扶正畅枢法对2型糖尿病口服降糖药继发性失效的证治研究
|
摘要
第一部分文献研究
2型糖尿病是严重危害人类健康的内分泌代谢性疾病,随着生活水平的提高和生活方式的改变,发病率不断上升,同时发病年龄也日渐年轻化。发病机制尚未完全明确,多数学者认为与遗传、免疫和多种环境因素有关。其病理生理与胰岛素分泌不足和胰岛素抵抗有关,胰岛素的功能降低以致不能被有效利用而引致糖、脂肪、蛋白质、水及电解质的代谢紊乱。持续性高血糖水平,会引起多种并发症影响心、脑、肾、眼、足和周围神经。如心脏病和中风,肾病可发展为肾衰竭,视网膜病变、白内障、青光眼会导致失明,足部严重溃疡而要截肢等的危害。
有效的把血糖控制在接近正常的水平,对减少微血管并发症,包括视网膜病变、肾病和神经病变有明显优势,因此,有效的控制血糖便成为目前的关热点。目前西药对血糖的初期控制相对比较理想,但随着病程的演变,口服降糖药继发性失效以致血糖控制不良的情况也屡见不鲜,为了进一步控制血糖,一般会加大药量或采取二联用药或多联用药,效果仍然不理想便改用胰岛素的注射来治疗。
历代中医典籍中并无“口服降糖药继发性失效”这个病名,这是现代医学在2型糖尿病的治疗过程中,为了证实药物的疗效和病程的控制情况,而设定相关的监控指标,祈望能够通过有关微观项目的检测来了解药物所起的作用,一旦发现药物失效,便可以及早更改用药以防止其并发症的出现。
虽然历代的中医典籍中并不直接有“糖尿病”这个病名,我们可以按2型糖尿病的表现而将其归类到“消渴”的范畴去考究。历代医家多数认为“消渴”以阴虚为标,燥热为本,故从滋阴清热治疗,但从长期的临床验证发现对2型糖尿病的防治未能起到根本的治疗作用。
本研究以《伤寒论》六经辨证为基础,提出三阴病脏腑虚寒在2型糖尿病的发病过程中起主导地位。从文献的考究到临床研究,发现糖尿病的基本病因就是本虚,重点在先天之本肾和后天之本脾的虚弱状态下,未能有效发挥其温照和固摄能力,属于太阴和少阴病的脾肾阳虚,精微物质流失而不能被充分利用,故令到身体更为虚弱,而糖尿病就是在这种正气不足的环境中形成的。由于能量不足,推动无力而导致病理产物的停滞,壅塞血管脉络,这个寒湿内停的邪实情况,也正就是糖尿病并发症的阶段。因此,本研究用温阳扶正,配合畅枢之法,扶正以固本,畅枢以利于祛邪,标本兼顾,在治疗上取得满意的疗效。
第二部分临床研究
研究目的：
本课题以研究中医中药的相关文献再配合现代医学的研究及导师的临床经验为基础,提出阳虚是2型糖尿病的主要病机,多伴有枢机不利为其特点的理论,并运用扶正(扶阳)畅枢之法治疗。通过观察应用本法为基础的临床疗效,进一步论证此法的正确性,为日后更深入的研究提供有价值的理论依据。
研究方法：
本课题为前瞻性研究,临床观察2型糖尿病口服降糖药继发性失效以致血糖控制不良的患者60例,均于2009年7月至2010年4月在广州中医药大学第一附属医院内分泌科门诊及住院就诊的患者,经中医六经辨证为三阴病或伴有枢机不利,按病情及就诊的先后次序,随机分到加用中药组30例、加用另类西药(拜糖平,罗格列酮)组15例和胰岛素组15例。纳入患者在适当饮食及运动,再配合糖尿病教育的基础上,分别在原用西药方案上加服扶正畅枢中药煎剂、改用或加用另类口服降糖药和改用胰岛素治疗,治疗周期为12周,三组间及各组治疗前后进行比较,观察患者治疗前后各项相关指标,包括血糖:FBG、2hPBG、HbAlc,临床症状积分、中医正邪评分量表及六经辨证观察等。所有数据均用SPSS17.0(PASW17)软件进行统计分析。并以P<0.05被认为检验的差别有统计学意义。
研究结果：
1.病例不能用单一的六经病作归纳,发病多以合病或并病的形式出现,三阴病13例,占22%;阴阳合病47例,占78%。
2.六经的分布次序为：1)少阴病为主证的占96.66%(58／60例),2)少阳病占次证的36.66%(22／60例),3)厥阴病占次证的31.66%(19／60例),4)太阴病占次证的16.66%(10／60例),5)阳明病占次证的13.33%(8／60例),6)太阳病则以伴随证占5%(3／60例)。引证了2型糖尿病口服降糖药继发性失效的病人多以少阴病阳虚为主,伴少阳枢机不利,采用温阳扶正并配以畅枢之法作治疗的正确性。
3.经统计学分析,各组的空腹血糖(FBG)、餐后血糖(2hPBG)和糖化血红蛋白(HbA1c)在治疗后的改善均有显着性差异(P<0.05)。三组间的疗效比较则无显著性差异(P>0.05)。
4.各组的中医临床症状积分比较(P<0.01),表示治疗效果有显著性差异。三组间的疗效比较则有显著性差异(P<0.01)。以治疗组的效果最为突出。按上述的疗效标准,结果治疗组(加中药组)显效率63.3%,总有效率100%;对照1组(加西药组)显效率33.3%,总有效率100%;对照2组(胰岛素组)显效率6.7%,有效60%,无效33.3%。
5.设计正邪评分量表作观察,结果发现这次研究的病人的虚证多数集中在阳虚、心虚和肾虚,这与六经的少阴病非常吻合;而实证则多数集中在气郁、寒湿和热结方面,这又与枢机不利的病机极度相似。正好证实病人的“虚”主要为“阳虚”,“实”重点就在“枢机不利”以致寒湿内停。
结论与启示：
2型糖尿病的本原于先天的禀赋不足,启动于后天的不良生活方式、饮食不节、情志不遂、劳逸失调。由于脏腑亏损及功能低下以致温照及运化无力,病理产物的积聚而成痰成瘀,阻碍气血运行,壅塞脉络,加重了恶性循环而令本病发展致不能逆转的局面。针对这个发病特点而使用扶正培本之法,配合调畅枢机的治疗,加强脏腑功能以促进病理产物的排出,扶正祛邪并用,标本虚实并顾,能有效干预病程,提高患者的生存质量。
2型糖尿病是个复杂而难治疾病,现代医学在目前仍未有治愈的方法,故以控制病情为目标,重点放在血糖控制方面。但发现在治疗上单靠口服西药是不长远的,因为药物继发性失效是个必然进程,最终要依赖胰岛素生存。就算加强血糖控制也不能阻止并发症的出现。因此,中医中药的介入治疗起着正面和积极的作用,大量研究报导可见,中医药的多靶点整体调节作用,可协助降血糖、减少西药的用量、减轻西药的副作用、改善生活质量和防治并发症等。中医的最大特色在于其“治未病”思想,在2型糖尿病的治疗全过程,如能找紧早期的介入,可望逆转病程;中期的介入也能帮助预防并发症;晚期的介入都能提高患者的生存质量。
2型糖尿病是以胰岛β细胞及胰岛素敏感性退化所形成,无论是口服降糖药和胰岛素都不能阻止其病程发展。本研究证明糖尿病以综合的治疗效果最为理想,使用西药也要配合康教育。从中医宏观的角度运用中药作出整体调节,效果令人鼓舞。中医中药有能力将血糖从波动中稳定下来,加药不是唯一的选择。
Part 1:Theoretical and literature study
Along with the lifting of living standard, changes of living habits, the incident rate of Type 2 diabetes mellitus (T2DM) is soaring, particularly the trend towards youngsters. T2DM is metabolic diseases which seriously undermines the health, Although the pathogenesis is still not well-defined, most of the scholars recognized that it should relate to heredity, immune system and multi-environmental factors. The disease is characterized by insulin resistance and progressiveβ-cell dysfunction.
