Electroacupuncture in glycemic control: Transitioning from clinical controversies to potential basic research

Abstract

Diabetes is a major global metabolic disorder, with the type 2 diabetes mellitus (T2DM) population in China expected to reach 168 million by 2050. Electroacupuncture (EA) and auricular acupuncture represent safe, accessible, and multi-targeted strategies for glycemic control with strong translational potential. Clinical studies indicate that EA, targeting trunk and limb acupoints, can significantly reduce fasting plasma glucose and glycated hemoglobin. Mechanistically, EA modulates the neuro-endocrine-immune axis, regulates gut microbiota, and activates insulin signaling pathways. Auricular acupuncture, through vagal innervation, may also exert rapid effects on glucose homeostasis via autonomic modulation. The review’s objective is to synthesize and critically evaluate current clinical trials and animal studies on EA and auricular acupuncture for glycemic control in diabetes, particularly T2DM, and to highlight translational implications, mechanistic insights, and evidence gaps. This review also emphasizes translational considerations by highlighting species differences between rodents and humans - an underappreciated yet critical factor influencing the clinical applicability of preclinical findings. Through the integration of recent research advances, the present review not only consolidates clinical and preclinical evidence but also advances a deeper mechanistic framework and underscores the importance of species-specific factors in bridging experimental research and patient care. Future progress requires rigorously designed, adequately powered, multicenter randomized controlled trials with standardized protocols to validate efficacy and define their role in precision diabetes management.

Key Words: Electroacupuncture; Blood glucose management; Clinical controversies; Basic research in acupuncture; Auricular acupuncture; Body acupuncture

Core Tip: This review examines electroacupuncture (EA) for glycemic control, addressing clinical controversies and underlying mechanisms. While EA shows promise in reducing blood glucose levels in type 2 diabetes, current clinical trials are limited by small sample sizes and heterogeneous designs, lacking robust international consensus. Basic research indicates that EA’s hypoglycemic effects involve modulating the neuro-endocrine-immune axis, enhancing insulin signaling, and improving gut microbiota. Future work should focus on optimizing EA protocols and developing standardized interventions to advance its clinical application in diabetes management.

INTRODUCTION

Diabetes mellitus, as the most prevalent chronic metabolic disease worldwide, exhibits a yearly escalation in incidence and complication burden. In China, the number of individuals aged 20-79 years with type 2 diabetes mellitus (T2DM) is expected to reach 168 million by 2050[1]. Recently, non-pharmacological interventions, particularly electroacupuncture (EA), have garnered attention for their potential in regulating glucose metabolism due to their ease of use and minimal side effects. Clinical studies demonstrate that needling at trunk and limb acupoints can significantly reduce fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) levels in patients with type 2 diabetes[2,3], while auricular acupuncture, owing to its convenience for self-management, is widely utilized in regions such as Europe, the Americas, and Australia, with multiple clinical reports supporting its hypoglycemic effects[4]. Nevertheless, its underlying mechanisms warrant further elucidation. Variability in study designs, small sample sizes, and insufficient randomization and blinding hinder the integration of conclusions across studies[5]. Additionally, many systematic reviews highlight the lack of large-scale, multicenter, rigorously bias-controlled randomized controlled trials (RCTs), preventing EA's efficacy from achieving broad international consensus[6]. Therefore, in-depth investigation of EA's neuro-endocrine mechanisms not only facilitates a scientific evaluation of its effectiveness but also provides theoretical foundational support for future multicenter clinical trial designs.

In contrast, mechanistic studies primarily utilizing experimental animals such as rats have fully demonstrated the scientific value and future potential of EA in hyperglycemia, with multiple independent teams[7] respectively reporting that EA at Zusanli (ST36) or Tianshu (ST25) acupoints can reduce blood glucose levels in diabetic animals, with mechanisms including modulation of gut microbiota and regulation of the neuro-immune axis. However, these studies typically focus on single acupoints, which differs from clinical EA for hyperglycemia that often targets multiple acupoints. The disparity between clinical and basic research arises from the different experimental design requirements: Animal models use single-acupoint stimulation to isolate mechanisms (e.g., activating specific neural pathways), while clinical practice focuses on multi-acupoint synergy to address complex metabolic networks, aiming to improve efficacy and tolerability. However, this gap presents an opportunity for optimization. By integrating core acupoints (e.g., ST36) identified from basic research with clinical data from multi-acupoint protocols, we can develop standardized approaches to reduce ineffective stimulation, enhance therapeutic consistency, and optimize acupuncture's clinical use for hyperglycemia (Figure 1). Recent studies have begun to bridge this gap by combining insights from both areas. One study, for example, explored the neuroanatomical regulation of gastric function in both mice and humans, integrating clinical trials to validate stimulation depth and intensity, providing a novel paradigm that translates basic mechanisms into clinical evidence and promotes the integration of single-acupoint research into multimodal clinical applications[8].

Figure 1 Graphical abstract. Clinical challenges (left), multi-target stimulation of key acupuncture points (middle), and potential mechanisms involving the nervous system, anti-inflammation, gut microbiota, and insulin signaling pathways (right) ultimately contribute to the development of future closed-loop wearable devices for personalized management. CGM: Continuous glucose monitoring; IL-1β: Interleukin-1β; SCFA: Short-chain fatty acid; LPS: Lipopolysaccharide. Created with biorender.com (Supplementary material).

Despite the fact that the existing evidence is not yet sufficient to establish a unified consensus, EA and auricular acupuncture have demonstrated considerable potential as safe, accessible, and multi-targeted strategies for glycemic control. This review first recapitulates the controversies and criticisms in clinical research; subsequently summarizes the progress in basic research on EA for hyperglycemia, including characteristics of animal models, experimental designs, primary intervention acupoints, and therapeutic effects; then discusses the differences in acupoint selection between clinical and basic research and the underlying reasons; and finally proposes potential future directions in mechanistic research on auricular and body acupuncture, with the aim of providing insights for the standardization of EA in blood glucose management and the integration of acupuncture into modern science. The target audience of this study includes clinicians and researchers involved in diabetes management and treatment, as well as scholars and professionals interested in non-pharmacological interventions for diabetes.

