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January 2003: Volume 45, Number 1

Diabetes--A Waterborne Disease?
by Dr. Kelly A. Reynolds, MSPH, Ph.D.

Recently, researchers have honed in on possible causes of type 1 (juvenile-onset) diabetes. Strong associations have surfaced relating drinking water acidity and exposure to enteroviruses to the disease. This new information reinforces the fact that waterborne disease isn't just about diarrhea anymore.

What is diabetes?
Approximately 17 million people in the United States (6.9 percent of the population) have diabetes; however, a third are unaware they even have the disease. The majority is diagnosed with type 2 diabetes (90-95 percent) while greater than 850,000 (possibly up to 1.7 million) Americans suffer from type 1.1

Diabetes is a metabolic disorder. Most of the food we eat is broken down to basic components including glucose that's absorbed into the blood stream and utilized as energy for cellular functions. Ideally, in the human pancreas, cells produce a hormone called insulin that facilitates the movement of glucose into the cells. This allows the body to convert blood sugar to energy. If these insulin-producing cells are absent or not functioning properly, the resultant condition is type 1 diabetes. Type 1 diabetes is frequently referred to as juvenile diabetes and commonly diagnosed in individuals before the age of 30, but it can occur at any age.

Conversely, type 2 diabetes is typically diagnosed in patients over the age of 40, but an increasing number of children are being diagnosed with a suspected link to childhood obesity. Type 2 diabetes is often controlled with diet and exercise, but may require supplemental medications. Another type of diabetes is gestational diabetes, affecting about 4 percent (135,000 cases each year) of all pregnant women in the United States. In gestational diabetes, placental hormones are thought to block the action of the mother’s insulin, causing a build-up of glucose in the blood. If left uncontrolled, diabetes can cause short-term and long-term health effects in the baby and should be promptly treated. Gestational diabetes usually subsides in the mother following birth.

Symptoms of diabetes
Diabetes is usually diagnosed using medical tests to monitor blood sugar levels in the blood. Sugar content is also detectable in urine. The symptoms of diabetes are somewhat vague and may be confused with a variety of other conditions. Symptoms include excessive thirst, frequent urination, hunger accompanied with weight loss, changes in sight, fatigue, vomiting or nausea, and sudden irritability.

Luckily, diabetes is a manageable disease and those afflicted are able to lead normal, healthy lives provided they follow a strict regimen of daily blood sugar testing and insulin injections. Appropriate levels of insulin must be maintained through a balance of injections, exercise and diet control, including monitoring the intake of sugars and carbohydrates. Blood sugar testing involves daily collection a blood sample, usually from a finger prick, and applying the sample to special glucose indicator paper strips. Electronic blood sugar monitors are also available and reduce errors in visual interpretation of results.

Diabetics are at increased risk of heart disease, strokes, and kidney, eye and nervous system disorders. Nerve damage common to diabetics result in increased injury and longer healing times for skin wounds. Skin and foot problems are also common and great care should be taken to monitor and prevent injury and progressive ulceration. Studies have shown that through diligent maintenance of blood glucose levels, most complications can be dramatically reduced. Beyond the health impacts of diabetes, the annual economic cost in 1997 was estimated at $98 billion in the United States alone.1

Cause of Type 1 diabetes
In general, the most common cause of type 1 diabetes is reported to be one’s own immune system. Designed to protect the resident host, the immune system can turn on the body, falsely perceiving the presence of a foreign substance and attacking the substance. In the case of type 1 diabetes, the immune system perceives insulin-producing cells of the pancreas as foreign and destroys them. This condition is often referred to as immune-mediated diabetes.

In addition, there appears to be a hereditary link to diabetes.2 A family history of the disease may indicate a higher prevalence in subsequent offspring, although many diabetics have no other affected family members and vice versa. The third most common classification is idiopathic type 1 diabetes, or diabetes due to unknown causes.

In the last year, scientists have made great progress in establishing a link to infectious viruses and diabetes. Although suspected for decades, direct evidence was lacking. Today, microbial research has directly targeted coxsackievirus B4 (CVB4), a common cause of viral infections in children.3,4,5 Coxsackieviruses are a member of the enterovirus group (along with polio). The many strains of coxsackievirus produce a variety of symptoms ranging from rashes to flu-like illness to eye infections.

CVB4 has been isolated from the pancreas of a child dying from type 1 diabetes. Further research on the virus strain showed that CVB4 induced a more pronounced immune response in persons diagnosed with type 1 diabetes. This outcome suggests that those with type 1 diabetes have been recently, or perhaps repeatedly, exposed to CVB4.3 Other research supports this theory, finding that insulin-producing cells are highly susceptible to coxsackievirus infection.4

These findings raise hope that a vaccine may be developed to prevent diabetes. In addition, type 1 diabetes has an apparent seasonal pattern, suggesting an infectious source. Children born between March and June are more likely to develop diabetes later in life. Researchers suspect that prenatal infections may play a role.5

Some researchers speculate that viruses somehow change the structure of pancreatic cells, causing an autoimmune attack against these altered and now “foreign” cells. Others theorize that pancreatic proteins are similar to viral proteins, particularly those of the coxsackievirus group, causing immune attack cells to destroy non-viral cells. Although not proven, still others believe that occasionally the introduction of certain foods (i.e., wheat, soy, cow’s milk) or food preservatives (i.e., nitrosamines) may be a factor, particularly when introduced in the first few months of life. Tracking specific causes of diabetes is most likely complicated by the contribution of numerous factors.