Insufficient Insulin secretion or dysfunction of insulin will lead to metabolic abnormality of glucose, lipid, protein, water and electrolyte. Persistent high level of blood glucose may provoke Diabetic complications, affecting the heart, brain, kidneys, eyes, feet and nerves. For instance, heart disease, stroke, kidney disease will result to final-stage renal failure; retinopathy, cataract and glaucoma will develop to blindness; the serious lower limbs ulcers will end up to amputation.
Controlling glycemic levels as close to the non-diabetic range as possible has demonstrated to have a powerful beneficial effect on diabetes-specific micro-vascular complications, including retinopathy, nephropathy, and neuropathy. In consequence, it made the effective treatment of hyperglycemia a top priority. Treatment with oral agents has clearly improved glycemic control in patients with T2DM at beginning stage. However, long-term glycemic control with these agents is hardly to achieve. Secondary failure is a consequence of increasing loss ofβ-cell function and insulin sensitivity due to disease progression.
To reinforce the treatment, usually will maximize the doses of the agent, or switch to another oral anti-diabetic agent or the addition of another agent (combination therapy). Current standards of practice recommends the addition of oral agents or insulin to a patient's ongoing therapy. However, many patients ultimately require insulin therapy to maintain glycemic control.
We could not find the terms of "Secondary failure of the oral anti-diabetic regimen " in the Ancient Chinese medicine scripts or treatises. This is the terms appearing in the course of healing T2DM by Western Medicine for the treatment of glycemic control. With the integration of laboratory data, it is used to monitor the level of blood glucose such that we could switch the medicine for the prevention of complications as soon as the control of blood glucose level deteriorates.
Despite the fact that there is no direct reflection of the terms "Diabetes Mellitus" from literatures or treatises of Chinese Medicine, we could categorize this T2DM to the scope of "Xiao Ke". However, for this disease, the majority of Traditional Chinese Medicine practitioners follow the rule of nourishing "Ying" and clearing "internal heat", because they believed "Yin" deficiency is the primary cause while dryness and heat are the secondary ones. Nevertheless, the healing results as per long terms clinical studies indicated that this method in prevention and healing of T2DM is far behind expectation.
This study adopted "the Six Meridian Syndrome from《Treatise of "Shang Han"》" as the fundamental, addressed that the issue of "Three Yin disease of Interior-cold syndrome" is playing a key role in T2DM. The cause of T2DM is due to inferior endowment, or the one with inherent insufficiency. The main argument is, due to the weakness of kidney (the inherent essence) and the deficiency of spleen (supplement after birth), they could not function well to fortify and warm the viscera, it is "Tai Yin" and "Xiao Yin" diseases in kidney and spleen of "Yang" deficiency. In consequence, nutrients is losing which in turn the body is even weaker. Above all, the vital essence become hollowized and at last T2DM will develop under such circumstance. As the vital essence is inadequate, the energy is too weak to sweep the body waste and so the circulation of "Qi" and fluid will be hindered and at last the body is being piled up with coldness and dampness. This is the stage towards T2DM complications. Therefore, in this research, we will formulate another method-reinforce the healthy "Qi", dredge "Qi" mechanism in order to fortify the healthy "Qi" and sweep away the piled up pathogens. This method pinpoints both the cause and the indication of T2DM, has achieved a satisfactory and significant result.
Part 2:Clinical Research
Objective:Based on the information from Chinese Medicine literatures, the support of modern medicine studies and instructions of my academic advisor, Prof. Zhu, this research is to prove the theory that deficiency in "Yang" is the major problem of T2DM, it also comes with blockage of "Qi" mechanism. We will observe the clinical results of using the method of warming and fortifying "Qi", dredging "Qi" mechanism to deal with T2DM in order to testify the correctness and beneficial to future studies.
Methods:This study is a prospective study, with the clinical observation of 60 patients on secondary failure of the oral antidiabetic regime in type 2 diabetes, in No.1 Affiliated Hospital of Guangzhou University of Chinese Medicine during the period from July 2009 to April 2010. The 60 cases those were diagnosed as the six-meridian differentiation in three "Yin" disease and/or with the blockage of "Qi" mechanism, were randomized into three groups, treatment group (add Chinese medicine) n=30, and control group 1 (add Acarbose, Rosiglitazone) n= 15, and control 2 group(add insulin) n= 15 (inpatient and outpatient). All patients received the same education course for diabetes, eating instruction and suggested quantity of physical activities. Before and after 12 weeks treatment period, we have taken the measuring data of FBG,2hPBG, HbAlc and observed clinical symptom score and create a " Vital Qi and pathogens Scale Points " and the six-meridian distribution. We compared the change of data before and after treatment, the data then was processed by SPSS17.0(PASW 17) statistic software. For all statistical test, aP value of less than 0.05 was considered to be statistically significant.
Results:
1. All cases cannot be generalized into (initial diagnosis) single six-meridians diseases, but with combination of syndromes and complications. 13 cases were categorized to three "Yin" diseases with 22%, and 47 cases were categorized to "Yin and Yang" combination diseases with 78%.
