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Acupuncture-assisted lifestyle intervention improve the metabolic status and spontaneous brain activity of type 2 diabetes Mellitus patients: a randomized, clinical trial

Diabetology & Metabolic Syndrome volume 16, Article number: 255 (2024) Cite this article

Abstract

Background

Aggressive weight management in patients with type 2 diabetes mellitus has demonstrated numerous metabolic advantages, however, existing therapies for weight control have not reached satisfactory results. This study aimed to evaluate the efficacy and safety of acupuncture in the weight management of type 2 diabetes mellitus (T2DM) patients by using a randomized, sham-controlled clinical trial design.

Methods

In this single-blind randomized clinical trial, 102 overweight adult T2DM patients were randomized into two groups. The control group receives diet, exercise, and sham acupuncture intervention, whereas the acupuncture group receives diet and exercise and acupuncture intervention, both for 1 month. Body weight and other anthropometric and laboratory indices were assessed at baseline and endpoint, meanwhile, the body fat content and spontaneous brain activity were measured by functional magnetic resonance imaging(fMRI)as the exploratory outcomes.

Results

No significant difference was observed between the studied parameters at the baseline. The body weight and BMI were significantly reduced both in the control and acupuncture groups after intervention, without statistical difference between the two groups. What’s interesting is that compared to the control, the acupuncture group displayed a greater improvement in central fat tissue. It notes that the acupuncture group achieved significant liver fat content reduction than the sham acupuncture group. At the same time, the spontaneous brain activity in the occipital lobe and parietal lobe significantly increased in the acupuncture group.

Conclusion

One month of acupuncture treatment preferentially improved ectopic fat deposition and was accompanied by changes in brain activity compared with the control group, even before significant changes in total body weight had occurred. further studies of longer duration are necessary for validation.

Trial registration

: The protocol of this clinical trial is registered at the Acupuncture-Moxibustion Clinical Trial Registry (AMCTR, http://www.acmctr.org/, No. AMCTR-IOR-20000341).

Background

Epidemiological studies indicate consistent increases in the prevalence of diabetes worldwide. According to the International Diabetes Federation, around 536.6 million people have diabetes mellitus [1], and this number is projected to be 783.2 million by 2045 [2]. At the same time, the obesity rate has increased rapidly in the past nearly 50 years, by 2016, over 9.6 hundred million (~ 39%) adults were overweight or obese [3]. The co-prevalence and additional abundant studies indicate the strong links between diabetes and obesity. Existing theory hypothesized that the accumulation of lipids in the liver and other ectopic sites leads to insulin resistance and insulin secretion deficiency, thereby resulting in high blood glucose [4]. Clinical and pathophysiological studies provide pieces of evidence that weight loss, especially the reduction of ectopic fat normalizes blood glucose levels [5], which indicates that remission of type 2 diabetes mellitus (T2DM) can be achieved via weight management.

The fundamental cause of being overweight is the imbalance between the consumption and expenditure of calories. It’s thought interactions of genetic predisposition, lifestyle, and environmental factors contribute to the disorder in energy metabolism, but the potential mechanisms underlying obesity remain unclear [6]. Currently, dietary restriction, physical exercise, chemical agents, and bariatric surgery are applied as conventional therapies to treat obesity [7], in which, lifestyle modification is often the first line of treatment for obesity, but also followed by minimal resultant weight loss [8]. The potential gastrointestinal adverse side effects and invasiveness greatly limit the use of anti-obesity drugs and surgery, respectively [9, 10]. Thus, alternative therapies are urgently needed to improve metabolism balance and weight management.

Existing studies indicate that acupuncture, a crucial medical therapy of traditional Chinese medicine, is efficacious in weight management [11, 12]. Referred obese individuals often experience side effects such as lean mass loss and weight regain after discontinuing exercise following lifestyle modifications [13, 14], the combination of lifestyle modification and acupuncture may be more helpful than any one approach in isolation [15, 16]. Previous systematic reviews have illustrated the positive effect of combined acupuncture on weight management [17, 18]. However, the conclusion should be interpreted with caution due to the high heterogeneity of the included trials, especially, since a large part of the trials were conducted with female volunteers and part of them did not strictly set the control group, which could lead to the overestimation of the acupuncture effect due to placebo effect [19].

