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. 2025 Jul 28;126(1):469–477. doi: 10.1007/s00421-025-05907-x

Neuromuscular electrical stimulation enhances glycemic control and carbohydrate utilization in sedentary, predominantly Hispanic overweight or obese individuals with hyperglycemia

Jehu N Apaflo 1, Gabriel Narvaez 1, Irene John Tomy 1, Ali Mossayebi 1, Zahra Fatahimeiabadi 1, Andrew J McAinch 2,3, John P Thyfault 4, Kisuk Min 5, Hyejin Jung 6, Amy E Wagler 7, Sudip Bajpeyi 1,✉
PMCID: PMC12880989  PMID: 40721518

Abstract

Introduction

Neuromuscular electrical stimulation (NMES) is used as a rehabilitation technique for individuals with physical function limitations and mobility impairments. However, the potential for NMES-induced muscle contraction to improve metabolic health is unclear. This study investigated the effect of NMES on glycemic control and energy expenditure in a predominantly Hispanic population.

Methods

Overweight/obese participants with hyperglycemia (N = 56 [Males: 19; Females: 37] Age: 33.3 ± 11.8 years; BMI: 34.8 ± 5.6 kg/m2) underwent 30 min of NMES on both quadriceps muscles after an overnight fast. Glucose levels were continuously measured for over 48 h, encompassing the stimulation day and a control day, using a continuous glucose monitor. Standardized eucaloric diet was provided on both days. Energy expenditure and substrate utilization were measured by indirect calorimetry before and during the NMES application.

Results

Thirty minutes of NMES treatment reduced glucose levels compared to baseline glucose (116.2 ± 2.7 mg/dL to 113.2 ± 2.5 mg/dL; p < 0.0001). Glycemic control determined by 24-h glucose variability/fluctuations was significantly lower on the day of NMES compared to the control day (18.0 ± 1.0 mg/dL vs 20.0 ± 1.2 mg/dL; p < 0.05). Energy expenditure (18.8 ± 0.3 kcal.Day−1.Kg−1 to 19.0 ± 0.3 kcal.Day−1.Kg−1; p < 0.05) and respiratory exchange ratio (0.79 ± 0.01 to 0.80 ± 0.01; p < 0.05) increased during stimulation compared to the baseline.

Conclusion

Acute application of NMES results in improvement in glycemic control and energy expenditure in the short term. Future studies are needed to determine if chronic NMES-induced muscle contraction can provide an alternate strategy to manage hyperglycemia.

Clinical trial registration

NCT03947697 May 2019.

Keywords: Continuous glucose monitoring (CGM), Energy expenditure, Glucose, Muscle contraction, Physical activity, Type 2 diabetes

Introduction

Physical inactivity is one of the major risk factors for insulin resistance, impaired glucose metabolism, hyperglycemia (fasting blood glucose between 100 mg/dL and 125 mg/dL), type 2 diabetes, and other metabolic diseases (Yaribeygi et al. 2021). Hyperglycemia is a core metabolic feature that precedes the onset of type 2 diabetes (Khan et al. 2019). It has been shown that approximately 38% of individuals with hyperglycemia will develop type 2 diabetes within nine years (Richter et al. 2018). However, the incidence rate of type 2 diabetes could be minimized by early intervention (Khan et al. 2019).

Muscle contraction-induced glucose uptake, such as exercise, is a potent glycemic control modality (Boulé et al. 2005) due to its capability to improve glucose uptake with and without insulin, as well as to improve other features of metabolism, putatively involved in glucose homeostasis and insulin sensitivity (Munan et al. 2020; Rose and Richter 2005). Unfortunately, adherence to physical activity is very low in most American populations, and our current environment encourages sedentary behavior (Solomon and Thyfault 2013; Piercy 2019). Moreover, physiological defects of obesity and type 2 diabetes, such as decreased lipid oxidation capacity, musculoskeletal pain, and peripheral neuropathy, limit these individuals' ability to exercise (Bajpeyi et al. 2011; Kelley et al. 1999; Prior et al. 2014; Vincent et al. 2012).

