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. Author manuscript; available in PMC: 2026 Jun 19.
Published in final edited form as: Neurosci Lett. 2024 Nov 15;844:138039. doi: 10.1016/j.neulet.2024.138039

Effects of Type II Diabetes on upper extremity muscle characteristics in older adults

Lauren I Gulley Cox a, Nicholas Dias b, Chuan Zhang b, Yingchun Zhang b, Stacey L Gorniak a,*
PMCID: PMC13277669  NIHMSID: NIHMS2178613  PMID: 39549828

Abstract

With one in every four older adults living with T2D and one in every two older adults meeting the criteria for prediabetes, neuromuscular changes due to T2D are likely to impact functional activities in this population. Limited work in evaluating motor unit number and size across muscles in the upper extremity in persons with Type II Diabetes (T2D) exists, mostly due to the traditional belief bias that the upper extremity is relatively spared in T2D as compared to the lower extremities. The purpose of the current study was to evaluate motor unit number and size (using electrophysiological motor unit number index (MUNIX) and motor unit size index (MUSIX)) across the upper extremity in older adults with T2D (n = 13) as compared to healthy age- and sex-matched controls (n = 12). Persons with T2D presented with more motor units and larger motor unit sizes (p < 0.05) as compared to age- and sex-matched control participants. These changes were not dependent upon muscle location within a limb, indicating systemic neuromuscular changes associated with T2D. These group effects were clarified when health state covariates (e.g., blood pressure) were accounted for. Findings are consistent with emerging data that show altered neuromuscular characteristics with health state considerations in persons with T2D.

Keywords: Neuromuscular dysfunction, Aging, Hypertension, Length-dependent neuropathy

1. Introduction

Approximately 380 million people worldwide are currently living with Type II Diabetes (T2D); one in every four older adults lives with T2D [1,2] and one in every two older adults meets the criteria for prediabetes [3]. The incidence of metabolic disease in older adults is much higher than at other times of the lifespan due to naturally occurring reduced metabolite clearance as the human body ages. Evidence of full-body functional impairments in persons living with T2D has been emerging over recent years [4–6]. While the incidence of T2D rises with age, alterations in neuromuscular characteristics and function with age alone predispose one to functional impairments with aging. The combination of age and T2D drives the potential for significant neuromuscular dysfunction and resultant functional impairments in persons living with T2D [7]. Recent studies support this idea, reinforcing the concept that functional impairments associated with T2D are not due to age and cutaneous tactile dysfunction alone [8–14]. Recent work from our lab indicates altered muscle function that likely contributes to functional impairments—particularly of the upper extremity—in older adults with T2D [10,11].

Characterization of motor unit number and size and functioning of the lower limbs in T2D has recently emerged. Loss of lower extremity strength concurrent with loss of motor units has been reported in the lower extremity in persons with T2D [15,16]. Additional work has also reported reorganization of motor units of the lower extremity in T2D [15,17]. One study compared motor unit loss and remodeling between single muscles of the upper and lower extremities (first dorsal interosseous (FDI) and tibialis anterior (TA), respectively) [15]. Motor unit loss was found to be more severe in lower extremities (specifically, in TA) as compared to the upper extremity (specifically, in FDI) in persons with T2D-associated peripheral neuropathy; as a result, the authors interpreted this finding as a length-dependent pattern of T2D-associated alteration to motor units.

Limited additional work has been done in evaluating motor unit number and size across muscles in the upper extremity in persons with T2D, mostly due to the traditional belief bias that the upper extremity is relatively spared in T2D as compared to the lower extremities given the absence of major clinical symptoms of motor impairments [18]. Our prior work contradicts this belief bias, such that the upper extremity demonstrates sensorimotor impairments—independent of T2D-associated peripheral neuropathy—that contribute to functional impairments in persons with T2D [8–12].

In light of these gaps, the focus of the current study was to evaluate motor unit number and size across the upper extremity in older adults with T2D. We hypothesized that persons with T2D will have fewer motor units and increased motor unit size in muscles of the upper extremity as compared to controls (Hypothesis 1), and that motor unit number and size will differ across the upper extremity muscles examined in persons with T2D as compared to controls due to length differences of nerves across the upper extremity (Hypothesis 2).