To validate the effectiveness and safety of the combination of acupuncture, exercise, and calorie restriction (CR) in improving the metabolic status of T2DM patients, we conducted this randomized clinical trial using a combination of sham acupuncture, exercise, and CR as a control. Furthermore, referring to the evidence that the experimental mechanism of acupuncture on obesity focuses on central nervous systems [20, 21] and adipose tissue [22, 23], the alterations in spontaneous brain activity are assessed using resting-state functional magnetic resonance imaging (rs-fMRI), meanwhile, bioelectrical impedance analysis and magnetic resonance imaging derived proton-density-fat-fraction (MRI-PDFF) were performed to analysis peripheral adipose tissue content. These advanced techniques promise to provide more evidence of the potential mechanisms involved.

Materials and methods

Study design

This trial is registered in Acupuncture-Moxibustion Clinical Trial Registry, (AMCTR, http://www.acmctr.org/, No. AMCTR-IOR-20000341). It follows the principles of the Declaration of Helsinki and the Good Clinical Practice Guideline. This study was reported following the Consolidated Standards of Reporting Trials (CONSORT) [24] and STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) [25] reporting guidelines. It has been reviewed and approved by the medical ethical committee of Zhongshan Hospital, Fudan University (Approved No. B2019-310R). Before randomization, all participants were requested to sign a written informed consent to decide whether they were willing to participate in this trial. They were informed of the details of the study and all the benefits and risks of participating in this trial.

Participants

All participants were diagnosed with T2DM, and referred by a doctor. Diagnosis of the T2DM was performed as presenting 1 or more of the following: (1) fasting plasma glucose (FPG) ≥ 7.0 mmol/L, (2) 2-h plasma glucose (2-h PG) value during a 75-g oral glucose tolerance test (OGTT) ≥ 11.1 mmol/L, (3) random plasma glucose ≥ 11.1 mmol/L. Referring to the Guidelines for Prevention and Control of Overweight and Obesity in Chinese Adults [26], overweight or obesity was defined as body mass index (BMI) ≥ 24 kg/m2 or ≥ 28 kg/m2. Other inclusion criteria were age, from 18 to 70 years old, and voluntary informed consent. The exclusion criteria included pregnancy and lactation; long-term courses of hormone drugs or weight loss supplements, severe organic diseases, such as advanced tumor, cardiac, hepatic, renal, or mental diseases; and unfit to receive treatment of acupuncture. After eligibility, informed consent was obtained from the participants and then confirmed.

The sample size calculation was based on the primary outcome. According to our pilot study, the mean reduction of body weight by a combination of exercise and acupuncture was 4.2 kg, with a standard deviation (SD) of 1.5 kg. To yield an 80%-statistical power with a two-sided significance level of 0.05, 36 participants per group were needed. Furthermore, assuming a dropout rate of 10%, meanwhile, referring to the requirement from higher authority (every group contains ≥ 50 participants), a total of 120 participants were determined.

Randomization and blindings

Qualified participants were randomly assigned by a computer-generated list to the acupuncture or control (sham acupuncture) group according to a ratio of 1:1. An independent mathematician used R 4.0 to generate a randomized sequence according to the order of participant enrollment, and a third party concealed the allocation sequence in sealed opaque envelopes. The acupuncturist will be made aware of group assignments prior to treatment. Throughout the study, participants, data collection staff, and data analysts will remain blinded to the treatment assignments. Additionally, participants will receive their treatments in separate rooms or at different times to prevent communication between them, and the acupuncturist will not disclose any information about the treatment programs to the participants. In the data summary stage, the three separation principles of researcher, operator, and statistician will be implemented. The control group followed a CR diet and engaged in exercise and sham acupuncture, while the acupuncture group received the diet guideline and engaged in exercise and acupuncture interventions.

Intervention

Diet protocol

The CR intervention was designed to reduce body weight via decreasing dietary consumption, meanwhile improving eating habits. All participants were prescribed a balanced diet that provided an energy deficit of 500 kcal per day, with a macronutrient distribution within the range of 45–60 energy percent (E%) carbohydrate, 15–20 E% protein, and 20–35 E% fat (< 7 E% saturated fat). The dietitian would provide individualized recommendations and recipes based on the qualitative evaluation of food diaries daily.