CLINICAL CONTROVERSIES

Acupoint selection and potential mechanisms in clinical EA for hyperglycemia

Body acupoints refer to acupoints located on any part of the human body, including the head, face, abdomen, back, waist, etc. (excluding the ear)[9], while auricular acupoints refer to acupoints distributed on the auricle[10]; these stimulation sites exert hypoglycemic effects from different perspectives. Acupuncture practitioners commonly employ body acupoints on the trunk and limbs, such as Zusanli (ST36) and Sanyinjiao (SP6)[11], as well as auricular targets like the pancreas area and endocrine area to assist in blood glucose reduction. Research by Lee et al[12] demonstrated that EA at ST36 (15 Hz, 30 minutes) enhances the muscle insulin receptor substrate (IRS)-1/AKT signaling pathway by stimulating the parasympathetic nervous system (with atropine completely blocking the hypoglycemic effect), thereby reducing blood glucose. For auricular acupoints, Guo et al[13] indicated that auricular vagus nerve stimulation can regulate autonomic nerves via the nucleus tractus solitarius to activate pancreatic β-cells, promoting insulin secretion and inhibiting glucagon release. Empirical studies also show that interventions at auricular acupoints such as AH6a, TF4, and AT4 can improve glucose metabolism. A meta-analysis by Yu et al[14] of 14 studies revealed that auricular acupressure combined with conventional treatment significantly reduced FBG, 2-hour postprandial blood glucose, and HbA1c in T2DM patients, while also improving lipid profiles and body mass index (BMI); through data mining, they identified AH6a, TF4 (endocrine), AT4, CO18, and CO10 as key auricular acupoints related to the regulation of the pancreas and digestive system. A meta-analysis by Hua et al[15] of 22 studies indicated that auricular acupuncture has significant effects in reducing fasting serum insulin levels and homeostasis model assessment insulin resistance (HOMA-IR), with its primary mechanism likely involving stimulation of the auricular vagus nerve to modulate autonomic nerves, which in turn improve pancreatic islet function and subsequently regulate insulin.

Dialectical thinking on clinical research of acupuncture for hyperglycemia

Existing research indicates that EA at specific acupoints has a significant short-term hypoglycemic effect, but its efficacy as a long-term management strategy for T2DM lacks support from high-quality evidence. Several RCTs have already evaluated the short-term effects of EA on blood glucose, with commonalities among these studies including: (1) Similar single-session durations: Clinical experiments using 30-minute stimulation periods on different body acupoints, all resulting in significant reductions in blood glucose levels; (2) Meta-analyses (all concerning EA) collectively demonstrating that EA stimulation can reduce FBG; and (3) Stimulation of Zusanli (ST36) and Zhongwan (CV12) can lower blood glucose levels. Existing research indicates that EA at specific acupoints [e.g., Zhongwan (CV12), Zusanli (ST36)] can significantly reduce FBG levels in T2DM patients in the short term. Existing research indicates that EA at specific acupoints [e.g., Zhongwan (CV12), Zusanli (ST36)] has a significant regulatory effect on blood glucose, with a single 30-minute treatment session yielding observable hypoglycemic effects; meta-analyses targeting specific populations (e.g., patients with non-alcoholic fatty liver disease) also support the effectiveness of EA in reducing FBG[16,17]. However, when evaluating the effectiveness of EA as a long-term management strategy for T2DM, the evidence appears relatively weak and insufficient. A key issue is the limited number of rigorous RCTs that use core long-term blood glucose control indicators such as HbA1c and the HOMA-IR as endpoints[18]. A recent meta-analysis by Li et al[19] that included 21 RCTs assessed this. The analysis found that, compared to oral hypoglycemic agents alone, combined EA and pharmacological treatment showed only limited improvements in long-term follow-up: The average reduction in FBG was modest (approximately 6.46 mg/dL), HOMA-IR exhibited mild improvement (mean difference -1.23), but more critical long-term indicators such as HbA1c and postprandial blood glucose did not demonstrate statistically significant benefits. Overall, the existing evidence suggests that EA may possess short-term hypoglycemic effects, but the evidence for its effectiveness as a long-term diabetes management strategy remains insufficient; reported positive outcomes are often of moderate or weak efficacy and are susceptible to influences from factors such as follow-up duration, treatment intensity, and protocols (e.g., acupoint selection, stimulation parameters). Therefore, although EA at specific acupoints demonstrates clear immediate hypoglycemic effects, its effectiveness and clinical value as a long-term management strategy for T2DM still require more high-quality, long-term follow-up RCTs to provide conclusive evidence.

Overall, clinical research on EA for hyperglycemia exhibits the following major issues: (1) Insufficient sample sizes (most studies involve only around 20 patients); (2) Methodological deficiencies; and (3) Inability to conduct double-blind experiments, resulting in uneven methodological quality. Due to substantial variations in inclusion and exclusion criteria, the available clinical trials exhibit high heterogeneity, making it inappropriate to perform a reliable meta-analysis. Multiple systematic reviews have identified recurrent flaws in acupuncture RCTs, including unclear or inadequate randomization, lack of blinding, and small sample sizes[20], which severely limit the strength of conclusions. Through re-evaluation of relevant system evaluations, it was found that most RCTs have low quality, with common deficiencies including lack of registration schemes, incomplete searches, and high risk of bias[21]. The quality of clinical evidence for EA therapy in diabetes management is dually constrained by its technical complexity and methodological limitations. The unique characteristics of EA therapy determine the heterogeneity of its outcomes and the controversies surrounding placebo effects. Many acupuncture studies “lack rigorous design (e.g., inadequate control groups, insufficient blinding), which restricts the reproducibility and generalizability of the results”. Different studies often employ sham EA (without current output), simple acupuncture, or conventional medications (e.g., oral hypoglycemic agents) as control groups. While this diversity enriches study designs, it further exacerbates outcome heterogeneity and perpetuates debates over placebo effects. Fundamentally, EA requires precise regulation of stimulation parameters (frequency, intensity, waveform), and practitioners must adjust these settings based on real-time feedback from both acupoint sensation and patient physiology (e.g., blood glucose fluctuations). This necessity makes true double-blind implementation extremely challenging, particularly in blinding the acupuncturist. It represents a core methodological barrier: Operator awareness of allocation may unconsciously influence point selection or stimulation settings [e.g., Zusanli (ST36) + Sanyinjiao (SP6) combination], thereby introducing performance bias and potentially exaggerating or diminishing observed hypoglycemic effects. This blinding limitation not only reduces the internal validity of the studies but may also lead to external validity issues: In clinical practice, the hypoglycemic effects of EA often depend on the practitioner's experience and the patient's immediate physiological feedback; if studies cannot simulate a true double-blind environment, the generalizability of their results to diabetic patient populations is compromised. From the perspective of evidence grading, such design flaws may lead to the downgrading of the evidence for EA in lowering blood glucose (e.g., low or very low quality in the GRADE system), thereby affecting its recommendation strength in diabetes clinical guidelines, for example, rendering it incomparable to standard hypoglycemic drugs (e.g., metformin). RCTs remain the gold standard to address most of these methodological deficits, as they enable proper randomization and control for confounding factors. However, even within randomized designs, the nature of EA often restricts feasible blinding to single-blind approaches. For example, due to program limitations, most RCTs of EA for insomnia could only be conducted using a single blind method. This methodological weakness, however, could be addressed through the adoption of standardized research protocols. It is recommended that future trials should rigorously implement randomization, blinding, and allocation concealment, and adhere to the PRISMA and STRICTA guidelines to enhance transparency and reproducibility, reporting full technical specifications of EA (e.g., waveform, frequency, intensity, acupoint prescription, needle retention time, and treatment duration). Such standardization would significantly improve research transparency and reproducibility. Second, the design of control groups should be optimized. Researchers should develop and validate scientifically sound sham acupuncture or simulated EA protocols capable of maintaining participant blinding, thereby improving the credibility of trial results.

