Original Article

Acupressure Therapy Inhibits the Development of DiabeticComplications in Chinese Patients with Type 2 Diabetes

Ke-Ke Jin, M.D.,1,* Lei Chen, M.D.,2,* Jing-Ye Pan, M.D.,3 Jian-Min Li, M.D.,4

Yang Wang, M.D.,1 and Fang-Yan Wang, M.D.1

Abstract

Objectives: The objectives of this study were to investigate the effects of acupressure therapy (AT) on thedevelopment and progression of diabetic complications in Chinese patients with type 2 diabetes (T2D).Design and methods: A total of 80 patients with T2D were recruited for a randomized clinical study of the effectof AT on the progression and development of diabetic complications, and 64 patients were followed up for3 years. All patients with T2D were treated with regular medicines and participated in diet and exerciseprograms for the control of hyperglycemia and hypertension. The patients in the AT group received additionaltreatment of a 90-minute AT 4–6 times per week for 3 consecutive years. Their blood lipids, fasting glucoselevels, and heart and kidney functions and nerve conduction velocity (NCV) were longitudinally monitoredbefore and every 12 months after AT.Results: Following AT therapy for 3 years, significantly lower levels of total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and higher levels of high-density lipoprotein-cholesterol (HDL-C) were observedand no significantly increased levels of serum creatinine and urine protein were detected in the AT group, ascompared with that in controls. Furthermore, the mean values of NCV in the AT group at 2 years post-treatmentwere significantly greater than those of controls and were further elevated at the end of this study. Therefore, ATinhibited the progression of hyperlipidemia and improved diabetes-associated kidney function and neuropathyin Chinese patients with T2D.Conclusions: AT may be an effective nonpharmacological adjunctive strategy for alleviating the developmentand progression of T2D-related complications.

Introduction

Type 2 diabetes (T2D) is a metabolic disorder affectingmultiple organs, and its incidence is increasing world-

wide. Currently, T2D affects more than 170 million individ-uals worldwide and 37 million in China, accounting for 90%of total patients with diabetes.1 It is estimated that in 2010, thetotal number of patients with diabetes will increase by nearly50%, particularly in the developing countries of Africa, Asia,and South America.2 Although the pathogenesis of T2D is stillelusive, the available medical treatments, together with in-tensive diet and exercise, have been shown to effectivelycontrol hyperglycemia and prolong the lifespan of patientswith diabetes.3,4 However, the longer lifespan of patients withdiabetes has led to the emergence of chronic diabetic com-plications, such as cardiovascular diseases, kidney failure,

and neuropathy, which are the major factors contributing tothe morbidity and mortality of patients with diabetes. Car-diovascular morbidity in patients with T2D is two to fourtimes greater than that of diabetes-free people.5 Importantly,recent studies showed that maintenance of near-normal gly-cemia by medical treatments and available therapeutic pro-grams failed to reduce the development of diabetes-relatedcardiovascular diseases significantly in patients with T2D.6,7

Apparently, the development of new strategies for the pre-vention and inhibition of diabetes-related complicationsshould be of great significance in improving the life quality ofpatients with T2D.

Therapeutic massage is a manual manipulation of thebody’s soft tissue for the purpose of stimulating circulationand promoting relaxation, leading to the improvement ofsystemic health.8 A number of studies have shown the

1Department of Pathophysiology, Wenzhou Medical College, Zhejiang, China.2Department of Orthopedics, 3Department of ICU, and 4Department of Pathology, The First Affiliated Hospital, Wenzhou Medical College,

Zhejiang, China.*These authors contributed equally to this work.

THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINEVolume 15, Number 9, 2009, pp. 1027–1032ª Mary Ann Liebert, Inc.DOI: 10.1089=acm.2008.0608

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subjective effects of massage on muscle relaxation and psy-chologic status, including alleviating insomnia,9 reducinganxiety,10 easing cancer-related pain, and regulating bloodpressures.11,12 Acupressure therapy (AT) is a safe and gentlealternative therapy used to relieve symptoms from manycommon disorders through thumbs and fingers (sometimesthe elbow) to exert pressure to specific acupoints along thebody meridians.13,14 Previous studies have demonstratedthat acupuncture stimulation ameliorated primary and sec-ondary symptoms of peripheral neuropathy, gastroparesis,diabetic retinopathy, diabetic paralytic squint, diabetic ne-phropathy, and diabetic encephalopathy in patients withT2D.15–19 Notably, acupuncture therapy has potential risk forinfection, which is very dangerous for patients with T2D. AThas been demonstrated to be a safe means for clinical prac-tices. However, little is known about whether AT could mod-ulate the development and progression of T2D-associatedcomplications in patients with T2D.