Exercise protocol

The exercise intervention was designed to increase energy expenditure and reduce lean mass loss to improve body composition via combining aerobic and resistance exercises [27, 28]. All participants take exercise five times weekly, including three times aerobic and two times resistance exercise. The exercise was approximately 30–40 min, followed by a sequence of static stretching exercises (~ 20 min) designed to improve flexibility. The types of aerobic exercise included brisk walking, jogging, cycling, swimming, and Taiji. The resistance training consists of a sequence exercise for upper-extremity and lower-extremity exercises, including shoulder presses, push-ups, dumbbell front raise, plank, squats, and glute bridge. Participants exercised at approximately 65% of their peak heart rate, which was gradually increased to 70 to 85% to reach the criteria of moderate-intensity exercise. The exercise is conducted under the distance instruction and supervision of a fitness instructor.

Acupuncture protocol

According to the theory of channels of Traditional Chinese Medicine, the following acupoints of Foot Yang Ming stomach channel were chosen refer to previous systematic reviews and consultations with specialists [23, 29]: Renying (ST9, level with the tip of and 1.5 cun lateral to the laryngeal prominence), Shuitu (ST10, 1 cun down from ST9, on the anterior border of sternocleidomastoideus muscle), Liangmen (ST21, 4 cun above the midline of the umbilicus, 2 cun lateral to the anterior midline of the abdomen), Tianshu (ST25, 2 cun lateral to the midline of the umbilicus), Guilai (ST29, 4 cun below the midline of the umbilicus, 2 cun lateral to the anterior midline of the abdomen), Zusanli (ST36, 3 cun below the lateral depression of patellar ligament, one finger width lateral from the anterior crest of the tibia), Fenglung (ST40, 8 cun superior to the tip of the external malleolus, two finger width lateral from the anterior crest of the tibia), Neiting (ST44, Proximal to the web margin between the 2nd and 3rd toes, at the junction posterior to the toe web of the red and white skin).

The acupuncture was completed by a professional acupuncturist with a Chinese medicine practitioner license from the Ministry of Health of the People’s Republic of China. In the authentic acupuncture group, each point was penetrated with disposable acupuncture needles (45 mm in length and 0.3 mm in diameter, Suzhou Medical Appliance Factory, Jiangsu Province, China) approximately 30 to 40 mm into the skin. The needles in ST25, ST29, ST36, and ST40 were connected to an electro-stimulator (G6805-2 A, Shanghai Huayi Medicinal Instruments Co., Ltd, Shanghai, China), producing electrical stimulation with a continuous 1 Hz wave for 10 min. In the sham acupuncture group, the needles were penetrated only 2–3 mm into the skin, and the needles in ST25, ST29, ST36, and ST40 were connected to the electro-stimulator without electrical stimulation. The needles were left for 30 min. The procedure was carried out once every 2 days, 15 times in total.

Outcomes measurement

Primary outcome measure

The primary outcome was the change in body weight after treatment.

Secondary outcome measure

Secondary outcomes included the change in BMI, waist-to-hip ratio (WHR), FPG, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and body fat content. The complete body measurements and scheduled laboratory tests were conducted before and after the intervention.

rs-fMRI outcome measures

The MRI experiment was performed using a 3.0 Tesla MR device (Discovery MR750, GE Healthcare, Wisconsin, USA), which is equipped with an 8-channel phased array head coil. The rs-fMRI data were acquired using an echo-planner imaging sequence with the following parameters: repetition time (TR) = 986 ms; echo time (TE) = 30 ms; flip angle (FA) = 52°; voxel size = 2.2 × 2.2 mm; field of view (FOV) = 220 × 220 mm2; slice thickness = 2.5 mm, 78 axial slice. Subsequently, high-resolution 3-Dimensional T1-weighted images were acquired using a whole-brain sagittal spoiled gradient echo (TR = 8.26 ms; TE = 3.24 ms; FA = 8°; voxel size = 0.8 × 0.8 × 0.8 mm; FOV = 256 × 256 mm, and 256 sagittal slices). During the MRI scan, participants were instructed to close their eyes but to remain awake.