A waterborne route?
If indeed coxsackieviruses cause a large portion of diabetes cases, what then is the route of exposure to these viruses? Coxsackieviruses are spread by the fecal-oral route or person-to-person via respiratory droplets. They are resistant to detergents, alcohol and wide pH ranges (pH 3-10) but are sensitive to heat (>50oC), ultraviolet (UV) light and free chlorine residuals of 0.3-0.5 milligrams per liter (mg/L). Coxsackieviruses have been found in raw and treated wastewater, rivers, canals and seawater. There's no evidence linking drinking water to CVB infections. Studies have found the virus survives coagulation-sedimentation and filtration methods of source drinking water treatment but they haven't been detected in finished water following proper conventional disinfection.

Drinking water, however, hasn't been eliminated as a link to diabetes. An association was made between diabetes and the acidity of drinking water.6 After testing 64 homes with diabetic children (type 1) and 250 without, researchers noticed those with more acidic tap water were nearly four times more likely to have type 1 diabetes.

Acidity is a measure of pH where 7 is neutral, below 7 is acidic, and above 7 is basic. Water pH levels between 6.2 and 6.9 were associated with type 1 diabetes. Notable is that acid levels in drinking water are insignificant compared to acidity in other foods and beverages. The researchers don't know why higher water acidity is related to diabetes and suspect it may be a marker for some other factor related to drinking water such as pathogen intrusion or survival, or leaching of distribution pipe components.

Conclusion
Much research has been conducted on health management of type 1 diabetes. New products are continually developed aimed at reducing the negative lifestyle impact on those afflicted with type 1 diabetes including wrist monitors for blood sugar levels, and inhaled insulin delivery instead of injections. Ultrasound devices are also being researched that measure blood levels without having to prick the skin. Fungal compounds show promise as an insulin surrogate, and unlike insulin—that's susceptible to digestive enzymes—the fungal compounds may be taken in pill form.7 Although promising in animal studies, the substance hasn't been used in humans yet. Laboratory studies have successfully produced cells that can create insulin.8 Future goals are to transplant these cells in the human body as a long-term management tool for diabetes. While all of these treatment advances are welcomed, it's hoped the definitive cause of type 1 diabetes will be determined and future advances will be to prevent the initial onset of the disease.

References
1. The American Diabetes Association at www.diabetes.org
2. Heljic, B., "The role of heredity in the etiology of diabetes mellitus," Medicinski Archiv., 49:19-21, 1995.
3. Varela-Calvino, R., et al., "Characterization of the T-cell response to coxsackievirus B4: evidence that effector memory cells predominate in patients with type 1 diabetes," Diabetes, 51:1745-53, 2002.
4. Fairweather, D., and N.R. Rose, "Type 1 diabetes: virus infection or autoimmune disease?" Nature Immunology, 3:338-40, 2002.
5. Rothwell, P.M., et al., "Seasonality of birth of patients with childhood diabetes in Britain," British Medical Journal, 312:1456-7, 1996.
6. Stene, L.C., et al., "Acidic drinking water and risk of childhood-onset type 1 diabetes," Diabetes Care, 25:1534-8, 2002.
7. Haak, T., "New developments in the treatment of type 1 diabetes mellitus," Experimental and Clinical Endocrinology and Diabetes, 107:S108-13, 1999.
8. Shapiro, A.M.J., et al., "Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen," The New England Journal of Medicine, 343:230-8, 2000.


About the author
Dr. Kelly A. Reynolds is a research scientist at the University of Arizona with a focus on development of rapid methods for detecting human pathogenic viruses in drinking water. She holds a master of science degree in public health (MSPH) from the University of South Florida and doctorate in microbiology from the University of Arizona. Reynolds also has been a member of the WC&P Technical Review Committee since 1997.

 
For earlier columns in this category, click on the link below or hit the 'List All' button.
Emerging Issues: Suspected Viral Pathogens of the Future  December 2002
The Importance of Water Quality to the Food Industry  November 2002
Water Quality Issues Along the US-Mexico Border  October 2002
Bioremediation: Using Microbes to Clean Up Hazardous Waste  September 2002
A Contaminant Candidate List: Prioritizing Drinking Water Contaminants  August 2002
Bacteria in Drinking Water -- Public Health Implications?  July 2002
Ultraviolet Light: An Alternative Disinfectant  June 2002
Eureka for Eukaryotes -- The Problem with Protozoa  May 2002
Microbial Resistance to Disinfectants  April 2002
Bacteria 101  March 2002
Children at Increased Risk of Waterborne Contamination  February 2002
The Prevalence of Nitrate Contamination in the United States  January 2002