To address this issue, a total of 64 patients with T2D wererecruited and randomly divided into the treatment andcontrol groups. We found that AT of patients with T2D for3 years significantly inhibited the progression of T2D-relatedhyperlipidemia and kidney disorder and improved theneuropathy. We discuss the implication of our findings.

Methods

Subjects

A total of 80 patients with T2D were recruited in thisstudy, and they received outpatient services at the Depart-ment of Osteology, the First Affiliated Hospital of WenzhouMedical College (Wenzhou, Zhejiang, China), from January2002 to May 2008. They were diagnosed according to the1997 American Diabetes Association diagnostic criteria fordiabetes: fasting blood glucose (FBG)�7.0 mmol=L or plasmaglucose �11.1 mmol=L, determined by 2-hour oral glucosetolerance test. Some patients with diabetic peripheral neu-ropathy (DPN) were diagnosed with nerve conduction ve-locity (NCV, <45 m=s), determined by the electromyogram,and complained of numbness and pain at the upper and=orlower extremities; diminished superficial sensation; and re-duced or absent tendon reflexes. All patients with T2D wereable to care for themselves. Individuals who were smokers,drinkers, or with recent and historical cardiovascular dis-eases, such as angina pectoris, myocardial infarction, stroke,and kidney failure, were excluded. Informed consent wasobtained from individual patients, and the experimentalprotocols of this study were approved by the InstitutionalReview Board of the Wenzhou Medical College.

Experimental design

Individual patients with diabetes were adaptively ran-domized by minimization into treated group (40) or controlgroup (40), based on marginal totals of the stratifying vari-ables to ensure that new patients were assigned to the group,which yielded the lowest imbalance score. During thestudying period, a total of 16 patients (8 patients from eachcontrol and treatment group) were lost for follow-up due totheir personal reason of moving out from the area.

The treatment group comprised 32 patients (15 male and17 female), between 35 and 70 years of age with a mean

55� 11.40 years, with T2D for 1.5–23 years (average11.30� 5.88). The control group contained 32 patients (14 maleand 18 female), aged from 36 to 68 (average 52.63� 9.76years) and with T2D for 0.5–22 years (average 11.44� 6.12).There were 17 or 19 patients with hypertension in the controlgroup or treatment group, respectively. Hypertension wasdiagnosed if a patient had systolic blood pressure higherthan 140 mm Hg or diastolic blood pressure higher than90 mm Hg. All patients agreed not to consume alcohol reg-ularly during the study period of 3 years.

Treatment

All participants received food and lifestyle education aboutthe diet=exercise programs, and medical treatments of me-thycobal (1.5 mg=day), fursultiamin (150 mg=day), and=orfufangdanshen diwan (810 mg=day) for alleviating DPN, andthose patients with hypertension were treated with benazepril(5–20 mg=day). During the study period, their FBG, post-prandial blood glucose (PBG), glycosylated hemoglobin, andblood pressure levels were monitored every 2 months foradjusting the dosage of drugs to correct hypertension andhyperglycemia. The patients in the treatment group receivedadditional care by AT over the whole body. They were given a90-minute of AT daily and 4–6 times per week for 3 consec-utive years. AT was carried out in patients at least 1 hour aftera meal and bath, and 30 minutes before a meal, by certifiedpractitioners in a community hospital who had received aminimum of 1000 hours of training and had professionalpractice for more than 3 years. Individual practitioners hadpassed the 2-week special training with a standard protocol of90-minute massage treatment we developed. During the AT,an individual patient lay down on a massage bed and wascovered with a thin and soft cotton sheet. A total of about 100acupoints along the meridians of his or her body were mas-saged, without use of any cream or lotion. Then 13 majoracupoints (pancreatic yu, spleen shu, weishu point, shenshu,sanjiao and bladder meridian on the back; huantiao on the hip;weizhong and chengshan on the leg; yongquan, taiyang, yuyao,jingming on the head) were repeatedly massaged, particularlyfor patients with both T2D and hypertension. A practitionerused his figure tip and thumb to vertically press and kneadindividual acupoints for 3 seconds=time and repeated10 times, and AT usually began from the acupoints in the legsand moved up. The strength of massage increased graduallyuntil the patients felt a little soreness, numbness, and disten-sion, but not pain, at the acupoint. Individual patients, whodid not receive AT 4 times in a special week, were compen-sated by more frequent AT treatments next week. All of thepatients received AT for more than 309 hours each year.

