Acute Effect of Acupuncture on Glycemic Control in Type 2 Diabetes Measured by Continuous Glucose Monitoring: A Pilot Study

Abstract

Introduction:

Acupuncture is a widely used technique for the treatment of diabetes in Asian countries. Nevertheless, there are few studies with appropriate methodological rigor evaluating its effectiveness and promoting a standardized procedure in the Western World.

Objectives:

Evaluate the short-term effect of acupuncture in the treatment of type 2 diabetes mellitus (DM2) using continuous glucose monitoring (CGM).

Methods:

In a randomized controlled prospective open-label study, we assigned 20 insulin-independent DM2 patients to undergo acupuncture (group 1) or control group (group 2). Participants underwent CGM for 14 days. In group 1, all patients were submitted to acupuncture 4, 8, and 12 days after installation of the monitoring system. Diabetes-specific treatment points were used in all patients (bladder 38, large intestine 4, kidney 24, stomach 36, and spleen 9). This study was approved by the ethics committee (CAAE—60576616.6.0000.5572).

Results:

There were no statistically significant differences in the baseline characteristics. In group 1, mean glucose level obtained through 14 days monitoring after acupuncture treatment was 143 ± 28.8 mg/dL, whereas in group 2, who did not receive acupuncture, the mean level was 165.8 ± 30.2 mg/dL (P = 0.015).

Conclusion:

In this randomized pilot study, there was an improvement in global glycemic control during the 14-day monitoring in the acupuncture group. Further studies with larger cohorts over a more extended period of time are needed.

Clinical Trials: RBR-3m45y3.

Introduction

Acupuncture has been used since primitive tools were first produced. It is part of the ancient Traditional Chinese Medicine and in China and East Asia has a long history of preventing and curing diseases.¹

The fundamental concepts of acupuncture include a holistic view and tailored treatments according to individual differentiation, despite the underlying disease. This form of approach constitutes the great differential of this therapy, but can also be considered the utmost barrier to its implementation by Western medicine, which demands standardized procedures, aiming at accurate and reproducible trials to prove safety and efficacy of any therapy to be implemented.²

Diabetes mellitus is a global major cause of morbidity and mortality, given its impact on macrocirculation (cardiovascular system) and microcirculation (eyes, kidneys, and nerves).³ Optimizing blood glucose control is demanding, since it requires balancing the need for glycemic control with the risk of hypoglycemia, and avoiding clinical inertia.⁴

The effect of acupuncture has already been demonstrated in obesity,⁵ hypertension,⁶ and dyslipidemia.⁷ Similarly, there are studies evaluating the effect of acupuncture therapy on diabetes and its complications.^8–10 The methodology of most studies is not adequate and many lack standardization.

Contemporary management of type 2 diabetes uses the 3-months-mean glycemia HbA1c to monitor control. Trial and observational evidence has shown that lowering HbA1c reduces the risk of the micro- and macrovascular complications of diabetes.^11–14

A continuous glucose monitoring (CGM) system has specific characteristics, being diverse from the traditional monitoring methods. It does not require finger prick and identifies glucose variations, especially nocturnal hypoglycemia. Although glycated hemoglobin is used routinely and consecrated in glucose monitoring, it does not reflect intra- and interday glycemic excursions.¹⁵

The objective of this study was to evaluate, with the adequate methodology, the short-term effect of acupuncture in the treatment of type 2 diabetes mellitus (DM2) using CGM to measure the results.

Methods

Study Design

In this randomized controlled prospective open-label study, we randomly assigned 20 insulin-independent DM2 patients to undergo acupuncture (group 1) or control group (group 2).

This study was approved by the ethics committee (CAAE—60576616.6.0000.5572—Plataforma Brazil No.) and the registration at Brazilian Registry of Clinical Trials was granted after the first patient was attended, so we do not consider it a clinical trial. All participants provided informed consent before any study procedure.

Participants

We consecutively screened 20 type 2 diabetic patients who agree to participate in the study. One research center located in Aparecida de Goiânia, State of Goiás, Brazil, attended all patients. The diabetes management was done by the same endocrinologist (S.V.) and acupuncture therapy was performed by the same acupuncturist (A.C.).

Per study protocol participants should be between 20 and 75 years, diagnosed with DM2 for at least 3 years, and with stable glycemic control (evaluated through glycated hemoglobin). The target A1c level for people with diabetes is usually <7%. The higher the hemoglobin A1c, higher the risk of having complications related to diabetes. In this study, we included patients with A1c <9%.

Patients should not be in use of glucocorticoids or insulin, be pregnant, or have record of nephrotic syndrome, hepatic insufficiency, hyperthyroidism, acromegaly, or renal insufficiency. Demographic data, baseline characteristics, biochemical, and metabolic profiles were analyzed before the intervention.

Procedure and Intervention

All selected participants underwent baseline blood tests, detailed consultation, and physical examination, as described in Table 1. Interval between blood collection and sensor installation varied between 3 and 5 days.

Table 1.