2. Distribution of six-meridian diseases were:1) Chief syndrome with "Shao Yin" accountable for 96.66%(58/60cases),2) Chief syndrome with "Shao Yang" accountable for 36.66%(22/60 cases),3) Chief syndrome with " Jue Yin" accountable for 31.66%(19/60 cases),4) Subordinate syndrome with "Tai Yin" accountable for 16.66%(10/60 cases),5) Subordinate syndrome with "Yang Ming" accountable for 13.33%(8/60 cases),6) Accompany syndrome with "Tai Yang" accountable for 5%(3/60 cases). Therefore, the majority of the patients in secondary failure of the oral anti-diabetic regimen with the aetiology is "Yang" deficiency in chief syndrome of "Shao Yin" and accompanied with blockage of "Qi" mechanism, that proves the correctness of our treatment by using the method of warming "Yang" and dredging the "Qi" mechanism.
3. Through the statistical analysis of relevant indicators by comparing that of before and after treatments, the improvement of FBG,2hPBG and HbAlc in each group are statistically significant (P<0.05). However, the above indicators among the groups are insignificant (P>0.05).
4. According to the comparison of syndrome scores, P< 0.01, it showed that there is significant difference of healing effect among groups, and that of the treatment group (with add-on Chinese Medicine) is the most outstanding one. Above all, The total effective rate of the treatment group (add Chinese medicine) is 100% with significant rate of 63.3%; The total effective rate of the control group 1(add Western medicine)is 100% with significant rate of 33.3%; The total effective rate of the control group 2(Insulin)is 60% with significant rate of 6.7%, and no effect 33.3%.
5. For the ease of observation and data handling, we have complied a table of《The quantitative analysis of hollowness of "Qi" and degree of pathogens》, the result showed that if the syndrome is deficiency in vital "Qi", most of them are with deficiency of "Yang", heart and or kidney as well, this indication matches closely with "Shao Yin" syndrome in Six Meridian. On the other hand, if it is in excessive syndrome, most of them are in depressive syndromes, coldness and dampness, and heat bound, which are manifested as blockage of "Qi" mechanism. It proved that deficiency syndrome is mainly in deficiency in "Yang" while excessive syndrome is mainly shown as blockage of "Qi " mechanism which is attributable to stagnation of coldness and dampness.
Conclusions and revelations:
The patients with T2DM are usually deficiency of heredity, and then triggered by bad living habits, random diet, emotional frustration and excessive comfort. Owing to the dysfunction of spleen and kidney, energy to circulate the system is insufficient and lead to stagnation of pathogens (phlegm or stasis) which in turn block the flow of blood and meridians and at last, the disease will then evolve to irreversible stage. To focus on these features of T2DM, we utilize the Treatment of using Chinease medicine to reinforce healthy "qi", in associate with the dredging of "Qi" mechanism, to fortify the organs'functions so as to sweep away the pathogens. Supporting the "Qi" and clearing away pathogens, both superficial characteristics and fundamental causes were taken care and so enhance the healing effect significantly, improve patient's quality of life.
T2DM is a thorny disease which is incurable even now with Modern Medicine Science, hence, the target is to control disease's development and glycemic control is the key. However, we found that the healing effect of prolonged use of oral anti-diabetic agent is not desirable. Secondary failure is a highly likely consequence, even with maximal doses or combination of multi-antidiabetic agents therapies. Patients will eventually rely on insulin therapy to maintain glycemic control, to survive. In spite of using the intensive therapy to restrict the blood glucose, diabetes complications are still inevitable.
Therefore, The add-on of Chinese medicine in the course of treatment can have positive and aggressive effect. According to the systematical reviews of articles and treaties, Chinese medicine performs multi-targeting action and comprehensive adjustment, can lower the level of blood glucose, reduce the side effects from the Western medicine, improve the quality of life and avoid those serious diabetes complications. "Theory of pre-emptive treatment of disease" is our principal character in Chinese medicine. To use Chinese medicine as add on therapy in early stage of T2DM could have good chance to reverse the disease, can minimize the chance of occurring complications in mid-stage, can still lift up a great extent of the quality of life even in final stage of the disease.
T2DM is associated with function declining ofβ-cell and degeneration of insulin sensitivity, neither oral anti-diabetic agents nor insulin are able to stop its deteriorating progression.
With this research, it shows the healing effect with integration of Chinese medicine is encouraging. Chinese medicine will use a holistic view to scan and to regulate the body condition, it indicates that Chinese medicine could stabilize the blood glucose level, provided a much better option but just add up the doses of Western medicine.