MRI-PDFF outcome measures

The acquisition was performed during a single breath-hold of 21 s. PDFF, and water fraction, were acquired automatically via iterative decomposition of water and fat with echo asymmetry and least squares estimation quantification. The parameters were listed as follows: TR = 6.4 ms, TE = Min Full, FA = 3°, matrix size = 160 × 160; FOV = 35 × 24 cm; bandwidth = 111.11 kHz, 24 axial slices with 10 mm slice gap. Quantitative analysis of PDFF was completed by a senior radiologist blinded to the subjects’ information. For the quantification of fat content, three regions of interest (ROI) with 150 mm2 in the area were placed at different locations in every interested organ, including the liver, pancreas, and psoas, avoiding the adjacent structures and the main vessel, and the average of the three ROIs was considered as the result of MRI-PDFF.

Data and statistical analysis

MRI data analysis

The MRI data were pre-processed using the DPABI toolbox v8.0 (www.rfmri.org) on the Matlab R2019a platform. This process mainly contained 6 steps: (1) DICOM format conversion, (2) removing the first ten scan volumes, (3) section timing correction, (4) correction of head movement, (5) spatial standardization, and (6) spatial smoothing. The images were spatially normalized into the standard Montreal Neurological Institute (MNI) template with a resampling voxel size of 3 × 3 × 3 mm3. Temporal bandpass filtrating (0.01–0.1 Hz) was performed to reduce the effect of low-frequency drifts and high-frequency noise.

Analysis of fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) analysis was performed using the DPARSF software in the DPABI toolbox. After spatial standardization, the linear tendency of the preprocessed data was removed by the linear regression method. To obtain individual fALFF values, the fast Fourier transform of each voxel signal of the time series in the whole brain image was performed and converted into the square root of the frequency domain power spectrum. In this study, fALFF was obtained as the division of the average square root of the power spectrum at each voxel across 0.01–0.1 Hz by the whole frequency range observed in the signal. Individual ReHo maps were generated by calculating Kendall’s coefficient of concordance (KCC) of the time series of every 27 neighboring voxels. Then the ReHo value was divided by the global mean KCC value in each subject for further statistical analysis. 2 × 2 repeated-measures ANOVA analysis of variance with intervention (control versus acupuncture) and time point (baseline versus follow-up) was performed to assess between-group differently of rs-fMRI activity. The regions with significant changes in the fALFF and ReHo values were considered as uncorrected p < 0.005 with cluster-extent ≥ 10 voxels.

Clinical data analysis

All clinical statistical analyses were performed in R 4.0. The primary outcome, change in body weight, was evaluated by repeated-measures analysis of variance. Baseline differences between groups and other outcome variables were assessed by Student’s t-test, Mann–Whitney U-test, or Chi-square test according to the data characteristics. The paired t-test between before and after interventions was performed with a paired samples t-test or Wilcoxon signed-rank test. Data were presented in mean values with an SD or as a number with a percentage. Significance was defined as a two-tailed value of 0.05.

Results

Baseline characteristics

From November 2020 to December 2022, 118 eligible individuals were recruited and randomized. Finally, 102 participants completed the intervention. The reasons for withdrawal included time conflict (n = 6), travel (n = 3), undesired efficacy (n = 1), and Covid-19 (n = 6). Figure 1 presents the participant flowchart. The baseline characteristics of the included participants are presented in Table 1. No significant difference between the two groups.

Fig. 1
figure 1

The flow of participants

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Table 1 Baseline and change of anthropometric and laboratory indices
Full size table