Parameter analysis

The blood and urine samples were collected from indi-vidual patients before and every 12 months post-AT for theanalysis of diabetes complication-associated parameters, in-cluding FBG, total triglycerides (TG), total cholesterol (TC),low-density lipoprotein-cholesterol (LDL-C), high-densitylipoprotein-cholesterol (HDL-C), blood urea nitrogen (BUN),serum creatinine (Scr), and urine protein (Upro) by routinebiochemical assays and the concentrations of HBA1c byvacuum column chromatography. The normal ranges ofthose parameters in the Chinese population were FBG 3.9–

1028 JIN ET AL.

6.1 mmol=L; HbA1C <7%; TC 3.40–5.20 mmol=L; TG 0.45–1.47 mmol=L; HDL-C 0.90–1.68 mmol=L; LDL-C 2.1–3.1 mmol=L; BUN 2.9–8.2 mmol=L; Scr 35–80 mmol=L; andUpro <150 mg=24 hours. Individual subjects were examinedby electrocardiogram, ultrasound cardiogram, and commonperoneal NCV (normal �45 m=s) every 12 months. The leftventricular hypertrophy for individual patients was evalu-ated by echocardiograph with the standard of left ventricularmass index (LVMI >131 g=m2 for male patients and LVMI>100 g=m2 for female patients).4 All of the tests were per-formed in a blind manner.

Statistical analysis

Data were expressed as mean� standard deviation, andthe difference between treatment and control groups wasstatistically analyzed by Student’s t test or analysis of vari-ance using the SPSS 10.0 PC program. The Fisher exactmethod was used for comparing the proportional data be-tween groups. A value of p< 0.05 was considered to bestatistically significant.

Results

Effect of AT on the progression of hyperlipidemiain Chinese patients with T2D

Patients with long-term T2D, even with effective control ofhyperglycemia, usually are at risk to develop T2D-related

complications, such as cardiovascular diseases, nephropathy,and neuropathy. Stress and inflammation are associated withthe pathogenic process of these complications, while AT hasbeen demonstrated to reduce stress and regulate inflamma-tion. To determine the impact of AT on the development ofT2D-related complications, a total of 80 patients with T2Dwere recruited and divided randomly into the AT treatmentand control groups. Due to personal reasons, 16 patients (8patients from the control or the experimental group) werelost for follow-up; the remaining 64 patients were followedup for 3 years. Their demographic characteristics and basicmeasurements are shown in Table 1. Obviously, all patientswith T2D, who underwent the medical treatments and par-ticipated in the diet and exercise program, showed normallevels of FBG and blood pressure, indicating that thesetherapies effectively controlled hyperglycemia and hyper-tension in Chinese patients with T2D and hypertension.Furthermore, there was no statistically significant differencesin the demographic features and biochemical measures(HbA1C) and body mass index in those two groups of pa-tients. These provide a base for determining the impact of ATon the development of T2D-related complications.

Hyperlipidemia is one of the risk factors for the develop-ment of cardiovascular diseases. To examine the impact ofAT on the progression of hyperlipidemia, the patients in thecontrol group were treated with medicines and diet=exerciseprograms, while the treatment group of patients receivedadditional AT for 3 years. Their blood samples were collectedbefore and every 12 months post AT and were measured forthe levels of TC, TG, HDL-C, and LDL-C by routine bio-chemical assays as shown in Table 2. Clearly, all patientswith T2D showed higher levels of TG, but normal levels ofTC, HDL-C, and LDL-C at the beginning of this study and nosignificant difference in the mean values of these measuresbetween two groups of patients. Three (3) years after thetreatment, the patients in the control group developed hy-perlipidemia, evidenced by higher levels of plasma TC andTG, which were significantly higher than those 3 years agoand also higher than those in the treatment group, whichshowed a moderate increase in the levels of TC and reducedlevels of TG. Furthermore, the levels of HDL-C in the controlgroup were significantly reduced and lower than those of thetreatment group. Notably, AT treatment reduced the con-centrations of LDL-C in the treatment group, which weresignificantly lower than those of the control group.

