Diabetic Peripheral Neuropathy

Introduction

The worldwide incidence of diabetes is on the rise and expected to increase to 629 million people (6% globally) by 2045 (Wild 2004, IDF 2017). Diabetic peripheral neuropathy (DPN) is a common, if not the most common, complication of diabetes: approximately 66% of type 1 diabetics and 59% of type 2 diabetics have objective evidence of DPN (Dyck 1993). Data from the National Health and Nutrition Examination Survey (NHANES) reported an overall prevalence of peripheral neuropathy around 15% with that number rising to 62% in people with diabetes (Gregg 2004).

Fortunately, painful neuropathy seems to affect only about 25% of patients with DM (Shillo 2019). Painful DPN is characterized as burning, achy, electric, or sharp pains while painless DPN produces numbness and tingling sensations without pain. The differences in what causes some patients to develop pain while others, with similar levels of neuropathy, to not have pain has yet to be delineated fully (Shillo 2019, Head 2006).

Pathogenesis of Diabetic Peripheral Neuropathy from a Biomedical Perspective

Small nerve fibers are sensory fibers that contribute to peripheral pain sensation through pin-pricks (painful touch) and temperature sensation. Large nerve fibers are sensory fibers that supply sensation for light touch, vibration, and proprioception (position of the body in space). While most DPN seems to be a combination of neuropathy involving both types of fibers, painful DPN seems to be more strongly associated with small fiber dysfunction (Shillo 2019). Gender, vascular alterations, genetics, beta endorphin levels in the CSF, and other factors play a role in determining whether a diabetic patient will develop painful or painless DPN (Tsigos 1995, Shillo 2019).

Diabetes is characterized by chronically high blood sugar levels; free glucose binds to proteins, fats, and nucleic acids, forming advanced glycation end products (AGEs) (Head 2006, Gkogkolou 2012). AGEs undergo further oxidative breakdown, particularly in the presence of reactive oxygen species (ROS) (van Dam 2002), and this leads to a wide variety of deleterious effects on the biochemical milieu at large and on proinflammatory pathways (including NFkB) (Gkogkolou 2012).

Endoplasmic reticulum stress-induced apoptosis is another important result of oxidative stress and leads to protein folding errors, accumulation of dysfunctional proteins, and calcium disruption (Pan 2019). As these proteins build up inside the cell, they also exert osmotic effects and generate further oxidative stress.

While glucose entry into muscle tissue is controlled by the GLUT4 transporter, glucose is able to move passively into nerve cells. The enzyme aldose reductase transforms glucose into sorbitol which then can be transformed into fructose by sorbitol dehydrogenase: these polyols are not able to move freely back out of the cells, creating an osmotic gradient that results in neuronal swelling (Head 2006). Fructose further leads to production of more AGEs and oxidative stress. Sorbitol and fructose diminish Na/K-ATPase activity, leading to decreased polarization of nerve cells, which impedes their ability to fire (Raccah 1998).

Nitric oxide also plays a role in Na/K-ATPase activity and neuronal nitric oxide synthase (nNOS) has been shown to be disrupted in diabetes (Head 2006). Nerve blood flow is also affected by nNOS, in part accounting for DPN as well as erectile dysfunction in diabetic men (Head 2006).

Pathogenesis of Diabetic Peripheral Neuropathy from Traditional East Asian Medical Perspective

Wasting-thirsting disorder, or xiao ke zheng, is caused by excessive drinking or eating and is characterized by excessive production of urine (polyuria), thirst, and numbness/peripheral nerve pain (Fang 2017, Ni 1995). Over time, xiao ke depletes qi and yin, which leads to xue stasis and qi stagnation. The resultant blockage of the channels results in the symptoms of neuropathy: xue stasis leading to more sharp pain, and qi stagnation leading to numbness and tingling (Ni 1995).

The primary organs involved in this pathology are the liver, spleen, and kidney. Treatment principles involve strengthening the spleen, transforming phlegm, nourishing liver and kidney, promoting circulation of xue and qi  dredging the channels), and harmonizing the zangfu (Tong 2010, Cheng 2010).