2. Materials and methods

2.1. Participants

Thirteen (13) independent community-dwelling older adults (7M, 6F) with a history of established T2D and 12 age- and sex-matched control participants (Control) (6M, 6F) were recruited for this study from the greater Houston area (population approx. 2.3 million), see Table 1 for demographics. Inclusion criteria for both groups was: age 60 years and above, history of moderate range bloodpressure (90/60 – 160/100 mmHg), and right-handed (laterality quotient (LQ) > 40, assessed with the Edinburgh Handedness Inventory). Exclusion criteria for both groups included: diagnosis of Type 1 Diabetes, diagnosis of T2D prior to age 18, history of uncontrolled hypertension, history of limb amputation, chemotherapy, or neurological diseases (Alzheimer’ Disease, Dementia, Charcot-Marie-Tooth Disorder, and other hereditary or compressional neuropathies), and pain in the extremities that limits activities of daily living. This study was approved by the Institutional Review Board (IRB) at the University of Houston in accordance with the Declaration of Helsinki. All participants provided written informed consent.

Table 1.

Values are mean ± SD or count. BMI = body mass index, DIA = diastole, HbA1c = glycated hemoglobin, HDL = high-density lipoprotein, LDL = low-density lipoprotein, LQ = laterality quotient, PN = peripheral neuropathy, SYS = systole, TC = total cholesterol.

T2D Controls
N (Males, Females) 13 (6, 7) 12 (6, 6)
Age (y) 69.6 ± 6.8 68.1 ± 4.5
Height (m) 1.655 ± 0.061 1.717 ± 0.099
Mass (kg) 92.3 ± 16.5 89.4 ± 28.7
BMI (kg/m2) 33.7 ± 7.2 30.3 ± 11.3
HbA1c (%) 6.4 ± 0.7 5.6 ± 0.5
LQ 88 ± 12 92 ± 12
SYS (mmHg) 133 ± 22 139 ± 15
DIA (mmHg) 70 ± 11 78 ± 11
PN 4 0
Disease duration (months) 104 ± 85 –
TC (mg/dL) 164 ± 27 194 ± 50
HDL (mg/dL) 55 ± 14 59 ± 9
LDL (mg/dL) 83 ± 18 105 ± 39
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2.2. Health status Information

Glycated hemoglobin (HbA1c), blood pressure, and cholesterol values were assessed for all study participants. Cholesterol and HbA1c were assessed using commercially available point of care evaluation kits (Cardiocheck + and A1c Now+, PTS Diagnostics, Indianapolis, IN, USA). Blood pressure was measured using a commercially available wrist-worn device (Omron Intellisense 10 series Blood Pressure Monitor, Model BP785, Bannockburn, IL, USA). History of prediabetes diagnosis was determined via self-report. Peripheral neuropathy (PN) status was determined by either clinical examination or EMG/NCV testing (per physician).

2.3. EMG recording

Multichannel surface EMG was recorded from each muscle using a bioamplifier (FE234 Quad BioAmp, ADInstruments, Colorado Springs, CO, USA) and PowerLab data acquisition system (PowerLab 8/35, ADinstruments, Colorado Springs, CO, USA). Prior to attaching surface electrodes (3 M Red Dot 2560 Foam Monitoring Electrodes with Sticky Gel, 3 M, Saint Paul, MN, USA), the skin was cleaned with alcohol. Surface electrodes used consisted of diaphoretic solid gel in disc shape; gel disc diameter was 18 mm, size of the electrode was 25 cm × 27 inclusive of foam adhesive materials. The longitudinal axis of each of the muscles (abductor pollicis brevis (APB), biceps brachii (BB), extensor digitorum (EDC), flexor digitorum superficialis (FDS), and triceps brachii (TRI)) was identified via palpation. Placement was based on [19]. Two surface electrodes were placed on the muscle belly, along the longitudinal axis of the respective muscle; center-to-center interelectrode distance was 26–30 mm. A reference electrode was placed on a bony process located proximally to the muscle being tested while a ground electrode was placed distally. EMG data was acquired continuously at 1,000 Hz using LabChart software (ADInstruments, Colorado Springs, CO, USA). Any channel crosstalk was inspected manually and electrodes were repositioned if evidence of channel crosstalk was present.