Table 1. Demographic Characteristics

of Study Subjects

Parameters Control Experiment p

Age (years) 52.63� 9.76 55.00� 11.40 0.374Gender (M=F) 14=18 15=17 1.000Duration of T2D (year) 11.44� 6.12 11.30� 5.88 0.926BMI (kg=m2) 23.50� 3.10 23.64� 3.42 0.864FPG (mmol=L) 5.75� 0.85 5.72� 0.97 0.907HbA1c (%) 7.24� 0.96 7.22� 0.91 0.930SBP (mm Hg) 126.69� 12.81 123.72� 11.70 0.337DBP (mm Hg) 77.84� 8.72 79.59� 8.35 0.403

Data are expressed as the mean� standard deviation of individualgroups (n¼ 32 per group).

T2D, type 2 diabetes; BMI, body–mass index; FPG, fasting plasmaglucose; HbA1c, glycosylated hemoglobin; SBP, systolic bloodpressure; DBP, diastolic blood pressure.

Table 2. The Effect of AT Therapy on the Hyperlipidemia and Heart Function

Group Time (month) n TC (mmol=L) TG (mmol=L) HDL-C (mmol=L) LDL-C (mmol=L) LVMI (g=m2)

Control 0 32 5.12� 1.09 2.16� 0.56 1.07� 0.23 2.93� 0.63 105� 2212 32 5.19� 0.99 2.31� 0.57 1.05� 0.26 2.81� 0.65 108� 2324 32 5.41� 1.00 2.44� 0.68 0.95� 0.23 2.83� 0.57 113� 2536 30 5.84� 1.09a,b 2.52� 0.66 0.90� 0.20a,b 2.94� 0.66 117� 23

Treatment 0 32 5.15� 1.02 2.21� 0.57 1.07� 0.24 2.84� 0.73 105� 2312 32 5.14� 1.09 2.11� 0.59 1.13� 0.28 2.81� 0.74 105� 2024 32 5.24� 1.09 2.12� 0.61 1.03� 0.22 2.64� 0.85 107� 2236 32 5.29� 0.92c 2.16� 0.51c 1.03� 0.25c 2.54� 0.69c 106� 25

ap< 0.05 versus the value at the beginning.bp< 0.05 versus the value at 12th month.cp< 0.05 versus control group at 36th month.AT, acupressure therapy; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density

lipoprotein-cholesterol; LVMI, left ventricular mass index.

ACUPRESSURE THERAPY FOR PATIENTS WITH DIABETES 1029

Further examination of heart function revealed that at theend of follow-up, the mean value of LVMI in the controlgroup increased by 12 g=m2 (significantly higher than that atthe beginning, p¼ 0.044), and 17 of 30 patients (excluding2 patients who died) showed left ventricular hypertrophy. Incontrast, the mean LVMI of the treatment group increased byonly 1 g=m2 with 1 new case of left ventricular hypertrophy.Notably, there were 2 patients from the control group died ofacute myocardial infarction or severe infection at the 30th or34th month of follow-up, respectively. In addition, an addi-tional 2 patients suffered from myocardial infarction, andthere were 2 patients with angina cordis in the control group.However, all patients in the treatment group survivedthroughout the study period. There was no single case ofmyocardial infarction and angina cordis in the treated group.Moreover, there were 5 new cases of hypertension in thecontrol group while there was only 1 in the treatment group.Similarly, 9 of 17 cases of patients with hypertension in thecontrol group needed to increase the dosage of medicine forthe continual control of their hypertension, but only 1 fromthe treatment group requested treatment with a higher doseof antihypertension drug throughout the observation period.

