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Diabetic neuropathy

Diabetic neuropathies are neuropathic disorders that are associated with diabetes mellitus. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; a painful polyneuropathy; autonomic neuropathy; and thoracoabdominal neuropathy. more...

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Diabetes is the leading cause of neuropathy in developed countries, and neuropathy is the most common complication and greatest source of morbidity and mortality in diabetes patients. It is estimated that the prevalence of neuropathy in diabetes patients is approximately 20%. Diabetic neuropathy is implicated in 50-75% of nontraumatic amputations.

The main risk factor for diabetic neuropathy is hyperglycemia. In the DCCT (Diabetes Control and Complications Trial, 1995) study, the annual incidence of neuropathy was 2% per year, but dropped to 0.56% with intensive treatment of Type 1 diabetics. The progression of neuropathy is dependent on the degree of glycemic control in both Type 1 and Type 2 diabetes. Duration of diabetes, age, cigarette smoking, hypertension, height and hyperlipidemia are also risk factors for diabetic neuropathy.

Pathology and pathogenesis

There are four factor involved in the development of diabetic neuropathy:

  1. Microvascular disease,
  2. Advanced glycated end products,
  3. Protein kinase C, and the
  4. Polyol pathway.

Microvascular disease

Vascular and neural diseases are closely related and intertwined. Blood vessels depend on normal nerve function, and nerves depend on adequate blood flow. The first pathological change in the microvasculature is vasoconstriction. As the disease progresses, neuronal dysfunction correlates closely with the development of vascular abnormalities, such as capillary basement membrane thickening and endothelial hyperplasia, which contribute to diminished oxygen tension and hypoxia. Neuronal ischemia is a well-established characteristic of diabetic neuropathy. Vasodilator agents (e.g., angiotensin-converting-enzyme inhibitors, α1-antagonists) can lead to substantial improvements in neuronal blood flow, with corresponding improvements in nerve conduction velocities. Thus, microvascular dysfunction occurs early in diabetes, parallels the progression of neural dysfunction, and may be sufficient to support the severity of structural, functional, and clinical changes observed in diabetic neuropathy.

Advanced glycated end products

Elevated intracellular levels of glucose cause a non-enzymatic covalent bonding with proteins, which alters their structure and destroys their function. Certain of these glycated proteins are implicated in the pathology of diabetic neuropathy and other long term complications of diabetes.

Protein kinase C (PKC)

PKC is implicated in the pathology of diabetic neuropathy. Increased levels of glucose cause an increase in intracellular diacylglycerol, which activates PKC. PKC inhibitors in animal models will increase nerve conduction velocity by increasing neuronal blood flow.


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Diabetic peripheral neuropathy - Chinese Medicine Update
From Townsend Letter for Doctors and Patients, 8/1/03 by Bob Flaws

Keywords: Chinese medicine, Chinese herbal medicine, diabetic peripheral neuropathy, Er Miao San (Two Wonders Powder)

In the last couple of years, numerous studies have been published in China on the Chinese medical treatment of diabetic peripheral neuropathy. In general, these studies suggest that diabetic peripheral neuropathy is due to a variable combination of 1) damp heat pouring downward causing 2) obstruction to the flow of qi and blood and 3) a qi and yin vacuity failing to nourish and moisten the sinews and vessels. This then results in burning pain, tingling, numbness, insensitivity, lack of strength, and muscular atrophy mostly in the lower extremities and mostly which is worse at night. According to Chinese medical theory, extremity pain is categorized as impediment condition (bi zheng), while numbness, insensitivity, and muscular atrophy fall under the category of wilting condition (wei zheng). Therefore, this condition is usually a combination of both impediment and wilting, and one of the famous formulas of Chinese medicine which treats both impediment and wilting when these conditions are due to or associated with damp heat pouring downward, is Er Miao San (Two Wonders Powder).