2型糖尿病是严重危害人类健康的内分泌代谢性疾病,随着生活水平的提高和生活方式的改变,发病率不断上升,同时发病年龄也日渐年轻化。发病机制尚未完全明确,多数学者认为与遗传、免疫和多种环境因素有关。其病理生理与胰岛素分泌不足和胰岛素抵抗有关,胰岛素的功能降低以致不能被有效利用而引致糖、脂肪、蛋白质、水及电解质的代谢紊乱。持续性高血糖水平,会引起多种并发症影响心、脑、肾、眼、足和周围神经。如心脏病和中风,肾病可发展为肾衰竭,视网膜病变、白内障、青光眼会导致失明,足部严重溃疡而要截肢等的危害。
有效的把血糖控制在接近正常的水平,对减少微血管并发症,包括视网膜病变、肾病和神经病变有明显优势,因此,有效的控制血糖便成为目前的关热点。目前西药对血糖的初期控制相对比较理想,但随着病程的演变,口服降糖药继发性失效以致血糖控制不良的情况也屡见不鲜,为了进一步控制血糖,一般会加大药量或采取二联用药或多联用药,效果仍然不理想便改用胰岛素的注射来治疗。
历代中医典籍中并无“口服降糖药继发性失效”这个病名,这是现代医学在2型糖尿病的治疗过程中,为了证实药物的疗效和病程的控制情况,而设定相关的监控指标,祈望能够通过有关微观项目的检测来了解药物所起的作用,一旦发现药物失效,便可以及早更改用药以防止其并发症的出现。
虽然历代的中医典籍中并不直接有“糖尿病”这个病名,我们可以按2型糖尿病的表现而将其归类到“消渴”的范畴去考究。历代医家多数认为“消渴”以阴虚为标,燥热为本,故从滋阴清热治疗,但从长期的临床验证发现对2型糖尿病的防治未能起到根本的治疗作用。
本研究以《伤寒论》六经辨证为基础,提出三阴病脏腑虚寒在2型糖尿病的发病过程中起主导地位。从文献的考究到临床研究,发现糖尿病的基本病因就是本虚,重点在先天之本肾和后天之本脾的虚弱状态下,未能有效发挥其温照和固摄能力,属于太阴和少阴病的脾肾阳虚,精微物质流失而不能被充分利用,故令到身体更为虚弱,而糖尿病就是在这种正气不足的环境中形成的。由于能量不足,推动无力而导致病理产物的停滞,壅塞血管脉络,这个寒湿内停的邪实情况,也正就是糖尿病并发症的阶段。因此,本研究用温阳扶正,配合畅枢之法,扶正以固本,畅枢以利于祛邪,标本兼顾,在治疗上取得满意的疗效。
第二部分临床研究
研究目的：
本课题以研究中医中药的相关文献再配合现代医学的研究及导师的临床经验为基础,提出阳虚是2型糖尿病的主要病机,多伴有枢机不利为其特点的理论,并运用扶正(扶阳)畅枢之法治疗。通过观察应用本法为基础的临床疗效,进一步论证此法的正确性,为日后更深入的研究提供有价值的理论依据。
研究方法：
本课题为前瞻性研究,临床观察2型糖尿病口服降糖药继发性失效以致血糖控制不良的患者60例,均于2009年7月至2010年4月在广州中医药大学第一附属医院内分泌科门诊及住院就诊的患者,经中医六经辨证为三阴病或伴有枢机不利,按病情及就诊的先后次序,随机分到加用中药组30例、加用另类西药(拜糖平,罗格列酮)组15例和胰岛素组15例。纳入患者在适当饮食及运动,再配合糖尿病教育的基础上,分别在原用西药方案上加服扶正畅枢中药煎剂、改用或加用另类口服降糖药和改用胰岛素治疗,治疗周期为12周,三组间及各组治疗前后进行比较,观察患者治疗前后各项相关指标,包括血糖:FBG、2hPBG、HbAlc,临床症状积分、中医正邪评分量表及六经辨证观察等。所有数据均用SPSS17.0(PASW17)软件进行统计分析。并以P<0.05被认为检验的差别有统计学意义。
研究结果：
1.病例不能用单一的六经病作归纳,发病多以合病或并病的形式出现,三阴病13例,占22%;阴阳合病47例,占78%。
2.六经的分布次序为：1)少阴病为主证的占96.66%(58／60例),2)少阳病占次证的36.66%(22／60例),3)厥阴病占次证的31.66%(19／60例),4)太阴病占次证的16.66%(10／60例),5)阳明病占次证的13.33%(8／60例),6)太阳病则以伴随证占5%(3／60例)。引证了2型糖尿病口服降糖药继发性失效的病人多以少阴病阳虚为主,伴少阳枢机不利,采用温阳扶正并配以畅枢之法作治疗的正确性。
3.经统计学分析,各组的空腹血糖(FBG)、餐后血糖(2hPBG)和糖化血红蛋白(HbA1c)在治疗后的改善均有显着性差异(P<0.05)。三组间的疗效比较则无显著性差异(P>0.05)。
4.各组的中医临床症状积分比较(P<0.01),表示治疗效果有显著性差异。三组间的疗效比较则有显著性差异(P<0.01)。以治疗组的效果最为突出。按上述的疗效标准,结果治疗组(加中药组)显效率63.3%,总有效率100%;对照1组(加西药组)显效率33.3%,总有效率100%;对照2组(胰岛素组)显效率6.7%,有效60%,无效33.3%。
5.设计正邪评分量表作观察,结果发现这次研究的病人的虚证多数集中在阳虚、心虚和肾虚,这与六经的少阴病非常吻合;而实证则多数集中在气郁、寒湿和热结方面,这又与枢机不利的病机极度相似。正好证实病人的“虚”主要为“阳虚”,“实”重点就在“枢机不利”以致寒湿内停。
结论与启示：
2型糖尿病的本原于先天的禀赋不足,启动于后天的不良生活方式、饮食不节、情志不遂、劳逸失调。由于脏腑亏损及功能低下以致温照及运化无力,病理产物的积聚而成痰成瘀,阻碍气血运行,壅塞脉络,加重了恶性循环而令本病发展致不能逆转的局面。针对这个发病特点而使用扶正培本之法,配合调畅枢机的治疗,加强脏腑功能以促进病理产物的排出,扶正祛邪并用,标本虚实并顾,能有效干预病程,提高患者的生存质量。
2型糖尿病是个复杂而难治疾病,现代医学在目前仍未有治愈的方法,故以控制病情为目标,重点放在血糖控制方面。但发现在治疗上单靠口服西药是不长远的,因为药物继发性失效是个必然进程,最终要依赖胰岛素生存。就算加强血糖控制也不能阻止并发症的出现。因此,中医中药的介入治疗起着正面和积极的作用,大量研究报导可见,中医药的多靶点整体调节作用,可协助降血糖、减少西药的用量、减轻西药的副作用、改善生活质量和防治并发症等。中医的最大特色在于其“治未病”思想,在2型糖尿病的治疗全过程,如能找紧早期的介入,可望逆转病程;中期的介入也能帮助预防并发症;晚期的介入都能提高患者的生存质量。
2型糖尿病是以胰岛β细胞及胰岛素敏感性退化所形成,无论是口服降糖药和胰岛素都不能阻止其病程发展。本研究证明糖尿病以综合的治疗效果最为理想,使用西药也要配合康教育。从中医宏观的角度运用中药作出整体调节,效果令人鼓舞。中医中药有能力将血糖从波动中稳定下来,加药不是唯一的选择。
Part 1:Theoretical and literature study
Along with the lifting of living standard, changes of living habits, the incident rate of Type 2 diabetes mellitus (T2DM) is soaring, particularly the trend towards youngsters. T2DM is metabolic diseases which seriously undermines the health, Although the pathogenesis is still not well-defined, most of the scholars recognized that it should relate to heredity, immune system and multi-environmental factors. The disease is characterized by insulin resistance and progressiveβ-cell dysfunction.
Insufficient Insulin secretion or dysfunction of insulin will lead to metabolic abnormality of glucose, lipid, protein, water and electrolyte. Persistent high level of blood glucose may provoke Diabetic complications, affecting the heart, brain, kidneys, eyes, feet and nerves. For instance, heart disease, stroke, kidney disease will result to final-stage renal failure; retinopathy, cataract and glaucoma will develop to blindness; the serious lower limbs ulcers will end up to amputation.
Controlling glycemic levels as close to the non-diabetic range as possible has demonstrated to have a powerful beneficial effect on diabetes-specific micro-vascular complications, including retinopathy, nephropathy, and neuropathy. In consequence, it made the effective treatment of hyperglycemia a top priority. Treatment with oral agents has clearly improved glycemic control in patients with T2DM at beginning stage. However, long-term glycemic control with these agents is hardly to achieve. Secondary failure is a consequence of increasing loss ofβ-cell function and insulin sensitivity due to disease progression.
To reinforce the treatment, usually will maximize the doses of the agent, or switch to another oral anti-diabetic agent or the addition of another agent (combination therapy). Current standards of practice recommends the addition of oral agents or insulin to a patient's ongoing therapy. However, many patients ultimately require insulin therapy to maintain glycemic control.
We could not find the terms of "Secondary failure of the oral anti-diabetic regimen " in the Ancient Chinese medicine scripts or treatises. This is the terms appearing in the course of healing T2DM by Western Medicine for the treatment of glycemic control. With the integration of laboratory data, it is used to monitor the level of blood glucose such that we could switch the medicine for the prevention of complications as soon as the control of blood glucose level deteriorates.