Together, these data demonstrated that AT inhibited theprogression of hyperlipidemia and development of cardio-vascular diseases in T2D Chinese patients.

AT reduced the deteriorationof diabetes-associated kidney function

Kidney disorders and nephropathy are common diabeticcomplications in patients with T2D. To evaluate the effect ofAT on the kidney function of patients with T2D, the bloodand urine samples were collected from treatment and controlpatients and the levels of blood BUN and Scr and proteinuriawere longitudinally monitored as shown in Table 3. Duringthe observation period, the concentrations of blood BUN, Scr,and proteinuria gradually increased in the control group andat the end of this study, the levels of blood Scr and pro-teinuria were significantly elevated, as compared with thosetested 3 years previously. The higher levels of blood BUNand Scr and proteinuria were indictors of the deterioration ofdiabetes-associated kidney function. In contrast, the levels ofblood BUN and Scr and proteinuria were only moderatelyelevated in the treatment group, although there was no sig-nificant difference, as compared with those of controls. The

moderate increases in the levels of BUN, Scr, and proteinuriasuggested that AT reduced the deterioration of diabetes-associated kidney function in Chinese patients with T2D.

AT reduced the severity of neuropathy

Diabetic neuropathy is a common and severe complicationin patients with T2D. To investigate the effect of AT on theseverity of neuropathy, patients from treatment and controlgroups were measured for their NCV, a special marker ofneuropathy used at the clinic. Most patients appeared tohave diabetic neuropathy at the beginning of this study, andthe mean values of NCV in treatment and control groups ofpatients were below the normal levels. Following observa-tions for 3 years, the levels of NCV in the control groupslightly increased, suggesting that regular medical treatmentwith diet and exercise programs improved neuronal re-sponses in patients with T2D (Fig. 1). Interestingly, the levelsof NCV were gradually elevated in the treatment group.

Table 3. The Effect of AT Therapy on Kidney Function

Group Time (month) n BUN (mmol=L) Scr (mmol=L) Upro (g=24 h)

Control 0 32 8.39� 3.55 77� 19 1.02� 1.2512 32 9.14� 4.15 76� 19 1.08� 1.1824 32 10.64� 4.75 85� 24 1.45� 1.3636 30 10.59� 5.28 94� 34a,b 1.93� 1.25a,b

Treatment 0 32 8.02� 3.96 79� 16 1.04� 1.2212 32 8.76� 3.56 72� 17 1.29� 1.1424 32 9.74� 5.07 80� 24 1.26� 1.2636 32 9.40� 4.74 84� 30 1.45� 1.20

ap< 0.05 versus the value at the beginning.bp< 0.05 versus the value of controls at 12th month.BUN, blood urea nitrogen; Scr, serum creatine; Upro, urine protein.AT, acupressure therapy.

60 ControlTreated

NC

V (

m/s

)

Time0 12 24 36 (mon)

50

40

30

20

** **

**

***

FIG. 1. Acupressure therapy (AT) improved nerve con-duction velocity (NCV). The NCV of individual patientswere measured longitudinally before and every 12 monthsafter AT. Data shown are the mean� standard deviation ofthe treatment and control groups (N¼ 32 or 30 per group).*p< 0.05; **p< 0.01.

1030 JIN ET AL.

Significantly higher levels of NCV were observed 1 year afterAT and the levels of NCV in the treated group were greaterthan that of controls 2 years after treatment. Prolonged ATfurther improved the neuronal conduction in the treatmentgroup of patients. Therefore, AT reduced the severity of di-abetic neuropathy in Chinese patients with T2D.

Discussion

Patients with T2D, even with effective control of hyper-glycemia, usually develop diabetic complications, such ascardiovascular, microvascular, nephropathy, and neuro-pathic diseases, which increase the morbidity and prematuremortality of T2D.17,20 The disorder of blood lipids, hyperlip-idemia, and low levels of HDL-C, and hypertension are riskfactors for the development of cardiovascular diseases.21,22

Diabetic peripheral neuropathy is the most common compli-cation in patients with diabetes, accounting for substantialmorbidity and mortality and resulting in huge health carecosts.23 Diabetic nephropathy is the leading cause of end-stage renal disease in the United States. Many patients withT2D develop proteinuria within 10–15 years of disease onsetand progress into macroalbuminuria, a decrease with poorcreatinine clearance, and finally renal failure.24,25 Thus, T2D-related complications are major challenges for human health.

