patients who had CTS, whereas diabetic patients with CTS were more likely to get carpal tunnel
release surgery with less need for maintenance follow-up appointments. This could lead to the differences in
outpatient visits between the two groups, which could partially explain the findings in our analysis.
To our knowledge, this study is the first to investigate the relation between CTS and diabetes in a
population-based setting in the United States. Our study utilized the NAMCS database, which encompasses
84% of all ambulatory visits in the United States. Compared with direct observation of outpatient visits, the
physician reporting method used in the NAMCS was found to be more accurate for procedures and
examinations [14].
Conclusions
Our study found no association between DM and CTS in adult ambulatory patients in the United States.
However, the limitations we addressed may have impacted our findings. Future population-based studies
utilizing a prospective study design and a larger sample size should be conducted to investigate the
association between hemoglobin A1c and CTS to assess whether well-controlled or uncontrolled diabetes
plays a role. Hemoglobin A1c level is generally accepted as a more accurate measure of diabetes control as
well as an individual’s health risks associated with diabetes. Furthermore, combining additional NAMCS,
emergency, and outpatient department data from multiple years would increase the sample size and produce
a more comprehensive sample of ambulatory care visits.
Additional Information
Disclosures
Human subjects: All authors have confirmed that this study did not involve human participants or tissue.
Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue.
Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the
following: Payment/services info: All authors have declared that no financial support was received from
any organization for the submitted work. Financial relationships: All authors have declared that they have
no financial relationships at present or within the previous three years with any organizations that might
have an interest in the submitted work. Other relationships: All authors have declared that there are no
other relationships or activities that could appear to have influenced the submitted work.
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