Patient Baseline Data (Before Sensor Installation)

Variable	Acupuncture	Control group	P
Demographics
Age (years)	63.5 ± 10	64.2 ± 13.4	0.85^a
Gender (% men)	50	60	0.73^a
Body mass index (kg/m²)	28.1 ± 3	27.9 ± 2.8	0.97^a
Diabetes control
Glycated hemoglobin-A1c (%)	7.1 ± 1.1	7.3 ± 0.6	0.63^a
Fasting glycemia, mg/dL (mmol/L)	137 (7.6)	139 (7.7)	0.97^a
Frutosamine, μmol/L (mmol/L)	322 (0.322)	327 (0.327)	0.73^a
Diabetes duration (years)	8 ± 4	7 ± 6	0.28^a
Classes of hypoglycemic (no.)	2.3 ± 0.8	2.4 ± 0.7	0.63^a
Presence of comorbidities
Self-reported history of retinopathy	10%	10%	1^b
Self-reported history of nephropathy	10%	20%	0.48^b
Self-reported history of neuropathy	10%	20%	0.48^b
Self-reported history of myocardial infarction	20%	20%	1^b
Self-reported history of stroke	0%	10%	0.73^b
Laboratory data
Total cholesterol, mg/dL (mmol/L)	159 (4.11)	157 (4.06)	0.98^a
High-density lipoprotein-cholesterol, mg/dL (mmol/L)	39 (1.0)	42 (1.08)	0.63^a
Low-density lipoprotein-cholesterol, mg/dL (mmol/L)	91 (2.35)	78 (2.01)	0.42^a
Triglycerides, mg/dL (mmol/L)	178 (2.0)	197 (2.22)	0.37^a
Albuminuria, mg/g (mg/mmol)	18.8 (2.12)	36.3 (4.1)	0.57^a
Serum creatinine, mg/dL (μmol/L)	1.1 (97.2)	1.0 (88.4)	0.21^a
TSH, mIU/L	1.6	1.5	0.28^a

Student's t-test.

Chi-square test.

TSH, thyroid stimulating hormone.

All participants underwent CGM, using the FreeStyle Libre^® system for 14 days period in which they were advised not to change their lifestyle, including diet, exercise, and medication. During the course of the study, all patients were instructed to follow usual lifestyle patterns and to maintain their physical activity similar to their usual levels while on both treatment arms.

No participant was using insulin. The mean number of hypoglycemic drugs were 2. All patients but 1 were using metformin. Other antidiabetic drugs included DPP-4 inhibitor, glitazone, sulfonylurea, and SGLT-2 inhibitor, used by 45%, 30%, 25%, and 25%, respectively.

The sensor consists of a round device of about 35 mm in diameter that is applied to the posterior region of the arm and a monitor reading the information sent by the sensor with touch screen. For blood glucose measurement, it is necessary to bring the monitor close to the sensor. At this point, the monitor scans the sensor, capturing and showing on your display the glucose value, as well as arrows and the patient's glycemia trend curve. These scans can be done as many times as the individual want throughout the day. The same sensor can remain on the patient for 14 days. When scanning for the measurement glucose, the monitor shows a graph with information about blood glucose levels in the past 8 hours, feature that brings you closer to monitoring devices glucose continuum.

Group 1 received acupuncture 4, 8, and 12 days after installation of the monitoring sensor. The decision to provide treatments on days 4, 8, and 12 was made in the attempt to standardize the study, since this is a pilot study. Duration of treatments (period between needle insertion and removal) was 30 minutes for all visits.

Diabetes-specific treatment points were used bilaterally in all group 1 patients (bladder 38, large intestine 4, kidney 24, stomach 36, and spleen 9). The rational for using these acupoints was based on published data as follows:

- Improve insulin resistance—stomach 36¹⁶

- Insulin sensitivity enhancement—stomach 36, large intestine 4, and spleen 9¹⁶

- Restores the level of insulin signaling-related molecules—stomach 36 and bladder 38¹⁷

- We used needles manufactured by Dong Bang, with the specifics: cable 2.0 cm, length 1.5 cm, and gauge 0.20 mm. A total of 10 needles were manually inserted from 1 cm in depth per patient per treatment in a 30-minute session. Each needle was manually stimulated (twirled clockwise) every 5 minutes.

Randomization

We performed a simple randomization, based on a single sequence of random assignments, dividing patients according to the order of consultation. All the patients were scheduled and assigned with no interference from the primary investigator, if they agree to participate, they were randomly assigned. Even patients underwent group 1 (treatment group) and odd patients underwent group 2 (control group). Figure 1 represents the study flowchart. First patient was recruited November 20, 2017, and last patient at April 11, 2018.

FIG. 1.

Study flowchart.

Primary Outcome Measure

All patients in both groups were subjected to evaluation by CGM for glycemic variability for 14 days. The primary endpoint for this study were 14-day glycemic average.