2.4. Nerve stimulation and CMAP

Maximum compound muscle action potential (CMAP) for each muscle was obtained by supra-maximal stimulation of the innervating nerve (APB: median; BB: musculocutaneous; ED: radial; FDS: median; TB: radial), with a DS7A muscle current stimulator (Digitimer, United Kingdom). Stimulation intensity generally started around 5–30 mA and was increased in increments of approximately 20 % until a maximal response was reached. The duration for a single pulse stimulation was 200 μs. The nerve was then stimulated with 120 % of the final intensity to confirm the maximum CMAP was reached and confirmed visually, consistent with [20].

2.5. Isometric contractions, surface EMG interference pattern (SIP), MUNIX, and MUSIX

For all tasks, participants were seated in a chair facing the testing table with his/her upper arms at approximately 20° of abduction in the frontal plane. The forearm of each participant rested on a padded surface with an elbow angle of approximately 135°in the sagittal plane. The wrist orientation was such that the hand was restrained in a neutral position (neutral flexion/extension, neutral radial/ulnar deviation) during testing. Participants performed isometric contractions via an externally fixed load cell (Model SM-500, Interface Force Measurement Solutions, Scottsdale, AZ, USA) with the hand in: pronation to evaluate TRI and EDC, and in supination to evaluate BB, FDS, and ABP. Directionally of the load cell was modified to accommodate force production during testing. Participants performed three maximum voluntary contraction (MVC) trials of 10–15 each, with one minute of rest between trials. The highest MVC force was used to determine the target forces for the submaximal contraction trials. After MVC trials, participants were asked to perform 30-second submaximal isometric contractions each at 5, 15, 25, 50, and 75 % MVC. Force produced by the subject was used as visual feedback to maintain the contraction level. This testing procedure was performed for all five muscles (APB, BB, EDC, FDS, and TRI).

The surface EMG interference pattern was recorded throughout each contraction at varying levels of force. Motor unit number index (MUNIX) was used to estimate the number of motor units contained in each muscle using maximum CMAP produced during voluntary isometric muscle contractions in 300 ms epochs. Additionally, motor unit size was estimated by calculating the motor unit size index (MUSIX), which is derived using MUNIX and CMAP values. Data underwent bandpass filtering (10–450 Hz) prior to analysis. Additional details on how to calculate CMAP, MUNIX, and MUSIX can be found in [21]. Note that guidance from [21] was used as this data set was collected prior to the release of updated guidelines in 2018 [22].

2.6. Statistical analysis

SPSS version 26.0 (SPSS IBM, New York, NY, USA) was used to perform parametric statistical analyses. Outliers were identified in SPPS using Tukey’s method during creation of initial boxplots of data. The following # of outliers were removed from the data set as indicated via Tukey’s method: CMAP (1 control, 1 T2D), MUNIX (2 control, 1 T2D), MUSIX (5 control, 4 T2D). Normality of data after outlier removal for each variable of interest was confirmed via Kolmogorov-Smirnov Normality test (α = 0.05). For each variable of interest, automatic linear modeling (ALM) was used to select significant covariates from health status data using forward stepwise selection in SPSS, consistent with our prior work in investigating health state covariate influences in T2D [12,23,24]. Follow-up correlation analyses were performed for all ALM-identified significant covariates. Potential covariates included: HbA1c, blood pressure (systole and diastole), cholesterol (Total, HDL, LDL), duration of diagnosis (in months), PN status (via indicator variable), prediabetes status (via indicator variable), body mass index (BMI), and age. Each potential covariate was considered as the evidence base suggests that each may contribute to neuromuscular dysfunction in persons with T2D. Data were analyzed using two-way ANCOVAs to compare between Groups (T2D and Control). Within-subject factors for neuromuscular evaluation was Muscle (APB, BB, EDC, FDS, and TRI) as was a Group x Muscle interaction.

