Several Common Complications from Diabetes May be Eased with β0ToxinA®

 Such auto-immune reaction may be due to infection with a specific virus or bacteria, or exposure to food-borne chemical toxins. The most common form of the disease – 90-95% of cases – is, however, type 2 diabetes (typically in overweight, older adults), characterised by a gradual loss of insulin resistance. In response to this more insulin may be produced, and this over-production exhausts the insulin-manufacturing cells in the pancreas. Alternatively, there may be simply insufficient insulin available, or what is available may be abnormal and therefore not able to work properly.
This condition has reached epidemic proportions worldwide, and often goes undiagnosed, because of its frequent lack of clear symptoms, at least in the pre-diabetes phase.

As the disease progresses, some potential warning signs include: excessive thirst, frequent urination, unexplained weight loss, dry, itchy skin, blurry eyesight. Some lifestyle changes, such as eating a balanced diet, lowering one's cholesterol, limiting carbohydrate and sugar intake, exercising, and maintaining a healthy weight may be effective means in battling diabetes. When uncontrolled, this condition increases a person's risk for retinopathy, non-healing wounds, sexual problems, and kidney failure. Diabetics also double their risk of cardiovascular death and stroke.

Diabetes cannot be cured, but it can be controlled. In the last ten years treatment options have greatly increased from the traditional insulin injections, and sulfonylureas to several classes of drugs being developed to normalise blood glucose, lipids, inflammatory factors, and blood pressure, to treat peripheral neuropathy, and other complications. Insulin can now be administered by inhaler, or oral aerosol. A continuous blood glucose monitor has been developed, incretins have recently become available in some countries and prevention has taken a giant leap with the discovery of the geneINGAP, a protein responsible for regenerating islet cells.

In at least two of the most common complications of diabetes botulinum toxin type A has been proven effective:

  • Gastroparesis

Gastroparesis is an often chronic disorder of delayed gastric emptying of which up to 50% of type 1 diabetic subjects suffer, with symptoms including nausea, vomiting, spasms of the stomach wall, early satiety, gastroesophageal reflux, anorexia, and weight loss. It may be caused by elevated pyloric pressures or damage to the vagus nerve, which controls the movement of food through the digestive tract. The latter, in turn, can occur if blood glucose levels remain high over a long period of time. Gastroparesis can worsen diabetes by making blood glucose levels erratic and more difficult to control. Medications used are promotility agents, like Domperidone and Metoclopramide, antiemetics, or Erythromycin. A battery-operated gastric neurostimulator has been developed that is surgically implanted and emits mild electrical pulses that help control nausea and vomiting in patients who are resistant to other treatments.

Since Botulinum toxin A inhibits the release of acetylcholine and produces transient paralysis when injected into smooth muscle, a few studies have examined its effect on the stomach. Indeed not only in an open-label trial on eight subjects (Brian E. Lacy et al., 2004) but in a 63-subject study (Bromer MQ et al., 2005) intrapyloric injection of botulinum toxin A have successfully improved symptoms in idiopathic and diabetic gastroparesis refractory to medical treatment by decreasing the prolonged contractions of the muscle between the stomach and the small intestine, and therefore altering gastric emptying scan time, and/or changing weight and insulin use.
In the small trial the subjects' pyloruses were injected with 200 units of botulinum toxin during upper endoscopy. Mean symptom scores declined from 27 to 12.1 in the 12-week follow-up period. While in Bromer MQ et a., 2005 large study 43% of participants had a response to the treatment that lasted a mean of approximately 5 months. Male gender was associated with a much higher response to this therapy; however, durability of response was unrelated to gender.

Figure 1. Organs affected by gastroparesis.