We examined the effect of AT on the development andprogression of T2D-related complications in Chinese patientswith T2D. First, we found that treatment with regular medi-cines and diet and exercise programs effectively controlledhyperglycemia and hypertension. However, these therapeuticstrategies failed to prevent the development of diabeticcomplications. Indeed, significantly higher levels of blood TC,TG, and Scr, lower levels of HDL-C, and severe proteinuria,the hallmarks of hyperlipidemia and kidney functional dis-order, were observed in the control group of patients. Second,following AT for 3 years, the mean levels of hyperlipidemia,Scr, and proteinuria in the treatment group were significantlyreduced, as compared with those in the control group. Fur-thermore, AT improved the NCV in patients with T2D, asevidenced by significantly elevated levels of NCV in thetreatment group of patients with T2D, as compared with thosein controls. These novel data indicate that AT can be used asan additional therapy for patients with T2D by reducingblood hyperlipidemia, improving kidney function and NCV,which should inhibit the development and progression ofT2D-related complications in patients with T2D.

Previous studies have shown that acupuncture stimulationcan ameliorate T2D-related complications.15–19 TraditionalChinese Medicine–style acupuncture is beneficial for painfuldiabetic neuropathy by improving nerve sensation at theclinic,15 and acupuncture has a definite therapeutic effect ondiabetic paralytic squint.16 Acupuncture can also improveclinical symptoms and blood rheology of patients with dia-betic nephropathy, inhibiting the progression of diabetic ne-phropathy.17,18 A previous study has shown that themechanism(s) by which acupuncture inhibits the develop-ment and progression of diabetic complications are likelymediated by regulating the levels of vascular active sub-stances, nitric oxide (NO) and endothelin (ET).19 Given thatAT acts in a similar manner to acupuncture, which appliespressure and massage to traditional acupoints,26 it is possiblethat AT also regulates the levels of vascular active substances,

NO and ET, inhibiting hyperlipidemia and improving kidneyfunction and neuropathy in patients with T2D. Moreover,acupuncture has been shown to modulate immune functionand inflammation has been attributed to the pathogenesis ofT2D-related complications.27,28 Conceivably, AT may alsodownregulate inflammation by modulating the function ofimmune cells. However, the precise mechanism(s) underlyingthe action of AT in the inhibition of hyperlipidemia and im-provement of T2D-related kidney disorder and neuropathyremain to be further investigated.

We recognized that this study had a few limitations. First,this study was performed in a relatively small sample size.Second, although all of the clinical tests were performed in ablind fashion, the patients and AT practitioners were notblinded for this study and control patients did not receiveplacebo massage treatment. Furthermore, even if no singlepatient complained for the long lasted AT, all of the AT-treated patients did spend lots time for this study. Therefore, acomplete double-blinded clinical trial for testing the effect ofAT for a short period on the development of T2D-associatedcomplications in a relatively large population is warranted.

In conclusion, AT appears to be an effective nonpharma-cological adjunctive treatment for alleviating the develop-ment and progression of T2D-related complications inpatients with T2D. Our novel data indicated that AT signif-icantly reduced hyperlipidemia and the progression of kid-ney disorder and neuropathy in patients with T2D.However, future studies are needed to elucidate the mech-anism(s) underlying the beneficial effect of AT on patientswith T2D in a large population.

Acknowledgments

This study was supported by grants from the NaturalScience Foundation of Zhe-Jiang Province, P.R. China (no.Y207495), a Research Project of the Department of Educationof Zhejiang Province of China (no. 20041064), ScientificGrants for Traditional Chinese Medicine of Zhejiang Pro-vince (no. 2007CA081), and by a Wenzhou Science andTechnology Project of Wenzhou municipal state (no.Y20060086).

Disclosure Statement

No competing financial interests exist.

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Address correspondence to:Lei Chen, M.D.

Department of OrthopedicsThe First Affiliated Hospital

Wenzhou Medical CollegeZhejiang 325000

China

E-mail: jkk6996@yahoo.com.cn

1032 JIN ET AL.