EA therapy possesses unique advantages. EA enables personalized treatment protocols through precise regulation of electrical parameters, which to some extent compensates for the shortcomings of traditional acupuncture; moreover, compared to the hypoglycemia risks associated with hypoglycemic drugs such as insulin, the side effects of EA are minimal. For example, EA can adjust stimulation intensity and frequency according to individual patient differences, thereby better inducing hypoglycemic responses. Additionally, EA therapy demonstrates good tolerability and safety in clinical practice, with few adverse reactions, providing strong support for its application in diabetes management[22]. In the future, innovative methods can be employed to mitigate current limitations, such as adopting patient blinding combined with objective biomarker assessments (e.g., continuous glucose monitoring or inflammatory marker levels), or introducing automated EA devices to minimize practitioner bias. Simultaneously, strengthening the design of multicenter, large-sample RCTs can help balance heterogeneity and provide a more reliable evidence base, ultimately promoting the transformation of EA from an empirical hypoglycemic intervention to an evidence-based medicine paradigm[23].

BASIC RESEARCH ON EA FOR HYPERGLYCEMIA AND ITS IMPLICATIONS FOR CLINICAL RESEARCH

Basic research in explaining clinical heterogeneity

While clinical studies often employ multi-acupoint protocols to enhance therapeutic efficacy through synergistic effects, basic research tends to focus on single-acupoint stimulation to isolate specific mechanisms. This methodological divergence, though seemingly contradictory, offers a unique opportunity to reconcile clinical heterogeneity with mechanistic clarity. By systematically investigating the physiological effects of individual acupoints (e.g., ST36 or CV12) in controlled animal models, researchers can identify core pathways - such as vagal activation or anti-inflammatory responses - that underlie EA’s glycemic benefits. These insights can then inform the optimization of clinical acupoint combinations, minimizing redundant stimulation and enhancing treatment precision. In addition, it is necessary to observe the mechanism of single-acupoint intervention based on the clinical phenomenon of multiple points, in order to optimize clinical research. Thus, basic research not only elucidates the biological foundations of EA but also provides a rational framework for refining clinical practice, ultimately bridging the gap between empirical multi-acupoint applications and evidence-based protocol design.

Characteristics of basic research on EA for hyperglycemia

Basic research on EA for hyperglycemia is primarily conducted in animals; understanding the characteristics of these animal models helps us comprehend the differences in the hypoglycemic effects of EA on humans and animals. Current models can relatively comprehensively reflect the damage to various organs under diabetic conditions. In the past five years, research on EA for hyperglycemia has mainly employed two types of models: First, the T2DM model induced by high-fat diet (HFD) combined with low-dose STZ, which more closely approximates the characteristics of insulin resistance and metabolic syndrome, and is commonly used to evaluate the improvement of insulin sensitivity by EA[24]. Genetic models such as Diabetic (db/db) mice possess advantages like spontaneous hyperglycemia and rapid progression of complications, facilitating the exploration of EA interventions for long-term metabolic abnormalities and organ complications[25]. In summary, the strategy of employing multiple models allows entry from different pathological nodes, such as insulin resistance and chronic inflammation, systematically reproducing glucose metabolism imbalances under controlled conditions, comprehensively assessing EA intervention effects, and exploring its mechanisms of action, thereby laying a solid experimental foundation for in-depth research (Table 1)[26]. However, owing to the substantial time and financial costs associated with such experiments, the number of teams conducting them is limited.

Table 1 Major animal models and corresponding acupoint selection in electroacupuncture for hypoglycemic research.

Model name	Number of published articles in WoS and PubMed (from the database to the present)	Number of published electroacupuncture articles in WoS and PubMed	Acupoints	Major references	Ref.
HFD + STZ; T2DM	15200	68	Tianshu (ST25) (88%), Zusanli (ST36)	Hypoglycemic effect of electroacupuncture	[3]
Diabetic (db/db) mice	8300	52	Yishu (EX-B3) (79%), Zusanli (ST36) (76%)	Electroacupuncture at Yishu (EX-B3) promotes β-cell regeneration via modulating pancreatic innervation in type 2 diabetic db/db mice	[26]

HFD: High-fat diet; STZ: Streptozotocin; T2DM: Type 2 diabetes mellitus.

Although animal experiments provide abundant mechanistic evidence for EA in hyperglycemia, high caution is warranted when extrapolating these results to clinical settings due to biases arising from interspecies differences. These differences are primarily manifested in three aspects: First, inherent differences in pancreatic islet structure and function. Rodents have a significantly higher proportion of pancreatic islet β-cells (75%-80%) compared to humans (50%-60%), with α-cells exhibiting peripheral distribution (whereas they are intermixed in humans), leading to species-specific insulin/glucagon secretion responses following EA[27]; second, differences in neuro-endocrine pathway sensitivity. Rodents are more sensitive to stimulation of the hepatic branch of the abdominal vagus nerve, while humans have a denser distribution of the auricular vagus nerve; the temporal dynamics of hypothalamic-pituitary-adrenal (HPA) axis feedback regulation differ markedly between rats (corticosterone half-life of 20 minutes) and humans (cortisol half-life of 60-90 minutes), affecting the evaluation of EA's anti-stress effects[28]; third, effects of metabolic rate and body size scaling. Mice have a basal metabolic rate approximately several times that of humans[29], whereas larger animals (e.g., pigs, dogs) more closely approximate human physiology. For instance, in the spontaneously diabetic minipig - a large-animal model whose pancreatic innervation and metabolic scaling more closely approximate human physiology - EA at ST36 must be delivered at 0.5 mA (continuous square wave, 5-10 Hz) to elicit a hypoglycaemic decrement equivalent to that observed in rodents at markedly lower current densities. This quantitative discrepancy underscores the necessity of species-specific calibration of electrical dose, rather than direct extrapolation of stimulation parameters validated in small-animal studies.