Neuromuscular electrical stimulation (NMES) is an alternative means of muscle contraction that circumvents most of the challenges of conventional exercise. It is a practical, non-invasive, cost-effective, and innovative method to induce muscle contraction among individuals who are less likely to engage in conventional exercise (Galvan et al. 2022). NMES has been widely used in rehabilitation to prevent muscle atrophy and to help bedridden individuals regain muscle mass and function (Lake 1992a, 1992b; Castro et al. 1999; Dudley et al. 1999; Griffin et al. 2009; Mahoney et al. 2005; Omura 1987; Thériault et al. 1996; Gondin et al. 2011).

However, little is known about the effectiveness of NMES in regulating glycemic control (average glucose and glucose fluctuations in post-absorptive and post-prandial conditions) in individuals who are sedentary and obese. Furthermore, the potential benefit of this muscle contraction modality in regulating blood glucose in an at-risk population (sedentary and obese) for diabetes has not been well investigated (Sanchez et al. 2023). Moreover, there is a lack of data on the acute effect of high-frequency NMES (Sanchez et al. 2023) which is necessary to design long-term chronic treatments that will be efficacious for optimal metabolic health benefits (Galvan et al. 2022).

This study was designed to test the hypothesis that acute NMES (i.e., one session) could improve glycemic control, increase energy expenditure, and increase respiratory exchange ratio (RER) in individuals from a predominantly Hispanic population who were hyperglycemic, sedentary, and overweight/obese. Interventions to improve glycemic control among individuals with a high risk of type 2 diabetes are important to prevent the disease (Smith-Marsh 2013). Asymptomatic impaired glycemic control usually precedes the onset of type 2 diabetes (American Diabetes Association Professional Practice Committee 2021) and can be monitored by the use of continuous glucose monitor (CGM) systems. This study focused on a Hispanic-dominant population because in the United States, the Hispanic population tends to have a higher prevalence of obesity and sedentariness as compared to non-Hispanic populations (Vidal et al. 2022). Thus, we compared the effects of NMES versus glycemic control with CGM, over 24 h, in a predominantly Hispanic population.

Methods

Participants and experimentation

Fifty-six sedentary overweight/obese individuals with hyperglycemia (19 males and 37 females) between the ages of 18 and 60 years participated in this study. Majority (86%) of the participants self-identified as being of Hispanic origin. Individuals were excluded from participating in the study if they were taking insulin sensitizing medications, smoking, consuming excess alcohol, were pregnant, or having conditions that confound blood glucose level, or insulin secretion. Participants’ body mass index (BMI) was determined by height and weight measurement to ensure they met the BMI requirement for overweight (BMI ≥ 25 < 30)/obesity (BMI ≥ 30). Sedentariness was defined as engaging in a moderate-vigorous physical activity that is not more than 150 min per week, as assessed by a seven-day waist-worn accelerometer (ActiGraph Corp., Pensacola, Florida). Hyperglycemia was defined as having fasting interstitial/blood glucose of 100 mg/dL or above. This study was approved by the University of Texas at El Paso Institutional Review Board and each participant signed a written informed consent form prior to participation. This study was registered (https://clinicaltrials.gov/study/NCT03947697).

Prior to the NMES intervention, participants were familiarized with NMES to identify the maximum tolerable stimulation intensity. Body composition was assessed using dual energy X-ray absorptiometry (GE Medical Systems, Lunar DXA; Madison, WI) and body circumference measurements. A standard diet was provided to control dietary effects on primary outcome measures for 24 h prior to the NMES test day (control day) as well as for the test day (48h of diet in total, while participants were on CGM). On the day of the experiment, electrodes were attached to the quadriceps muscles of participants, and they underwent electrical stimulation for 30 min in a supine position. Metabolic rate and respiratory exchange ratio were measured continuously throughout the 30 min intervention (Fig. 1).

Fig. 1.