Despite the fact that there is no direct reflection of the terms "Diabetes Mellitus" from literatures or treatises of Chinese Medicine, we could categorize this T2DM to the scope of "Xiao Ke". However, for this disease, the majority of Traditional Chinese Medicine practitioners follow the rule of nourishing "Ying" and clearing "internal heat", because they believed "Yin" deficiency is the primary cause while dryness and heat are the secondary ones. Nevertheless, the healing results as per long terms clinical studies indicated that this method in prevention and healing of T2DM is far behind expectation.
This study adopted "the Six Meridian Syndrome from《Treatise of "Shang Han"》" as the fundamental, addressed that the issue of "Three Yin disease of Interior-cold syndrome" is playing a key role in T2DM. The cause of T2DM is due to inferior endowment, or the one with inherent insufficiency. The main argument is, due to the weakness of kidney (the inherent essence) and the deficiency of spleen (supplement after birth), they could not function well to fortify and warm the viscera, it is "Tai Yin" and "Xiao Yin" diseases in kidney and spleen of "Yang" deficiency. In consequence, nutrients is losing which in turn the body is even weaker. Above all, the vital essence become hollowized and at last T2DM will develop under such circumstance. As the vital essence is inadequate, the energy is too weak to sweep the body waste and so the circulation of "Qi" and fluid will be hindered and at last the body is being piled up with coldness and dampness. This is the stage towards T2DM complications. Therefore, in this research, we will formulate another method-reinforce the healthy "Qi", dredge "Qi" mechanism in order to fortify the healthy "Qi" and sweep away the piled up pathogens. This method pinpoints both the cause and the indication of T2DM, has achieved a satisfactory and significant result.
Part 2:Clinical Research
Objective:Based on the information from Chinese Medicine literatures, the support of modern medicine studies and instructions of my academic advisor, Prof. Zhu, this research is to prove the theory that deficiency in "Yang" is the major problem of T2DM, it also comes with blockage of "Qi" mechanism. We will observe the clinical results of using the method of warming and fortifying "Qi", dredging "Qi" mechanism to deal with T2DM in order to testify the correctness and beneficial to future studies.
Methods:This study is a prospective study, with the clinical observation of 60 patients on secondary failure of the oral antidiabetic regime in type 2 diabetes, in No.1 Affiliated Hospital of Guangzhou University of Chinese Medicine during the period from July 2009 to April 2010. The 60 cases those were diagnosed as the six-meridian differentiation in three "Yin" disease and/or with the blockage of "Qi" mechanism, were randomized into three groups, treatment group (add Chinese medicine) n=30, and control group 1 (add Acarbose, Rosiglitazone) n= 15, and control 2 group(add insulin) n= 15 (inpatient and outpatient). All patients received the same education course for diabetes, eating instruction and suggested quantity of physical activities. Before and after 12 weeks treatment period, we have taken the measuring data of FBG,2hPBG, HbAlc and observed clinical symptom score and create a " Vital Qi and pathogens Scale Points " and the six-meridian distribution. We compared the change of data before and after treatment, the data then was processed by SPSS17.0(PASW 17) statistic software. For all statistical test, aP value of less than 0.05 was considered to be statistically significant.
Results:
1. All cases cannot be generalized into (initial diagnosis) single six-meridians diseases, but with combination of syndromes and complications. 13 cases were categorized to three "Yin" diseases with 22%, and 47 cases were categorized to "Yin and Yang" combination diseases with 78%.
2. Distribution of six-meridian diseases were:1) Chief syndrome with "Shao Yin" accountable for 96.66%(58/60cases),2) Chief syndrome with "Shao Yang" accountable for 36.66%(22/60 cases),3) Chief syndrome with " Jue Yin" accountable for 31.66%(19/60 cases),4) Subordinate syndrome with "Tai Yin" accountable for 16.66%(10/60 cases),5) Subordinate syndrome with "Yang Ming" accountable for 13.33%(8/60 cases),6) Accompany syndrome with "Tai Yang" accountable for 5%(3/60 cases). Therefore, the majority of the patients in secondary failure of the oral anti-diabetic regimen with the aetiology is "Yang" deficiency in chief syndrome of "Shao Yin" and accompanied with blockage of "Qi" mechanism, that proves the correctness of our treatment by using the method of warming "Yang" and dredging the "Qi" mechanism.
3. Through the statistical analysis of relevant indicators by comparing that of before and after treatments, the improvement of FBG,2hPBG and HbAlc in each group are statistically significant (P<0.05). However, the above indicators among the groups are insignificant (P>0.05).
4. According to the comparison of syndrome scores, P< 0.01, it showed that there is significant difference of healing effect among groups, and that of the treatment group (with add-on Chinese Medicine) is the most outstanding one. Above all, The total effective rate of the treatment group (add Chinese medicine) is 100% with significant rate of 63.3%; The total effective rate of the control group 1(add Western medicine)is 100% with significant rate of 33.3%; The total effective rate of the control group 2(Insulin)is 60% with significant rate of 6.7%, and no effect 33.3%.
5. For the ease of observation and data handling, we have complied a table of《The quantitative analysis of hollowness of "Qi" and degree of pathogens》, the result showed that if the syndrome is deficiency in vital "Qi", most of them are with deficiency of "Yang", heart and or kidney as well, this indication matches closely with "Shao Yin" syndrome in Six Meridian. On the other hand, if it is in excessive syndrome, most of them are in depressive syndromes, coldness and dampness, and heat bound, which are manifested as blockage of "Qi" mechanism. It proved that deficiency syndrome is mainly in deficiency in "Yang" while excessive syndrome is mainly shown as blockage of "Qi " mechanism which is attributable to stagnation of coldness and dampness.
Conclusions and revelations:
The patients with T2DM are usually deficiency of heredity, and then triggered by bad living habits, random diet, emotional frustration and excessive comfort. Owing to the dysfunction of spleen and kidney, energy to circulate the system is insufficient and lead to stagnation of pathogens (phlegm or stasis) which in turn block the flow of blood and meridians and at last, the disease will then evolve to irreversible stage. To focus on these features of T2DM, we utilize the Treatment of using Chinease medicine to reinforce healthy "qi", in associate with the dredging of "Qi" mechanism, to fortify the organs'functions so as to sweep away the pathogens. Supporting the "Qi" and clearing away pathogens, both superficial characteristics and fundamental causes were taken care and so enhance the healing effect significantly, improve patient's quality of life.
T2DM is a thorny disease which is incurable even now with Modern Medicine Science, hence, the target is to control disease's development and glycemic control is the key. However, we found that the healing effect of prolonged use of oral anti-diabetic agent is not desirable. Secondary failure is a highly likely consequence, even with maximal doses or combination of multi-antidiabetic agents therapies. Patients will eventually rely on insulin therapy to maintain glycemic control, to survive. In spite of using the intensive therapy to restrict the blood glucose, diabetes complications are still inevitable.