In basic research, the focus of studies on EA intervention strategies centers on classical acupoints, stimulation parameters, and the synergistic effects exerted by the combined use of multiple acupoints (i.e., multi-acupoint superiority over single-acupoint). Electrical stimulation of classical acupoints such as Zusanli (ST36) and Zhongwan (CV12) has been confirmed to stably reduce FBG, with mechanisms closely related to β-endorphin release and opioid receptor activation. Regarding stimulation parameters, commonly used frequencies are concentrated between 2-15 Hz, with waveforms primarily consisting of continuous waves or dilatational waves; single-session stimulation durations are typically 30-60 minutes, and treatment courses often span 2-4 weeks. Additionally, a few studies have explored the combined application of EA with oral hypoglycemic agents (e.g., acarbose), finding synergistic enhancements in reducing blood glucose and improving insulin curves. However, current research also exposes key issues, such as inconsistencies in EA parameter standards and insufficient control group designs, which severely impact the horizontal comparability and experimental reproducibility of results; these are critical directions for future optimization of intervention strategies (Tables 2 and 3)[30-34].

Table 2 Main stimulation parameters and corresponding acupoints in electroacupuncture for hypoglycemic research.

Stimulation frequency and current intensity	Waveform	Acupoints	Treatment duration	Ref.
2 Hz, 1 mA	Continuous	Zusanli (ST36)	20 minutes/session, once daily for 4 weeks	[30]
2 Hz, 1 mA	Continuous	Zhongwan (CV12), Zusanli (ST36), Guanyuan (CV4), Fenglong (ST40)	15 minutes/session, every other day for 8 weeks	[26]
10 Hz, 2 mA	Continuous	Zhongwan (CV12)	30 minutes/session, every other day for 3 weeks	[3]
15 Hz, 1-2 mA	Continuous	Zusanli (ST36), Zhongwan (CV12)	20-30 minutes/session, once daily for 4 weeks	[12]
2-10 Hz, 1.5-2 mA, 100 Hz, 3 mA	Sparse-dense wave, interrupted wave	Tianshu (ST25), Zusanli (ST36), Shenshu (BL23)	30 minutes/session, every other day for 3 weeks	[3]
10 Hz, 1-3 mA	Sparse-dense wave	Tianshu (ST25)	30 minutes/session, once daily for 2 weeks	[2]

Table 3 Types of animals used in electroacupuncture for hypoglycemic research.

Species	Diabetic state	Acupoints (bilateral or unilateral)	Frequency (Hz)	Duration	Current (mA)	Effect description	Mechanism research conclusion	Ref.
Rat	Type 1 diabetes (fasted)	Zusanli (ST36) (ST36, bilateral)	15	30-60 minutes	-	Reduces fasting blood sugar	Activates vagus nerve-liver axis: Enhances parasympathetic activity, promotes glycogen synthesis in liver and inhibits gluconeogenesis	[31]
	Type 1 diabetes (STZ induced)	Zusanli (ST36) (ST36, bilateral)	15	30/60 minutes	-	Enhances insulin signaling protein expression, significantly lowers blood sugar	Modulates IRS-1/AKT pathway: Stimulates vagus nerve to release acetylcholine, activating insulin signaling pathways in skeletal muscle and liver	[32]
	Type 2 diabetes (fasted)	Zusanli (ST36) (ST36, bilateral)	2	20 minutes	1	Reduces blood sugar	Inhibits hypothalamic inflammation: Modulates HPA axis, reduces corticosterone levels, alleviates inflammation and improves insulin resistance	[33]
	Type 2 diabetes (HFD + low-dose STZ induced)	Zusanli (ST36), Pishu (BL20), bilateral	15	30 minutes per session, once per day for 14 days	1	Significantly improves insulin sensitivity	Reshapes gut microbiota: Increases SCFA-producing bacteria, reduces LPS levels, alleviates systemic inflammation, improves insulin sensitivity	[25]
Mouse	Normal (fasted)	Zusanli (ST36), bilateral	15	30 minutes	-	Reduces blood sugar	Activates cholinergic anti-inflammatory pathway: Enhances vagus nerve activity, inhibits splenic TNF-α release, reduces inflammation	[24]
	Type 2 diabetes (HFD)	Guanyuan (CV4) + Zhongwan (CV12), bilateral	3	30 minutes	-	Significantly lowers postprandial blood sugar	Activates cholinergic anti-inflammatory pathway: Enhances vagus nerve activity, inhibits splenic TNF-α release, reduces inflammation	[34]
	Type 2 diabetes (STZ induced)	Zusanli (ST36), bilateral	10	30 minutes per day, for 8 weeks	1-3	Lowers random blood sugar and fasting blood sugar	Promotes β-cell regeneration: Modulates PINS, activates β-cell proliferation signals (e.g., PDX-1), inhibits pancreatic fibrosis	[2]

HPA: Hypothalamic-pituitary-adrenal; SCFA: Short-chain fatty acid; LPS: Lipopolysaccharide; TNF-α: Tumor necrosis factor alpha; PINS: Pancreatic intrinsic nerves; HFD: High-fat diet; IRS: Insulin receptor substrate; STZ: Streptozotocin.