Fig. 1

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Study design

Dietary control

Participants were provided with breakfast, lunch, dinner, and snacks before and during the NMES experiment, to control for any dietary effects on blood glucose and insulin sensitivity, as we have done before (Amador et al. 2020; Meza et al. 2022). Meals were designed to comply with the US Department of Agriculture (USDA) 2015–2020 Dietary Guidelines for Americans and individualized to participant preferences/allergies. The standardized diet consisted of macronutrient energy contents of ~ 55% carbohydrates, ~ 15% protein, and ~ 30% fat (< 10% of total fat consisting of saturated fat). The Mifflin St. Jour equation (Mifflin et al. 1990) multiplied by a factor of four (estimated mean physical activity level of participants) was utilized to estimate total daily energy requirements of participants.

Energy expenditure and substrate utilization

Energy expenditure and substrate utilization were measured using indirect calorimetry (Parvomedics TrueOne 2400 metabolic cart) with a clear ventilated canopy and dilution pump as previously described (Galvan et al. 2022). Participants were placed into a semi-recumbent position with a hood canopy over their head to obtain measurements of oxygen utilized and carbon dioxide produced. Participants were fasted for at least 8 h and were asked to refrain from caffeine and high intensity physical activities the day before the test. On the day of the experiment, resting metabolic rate was measured for 20 min, following which metabolic rate was continuously measured while NMES was induced for 30 min. Instructions were given to the participants to minimize body movements and to remain awake for the entire measurement.

Continuous glucose monitoring

Interstitial glucose levels were measured on the day of stimulation as well as on the control day, using a CGM device (Dexcom G6 Pro CGM System, Dexcom, Inc, CA) attached to the abdomen. The CGM device was attached at least 24 h before the test day and remained on the participants for a minimum of 24 h after the test.

Electrical stimulation protocol

NMES was performed using QuadStar® II Digital MultiModality Combo Device (TENS-INF-NMS) (BioMedical Life Systems, Vista, CA) with eight 2″ × 2″ square electrodes (BioMedical Life Systems, Vista, CA) according to our previously published protocol (Galvan et al. 2022). The electrodes were placed bilaterally in the proximal and distal locations of the quadriceps using anatomical reference points. The stimulation device was set to cycled biphasic waveform with pulse duration of 300 μs and frequency set to 50 Hz. Fifty hertz is regarded as high frequency, while a frequency below 50 Hz is deemed low frequency (Galvan et al. 2022). The stimulation was applied continuously for 30 min using a duty cycle of 1:3 (10-s ON to 30-s OFF time ratio) with a 2-s ramp ON and a 2-s ramp OFF time. The intensity of stimulation administered varied between 1 and 120 mA according to the maximum tolerance of each participant. The maximum tolerable intensity was determined by gradually increasing stimulation intensity until participants indicated the maximum intensity beyond which they felt pain from the stimulation. Each individual’s intensity was recorded.

Statistical analysis

Results were analyzed using GraphPad Prism, Version 10.2.3. Normality was assessed by Shapiro–Wilk test. Normally distributed parameters were analyzed using t-test and one-way ANOVA with Dunnett’s multiple comparisons test. Respiratory exchange ratio parameters were involved in the ANOVA analysis. Non-parametric tests (Wilcoxon test and Friedman test with Dunn’s multiple comparisons test) were used to analyze parameters that were not normally distributed. A p < 0.05 was considered significant, and values are presented as means ± Standard Deviation (SD) or Standard Error of Mean (SEM).

Results

The descriptive characteristics of the participants are shown in Table 1. There were 19 males and 37 females in this study, all of whom had fasting glucose level of 100 mg/dL or higher. Nineteen percent of the participants had diabetes (fasting glucose of 126 mg/dL or above). Twenty percent were classified as overweight and 80% were obese.

Table 1.

Characteristics of study participants

Participants characteristics Mean ± SD
Age (years) 33.3 ± 11.8
Body mass index (Kg/m2) 34.8 ± 5.6
Body fat (%) 45.2 ± 8.6
Lean mass (kg) 49.8 ± 9.5
Systolic blood pressure (mmHg) 111 ± 11
Diastolic blood pressure (mmHg) 73 ± 9
Heart rate (bpm) 70 ± 13
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Glycemic control