Changes in body weight and blood glucose

As shown in Table 1, five weeks of treatment reduced 0.89 ± 1.94 kg (p = 0.003) body weight of the acupuncture group, while it was 1.03 kg ± 1.79 kg (p < 0.001) in the sham control. Similarly, the mean reduction of BMI after treatment is 0.31 ± 0.71 kg/m2 (p = 0.008) and 0.4 ± 0.64 kg/m2 (p < 0.001) in the acupuncture and sham acupuncture groups, respectively. However, there is neither significance on reduction of body weight (p = 0.763) or BMI (p = 0.558) between acupuncture and sham acupuncture groups. In blood glucose, the fasting plasma blood glucose significantly reduces both in the acupuncture (-0.44 ± 1.46 mmol/L, p = 0.015) and sham acupuncture (-0.37 ± 1.46 mmol/L, p = 0.037) groups, however, the 2 h postprandial blood glucose (-1.38 ± 2.80 mmol/L, p = 0.001) and HbA1c (-0.18 ± 0.43 mmol/L, p = 0.01) only decrease in the acupuncture group, which might indicate the potential benefit on blood glucose control of acupuncture treatment.

Change of body adipose tissue

Based on voluntariness, the bioelectrical impedance analysis and MRI-PDFF were conducted to investigate the effect of acupuncture intervention on fat tissue at baseline and end-point on 74 participants (39 in the control group and 35 in the acupuncture group). As shown in Table 2, fat content, including psoas fat (-1.35 ± 3.66%, p = 0.049), body fat (-0.99 ± 1.63%, p = 0.004), and visceral fat area (-6.23 ± 9.06 cm2, p = 0.001) significantly decrease in the acupuncture group after intervention. Meanwhile, the liver fat content reduced both in the acupuncture group (-3.31 ± 3.68%, p < 0.001) and the control group (-0.99 ± 2.84%, p = 0.032). What is noteworthy is that the liver fat content of the acupuncture group decreases larger (p = 0.038, Table 2), almost 20% lower than baseline.

Table 2 Baseline and change of body composition and adipose tissue
Full size table

Rs-fMRI activity alterations

The rs-fMRI examination is conducted based on the principle of voluntariness, occurring one day before the intervention officially begins and one day after its completion. To evaluate the impact of acupuncture intervention on rs-fMRI activity, a 2 × 2 repeated-measures ANOVA analysis of variance was conducted. Before the intervention, no significant differences were observed between the control and acupuncture groups. However, as shown in Fig. 2A; Table 3, the acupuncture groups showed significantly increased fALFF in the left medial occipital gyrus (MOG_L, p = 0.047), and right calcarine cortex (p = 0.018) compared to the controls. In ReHo analysis, bilateral cuneus (p = 0.034), and right inferior parietal lobule (IPL_R, p = 0.016) significantly increased in the acupuncture group (Fig. 2B; Table 3).

Fig. 2
figure 2

Difference in whole brain (A) fALFF, and (B) ReHo using 2 × 2 repeated-measures ANOVA analysis of variance between acupuncture and control group (p < 0.05, Bonferroni corrected). Color scale denotes the t value. z, Montreal Neurological Institute coordinates; Left in picture is left in the brain

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Table 3 Differences in fALFF and ReHo values between the acupuncture and control groups (p < 0.05)
Full size table

Safety assessment

No abnormalities were reported in vital signs or laboratory tests. Two participants in the sham acupuncture group and three participants in the acupuncture group have minor abdominal hematomas. Relief was achieved without treatment. No other adverse events (AEs) were documented.

Discussion

To the best of our knowledge, this is the first randomized clinical trial focused on the effect of acupuncture-assisted treatment on weight management of overweight T2DM patients. Using sham acupuncture as a control ensures that the observed physiological changes can be attributed specifically to the acupoint effect. The short-term acupuncture-assisted weight management was not superior to sham control. However, it is noted that a one-month acupuncture treatment significantly decreases the liver fat content in overweight patients with T2DM. This finding suggests potential benefits of acupuncture in reducing ectopic fat accumulation. Further studies are required to validate and explore the role of acupuncture in fat metabolism.