Mechanisms of EA for hyperglycemia: Clear findings from single-acupoint studies

Existing mechanistic studies have revealed key pathways through which EA exerts its role in blood glucose control, with neurobiological mechanisms and anti-inflammatory pathways being the focal points of research; these findings primarily originate from animal experiments stimulating body acupoints rather than auricular acupoints, and most target single acupoints such as ST25, ST36, CV12, and CV4. First, in terms of neurobiological mechanisms, EA demonstrates significant regulatory capacity on the autonomic nervous system (ANS), which is considered one of the core components of its hypoglycemic effects. Studies have found that EA at specific acupoints (e.g., Zhongwan CV12, Tianshu ST25) can enhance parasympathetic nervous activity (particularly the vagus nerve), improve local tissue blood circulation and glucose utilization, thereby contributing to blood glucose reduction. Further research indicates that EA stimulation of specific acupoints, such as Yishu (EX-B3), can directly regulate the pancreatic intrinsic nerves (PINS), thereby improving pancreatic β-cell function, promoting normal insulin secretion or improving its efficacy, and achieving the goal of blood glucose reduction; by modulating the HPA axis, it reduces levels of stress hormones such as cortisol, corrects endocrine disruptions, and indirectly exerts beneficial effects on glucose metabolism. Concurrently, studies suggest that EA can activate intracellular insulin signaling pathways, such as the PI3K/Akt pathway, enhancing glucose uptake and utilization in peripheral tissues like skeletal muscle and adipose, and improving insulin sensitivity. For example, EA stimulation of Zusanli (ST36) and Shenshu (BL23) has been reported to upregulate the expression of IRS, PI3K, Akt2, and glucose transporters [e.g., glucose transporter 2 (GLUT2), GLUT4], reducing fasting insulin levels and indicating its positive regulatory role on insulin signal transduction[35]. Therefore, EA at specific single acupoints (e.g., ST36, CV12, EX-B3) primarily regulates blood glucose by enhancing parasympathetic nervous activity, modulating PINS, improving HPA axis function, and activating PI3K/Akt insulin signaling pathways in peripheral tissues (e.g., muscle, liver).

Second, anti-inflammatory pathways are also one of the primary mechanisms through which EA exerts its hypoglycemic effects. Chronic low-grade inflammation is a critical pathophysiological basis for the onset and progression of type 2 diabetes, closely associated with insulin resistance. Animal experiments indicate that EA possesses significant anti-inflammatory effects. It can inhibit the activation of the NLRP3 inflammasome, thereby reducing the production and release of key pro-inflammatory cytokines such as interleukin-1β (IL-1β), alleviating the body's inflammatory state, and improving insulin resistance[36]. Further studies suggest that EA may reshape the gut microbiota by modulating its composition and function. For instance, by increasing the abundance of beneficial bacterial populations [e.g., short-chain fatty acid (SCFA)-producing bacteria] and reducing harmful bacteria and their metabolites [e.g., lipopolysaccharide (LPS)] entering the bloodstream, it lowers systemic inflammatory responses and improves intestinal barrier function, which holds significant implications for blood glucose control and amelioration of metabolic syndrome[37]. Additionally, EA may improve vascular endothelial function, for example, by increasing endothelial nitric oxide synthase expression, mitigating diabetes-related vascular complications, which is also part of its comprehensive therapeutic effects. Moreover, EA stimulation of Yishu acupoint (EX-B3) exerts hypoglycemic effects by modulating pancreatic intrinsic neural segments in T2DM rat models. By targeting and regulating autonomic neural signals from the celiac ganglion to the pancreas, it improves disrupted intrapancreatic neuro-endocrine dialogue; through neuro-mediated anti-inflammatory and antioxidant effects, it mitigates β-cell damage and promotes insulin synthesis and release; neuro-reflex-mediated islet protection and enhanced insulin secretion can directly reduce blood glucose levels in experimental T2DM rats. Therefore, EA improves insulin resistance and blood glucose control through multiple anti-inflammatory pathways, including inhibition of key inflammatory pathways (e.g., NLRP3 inflammasome), reduction of pro-inflammatory factors (e.g., IL-1β), reshaping of gut microbiota (increasing SCFA-producing bacteria, reducing LPS), and improvement of endothelial function. Combining Table 3[31-34], it is essential to recognize that each basic study on EA for hyperglycemia is essentially a highly specific permutation and combination (frequency and acupoints): Namely, only stimulation with specific parameters (e.g., 15 Hz frequency) on specific acupoints (e.g., bilateral ST36) for a specific course (e.g., 30 minutes/session, once daily, for 4 weeks) can achieve hypoglycemic effects in specific models (e.g., STZ-induced type I diabetic rats). On the one hand, we need to identify the optimal parameters for single-acupoint stimulation to enhance the reproducibility of acupuncture's hypoglycemic efficacy; on the other hand, we aim for such parameter adjustments to exhibit broad, cross-species applicability.

In summary, mechanistic research on EA for hyperglycemia has made significant progress at the animal experiment level, revealing its multi-target and multi-pathway characteristics. Current evidence strongly supports that EA primarily achieves blood glucose control through complex neurobiological regulation (involving the ANS, PINS, HPA axis, and insulin signaling pathways, among others) as well as effective anti-inflammatory pathways (including inhibition of inflammasomes, modulation of cytokine networks, and improvement of gut microbiota) (Figure 2 and Table 4)[38-40].

Figure 2 Mechanisms of electroacupuncture in regulating blood glucose. Electroacupuncture (EA) regulates blood glucose through multidimensional pathways involving the neuro-immune-gut microbiota-insulin signaling axis. A: EA significantly impacts the autonomic nervous system by enhancing parasympathetic activity, particularly through the vagus nerve. This effect leads to improved local tissue blood circulation and enhanced glucose utilization. Moreover, through stimulation of specific acupuncture points, EA can directly modulate pancreatic intrinsic nerves, thereby protecting pancreatic β-cell function and promoting normal insulin secretion, which ultimately helps to reduce blood glucose levels. Furthermore, by regulating the hypothalamic-pituitary-adrenal axis, EA can lower hormone levels, correct endocrine imbalances, and indirectly improve glucose metabolism. EA also activates the PI3K/Akt insulin signaling pathway in peripheral tissues, such as skeletal muscle and adipose tissue, thereby increasing glucose uptake; B: EA inhibits inflammasome activation, reducing the production of pro-inflammatory cytokines such as interleukin-1β, alleviating systemic inflammation, and improving insulin resistance. EA also enhances endothelial function by upregulating the expression of endothelial nitric oxide synthase, thereby alleviating vascular complications associated with diabetes; C: EA may remodel the gut microbiota by altering its composition and function, increasing the abundance of beneficial bacteria while decreasing harmful bacteria and their metabolites. This shift helps reduce systemic inflammation and improve gut barrier function. HPA: Hypothalamic-pituitary-adrenal; PINS: Pancreatic intrinsic nerves; eNOS: Endothelial nitric oxide synthase; TNF-α: Tumor necrosis factor α; IL: Interleukin; GLUT: Glucose transporter. Created with biorender.com (Supplementary material).