3. Results

3.1. CMAP

A baseline two-way ANOVA was performed for maximum CMAP amplitude with Group (T2D and Control) and Muscle (APB, BB, EDC, FDS, and TRI) as main factors, data can be found in Fig. 1A. No significant main effects of Group, Muscle, nor Group x Muscle were found.

Fig. 1.

Fig. 1.

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CMAP, MUNIX, and MUSIX values. Data from study participants are shown via violin plots in panels A, C, and E. Average ± SE values of CMAP, MUNIX, and MUSIX data generated as a result of ANCOVA models shown for reference to clarify Group effects in panels B, D, and F. Data are shown for the T2D and control group, as well as each individual muscle (TRI, FDS, EDC, BB, and APB).

ALM modeling indicated BMI, Diastole, and PN status as covariates in the CMAP amplitude model which strengthened the Group effect, Fig. 1B. Follow-up ANCOVA was performed with Group and Muscle as main factors and BMI, Diastole, and PN status as covariates. Group (F1,68 = 5.93, p < 0.05), BMI (F1,68 = 4.61, p < 0.05), Diastole (F1,68 = 5.29, p < 0.05), and PN status (F1,68 = 4.415, p < 0.05) were all found to be significant. No interaction between Group x Muscle was found in the follow-up ANCOVA. CMAP amplitude was found to be significantly positively correlated with Diastole (r94 = 0.211, p < 0.05) and PN status (r94 = 0.207, p < 0.05).

3.2. MUNIX

A baseline two-way ANCOVA was performed for MUNIX with Group (T2D and Control) and Muscle (APB, BB, EDC, FDS, and TRI) as main factors. No main effects or interactions were found, Fig. 1C.

ALM modeling indicated Diastole and Duration as covariates in the MUNIX model which revealed the Group effect, Fig. 1D. Follow-up ANCOVA was performed with Group and Muscle as between main and Diastole and Duration as covariates. A significant main effect of Group (F1,67 = 11.56, p < 0.001) emerged with Diastole (F1,67 = 6.27, p < 0.05) and disease Duration (F1,72 = 7.150, p < 0.01) included in the model. No interaction between Group x Muscle was found in the follow-up ANCOVA. MUNIX was found to be significantly positively correlated with Diastole (r92 = 0.228, p < 0.05).

3.3. MUSIX

A baseline two-way ANOVA was performed for MUSIX with Group (T2D and Control) and Muscle (APB, BB, EDC, FDS, and TRI) as main factors. Group (F1,64 = 4.59, p < 0.05) was found to be significantly such that T2D had significantly larger overall MUSIX as compared to Controls, Fig. 1E. An interaction effect of Group x Muscle was also found (F4,64 = 2.59, p < 0.05), Fig. 1E.

While ALM identified Age, Duration, and Diastole as potential covariates for the MUSIX model, the follow-up ANCOVA did not produce any significant covariates when Age, Duration, and Diastole were included in the model, average data from model shown in Fig. 1F. Neither main effect of Group or Muscle was present, but the Group x Muscle interaction was significant (F4,61 = 2.70, p < 0.05) in the follow-up ANCOVA. MUSIX was found to be significantly negatively correlated with Diastole (r86 = −0.267, p < 0.05).

4. Discussion

The purpose of this study was to evaluate motor unit number and size across the upper extremity in older adults with T2D as compared to age-and sex-matched controls. In Hypothesis 1, we expected persons with T2D would have fewer motor units and increased motor unit size in muscles of the upper extremity as compared to controls. This hypothesis partially supported, particularly when the consideration of health state covariates such as diastole was considered across groups, such that persons with T2D appear to have more motor units and larger-sized motor units. In Hypothesis 2, we expected motor unit number and size would differ across the upper extremity muscles examined in persons with T2D. This hypothesis was not supported, suggesting that the previously reported length dependency in T2D-associated motor unit alterations between the upper and lower extremities does not hold for within-limb analyses of the upper extremity. In the following paragraphs, we discuss these findings in light of factors that appear to impact muscle remodeling in T2D, including electrophysiological changes and long-term metabolic influences of the disease state (including hypertension and its treatment) on the neuromuscular junction and muscle fiber type.