In the one-month treatment, significant body weight reduction and improvement in blood glucose management in both groups are observed, which agrees with the existing research that exercise [30] and calorie restriction [31] have positive effects on weight control and blood glucose management. Although there was no significant difference in the degree of weight loss between the two groups, the acupuncture group experienced a greater reduction in weight. This may be due to the small sample size or the short duration of the intervention, which might not be sufficient to show a significant difference between the two groups. Interestingly, compared to sham acupuncture, acupuncture treatment significantly decreases the ectopic fat accumulation, especially in liver. Existing studies illustrate liver fat as the most rapidly mobilized ectopic fat stored during weight loss interventions [32, 33], which might indicate the role of liver fat content as a sensitive indicator of metabolic status. Referring to its crucial role as a therapeutical target tissue for T2DM [34], the specific role of liver fat in the improvement of metabolic status [35], and the potential mechanism underlying acupuncture’s efficacy warrant further investigation. Highlighting liver fat content as an acupuncture target has been a trigger for subsequent clinical trials. (Chinese Clinical Trial Registry, CHICTR, http://www.chictr.org.cn/, No. ChiCTR2400083721).

In previous studies, the brain attracted lots of attention as the primary target organ of acupuncture [36, 37]. Differential analysis of fALFF and ReHo revealed that spontaneous activity primarily enhanced brain area mainly in the occipital lobe (MOG_L, right calcarine cortex, and bilateral cuneus) and parietal lobe (inferior parietal lobule) in the acupuncture group. Existed studies have demonstrated significantly decreased ALFF and ReHo values in the occipital lobe and parietal lobe among patients with T2D [38], which are correlated with impaired neurocognitive performance [38, 39]. The partially restored activity in the cognition-related brain area following acupuncture suggests the potential therapeutic effects of acupuncture against cognitive disorders induced by T2DM. However, the exploration of brain activity alterations in metabolic diseases is still in its early stages. The role of the brain in mediating the impact of acupuncture on metabolic status remains elusive and requires further investigation. Therefore, the significant brain activity observed after acupuncture treatment in this paper should be regarded as a descriptive result that can provide a reference for future studies.

Although previous studies have been trying to identify potential participants and molecular pathways involved in the effects of acupuncture on promoting fat reduction [40, 41] and improving cognitive impairment [42], further experimentation is needed to elucidate the specific mechanisms. Additionally, comprehensively understanding the complex interaction between acupoints and physiological responses remains a significant challenge in unraveling the underlying mechanism of acupuncture and evaluating optimal clinical parameters.

Our study has several limitations. First, due to the limited financial support and labor, the treatment lasted for only one month, the more significant result might be obtained through a long-term intervention. Besides, longer-term follow-ups are required to understand the full benefits of these interventions on health outcomes. Second, this study focuses on the weight management of T2DM patients, some of them receiving constant drug therapy to control blood glucose. Although, the differential analysis on drug use between the two groups did not display significance, and the result of excluding drug users agrees with the no-exclude result, which partially eliminates the worry about the physiological effect of drug use, the possible drug use-induced bias on the result of interventions still worth attention. Third, this study takes superficial needling as a sham acupuncture method, which is not a real placebo. This procedure still needed to penetrate the skin of the acupoint shallowly which can cause needle sensation. Therefore, the acupuncture-induced physiological alterations are strictly due to the acupoint effect. Thus, the control procedure should be improved and well-designed in future trials to obtain a comprehensive understanding of the effectiveness of acupuncture. In light of the issues above, future studies will be designed with a longer intervention duration and a larger number of participants. Besides, investigation into these potential mechanisms will contribute to the development of therapeutic strategies aimed at improving metabolic status.

In summary, the short-term acupuncture-assisted weight management was not superior to sham control. However, it is noteworthy that acupuncture intervention significantly reduced ectopic fat accumulation, especially in the liver. Besides, the rs-fMRI analysis revealed potential spontaneous brain activity associated with acupuncture. Both efficacy and safety profiles indicated that acupuncture could be used as a supplement therapy for managing metabolic status.

Data availability

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

2-h PG:

2-h plasma glucose

AMCTR:

Acupuncture-Moxibustion Clinical Trial Registry

BMI:

Body mass index

CONSORT:

Consolidated Standards of Reporting Trials

CR:

Calorie restriction

fALFF:

Fractional amplitude of low-frequency fluctuation

FPG:

Fasting plasma glucose

KCC:

Kendall’s coefficient of concordance

MNI:

Montreal Neurological Institute

MRI-PDFF:

Magnetic resonance imaging derived proton-density-fat-fraction

OGTT:

Oral glucose tolerance test

ReHo:

Regional homogeneity

ROI:

Regions of interest

rs-fMRI:

Resting-state functional magnetic resonance imaging

SD:

standard deviation

STRICTA:

STandards for Reporting Interventions in Clinical Trials of Acupuncture

T2DM:

type 2 diabetes mellitus

WHR:

Waist-to-hip ratio

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Acknowledgements

The authors gratefully acknowledge the hospital staff for their excellent facilities and support. We also thank the Guangzhou Nanda Fite Medical Health Technology Co., Ltd. for support in diet and exercise intervention.