Table 4 Classification of main mechanisms in electroacupuncture for hypoglycemic research.

Specific mechanism	Supporting evidence	Relevant acupoints	Experimental subjects	Ref.
HPA axis regulation	Reduces adrenal corticosteroids (such as cortisol), improves endocrine disorders	Yishu (EX-B3)	T2DM rats	[3]
Anti-inflammatory pathway	Inhibits NLRP3 inflammasome activation, reduces IL-1β, improves chronic inflammation	Non-specific	STZ-induced diabetic rats, HFD high-fat diet mice, db/db genetically diabetic mice, OLETF obese diabetic rats	[12]
Neurobiological mechanism	Enhances parasympathetic nerve (e.g., vagus nerve) activity, improves local circulation and glucose consumption	Zhongwan (CV12), Tianshu (ST25), etc.	OLETF rats	[38]
Gut microbiota and inflammation control	Increases SCFAs, reduces circulating LPS levels, lowers systemic inflammation	Zhongwan (CV12), Tianshu (ST25), Zusanli (ST36)	T2DM model	[26]
Insulin signaling pathway activation	Activates PI3K/Akt pathway, enhances GLUT2 and GCK mRNA expression, reduces fasting insulin levels	Zusanli (ST36), Shenshu (BL23)	T2DM rats	[3]
ta-VNS	Stimulates auricular vagus nerve via projections from the vagus nerve (ABVN) to the NTS, affects the concentration changes of the neurotransmitters noradrenaline, GABA and ACh in the central nervous system	Non-specific	Humans, SD rats	[39,40]

LPS: Lipopolysaccharide; ACh: Acetylcholine; GABA: Γ-aminobutyric acid; NTS: Nucleus tractus solitaries; ta-VNS: Transcutaneous auricular vagus nerve stimulation; HPA: Hypothalamic-pituitary-adrenal; SCFA: Short-chain fatty acid; HFD: High-fat diet; STZ: Streptozotocin; IL: Interleukin; GLUT2: Glucose transporter 2; GCK: Glucokinase; NTS: Nucleus tractus solitaries; SD rats: Sprague-Dawley rats.

DOMINANT POSITION OF ACUPUNCTURE HYPOGLYCEMIC THERAPY IN CLINICAL APPLICATION, RESEARCH CHALLENGES, AND MECHANISM-BASED OPTIMIZATION STRATEGIES

Dominant position of auricular acupuncture in clinical application and challenges in acupuncture hyperglycemia research

The stimulation targets of auricular acupuncture are localized to the auricle, which contains a rich neural distribution, particularly the auricular branch of the vagus nerve - the only cutaneous sensory branch of the vagus nerve. Mechanistically, converging evidence from human neuroimaging and physiological studies indicates that cymba conchae stimulation engages brainstem autonomic nuclei, notably the nucleus tractus solitarius, and exerts a causal influence on cardiovagal outflow, providing a direct pathway from auricular input to central autonomic control relevant to glycemic regulation[41]. Auricular acupuncture or auricular acupressure can induce vagal tone, potentially regulating cardiovascular, respiratory, and gastrointestinal functions through autonomic and central nervous system linkages[42]. Beyond tonic effects, transcutaneous electrical nerve stimulation (taVNS) strengthens stomach-brain coupling via a vagal afferent pathway from NTS to midbrain, a mechanism plausibly linked to modulation of meal-related glucose excursions and appetite[43]. Unlike body acupuncture, which is thought to modulate physiological processes through the neuro-endocrine-immune network, auricular acupuncture may act more directly on the ANS via sympathetic and parasympathetic pathways. This more direct neural engagement may underlie reports of rapid physiological responses in certain clinical settings, although comparative effectiveness data remain limited. Clinical practice suggest that auricular interventions may have beneficial effects in conditions such as depression, epilepsy, and weight management, with some studies reporting modest reductions in body weight and BMI. Yeh et al[44] further noted that auricular acupressure also has therapeutic effects on chronic low back pain, with advantages such as low cost and ease of operation, which may explain the broader clinical superiority of auricular acupuncture over body acupuncture. On the metabolic axis, contemporary integrative reviews show that vagal pathways coordinate multi-organ glucose control, from islet hormone secretion to hepatic glucose output and peripheral uptake, supporting the rationale that auricular vagal stimulation can influence systemic glycemia when targets and parameters are appropriate[45]. Preliminary clinical studies have reported positive outcomes with auricular acupuncture in diabetes management[46]. Researchers from Guatemala successfully reduced blood glucose levels in type 2 diabetes patients through two weeks of acupuncture at specific auricular acupoints (e.g., endocrine, pancreas, Shenmen, liver, thalamus, spleen, kidney). Similarly, auricular static magnetic therapy and auricular electrical stimulation devices have demonstrated positive effects on HbA1c reduction and blood glucose stabilization.

Although these preliminary evidences highlight the clinical potential of auricular acupuncture in the field of hyperglycemia, fundamental challenges remain in basic research on auricular acupuncture for hyperglycemia. First, experimental models predominantly employ mice or rats, whose auricular structures are relatively simple, with acupoints difficult to precisely distinguish, and neural distributions exhibiting significant differences from humans, leading to difficulties in directly extrapolating animal experiment results to clinical practice. In humans, the cymba conchae and the cartilaginous posterior wall of the external acoustic meatus are ABVN-dominant targets and prime sites for stimulation. These regions often overlap with the auriculotemporal nerve (ATN) and the great auricular nerve (GAN), with overlap varying across individuals. Microstructural features further shape responses. Most auricular sensory fibers - ABVN included - course between the skin and cartilage at a depth of roughly 1-1.5 mm, which should guide needle penetration, electrode geometry, and reporting of tissue layers[47]. Rodent pinnae differ in architecture. They are thinner and more elongated, with cutaneous supply dominated by GAN/ATN homologs and comparatively less lateral contribution from ABVN; ABVN influence becomes clearer near the ear-canal axis rather than the lateral surface[48]. Human target sites therefore do not map one-to-one onto rodent ears, and naive site matching risks anatomical non-homology and divergent current spread. Rodent studies do show that auricular stimulation can recruit the nucleus tractus solitarius, confirming an ear-to-brainstem pathway. Activation thresholds and fiber spectra may still diverge from humans since tissue properties differ across species. For example, although mouse models demonstrate that auricular acupuncture can activate the vagus nerve to reduce blood glucose levels, human auricular anatomy is more complex, involving increased individual variability factors, thereby diminishing the feasibility of translation into clinical protocols[49]. In addition, auricular acupoint localization and stimulation methods are highly individualized - for instance, employing techniques such as filiform needle perpendicular insertion, magnetic bead embedding, or acupressure - resulting in excessive operational variability that leads to limited reproducibility of research outcomes. In clinical trials, even for the same acupoint such as Shenmen, differences in patients' ear shapes may cause localization deviations, compounded by personalized adjustments in stimulation intensity and duration, further amplifying variability[50]. These challenges not only affect the reliability of evidence but also hinder the standardized application of auricular acupuncture in diabetes management.