  • Foot ulcers

In addition to a loss of pain, that may make a small sore, cut or blister go unnoticed, diabetics often have impaired wound healing. Thus, if the sore becomes infected, it may lead to the development of a foot ulcer. A study in the Journal of the American Medical Association estimates the lifetime risk of a foot ulcer (mostly on the sole) for a patient with diabetes is about 15%. These ulcers can take a very long time to heal and researchers report a very high recurrence rate after healing: 60 to 80% within the first month , maybe because the affected skin is not tough enough to tolerate the pressures of walking, 28% at 12 months, and 100 % at 40 months. Any ulcer may then develop into a limb-threatening infection. Diabetics are indeed 10 to 30 times more likely than the general population to require a foot amputation. Each year, foot ulcers lead to more than 82,000 amputations, in most cases in type 2 diabetes sufferers.
Researchers at Washington University School of Medicine in St. Louis are carrying out a study on diabetic volunteers with recurrent foot ulcers to determine whether botulinum toxin injections may be effective. During five study visits over a two-year period, volunteers will undergo wound care assessment, and evaluation of balance, muscle strength, sensory skills and heel bone density. During one study visit either 200 or 300 units of BTA will be injected into six different sites in their calf muscle. In past studies, patients who underwent surgery to lengthen the Achilles tendon reduced their risk of ulcer recurrence. Lengthening the Achilles tendon weakened the calf muscle and diminished the pressure on the ball of the foot, where ulcers occur. Botulinum toxin injections — which have been shown to weaken calf muscles in other studies — should have the same effect. The toxin will weaken the muscle that pushes the foot forward while walking, so that patients cannot develop a high pressure under their foot. The foot will then be placed in a cast (which is the standard treatment) to allow the ulcer time to heal. The effects of botulinum eventually wear off, and when the calf muscle returns to full strength in six to eight weeks, researchers hope the area will be healed enough so that ulceration doesn't recur. The study is a preliminary investigation, yet, if results are promising, larger studies will be performed and β0ToxinA® could become a standard treatment for diabetic foot wounds.


And that may still not be all β0ToxinA® has in store for diabetic sufferers. Another facet of peripheral neuropathy is numbness, tingling, or pain in the affected limbs, usually feet, symptoms that are generally treated with medications such as anti-convulsants, anti-depressants, or analgesics, with varying results. According to a study presented at an annual conference of the American Academy of Neurology, animals with diabetic neuropathy who were injected with botulinum toxin A, became less sensitive to pain for up to 15 days. In June, a single-centre, randomized, double-blinded, placebo control 1-year long study has been started at the Taipei Medical University Hospital. 15 randomly selected type-2 diabetic volunteers with neuropathic foot pain out of 30 are receiving intra-dermal botulinum injection after topical anaesthesia, at a dose of 0.5-1U/cm2 for a total of 50 U/foot. A follow-up visit and assessment is being performed at 1, 4, 8, 12 weeks following treatment. A cross-over of injection in the BTA and placebo group will be taken at the 12th week and then the assessments will be repeated at 1, 4, 8, and 12 weeks. Further research is needed, but one thing is already clear: β0ToxinA® is still able to surprise us.


  • Ben-Youssef R, Baron PW, Franco E, Walter MH, Lewis T, Ojogho O., Intrapyloric injection of botulinum toxin a for the treatment of persistent gastroparesis following successful pancreas transplantation. Am J Transplant. 2006 Jan;6(1):214-8.
  • Bromer MQ, Friedenberg F, Miller LS, Fisher RS, Swartz K, Parkman HP, Endoscopic pyloric injection of botulinum toxin A for the treatment of refractory gastroparesis. Gastrointest Endosc. 2005 Jun;61(7):833-9.
  • Campbell R. Keith, Baker Daniel, New and emerging diabetes medications and devices DOC News. 2006 June 1, Volume 3 Number 6 p. 4.
  • Duke Williams Diane, Study evaluates Botox injections for treating diabetic foot ulcers, Washington University in St. Louis News and Information,
  • King H, Rewers M, WHO, and Ad Hoc Diabetes Reporting Group: Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults. Diabetes Care 1993 16:157–177.
  • Lacy Brian E., Crowell Michael D., Schettler-Duncan Ann, Mathis Carole, Pasricha Pankaj J., The Treatment of Diabetic Gastroparesis With Botulinum Toxin Injection of the Pylorus Diabetes Care 2004 27:2341-2347.
  • Parmet Sharon, Glass Tiffany J., Glass Richard M. Diabetic Foot Ulcers JAMA. 2005; 293:260.

To learn more about this condition, you can visit the websites of the American Diabetes Association and the National Institute of Diabetes and Digestive and Kidney Diseases, the primary NIH organization for research on Diabetes

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