Er Miao San was created by the famous Yuan dynasty Chinese doctor, Zhu Dan-xi, and is found in his Dan Xi Xin Fa (Dan-xi's Heart [or Secret] Methods). In its standard form, it is comprised of two ingredients: Cortex Phellodendri (Huang Bai) and Rhizoma Atractylodis (Cang Zhu). Huang Bai is a bitter, cold medicinal which clears hest and dries dampness, while Cang Zhu is a bitter, warm medicinal which also aromatically transforms and dries dampness. In addition, Cang Zhu is known to relieve limb pain when that limb pain is associated with dampness. This simple, two-medicinal formula clears heat and dries dampness especially in the lower half of the body. When modified with added ingredients, it is used to treat a wide variety of rheumatological, dermatological, and gynecological complaints associated with damp heat below. In issue #1, 2003 of An Hui Zhong Yi Lin Chuang Za Zhi (The Clinical Journal of Anhui Chinese Medicine), Xie Min-hua and Wu Hong of Guangdong published an article titled, "The Treatment of 32 Cases of Diabetic Peripheral Neuropathy with Jia Wei Er Miao San (Added Flavors Two Wonders Powder) Combined with Externally Applied Chinese Medicinals." This article appeared on pages 14-15 of that journal, and, since it used such a famous standard Chinese medicinal formula, I believe it bears reporting below.

Cohort description

The 32 patients described in this article were a mixture of in- and out-patients from the authors' two hospitals in Huizhou, Guangdong. All these patients were suffering from type 2 diabetes mellitus according to World Health Organization (WHO) diagnostic criteria. Among these patients, there were 19 males and 13 females aged 43-61 years, with an average age of 49.5 years. The duration of peripheral neuropathy of these patients ranged from 15 days to 3.5 years, with an average disease duration of two years. Patients who had any other neurological disease were excluded from this study. The main clinical signs and symptoms of these patients were aching and pain in the tips of the extremities in 28 cases, decreased sensitivity in 25 cases, numbness and tingling in 22 cases, and lack of strength in the extremities in 21 cases.

Treatment method

During this study, all the patients continued on their normal hypoglycemic drugs. However, they all stopped using vitamin B or any other medications for their peripheral neuropathy. In addition, they were orally administered one packet of the following Chinese medicinals per day after being decocted in water: Cortex Phellodendri (Huang Bai), 15g, Rhizoma Atractylodis (Cang Zhu), 15g, Semen Coicis Lachryma-jobi (Yi Yi Ren), 20g, Radix Ligustici Wallichii (Chuan Xiong), 15g, Radix Salviae Miltiorrhizae (Dan Shen), 15g, Sclerotium Poriae Cocos (Fu Ling), 15g, Radix Rubrus Paeoniae Lactifiorae (Chi Shao), 15g, Rhizoma Atractylodis Macrocephalae (Bai Zhu), 15g, and Lumbricus (Di Long), 15g. If there was lack of strength in the extremities, 20 grams of Radix Astragali Membranacei (Huang Qi), 15 grams of Radix Pseudostellariae Heterophyllae (Tai Zi Shen), and 10 grams of Pericarpium Citri Reticulatae (Chen Pi) were added. If aching and pain were severe, 12 grams of Semen Pruni Persicae (Tao Ren) and 15 grams of Fructus Chaenomelis Lagenariae (Mu Gua) were added. If numbness of the extremities was severe, 10 grams of Eupolyphaga Seu Ophistoplatia (Di Bie Chong), 15 grams of Squama Manitis Pentadactylis (Chuan Shan Jia), and 10 grams of Agkistrodon Seu Bungarus (Bai Hua She) were added.