4.1. Electrophysiological influences

Smaller CMAP amplitudes and reduced number of motor units have been reported in lower extremity muscles and FDI muscle of the hand in persons with T2D in prior studies using the motor unit number (MUNE) approach [15–17]. To our knowledge, our study is the first to use the MUNIX method to characterize motor units in persons with T2D. MUNIX was used for this population, as it is generally more tolerable with respect to the number and duration of nerve stimulations to be delivered during the evaluation [25]. Given the high likelihood of peripheral nerve damage and potential resultant pain in persons with T2D, a more tolerable electrophysiological approach is warranted. Contradictory to prior findings in T2D, our T2D group had increased mean MUNIX and mean maximum CMAP amplitude when compared to the control group. These results suggest that the maximum electrophysiological size of the entire motor pool in muscles of the upper extremity in persons with T2D is altered due to the chronic neurotoxicity of T2D. This effect was clearer once differences in health state covariates between the two groups were accounted for (Fig. 1B and D). This is an intriguing finding in terms of peripheral contributions to subtle manual dysfunction in persons with T2D [4,6,8]. These motor unit changes along with subtle tactile, altered muscle hemodynamics, and proprioceptive deficits in T2D [9–12] and altered cortical activation patterns [23] all contribute to upper extremity dysfunction in T2D.

Changes in MUNIX and CMAP were accompanied by a trend of larger MUSIX values in the T2D group. Typically, in diseased populations where the number of motor units is lower than in controls, motor unit size must increase as a regulatory mechanism to compensate for lost motor units. In older adults—especially those with sarcopenia—reinnervation may be impaired, further contributing to the age-related advancement of sarcopenia with time [26,27]. Our data suggest potential compensatory motor unit sprouting and remodeling in T2D, potentially as a protective mechanism in the upper extremity—consistent with MUNE findings in rodent models of T2D [28,29]. It is likely that remodeling of the muscle occurs as the disease progresses, resulting in motor unit loss and T2D-associated sarcopenia late in the disease stage [30].

4.2. Impact of metabolic disease

Prolonged hyperglycemia has been associated with morphological changes to the neuromuscular junction [28], such that development of peripheral neuropathy in persons with T2D is an ongoing event—indicating subclinical neuromuscular deficits in persons with T2D throughout the disease state [18]. Clinical presentation of peripheral neuropathy only becomes evident to the clinician once a critical number of neuromuscular fascicles are impacted [18]. Evidence indicates that the changes at the neuromuscular junction are due to alterations to acetylcholine receptor clusters at the motor end plate as well as the development of nerve lesions [28,29]. These changes are accompanied by structural changes to the neuronal body, including eventual neuron dropout over time [29]. These long-term temporal changes may be moderated by stimulation of insulin production, as insulin has shown neurotrophic properties—particularly in reference to preservation of motor end plates and sensory function [31–33]. Evidence also indicates that insulin signaling plays an important role in compensatory neuronal (and likely motor unit) sprouting and control of synaptic density [32,34]. Altogether, this indicates that neuromuscular changes in T2D could potentially be moderated by aggressive disease management, including enhanced stimulation of insulin production throughout the disease trajectory.

In addition to neurologically-oriented changes with increased disease duration in T2D, muscle tissue physiology has been found to be altered in T2D. For example, insulin signaling within skeletal muscle is modified in T2D [35]. Additionally, hyperglycemia over time has been found to not only promote muscle atrophy [36], but to also influence the muscle fiber type composition across the body. A proportional shift from higher numbers of Type I (slow oxidative, insulin sensitive) to higher numbers of Type II (fast twitch glycolic, insulin resistant) fibers has been found [37–39] in persons who are insulin resistant. Thus, systemic changes to the neuromuscular system likely contribute to the sensorimotor dysfunction reported in persons living with the disease.