Thirty minutes of NMES improved glycemic control parameters (fasting glucose level and glucose variability) (Fig. 2). Figure 2a, b shows a reduction in glucose levels post-stimulation (113.2 ± 2.5 mg/dL) as compared to glucose levels during stimulation (117.5 ± 2.7 mg/dL; p < 0.0001) and right before the onset of stimulation (Baseline) (116.2 ± 2.7 mg/dL; p < 0.0001 measured by CGM. Comparing the mean 24-h glucose levels on the day of stimulation (123.8 ± 2.3 mg/dL) and control day (124.7 ± 2.6 mg/dL), no significant difference (p > 0.05) was observed (Fig. 2c). However, the mean difference of maximum to minimum glucose excursions tended to be lower on the day of stimulation (90.9 ± 5.2 mg/dL) as compared to the control day without stimulation (102.6 ± 6.8 mg/dL; p = 0.06) (Fig. 2d). Moreover, on the day of stimulation, glucose variability (Fig. 2e) measured by the 24-h glucose standard deviation was significantly lower (18.0 ± 1.0 mg/dL) than on the control day without stimulation (20.0 ± 1.2 mg/dL; p < 0.05).

Fig. 2.

Fig. 2

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Continuous glucose monitoring (CGM) values before, during (30 min), and after (30 min) NMES (a, b); N = 44. Line graphs showing 5 min glucose time points (a). Mean glucose values at different phases of the stimulation (b). Two-day glycemic control measured by CGM on the day before NMES and on the day of NMES (c–e); N = 32. Average 24-h glucose values (c). Mean difference of maximum to minimum (Δ max–min) glucose excursions (d). Glycemic variability estimated by 24-h glucose standard deviation (SD) (e). Data presented as individual responses (a) or Mean ± SEM (b–e). *p < 0.05; ****p < 0.0001

Energy expenditure and substrate utilization

There was a significant increase in energy expenditure during the first 5 min of NMES (18.8 ± 0.3 kcal.Day−1.Kg−1 to 19.5 ± 0.4 kcal.Day−1.Kg−1; p < 0.001), but this reverted to near baseline levels after 30 min of stimulation (p > 0.05) (Fig. 3a). Compared to baseline energy expenditure level (18.8 ± 0.3 kcal.Day−1.Kg−1) the average energy expenditure during the entire 30 min of stimulation (19.0 ± 0.3 kcal.Day−1.Kg−1) increased significantly (p < 0.05) (Fig. 3b). Glucose utilization measured by RER increased significantly during stimulation (0.79 ± 0.01 to 0.80 ± 0.01; p < 0.005), with the most pronounced decrease occurring during the first 5 min of stimulation (0.79 ± 0.01 to 0.82 ± 0.01; p < 0.001) (Fig. 3c and Fig. 3d).

Fig. 3.

Fig. 3

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Energy expenditure at baseline and during NMES (a). Energy expenditure at baseline compared to mean of energy expenditure during NMES (b). Respiratory exchange ratio at baseline and during NMES (c). Respiratory exchange ratio at baseline compared to mean respiratory exchange ratio during NMES (d). Data presented as Mean ± SEM. (N = 57); *p < 0.05; **p < 0.005; ***p < 0.001

Discussion

This study showed that 30 min of NMES significantly improved glycemic control in individuals with prediabetes, who predominantly identified as Hispanic and were overweight/obese. There were significant reductions in fasting glucose, maximum to minimum glucose excursions, and glucose variability measured by free-living CGM after acute NMES treatment compared to control. Glucose utilization, as indicated by increased RER as well as energy expenditure, also increased during the stimulation period.

This is the first study to demonstrate a reduction in 24-h glucose variability on the day participants received NMES compared to the control day. CGM provides a comprehensive assessment of glycemia with multiple intermittent glucose level measurements and glucose variability/fluctuation indices (Danne et al. 2017), serving as an important modality to evaluate the effect of NMES on glycemic control. Higher glucose variability, which reflects poor glycemic control, has been associated with the development of hyperglycemia and diabetes complications (Suh and Kim 2015). Glucose variability is emerging as one of the preferred targets for improving blood glucose control and diabetes management in place of conventional glycemic control indices such as blood glucose and HbA1c levels (Suh and Kim 2015). This is the first study that reveals new areas of glycemic control improvement, specifically 24-h glucose variability, with NMES use.