To overcome these bottlenecks, it is necessary to develop more precise acupoint mapping technologies and unified stimulation protocols, thereby bridging the gap between basic research and clinical practice. We propose progress in three areas: Localization, parameters, and translation. First, establish a standardized auricular acupoint localization system by constructing a 3D atlas of neurovascular structures, supported by VR/AR navigation and wearable products using surface scanning, skin impedance, or high-frequency ultrasound, to ensure reproducible and individualized acupoint selection. Second, formulate unified stimulation prescriptions and reporting standards (frequency, pulse width, duty cycle, intensity upper limits, and treatment courses), and develop wearable auricular vagus stimulation devices with closed-loop parameter adjustment capabilities, utilizing objective indicators such as skin impedance, heart rate variability, and continuous glucose monitoring (CGM) metrics like TIR/GMI for automatic titration and quality control. Third, incorporate larger animal models beyond rodents (that more closely approximate human auricular and vagal distributions, e.g., minipigs, dogs, rabbits, or non-human primates) in basic research, and combine them with neural tracing, electrophysiology, and chemical/genetic blockade to validate key pathways, while scaling stimulation parameters across species based on body surface dimensions and metabolic rates. Simultaneously, it is recommended to establish multicenter shared databases of parameters and effects to iteratively optimize standardized protocols and translational pathways for auricular acupuncture in hyperglycemia through data-driven approaches.

How basic research drives clinical development: Clinical acupoint optimization protocols based on basic research

Supported by basic research, EA therapy and body acupoint therapy have been widely applied in the clinical management of blood glucose control in diabetes. Clinical studies indicate that traditional multi-acupoint EA protocols, while capable of achieving significant therapeutic effects, may result in lower patient compliance due to the complexity of the treatment regimens. Therefore, researchers and clinicians have begun exploring ways to reduce the number of acupoints used while ensuring therapeutic efficacy, thereby enhancing treatment convenience and patient adherence. Taking T2DM as an example, traditional acupuncture protocols often employ multi-acupoint combined interventions, focusing on acupoints along the spleen and stomach meridians and those related to metabolic regulation, such as Zusanli (ST36), Zhongwan (CV12), Sanyinjiao (SP6), Shenshu (BL23), and Neiguan (PC6), aimed at improving digestive and absorptive functions, promoting energy metabolism, enhancing bodily immunity, and regulating endocrine functions. Notably, some treatment protocols, building on traditional acupuncture, further integrate composite therapies such as EA, auricular acupuncture (e.g., selecting auricular concha secretion point, pancreaticobiliary area), and acupoint thread embedding; such multi-target comprehensive treatments not only enhance efficacy but also help reduce the number of acupoints.

Additionally, researchers can draw inspiration from advances in basic research, deriving insights from core pathways and circuits of EA in glucose control to optimize and streamline treatment acupoints. Multiple basic studies have confirmed that using a limited number of high-efficiency acupoints for EA can achieve therapeutic effects comparable to those of traditional multi-acupoint protocols within a shorter time frame. This strategy simplifies the treatment process, reduces patient burden, and significantly improves adherence. At the same time, it facilitates the clinical translation of basic research findings. In clinical practice, the aforementioned approaches to reducing EA acupoint application are typically used in combination, thereby forming effective synergies and enhancing clinical efficacy. By optimizing treatment protocols and employing a few high-efficiency acupoints [e.g., Zusanli (ST36), Neiguan] for EA treatment, it is possible to improve patients' treatment experience and satisfaction while ensuring therapeutic effects, thereby further advancing the clinical application of acupuncture therapy. Protocols that streamline multi-acupoint approaches to three key acupoints such as Zusanli (ST36), Sanyinjiao (SP6), and Yishu (EX-B3) can maintain favorable therapeutic effects through comprehensive regulation of the gastrointestinal system, pancreatic nerves, and dual neuro-endocrine pathways. These optimized acupoint application protocols not only improve clinical treatment adherence but also significantly reduce treatment complexity and discomfort, holding substantial clinical application value.

FUTURE DIRECTIONS IN RESEARCH ON THE MECHANISMS OF ACUPUNCTURE IN REDUCING BLOOD GLUCOSE

Mechanism-based acupoint optimization strategies

Guided by foundational neuroscience research, a key strategy for refining acupuncture protocols in diabetes involves streamlining acupoint selection based on mechanistic insights. This can be achieved by merging acupoints that share common spinal segment innervation. The concept of a “spinal segment” originates from the neuroanatomical theory of “segmental innervation”, which posits that specific spinal segments (e.g., thoracic T1-T12, lumbar L1-L5) provide neural supply to their corresponding dermatomes (skin regions) and myotomes, thereby transmitting sensory, motor, and autonomic neural impulses[51]. Histological analyses and imaging studies have revealed that acupoints exhibit widespread and anatomically specific neural projections in the brain, forming neural circuits that participate in fundamental physiological functions[52]. Notably, acupoints can be mapped to defined spinal segmental neural projections - for instance, acupoints on the lower limbs are typically associated with the lumbosacral spinal cord. Therefore, by merging acupoints within the same spinal segment - combining those innervated by the same or adjacent spinal segments - it is possible to synergistically activate shared spinal reflex arcs and related neural pathways, thereby enhancing stimulation efficiency and avoiding redundancy. For example, integrating lower limb acupoints such as Zusanli (ST36) and Sanyinjiao (SP6) - which correspond to the neuronal networks of the L4-S1 segments - can activate shared reflex arcs and cover multiple metabolic pathways without redundant stimulation, as studies show that spinal segmental organization allows a single input to elicit multiple output reflexes, thereby optimizing peripheral neural integration[53]. Similarly, prioritizing acupoints with well-elucidated neurophysiological pathways relies on neuroimaging evidence, such as excluding certain Back-Shu acupoints if they fail to reliably activate thalamo-cortical networks to modulate the endocrine axis. Magnetic resonance imaging studies confirm that peripheral stimulation must engage specific thalamic pathways to influence metabolic regulation; otherwise, it produces only non-specific effects[54], which aligns with the principle of removing ineffective neural pathways[55]. As a novel approach, introducing the concept of neural network modularization can further streamline acupoints. Neural network modularization here refers to viewing the complex central and peripheral neural networks as a system composed of distinct functional modules. In the context of acupoint optimization, it involves categorizing synergistic acupoint groups into core functional modules (e.g., abdominal acupoints activating vagus nerve-dominated autonomic regulation) and auxiliary modules (e.g., limb acupoints enhancing local circulation)[56]. By validating the minimal effective connections between modules (e.g., based on graph theory-based brain network analysis), dynamic adjustment can be achieved using only 2-3 representative acupoints. Integrating real-time feedback such as heart rate variability can further enhance hypoglycemic efficiency. This modular approach not only has the potential to compress the traditional multi acupoint scheme by more than 30%, but also bridges the mechanisms between peripheral stimulation and central metabolic control[57].