Therefore, The add-on of Chinese medicine in the course of treatment can have positive and aggressive effect. According to the systematical reviews of articles and treaties, Chinese medicine performs multi-targeting action and comprehensive adjustment, can lower the level of blood glucose, reduce the side effects from the Western medicine, improve the quality of life and avoid those serious diabetes complications. "Theory of pre-emptive treatment of disease" is our principal character in Chinese medicine. To use Chinese medicine as add on therapy in early stage of T2DM could have good chance to reverse the disease, can minimize the chance of occurring complications in mid-stage, can still lift up a great extent of the quality of life even in final stage of the disease.
T2DM is associated with function declining ofβ-cell and degeneration of insulin sensitivity, neither oral anti-diabetic agents nor insulin are able to stop its deteriorating progression.
With this research, it shows the healing effect with integration of Chinese medicine is encouraging. Chinese medicine will use a holistic view to scan and to regulate the body condition, it indicates that Chinese medicine could stabilize the blood glucose level, provided a much better option but just add up the doses of Western medicine.
引文
[1]David M. Nathan, John B. Buse, Mayer B. Davidson, et al. Medical management of hyperglycemia in type 2 diabetes:A consensus algorithm for the initiation and adjustment of therapy. Diabetes Care,2009,32(1): 1-11.
[2]林兰编着.现代中医糖尿病学,北京：人民卫生出版社,2008年,第一版,222
[3]饶颖译,郑少雄.2型糖尿病高血糖治疗起始和调节的共识：美国糖尿病协会与欧洲糖尿病研究协会联合声明.国际内分泌代谢杂志,2009,29(1)：60-65.
[4]高俭,夏建军等.Ⅱ型糖尿病血糖控制不良原因分析及临床对策.中国疗养医学,2007,16(8)：476-477.
[5]朱春霞.糖尿病患者血糖控制不良与药物相关因素分析.现代医药卫生,2005,21(11)：1386.
[6]施法兴,潘云龙,朱研等.继发性磺脲类失效糖尿病人C肽释放试验和意义.江苏医药,1995,21(9)：587-589.
[7]朱铁虹,尹潍,张卫华等.胰淀素对优降糖刺激大鼠胰岛素分泌作用的影响及其机制.中华内科杂志,1999,38：248-250.
[8]李焱,程桦,锺光恕等.优降糖继发失效患者对萄葡糖及胰升糖素的不同反应.中华内分泌代谢杂志,1998,14(5)：309-311.
[9]陈怡霓等.继发磺脲类药失效病理机制的探讨.中华检验医学杂志,2003,12(26)：768-769.
[10]雷国大.诺和龙与二甲双胍治疗继发失效性糖尿病的疗效观察.中国医师杂志,2006年增刊,321-322.
[11]张金成,王光亚,唐诗玲等.诺和灵N联合二甲双胍治疗2型糖尿病临床观察.实用糖尿病杂志,2005,1(6)：23-24.
[12]张萍,傅一明,陈奇盛等.口服降糖药联合胰岛素治疗2型糖尿病磺酰脲类药.物继发性失效的疗效.中国糖尿病杂志,2009,17(2)：128-130.
[13]张萍,梁慧,蓝海云等.不同方式联合药物治疗2型糖尿病继发性失效的疗效探讨.临床医学,2006,26(1)：15-17.
[14]宁光,王琴琴,李娴等.磺脲类合并二甲双胍继发失效的2型糖尿病加用拜糖 平的疗效观察.中华内分泌代谢杂志,1998,14(2)：100-102.
[15]陈岗梅,陈志辉等.罗格列酮钠片联合治疗血糖控制不良的2型糖尿病疗效观察.广州医药,2006,37(3)：24.
[16]曾兆良.磺脲类合并二甲双胍继发失效的2型糖尿病加用胰岛素疗效观察.广西医科大学学报,1999,16(4)：489.
[17]霍丽梅,陈树春,叶蔚.联合用药治疗2型糖尿病继发失效38例疗效观察.现代中西医结合杂志,2001,10(19)：1830-1831.
[18]徐英影,张文.胰岛素治疗口服降糖药继发性失效的2型糖尿病的疗效观察.上海医药,2002,23(6)：255-256.
[19]何坚,刘式祺,罗广.胰岛素类似物对血糖控制不良2型糖尿病患者的临床观察.实用医学杂志,2007,23(12)：1944.
[20]罗蕾.甘精胰岛素治疗难治性高血糖的临床观察.实用糖尿病杂志,2008,5(2)：16.
[21]俞娉,吴佳丽,李利.格列吡嗪控释片治疗血糖控制不良的2型糖尿病的疗效观察.浙江临床医学,2007,9(5)：679.
[22]郑少雄.解读2009年ADA和EASD关于2型糖尿病高血糖处理的共识.国际内分泌代谢杂志,2009,29(1)：66-67.
[23]章红英.吕仁和诊治消渴病的经验及从师体会.北京中医,1996：6(40)：40
[24]汪栋才等,熊曼琪运用经方治疗糖尿病经验,中国医药学报,2000：15(3)：42
[25]李可著.李可老中医急危重症疑难病经验专辑.山西科学技术出版社,2002,第一版,406
[26]刘力红.思考中医,桂林：广西师范大学出版社,2003年,第2版.459-460
[27]李赛美,朱章志主编.经方研究与临床发微.北京：人民卫生出版社,2008年,第一版.132-140.
[28]赵英英.中医换水疗法浅论,世界中西医结合杂志,2009,4(3)：159-161
[29]赵进喜,王富龙.伤寒论与中医现代临床,北京：人民军医出版社,2006年,第1版.127-143
[30]樊建,夏中和辨治糖尿病经验,中国中医急症,2005,14(3)：248
[31]国家中医药管理局中华本草编委会.中华本草.上海科学技术出版社1999：6389,6264,6666.
[32]中国国家药典委员会.中国药典.一部,2000.1.
[33]郭洁文,潘竞锵,邱光清等.荔枝核增强2型糖尿病胰岛素抵抗大鼠胰岛素敏感性作用.中国新药杂志,2003,12(7)：526-529
[34]白红艳,邹文俊,高小平.葛根对地塞米松诱导的胰岛素抵抗的影响.中国中药杂志,2004,29(4)：356-358
[35]鲁瑾等.黄蓍预防肿瘤坏死因子-a所致胰岛素抵抗的影响.中国中西医结合杂志,1999,19(7)：402.
[36]钱东生.山茱萸乙醇提取液对NIDDN大鼠骨骼肌GLUT4表达影响的实验研究.中国中药杂志,2001,26(12)：859.