Our findings support previous studies that used CGM in patients with diabetes (Macedo et al. 2024; Tsurumi et al. 2022), corroborating the argument that NMES is a potential glycemic control intervention for hyperglycemia management. We previously conducted a systematic review that reported a reduction in blood glucose levels in response to acute NMES intervention; however, studies with individuals with obesity and/or who are sedentary are scarce (Sanchez et al. 2023). While one previous study in individuals with obesity and pre-obesity showed decreases in blood glucose, glucose area under the curve (AUC), and insulin levels after NMES use (Kimura et al. 2010), it used low-frequency NMES, had a small sample size (N = 14), and included only male participants. Moreover, that study was performed in participants with transiently induced hyperglycemia (meal tolerance test) as opposed to our study participants with physiological fasting hyperglycemia.

Given that hyperglycemia, obesity, and sedentariness are major risk factors for diabetes, the application of NMES in this population can have significant implications for the prevention of type 2 diabetes. To the best of our knowledge, this is the only study, besides our previous pilot study (Galvan et al. 2022), to evaluate NMES intervention in a population of predominantly Hispanic Americans, a population known to have a high risk of diabetes (Schneiderman et al. 2014) with a case fatality rate that is 1.3 times higher than non-Hispanic white populations (Kposowa 2013). Socioeconomic barriers to physical activity are the likely factors that explain the high diabetes risk and low prognosis disparity in Hispanic populations (Chang et al. 2018). The implementation of NMES in this population, therefore, holds positive potential to overcome poverty limitations and the perceived barriers to exercise, such as lack of willpower, lack of energy, time constraints, fear of injury, and negative self-image (Kposowa 2013; Chang et al. 2018) that prevails in Hispanic communities.

The physiological changes induced by NMES to improve glycemic control are not well established. At the level of the muscle, it has long been established that muscle contraction increases both insulin-independent and insulin-dependent pathways of muscle glucose uptake into both healthy muscle and insulin-resistant muscle (Thyfault 2008). Moreover, there appears to be a synergy of muscle contraction and insulin to increase glucose uptake into skeletal muscle that is defined as insulin resistant (Thyfault 2008). This synergy has been shown to occur via AS160 phosphorylation, the converging molecule for insulin-dependent and insulin-independent pathways of Glut4 translocation and glucose uptake (Thyfault 2008; Santos et al. 2008). Muscle contraction-induced glucose uptake occurs via AMPK phosphorylation and Calcium–Calmodulin signaling (Santos et al. 2008). Whether NMES-induced decrease in blood glucose is regulated via the same pathways is unclear. Thus, future work is required to determine the exact signaling mechanism in skeletal muscle responsible for eliciting a decrease in blood glucose.

In this study, there was an increase in energy expenditure and RER during the stimulation period. Our previous systematic review showed that these changes are commonly reported outcomes during NMES treatment (Sanchez et al. 2023); nevertheless, the Kimura et al. study, which employed participants with obesity/pre-obesity, showed no change in RER (Kimura et al. 2010). Akin to conventional exercise, NMES-induced muscle contraction is expected to increase energy expenditure and the demand for oxygen (Hsu et al. 2011). While NMES-induced increase in energy expenditure has been reported to be independent of body fat percentage, intensity of the stimulation is a plausible factor (Hsu et al. 2011). The primary source of metabolic fuel utilized by working skeletal muscle is either carbohydrates or fat (Mul et al. 2015); however, the preference for a particular fuel type depends on the muscle fiber type being stimulated (Verbrugge et al. 2022).

While conventional exercise follows the size principle of first stimulating type I oxidative fibers before the glycolytic type II fibers (Henneman et al. 1965), NMES is known to stimulate both type I and type II muscle fibers in a non-selective pattern (Gregory and Bickel 2005) which may result in a relatively higher utilization of carbohydrates. In our study, the proportion of glucose utilization tended to increase as indicated by the increase in RER. Unlike the other studies that were conducted in fed conditions (Sanchez et al. 2023), our participants were assessed in the fasting state during lab-based measures; hence, increased preference for carbohydrate over fat is not expected to be very pronounced. The increase in both RER and energy expenditure reported in our study is an indication of increased substrate utilization, specifically glucose utilization, substantiating the observed decrease in glucose levels.