In addition to the orally administered Chinese medicinals, equal amounts of the following medicinals were ground into fine powder and mixed together: Rhizoma Corydalis Yanhusuo (Yan Hu Suo), Ramulus Mori Albi (Sang Zhi), Herba Impatientis Balsaminae Seu Speranskiae Tuberculatae (Tou Gu Cao), and Semen Pruni Persicae (Tao Ren). The resulting powder was mixed with ginger juice to form a paste. Each night, some of this paste was applied bilaterally to Yong Quan (Ki 1) for two hours before going to bed. Yong Quan is an acupuncture point in the center of the sole of the foot. This combination of internally administered and externally applied Chinese medicinals was continued for three weeks before assessing its efficacy.

Treatment outcomes

Prior to the commencement of therapy, each patient was asked to rate four clinical parameters of their peripheral neuropathy: pain in the extremities, decrease in sensitivity, numbness and tingling, and lack of strength in the extremities. Responses were categorized into none, slight, moderate, and heavy or severe. After treatment, if any of these clinical symptoms improved by one degree or stage or more, the treatment was considered to have had an effect. If any symptom got worse by one or more degree or stage, this was considered an adverse reaction. Anything else was considered no effect. Based on these criteria, of the 28 cases who experienced extremity aching and pain, 25 got some effect, two got no effect, and one had an adverse reaction. Therefore, in terms of extremity aching and pain, the total amelioration rate was reported as 89.3%. In terms of decrease in skin sensitivity, out of the 25 patients who reported this symptom, 21 got some effect and four got no effect for a total amelioration rate of 84.0%. Of the 22 patients with numbness and tingling, 18 got some effect, three got no effect, and one had an adverse reaction, for a total amelioration rate of 81.8%. And finally, in terms of lack of strength in the extremities, of the 21 patients who reported this, 17 got some effect and four got no effect, for a total amelioration rate of 81.0%. In addition, mean nerve conduction tests from before to after treatment were markedly faster. However, there was no marked mean statistical change in either fasting or two hour postprandial blood glucose levels from before to after treatment.


According to Drs. Xie and Wu, the disease mechanisms of this condition are impediment and obstruction of the channels and vessels so that the qi and blood do not flow easily and smoothly. Since the blood vessels are not harmonious, there is tingling and numbness of the extremities and aching and pain. (This based on the Chinese medical statement of fact: "If there is pain, there is no free flow; if there is free flow, there is no pain.") If dampness is retained in the muscles and flesh, it obstructs and causes stagnation in the joints. This dampness obstructs the free flow of yang qi which backs up and becomes depressed, transforming into heat. This dampness and heat combine to form damp heat which blocks and obstructs the vessels and joints. This results in the qi and blood becoming depressed, stagnant, and not freely flowing. Therefore, Drs. Xie and Wu think that the appropriate treatment principles for this condition are to clear heat and eliminate dampness, nourish and quicken the blood, free the flow of the network vessels and stop pain. Consequently, within this formula, Huang Bai and Cang Zhu clear heat and dry dampness. Fu Ling and Yi Yi Ren fortify the spleen and percolate dampness. Dan Shen, Chi Shao, and Di Long nourish and quicken the blood, transform stasis and free the flow of the network vessels. Bai Zhu and Chuan Xiong supplement and boost the qi and blood. When the qi moves, the blood moves; and when there is free flow, there is no pain. The Chinese medicinals applied to Yong Quan strengthen the promotion of the flow of qi and blood through the channels and vessels of the lower extremities and thus help the internally administered medicinals do their job. In fact, it is my own clinical experience that the simultaneous external treatment of peripheral neuropathy, whether by herbal soaks, compresses, poultices, or acupuncture-moxibustion, definitely enhances the outcomes of internally administered Chinese medicinals. Since this external application uses a Chinese herbal paste applied for two hours before bed, it is relatively cheap, easy, and not very messy.

Bob Flaws, Dipl. Ac & CH FNAAOM, FRCHM

c/o Blue Poppy Press * 5441 Western Ave. #2 * Boulder, Colorado 80301 USA

COPYRIGHT 2003 The Townsend Letter Group
COPYRIGHT 2003 Gale Group

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