[37]扈清云,李艳君,王景涛等.刺五加叶皂苷对Ⅱ型糖尿病大鼠胰岛素分泌影响的形态学研究.黑龙江医药科学,2003,26(6)：21-22
[38]狄灵,厉英倩,张薇.参蓍降糖颗粒对实验性糖尿病大鼠胰岛β细胞、C肽及血浆胰岛素释放的影响.第四军医大学学报,2003,24(19)：1774-1776.
[39]全吉淑,尹学哲,金明.大豆皂苷对α-葡萄糖苷酶抑制作用的研究.中药材,2003,26(9)：654-656
[40]王宁,艾静,杨梅等.血糖安对2型糖尿病大鼠小肠α-葡萄糖苷酶mRNA表达的影响.哈尔滨医科大学学报,2003,37(6)：471-473
[41]陈瑞华,任义锺.针灸治疗非胰岛素依赖型糖尿病75例疗效观察.上海针灸杂志,2007,26(1)：8-9.
[42]廖辉,席萍,陈强等.针刺、艾灸、针加灸胃脘下俞穴治疗糖尿病临床观察.中国针灸,2007,27(7)：482-485.
[43]张慧岭,薄丽亚.逄时针灸治疗糖尿病临床观察.中国针灸,2003,23(1)：13-14.
[44]宋灵仙,王哲慧.从三焦经穴论治糖尿病92例.针灸临床杂志,2005,21(4)：4-6.
[45]曲齐生,杨善军.针刺夹脊穴对2型糖尿病患者胰岛素抵抗疗效观察.中医药信息,2007,24(1)：50-51.
[46]郭庆军,杨树文.中药治疗2型糖尿病磺脲类药物继发性失效18例.辽宁中医药大学学报,2006,8(4)：83.
[47]王小萍.活血养阴补肾健脾法治疗2型糖尿病磺脲类药物继发性失效疗效 观察.实用中医内科杂志,2003,17(6)：504.
[48]于兆秀.参蓍降糖颗粒治疗磺脲类药物继发性失效糖尿病38例疗效分析.工企医刊,2003,16(5)：3-4.
[49]方琦,胡顺金,冷治文.消渴丸对优降糖继发性失效的2型糖尿病的疗效观察及机理探讨.安徽中医临床杂志,2000,11(23)：47-48.
[50]刘兴东.六味地黄汤加味结合二甲双胍治疗糖尿病20例临床观察.医学理论与实践,2006,19(9)：1044-1045.
[51]詹锐文.养阴降糖片联合二甲双胍治疗2型糖尿病120例疗效观察.河北中医,2004,10(2)：748.
[52]陈苹等.益气养阴活血通腑法治疗2型糖尿病磺脲类药继发性失效的临床观察.中国中西医结合杂志,2004,24(7)：585-588.
[53]薛莉等.降糖精治疗磺脲类继发性失效2型糖尿病效果观察.中国交通医学杂志,2005,19(6)：611.
[54]陈忠伟.益气养阴法治疗糖尿病磺脲类药物继发性失效35例.江苏中医药,2002,23(2)：29.
[55]富琳岩等.格列本脲继发性失效对策的临床研究.黑龙江医药科学,2001,24(5)：59.
[56]杨雨田,杨悦娅.中药治疗2型糖尿病口服磺脲类降糖药失效.辽宁中医杂志,2002,29(4)：205-206.
[57]张秀芳.黄连素在磺脲类降糖药继发性失效中的应用.中医药临床杂志,2005,17(6)：549-550.
[58]牟吉荣,徐刚,林云素.中西医结合治疗药物继发性失效2型糖尿病31例.实用中医药杂志,2002,18(2)：24-25.
[59]李乐愚.健脾增敏汤治疗磺脲类药继发性失效2型糖尿病40例临床观察.新中医,2009,41(2)：32-33.
[60]张英来,张军,谢富明.中西医结合治疗继发性磺脲类失效2型糖尿病98例.上海中医药杂志,2004,38(7)：18-19.
[61]简小兵,戴莲仪,王文英等,中西医结合治疗2型糖尿病口服降糖药继发性失效20例临床观察.中国中医药科技,2004,11(5)：302-303.
[2]林兰编着.现代中医糖尿病学,北京：人民卫生出版社,2008年,第一版,222
[3]饶颖译,郑少雄.2型糖尿病高血糖治疗起始和调节的共识：美国糖尿病协会与欧洲糖尿病研究协会联合声明.国际内分泌代谢杂志,2009,29(1)：60-65.
[4]高俭,夏建军等.Ⅱ型糖尿病血糖控制不良原因分析及临床对策.中国疗养医学,2007,16(8)：476-477.
[5]朱春霞.糖尿病患者血糖控制不良与药物相关因素分析.现代医药卫生,2005,21(11)：1386.
[6]施法兴,潘云龙,朱研等.继发性磺脲类失效糖尿病人C肽释放试验和意义.江苏医药,1995,21(9)：587-589.
[7]朱铁虹,尹潍,张卫华等.胰淀素对优降糖刺激大鼠胰岛素分泌作用的影响及其机制.中华内科杂志,1999,38：248-250.
[8]李焱,程桦,锺光恕等.优降糖继发失效患者对萄葡糖及胰升糖素的不同反应.中华内分泌代谢杂志,1998,14(5)：309-311.
[9]陈怡霓等.继发磺脲类药失效病理机制的探讨.中华检验医学杂志,2003,12(26)：768-769.
[10]雷国大.诺和龙与二甲双胍治疗继发失效性糖尿病的疗效观察.中国医师杂志,2006年增刊,321-322.
[11]张金成,王光亚,唐诗玲等.诺和灵N联合二甲双胍治疗2型糖尿病临床观察.实用糖尿病杂志,2005,1(6)：23-24.
[12]张萍,傅一明,陈奇盛等.口服降糖药联合胰岛素治疗2型糖尿病磺酰脲类药.物继发性失效的疗效.中国糖尿病杂志,2009,17(2)：128-130.
[13]张萍,梁慧,蓝海云等.不同方式联合药物治疗2型糖尿病继发性失效的疗效探讨.临床医学,2006,26(1)：15-17.
[14]宁光,王琴琴,李娴等.磺脲类合并二甲双胍继发失效的2型糖尿病加用拜糖 平的疗效观察.中华内分泌代谢杂志,1998,14(2)：100-102.
[15]陈岗梅,陈志辉等.罗格列酮钠片联合治疗血糖控制不良的2型糖尿病疗效观察.广州医药,2006,37(3)：24.
[16]曾兆良.磺脲类合并二甲双胍继发失效的2型糖尿病加用胰岛素疗效观察.广西医科大学学报,1999,16(4)：489.
[17]霍丽梅,陈树春,叶蔚.联合用药治疗2型糖尿病继发失效38例疗效观察.现代中西医结合杂志,2001,10(19)：1830-1831.