In addition to the direct metabolic impacts of T2D, cardiovascular disease is the most common comorbidity in persons living with T2D. Up to 80 % of persons with T2D are hypertensive and are more likely to be treated for hypertension as compared to healthy age-matched controls [40,41]. Hypertension has historically been associated with smooth muscle remodeling [42]; recent evidence indicates additional impacts of hypertension to skeletal muscle [43,44], including potential resultant neuromuscular remodeling [45]. Prior findings in our lab also point to a relationship between hypertension and the development of sensorimotor and neuromuscular aberrations in T2D [10–12,23]. The data in this study also support a relationship between hypertension and neuromuscular aberrations in skeletal muscle. Both groups in this study exhibited average systolic blood pressure values consistent with Hypertension Stage 1 [46]; however, both groups did exhibit normal to elevated levels of diastolic blood pressure. The higher average blood pressure values in the control group are likely due to untreated hypertension within the group, whereas the T2D group was likely actively undergoing medical management of hypertension due to its comorbid presence in most persons with T2D. In controlling for this discrepancy in diastole, group effects on CMAP amplitude, motor unit number, and motor unit size were clarified such that higher diastole values were associated with increased CMAP amplitude and motor unit number, but smaller motor unit sizes. This indicates that blood pressure is an important health state covariate that should be considered when assessing neuromotor function in older adults, independent of metabolic health state—consistent with ongoing work in our lab.

5. Limitations

While this study is an incremental step to understanding how health state variability may contribute to motor unit changes due to aging and metabolic disease, we acknowledge one limitation of this project includes a small sample size that did not permit evaluation of male and female participants separately. Given recent evidence of sex-based differences in the manifestation of sensorimotor deficits and neuromuscular changes in persons with T2D [10,12], more work is needed in this area. Data generated in this study were collected using guidance from [21] as this data set was collected prior to the release of updated guidelines in 2018 [22]. Major differences in the approach employed in the generation of this data set include the use of 300 ms epochs and standardized electrode placement, as per [19]. The use of 300 ms epochs meets the minimum epoch duration as per [22] to identify tremor, but not the recommended 500 ms. Our data was collected using a standardized electrode placement to ensure reproducibility of the data, in contrast to “electrode placement for CMAP optimization” as endorsed in [22].

6. Conclusion

The purpose of this study was to evaluate motor unit number and size across the upper extremity in older adults with T2D as compared to healthy age- and sex-matched controls. Persons with T2D present with more motor units of larger size. Consideration of health state covariates clarified these group differences. These changes are not dependent upon muscle location within a limb, indicating systemic neuromuscular changes associated with T2D.

Significance statement.

The data in this project indicate significant changes in motor unit characteristics of the upper extremity in persons with Type 2 Diabetes that do not appear to be length-dependent and are influenced by health state indicators such as blood pressure.

Funding

This project was funded by 1R01CA200263–01 via subcontract to SLG and 1R56AG080816-01 to SLG. Support for materials for this project was provided by the University of Houston GEAR Grant program to SLG.

Footnotes

Declaration of generative AI use

The authors did not utilize generative AI in the writing process for this project.

Participant consent

This study was approved by the Institutional Review Board (IRB) at the University of Houston in accordance with Declaration of Helsinki. All participants provided written informed consent.

Ethical publication statement

We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

CRediT authorship contribution statement

Lauren I. Gulley Cox: Writing – review & editing, Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation. Nicholas Dias: Writing – review & editing, Resources, Methodology, Investigation, Formal analysis. Chuan Zhang: Writing – review & editing, Software, Methodology, Investigation, Formal analysis. Yingchun Zhang: Writing – review & editing, Supervision, Resources, Project administration, Methodology, Conceptualization. Stacey L. Gorniak: Writing – review & editing, Visualization, Supervision, Resources, Project administration, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability

Data will be made available on reasonable request.

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