Integration of acupuncture and wearable technology pathways

The convergence of acupuncture principles with advanced bioengineering is paving the way for intelligent, personalized glycemic management tools. Basic research utilizing high-resolution neuroimaging (e.g., functional magnetic resonance imaging) can map brain network dynamics elicited by acupoint stimulation, clarifying how electrical parameters precisely modulate the HPA axis and vagal pathways. This provides a data-driven foundation for personalized protocols[58]. Simultaneously, artificial intelligence (AI) algorithms can analyze real-time physiological streams - such as CGM data and heart rate variability (HRV) - to simulate multimodal neural feedback. This enables the optimization of key stimulation parameters - including frequency (e.g., 2-15 Hz), intensity (e.g., 0.5-2 mA), and duration - based on objective physiological feedback, moving beyond empirical adjustment to maximize anti-inflammatory and insulin-sensitizing effects[59]. Building on this, the development of closed-loop wearable devices represents a significant advancement. Existing technical prototypes, such as smart earpieces employing taVNS or limb patches utilizing transcutaneous electrical acupoint stimulation (TEAS), are being designed to monitor physiological signals (e.g., skin impedance, simplified EEG/EMG) and dynamically adjust stimulation parameters within predefined safety limits[60,61]. Conceptualized future technology forms envision fully integrated systems where AI-driven algorithms automatically titrate stimulation parameters in real-time based on CGM-derived feedback signals (e.g., time in range trends, glucose rate of change) and other physiological indicator thresholds (e.g., HRV indices). The aim is to create adaptive closed-loop circuits that precisely target core neural modules (e.g., vagus nerve branches), enhancing hypoglycemic durability and patient adherence while minimizing side effects[62].

Implications for diabetes management and public health

The "medicine-health maintenance integration" model seeks to translate optimized auricular stimulation into viable adjunctive methods to pharmacological therapy for home-based glycemic management. Clinical studies on acupuncture adjunctive to glucose-lowering drugs have shown promising results in improving glycemic indicators, although the evidence level requires further strengthening by larger, rigorous trials[63]. This model facilitates the development of user-friendly devices (e.g., smart earpieces for taVNS) for home use, applying low-intensity stimulation (e.g., 2-10 Hz, 0.5-1 mA) to key auricular points (e.g., AH6a, TF4, Shenmen). When used adjunctively with standard oral hypoglycemic agents (e.g., metformin), these interventions aim to enhance synergistic effects and potentially reduce medication dependency. Supported by education and mobile health apps, users can adjust stimulation based on real-time CGM feedback, enabling individualized management. This approach bridges clinical oversight with home-based self-care, incorporates safety models, and mitigates over-medicalization risks[64]. Promoting these home-based protocols involves integrating wearable technology with pharmacotherapy into closed-loop systems. Evidence suggests that non-invasive vagus nerve stimulation in home settings may reduce HbA1c and, via long-term neuro-endocrine regulation, potentially lower diabetes complication risks[65]. This approach suits middle-aged and elderly patients, emphasizing prevention and shifting care from hospitals to communities. Multicenter trials indicate that combining this stimulation with drugs can reduce blood sugar levels by 20%-30%, achieving significant synergistic effects and providing a sustainable, low-cost solution[66]. Crucially, promoting these devices necessitates comprehensive risk mitigation. Safety mechanisms (e.g., parameter ceilings, auto-shutoff), clear guidance, and remote medical support for data monitoring and personalized adjustments are essential to prevent over-stimulation or misuse, thereby ensuring safety and compliance[67]. If successfully implemented, this integrated approach could transition auricular stimulation into a common adjunctive home-care practice, potentially alleviating the public health burden of diabetes.

CONCLUSION

In conclusion, EA and auricular acupuncture show substantial potential as non-pharmacological interventions for blood glucose regulation in individuals with T2DM. Both therapies have demonstrated significant short-term benefits, with evidence supporting their hypoglycemic effects via multiple mechanisms, including modulation of the autonomic nervous system, enhancement of insulin sensitivity, and anti-inflammatory pathways. However, clinical research continues to be hindered by methodological challenges, including small sample sizes, insufficient blinding, and heterogeneity in study designs, which hinder the ability to generalize findings and establish long-term efficacy[68]. Basic research has played a pivotal role in elucidating the neurobiological and anti-inflammatory mechanisms underlying EA’s effects, offering valuable insights for optimizing acupuncture protocols. Notably, the integration of single-acupoint studies with clinical multi-acupoint applications could lead to more standardized and effective treatments, enhancing both therapeutic efficacy and patient adherence. Furthermore, advancements in wearable technology and AI-driven systems promise to revolutionize the integration of acupuncture into diabetes management by providing real-time, personalized adjustments to treatment parameters based on physiological feedback. Despite the promising findings, further large-scale, multicenter, randomized controlled trials are essential to validate the long-term efficacy and establish standardized treatment protocols. Ultimately, bridging the gap between basic research and clinical application, while optimizing treatment parameters and acupoint selection, could pave the way for incorporating acupuncture as a mainstream adjunctive therapy in diabetes care, potentially alleviating the growing public health burden of diabetes.