[18]徐英影,张文.胰岛素治疗口服降糖药继发性失效的2型糖尿病的疗效观察.上海医药,2002,23(6)：255-256.
[19]何坚,刘式祺,罗广.胰岛素类似物对血糖控制不良2型糖尿病患者的临床观察.实用医学杂志,2007,23(12)：1944.
[20]罗蕾.甘精胰岛素治疗难治性高血糖的临床观察.实用糖尿病杂志,2008,5(2)：16.
[21]俞娉,吴佳丽,李利.格列吡嗪控释片治疗血糖控制不良的2型糖尿病的疗效观察.浙江临床医学,2007,9(5)：679.
[22]郑少雄.解读2009年ADA和EASD关于2型糖尿病高血糖处理的共识.国际内分泌代谢杂志,2009,29(1)：66-67.
[23]章红英.吕仁和诊治消渴病的经验及从师体会.北京中医,1996：6(40)：40
[24]汪栋才等,熊曼琪运用经方治疗糖尿病经验,中国医药学报,2000：15(3)：42
[25]李可著.李可老中医急危重症疑难病经验专辑.山西科学技术出版社,2002,第一版,406
[26]刘力红.思考中医,桂林：广西师范大学出版社,2003年,第2版.459-460
[27]李赛美,朱章志主编.经方研究与临床发微.北京：人民卫生出版社,2008年,第一版.132-140.
[28]赵英英.中医换水疗法浅论,世界中西医结合杂志,2009,4(3)：159-161
[29]赵进喜,王富龙.伤寒论与中医现代临床,北京：人民军医出版社,2006年,第1版.127-143
[30]樊建,夏中和辨治糖尿病经验,中国中医急症,2005,14(3)：248
[31]国家中医药管理局中华本草编委会.中华本草.上海科学技术出版社1999：6389,6264,6666.
[32]中国国家药典委员会.中国药典.一部,2000.1.
[33]郭洁文,潘竞锵,邱光清等.荔枝核增强2型糖尿病胰岛素抵抗大鼠胰岛素敏感性作用.中国新药杂志,2003,12(7)：526-529
[34]白红艳,邹文俊,高小平.葛根对地塞米松诱导的胰岛素抵抗的影响.中国中药杂志,2004,29(4)：356-358
[35]鲁瑾等.黄蓍预防肿瘤坏死因子-a所致胰岛素抵抗的影响.中国中西医结合杂志,1999,19(7)：402.
[36]钱东生.山茱萸乙醇提取液对NIDDN大鼠骨骼肌GLUT4表达影响的实验研究.中国中药杂志,2001,26(12)：859.
[37]扈清云,李艳君,王景涛等.刺五加叶皂苷对Ⅱ型糖尿病大鼠胰岛素分泌影响的形态学研究.黑龙江医药科学,2003,26(6)：21-22
[38]狄灵,厉英倩,张薇.参蓍降糖颗粒对实验性糖尿病大鼠胰岛β细胞、C肽及血浆胰岛素释放的影响.第四军医大学学报,2003,24(19)：1774-1776.
[39]全吉淑,尹学哲,金明.大豆皂苷对α-葡萄糖苷酶抑制作用的研究.中药材,2003,26(9)：654-656
[40]王宁,艾静,杨梅等.血糖安对2型糖尿病大鼠小肠α-葡萄糖苷酶mRNA表达的影响.哈尔滨医科大学学报,2003,37(6)：471-473
[41]陈瑞华,任义锺.针灸治疗非胰岛素依赖型糖尿病75例疗效观察.上海针灸杂志,2007,26(1)：8-9.
[42]廖辉,席萍,陈强等.针刺、艾灸、针加灸胃脘下俞穴治疗糖尿病临床观察.中国针灸,2007,27(7)：482-485.
[43]张慧岭,薄丽亚.逄时针灸治疗糖尿病临床观察.中国针灸,2003,23(1)：13-14.
[44]宋灵仙,王哲慧.从三焦经穴论治糖尿病92例.针灸临床杂志,2005,21(4)：4-6.
[45]曲齐生,杨善军.针刺夹脊穴对2型糖尿病患者胰岛素抵抗疗效观察.中医药信息,2007,24(1)：50-51.
[46]郭庆军,杨树文.中药治疗2型糖尿病磺脲类药物继发性失效18例.辽宁中医药大学学报,2006,8(4)：83.
[47]王小萍.活血养阴补肾健脾法治疗2型糖尿病磺脲类药物继发性失效疗效 观察.实用中医内科杂志,2003,17(6)：504.
[48]于兆秀.参蓍降糖颗粒治疗磺脲类药物继发性失效糖尿病38例疗效分析.工企医刊,2003,16(5)：3-4.
[49]方琦,胡顺金,冷治文.消渴丸对优降糖继发性失效的2型糖尿病的疗效观察及机理探讨.安徽中医临床杂志,2000,11(23)：47-48.
[50]刘兴东.六味地黄汤加味结合二甲双胍治疗糖尿病20例临床观察.医学理论与实践,2006,19(9)：1044-1045.
[51]詹锐文.养阴降糖片联合二甲双胍治疗2型糖尿病120例疗效观察.河北中医,2004,10(2)：748.
[52]陈苹等.益气养阴活血通腑法治疗2型糖尿病磺脲类药继发性失效的临床观察.中国中西医结合杂志,2004,24(7)：585-588.
[53]薛莉等.降糖精治疗磺脲类继发性失效2型糖尿病效果观察.中国交通医学杂志,2005,19(6)：611.
[54]陈忠伟.益气养阴法治疗糖尿病磺脲类药物继发性失效35例.江苏中医药,2002,23(2)：29.
[55]富琳岩等.格列本脲继发性失效对策的临床研究.黑龙江医药科学,2001,24(5)：59.
[56]杨雨田,杨悦娅.中药治疗2型糖尿病口服磺脲类降糖药失效.辽宁中医杂志,2002,29(4)：205-206.
[57]张秀芳.黄连素在磺脲类降糖药继发性失效中的应用.中医药临床杂志,2005,17(6)：549-550.
[58]牟吉荣,徐刚,林云素.中西医结合治疗药物继发性失效2型糖尿病31例.实用中医药杂志,2002,18(2)：24-25.
[59]李乐愚.健脾增敏汤治疗磺脲类药继发性失效2型糖尿病40例临床观察.新中医,2009,41(2)：32-33.
[60]张英来,张军,谢富明.中西医结合治疗继发性磺脲类失效2型糖尿病98例.上海中医药杂志,2004,38(7)：18-19.
[61]简小兵,戴莲仪,王文英等,中西医结合治疗2型糖尿病口服降糖药继发性失效20例临床观察.中国中医药科技,2004,11(5)：302-303.