Statistical Analyses

Values are presented as the mean (standard deviation) or percentage. The analyses were conducted using the Statistical Package for Social Science software version 19.0 (SPSS, Inc., Chicago, IL) and Stata 13 (StataCorp, College Station, TX). Student's t-test was used to compare the means (or distribution) of the 2 study arms for continuous variables. A chi-square test was used to compare proportions for categorical variables. P < 0.05 was considered significant.

Results

A total of 20 subjects were recruited for the study. All patients fulfilled the study protocol and no technical issues were reported.

Of the 20 DM2 patients, 10 underwent acupuncture therapy, using predefined points.

The baseline data are detailed in Table 1. None of the items showed a statistically significant difference. Overall, we can consider this as a well-controlled group, gender-balanced, and mid-term diabetes duration.

The A1c was >7% in 5 and 7 patients in group 1 and 2, respectively.

Low-density lipoprotein-cholesterol was >100 mg/dL (2.58 mmol/L) in 3 and 2 patients in group 1 and 2, respectively.

One patient in group 1 had an albuminuria >30 mg/g (3.39 mg/mmol). Three patients in group 2 had an albuminuria >30 mg/g (3.39 mg/mmol).

Regarding oral therapy, 1 patient in each group was in use of metformin alone. Two drug classes were used by 6 and 4 patients in group 1 and 2, respectively. Only 1 patient in group 1 used 4 drug classes.

CGM Data

At baseline (sensor day 1), the mean 24-hour glucose was 152.9 mg/dL (8.5 mmol/L) in group 1 and 155.9 mg/dL (8.8 mmol/L) for group 2.

In group 1, mean glucose level obtained through 14 days monitoring after acupuncture treatment was 143 ± 28.8 mg/dL (7.9 ± 1.6 mmol/L), whereas in group 2, who did not receive acupuncture, the mean level was 165.8 ± 30.2 mg/dL (9.2 ± 1.7 mmol/L) P = 0.015 (Fig. 2).

FIG. 2.

Boxplot of mean 14-day sensor glucose monitoring.

It is worthy to note that in patients who received acupuncture, there was no statistical difference in mean 24-hour glycemia between treatment days (142 mg/dL–7.9 mmol/L) and nontreatment days (144 mg/dL–8.0 mmol/L). All data related to CGM can be seen in the Supplementary Fig. S1.

Discussion

The results of this pilot short-term randomized study showed that acupuncture in addition to standard care was superior to standard of care alone in terms of glycemic control in noninsulin-dependent (type II) diabetes mellitus.

Despite the small sample, there were no significant differences in baseline characteristics, and even so the mean glucose measured with CGM showed a significant difference in 14-day analysis (143 mg/dL vs. 165 mg/dL; P = 0.015)

The greater the baseline A1c, the better the response of any hypoglycemic therapy.¹⁸ Even starting from an average A1c close to the 7% goal, acupuncture therapy was able to decrease 22 mg/dL in the 14-day average.

The mechanisms behind acupuncture action on glycemic control are varied and are still being investigated.¹⁹ The effect on glucose metabolism appears to be better when endogenous insulin secretion is still preserved. Either in type 1 diabetes or patients with type 2 diabetes where insulin secretion is not adequate, acupuncture does not show efficacy.²⁰

Glycemic effects of acupuncture are related to insulin secretion status, but ultimately, insulin sensitivity is the goal in any enhancement of insulin action.²¹ Acupuncture shows a positive effect on glucose transport in skeletal muscles, leads to ameliorated responsiveness to insulin through excitation of somatic afferent fibers and causes a recovery of insulin signal proteins such as IRS1 and GLUT4.²²

When analyzing the daily averages provided by the glucose sensor, we observe that patients did not present a difference in glycemic control between days in which they received or did not receive needle treatment. This is possibly related to insulin sensitivity effect, rather than insulin secretion effect, although this hypothesis needs confirmation.

One of the main advantages of acupuncture treatment is the tailored treatment. Compared with conventional treatment, acupuncture has also a low cost, but can cause local pain, infection, or inflammation.²³

Although this was a pilot study, we were able to evaluate the acute effect of acupuncture on glycemic control using a cutting-edge technology.

Limitations of the Study

Even the prospective controlled study has methodological problems, including difficulties, if not impossibility, in the blinding process, finding an appropriate placebo or control treatment, and having patient expectations of the efficacy of acupuncture as a major confounding factor.

Another weakness in our study was not to explore the mechanisms underlying the effect, limited number (N = 20) of participants, the relatively short duration (14 days) of the trial and the reliance on self-reporting regarding to activity, diet, and other behavioral changes.

A longer trial should be performed, including a larger sample, a longer follow-up, and another glucose control method of analysis should be used for a more robust conclusion. The importance of this study consisted in the use of a new technology and to demonstrate that even small numbers of acupuncture sessions can improve glycemic control.

Conclusions

We can conclude that in this randomized pilot study, there was an improvement in global glycemic control during the 14-day monitoring in the acupuncture group. Further studies with larger cohorts should be performed.

Footnotes

Author Disclosure Statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the article, including Abbott FreeStyle Libre system.

Funding Information

No funding was received for this article.

Supplementary Material

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Supplementary Material

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