NMES is a simple and non-invasive technique to induce muscle contraction, that is usually well tolerated by users and possess little to no adverse events (Xu et al. 2024; O’Connor et al. 2018). Due to its portability, NMES can be applied unsupervised by the user at home (O’Connor et al. 2018). It is a safe intervention that requires minimum participant cooperation and is inexpensive (Xu et al. 2024). Compared to conventional exercise programs, home-based self-administration of NMES could be cost and time effective, as participants do not need to travel to a training center to administer it. Moreover, its multitasking-friendly design enhances user flexibility and promotes higher adherence rates. Our recent meta-analysis demonstrated that people who perform conventional exercise can incorporate NMES in their routine workout for an additive effect on muscle mass and strength improvement (Narvaez et al. 2025). NMES as a glycemic control modality could be customized to suit the needs of various individuals/populations by leveraging these unique benefits and advantages.

While we acknowledge that this study was not a randomized control trial to include a sham group, this study was carefully designed to ensure stability of blood glucose by consistently collecting all data at fasted state and in supine position to evaluate glucose, energy expenditure, and glucose utilization during stimulation state compared to baseline. This is the first study to investigate the acute effect of high-frequency NMES on fasting glucose in participants who were overweight/obese, and with a relatively high sample size compared to previous studies identified by our previous systematic review (Sanchez et al. 2023). The standardized eucaloric diet control employed also reinforces the robustness of the study by minimizing the impact of varied food macronutrients on blood glucose.

In conclusion, this study showed lowered glucose following 30 min of NMES intervention in individuals who were hyperglycemic, sedentary, and overweight/obese. We also found reduced levels of glucose excursions and variability measured by CGM after a 24-h period following NMES treatment. The increase in glycemic control was accompanied by an increase in energy expenditure and glucose utilization (RER) levels. This study shows the potential of NMES to serve as a short-term glucose management modality; therefore, further studies are needed to evaluate its long-term effect for diabetes prevention/management. Furthermore, future studies should explore ways to maximize the effect of NMES by simultaneously stimulating multiple muscles via a whole-body electrical stimulation system and determine the optimal window of time to have maximum effect.

Acknowledgements

The authors thank Ulices Villalobos, Joshua Labadah, MPhil, and Victoria Rocha, BS, of the MiNER Laboratory for their assistance in data collection and data tabulation. They received no financial support for their participation.

Abbreviations

NMES

Neuromuscular electrical stimulation

CGM

Continuous glucose monitor

RER

Respiratory exchange ratio

HbA1c

Glycated hemoglobin

DXA

Dual energy X-ray absorptiometry

USDA

United States Department of Agriculture

Author contributions

This study was conceptualized by S.B. J.N.A., A.M., and S.B. were involved in the design of the project, data acquisition, analysis, and interpretation of the work. G.N., I.J.T., and Z.F. contributed to the data acquisition, analysis, and interpretation of the work. A.J.M. was involved in the design of the work and interpretation of data for the work. J.P.T., K.M., H.J., and A.E.W. contributed to the interpretation of data for the work. J.N.A. wrote the first draft of the manuscript. All authors revised the manuscript, approved the final version for submission/publication in the journal, and agreed to be accountable for all aspects of the work. S.B. is the guarantor of this work and, as such, has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Funding

This study was supported by grants awarded to SB by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health under award number R01DK132430 and the J. Edward and Helen M. C. Stern Endowed Professorship. A.M., G.N., and J.N.A. were recipients of the Dodson Research Grant, The University of Texas, El Paso. A.M. was awarded Texas American College of Sports Medicine Student Research Development Grant (SRDA). I.J.T. was awarded the American Physiological Society’s (APS) Summer Undergraduate Research Fellowship (SURF).

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Conflict of interest

The authors have no conflict of interest to disclose. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. The study approval was granted by the University of Texas Institutional Review Board.

Consent to participate and publish

Informed consent was obtained from all individual participants included in this study.

Footnotes

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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