Funding

This research was funded by Natural Science Foundation of Shanghai (21ZR141320), Shanghai Municipal Health Commission [ZY(2018–2020)-FWTX-301], the Guidance Project from Shanghai Science and Technology Commission (19401931100), Fudan Zhangjiang Clinical Medicine Innovation Fund Project (KP7202117), the National Key R&D Program of China (2019YFA0801900, 2018YFA0800300), National Natural Science Foundation of China (No. 92357304, No. 92249302), Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202001), Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Aculty Resources Project of College of Life Sciences, Inner Mongolia University (2022 − 102).

Author information

Author notes

  1. Zhitian Zhang, Kaixuan Bao and Jiaojiao Liu contributed equally to this work.

  2. Hongmei Yan, Xiangyu Wang, and Jian Gao should be considered the joint senior author.

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Zhitian Zhang, Jiaojiao Liu, Tiemin Liu & Hongmei Yan

  2. Human Phenome Institute, Fudan University, Shanghai, 201203, China

    Kaixuan Bao, Jiawei Han, Guo Zhou & Tiemin Liu

  3. Department of traditional Chinese medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Chunfei Jiang & Xiangyu Wang

  4. Department of Nutrition, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Chunyan Ji & Jian Gao

  5. Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, 201203, China

    Jiawei Han

  6. Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Xiaoyu Liu

  7. State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China

    Tiemin Liu

  8. Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism & Integrative Biology, Fudan University, Shanghai, 200433, China

    Tiemin Liu

  9. School of Life Sciences, Inner Mongolia University, Hohhot, 010020, Inner Mongolia, China

    Tiemin Liu

  10. Fudan Zhangjiang Institute, Shanghai, 201203, China

    Xiangyu Wang

  11. Fudan Institute for Metabolic Diseases, Shanghai, 200032, China

    Hongmei Yan

  12. Department of Endocrinology and Metabolism, Wusong Branch of Zhongshan Hospital, Fudan University, Shanghai, 200940, China

    Hongmei Yan

Authors
  1. Zhitian Zhang
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  2. Kaixuan Bao
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  3. Jiaojiao Liu
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  4. Chunfei Jiang
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  5. Chunyan Ji
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  6. Jiawei Han
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  7. Guo Zhou
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  8. Xiaoyu Liu
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  9. Tiemin Liu
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  10. Jian Gao
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  11. Xiangyu Wang
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  12. Hongmei Yan
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Contributions

H.Y., X.W., and J.G. designed the experimental plan. X.W., Z.Z., C.J. (Chunfei Jiang), C.J. (Chunyan Ji), and J.H. performed the experiments. K.B., J.L., G.Z., and X.L. analyzed the data. K.B. and J.L. drafted the manuscript and incorporated edits and comments from H.Y., X.W., J.G., T.L., and all other authors. Each author accepted the submitted version of the paper and made contributions to it.

Corresponding authors

Correspondence to Jian Gao, Xiangyu Wang or Hongmei Yan.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the medical ethical committee of Zhongshan Hospital, Fudan University (Approved No. B2019-310R). Every member of the study endorsed an informed consent form. Every procedure used in this investigation complied with the Helsinki Declaration.

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Not applicable.

Competing interests

The authors declare no competing interests.

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Zhang, Z., Bao, K., Liu, J. et al. Acupuncture-assisted lifestyle intervention improve the metabolic status and spontaneous brain activity of type 2 diabetes Mellitus patients: a randomized, clinical trial. Diabetol Metab Syndr 16, 255 (2024). https://doi.org/10.1186/s13098-024-01489-4

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Keywords

Diabetology & Metabolic Syndrome

ISSN: 1758-5996

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