Utility of Acupuncture in Diabetic Peripheral Neuropathy

Because DPN leads to increased risk of ulceration, disability, infection, and amputation, it is of great interest to find inexpensive, widely accessible, effective modalities of treatment for this condition (NIH 1998). Acupuncture is one such modality that has been repeatedly demonstrated to be effective in treatment of DPN (Chen 2013, Nash 2019, NIH 1998). It has further been shown to improve some of the hallmarks of DM: insulin resistance (Martinez 2016), fasting blood glucose (Tjipto 2014), and oral glucose tolerance (Tjipto 2014).

The mechanism of action of acupuncture on the attenuation and reversal of DPN has yet to be fully elucidated, however, reduction in nerve cell apoptosis and reduced endoplasmic reticulum stress as evaluated by cellular markers of apoptosis may be causal factors (Pan 2019).

Stylistic differences in acupuncture point selection have yielded similar results in efficacy when comparing TCM to Japanese style (Ahn 2007) or when evaluating a protocolized neuroanatomical/structural approach (Dimitrova 2017). The “best points” to use in the treatment of DPN, therefore, have yet to be determined.

Common points are selected because of their broad utility. While the literature was not reviewed comprehensively by this author, common point selection principles included those that followed the treatment principles above. These points include ST-36, SP-6, back shu points (for LR, SP,KI), pi gen, ST-40, LI-4, 10 and 11, SP-9, and TB-5 (Dimitrova 2018, Pan 2019, Tong 2010, Dimitrova 2017, Nash 2019, Chen 2013, Ahn 2007).

Local points that follow nervous pathways are often chosen because they open the channels and treat local disturbances: these include ba feng and ba xie, LR-3, KI-3 and 7, GB-34 and 41, ST-41, 43 and 44, SP-3 and 8, and BL-58 and 60 (Dimitrova 2018, Pan 2019, Tong 2010, Dimitrova 2017, Nash 2019, Chen 2013, Ahn 2007).

Utility of Moxibustion in Diabetic Peripheral Neuropathy

Moxibustion is another commonly used and inexpensive treatment modality for DPN. It has been shown to improve fasting blood glucose levels, glycosylated hematoglobin, nitric oxide and plasma endothelin levels (Zhongguo 2008). Again, the mechanism of action is unclear but an interesting study evaluating moxibustion’s effects on markers of neuroinflammation (Nrf2, NFkB, IL1B, IL6, and IL8) shows promise (Li 2019).

Points selected in the two studies above included ST-36, BL-2, 23 and 26, KI-1, and yi shu (Zhongguo 2008 and Li 2019).

Discussion

In my clinical experience, the points described in the literature cited above are reasonable, but I was surprised that none of the citations included wei guan xia shu. WGXS generates body fluids and raises the pure qi. It further controls the “lower stomach,” which can be considered to mean the pancreatic and bilious contributions to digestion. More specifically, the first stomach (anatomic stomach) supplies the pepsin and acid required to activate all of the digestive enzymes supplied by the distal organs of the liver and  pancreas as the chyme enters the duodenum. The anatomic
overlay of the posterior lobe of the liver and medial pancreas, dermatome mapping, and traditional East Asian medical indications for this point all indicate its powerful capacity to regulate the pancreas. I commonly incorporate this point as a root treatment component for DPN or retain needles there for a back treatment.

In patients who present with more of a deficiency pattern, I often use the stomach channel as a yang qi primer for the SP by incorporating ST-22, ST-23 or 24. These points strengthen the SP and harmonize ST. Specifically, ST-22 further regulates water metabolism (helpful in polyuria or fluid retention); ST-23 transforms phlegm (helpful in gastroparesis); and ST-24 transforms phlegm and stops vomiting (helpful in gastroparesis). Once the qi is flowing, I will remove those needles and gently stimulate the ST qi line (between ST-39 and 41 along the lateral tibia in the tendon of the anterior tibialis muscle) where I will retain a needle. In severely deficient patients, half rice-grain sized direct moxa works well  on these abdominal points: 3-5 cones.

Conclusion

The incidence and prevalence of diabetes continues to rise, as does the corresponding level of diabetic peripheral neuropathy. While there is little that can be done to attenuate or reverse the pathological process of DPN, from a biomedical and a traditional East Asian medical perspective, acupuncture is an effective treatment for DPN. Moxibustion, while less explicated, appears to also have a strong effect. Points that support the qi and yin, that open the meridians to release the qi stagnation and xue stasis, and that offer root treatment support to the SP, LV, and KI are indicated and effective.
References

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