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Of Mice, Dogs, and Men


I'm not sure if frogs get diabetes, but Amy did. She blogs about life with diabetes, and has written a book, A Smart Woman's Guide to Diabetes, Authentic Advice on Everything from Eating to Dating to Motherhood.
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Do Animals Get Diabetes?

Yes. Some animals do get diabetes naturally or in the wild, including apes, pigs, sheep, horses, cats, and dogs. All mammals produce insulin, and will develop diabetes (defined as high blood glucose levels) if their pancreatic beta cells are removed. Vets classify canine diabetes into "insulin deficiency diabetes" and "insulin resistance" diabetes (somewhat analogous to type 1 and type 2 in humans). Female dogs may also develop a canine form of gestational diabetes. There is some evidence that dogs do actually develop a form of autoimmune diabetes, that is more similar to Latent Autoimmune Diabetes in Adults (LADA) than to childhood type 1 diabetes. (Gale 2005c; Nelson and Reusch, 2014), although overall, canine diabetes is very similar to type 1 (O'Kell et al. 2017). Interestingly, some of the same autoantibodies found in humans with type 1 diabetes have also been found in some dogs with diabetes (Davison et al. 2008), although not all studies have found these antibodies in dogs with diabetes (Ahlgren et al. 2014). Technically, only humans get type 1 diabetes (Gale 2008), although some authors do use the term type 1 to describe autoimmune diabetes in animals. Cats, meanwhile, develop a diabetes that is more similar to type 2 (Nelson and Reusch, 2014).
 
Scientists generally use rodents as animal models of type 1 diabetes in the laboratory. The two main rodent strains used are non-obese diabetic (NOD) mice and Biobreeding (BB) rats. These rodents have been bred to spontaneously develop diabetes. Both animals develop a form of autoimmune diabetes that includes the presence of some autoantibodies, although there are also differences between the autoimmune diabetes in these animals and type 1 diabetes in humans. While these animals may be useful for some purposes (such as developing a cure for type 1 diabetes once it develops, or identifying biological mechanisms), their usefulness is also in question.

Preventing Diabetes in NOD Mice

How useful are NOD mice for predicting the effects of various environmental factors to either cause or prevent type 1 diabetes in humans? Perhaps not very. Most interventions-- at last count, 195 of them-- delay or prevent diabetes in NOD mice (Roep and Atkinson 2004). Some of these interventions have been tried in people and have not successfully prevented or delayed type 1 diabetes. For example:
Some researchers have used NOD mice to investigate the potential role of environmental chemicals in the development of autoimmune diabetes. Some studies on chemicals and NOD mice found that some chemicals do not accelerate or can even delay diabetes in NOD mice: mercury (Brenden et al. 2001), trichloroethylene (Ravel et al. 2005), arsenic (Lee et al. 2015), dioxin (Kerkvliet et al. 2009), and even nicotine (Mabley et al. 2002). Yet most of these chemicals have been found to accelerate autoimmunity in other strains of mice, and sometimes in humans as well. What these findings mean for humans is not clear. 

Two studies have found that BPA exposure accelerates insulitis and diabetes development in NOD mice (Bodin et al. 2013 and Bodin et al. 2014). The first study found that long-term exposure to BPA at relatively high levels accelerated insulitis in NOD mice. The second found that exposing mothers to BPA caused their female offspring to have more severe and higher incidence of insulitis. The authors write, "In conclusion, transmaternal BPA exposure, in utero and through lactation, accelerated the spontaneous diabetes development in NOD mice. This acceleration appeared to be related to early life modulatory effects on the immune system, resulting in adverse effects later in life." (Bodin et al. 2014). Another study by these authors, on another chemical, a perfluorinated compound, found that it accelerated insulitis but not diabetes in NOD mice (Bodin et al. 2016).

Another study found that chronic, high-dose exposure to DDE increased the incidence and severity of diabetes in NOD mice, and that DDE acted via the immune system and affected T-cell function (Cetkovic-Cvrlje et al. 2015).
 
Van der Werf et al. (2007) suggests that NOD mice are probably not appropriate to use for studying the role of viruses in the development of type 1 diabetes in humans; likewise, NOD mice may not be entirely appropriate to use to examine the effects of environmental chemicals on type 1 diabetes in humans. Researchers have in fact joked, "If you look cross-eyed at NOD mice, you prevent diabetes" (Roep and Atkinson 2004), although others point out that not quite everything prevents diabetes in NOD mice, and that the effects of various interventions may depend on timing and dosage (Shoda et al. 2005). Personally, I would not suggest giving children mercury, trichloroethylene, arsenic, nicotine, or dioxin with the hope that they might prevent type 1 diabetes, despite their apparently beneficial effects on NOD mice.

While animal studies may be occasionally informative, we really need studies on humans who are exposed to these chemicals, at different levels, and at different periods of life, and in mixtures that we encounter in the real world, to really see what the effects on humans will be.

Other Animals and Diabetes

Can other animals be used to study the potential effects of chemicals or other environmental factors on the development of type 1 diabetes? Perhaps. I have not found any studies on chemicals and BB rats, and I do not know if these animals could be a useful model or not. Perhaps dogs can, but I am not going to advocate for medical research on dogs.
 
Most convincing might be the ability of chemicals to induce diabetes in animals that are not prone to develop the disease. Helgason et al. (1982), for example, found that if mice consumed meat cured with nitrite before mating and during pregnancy, and their offspring consumed it for a time, then some of the offspring developed glucose abnormalities and diabetes. This strain of mice does not normally develop diabetes. This study supports previous findings in humans suggesting that parental consumption of this meat around the time of conception can lead to the development of type 1 diabetes in their children (see the nitrate and nitrite page for information).

Interestingly, zebrafish are one animal that is becoming useful in studying the effects of toxic chemicals (zebrafish studies are described on numerous pages on this website). It also turns out that the zebrafish pancreas develops similarly to the human pancreas. These fish are now being used to try to figure out a potential cure for diabetes (Prince et al. 2017).

Other Animals and Autoimmunity

A number of pages on this website discuss the ability of chemicals to induce or exacerbate autoimmunity in various strains of rodents (see, for example, the pages on bisphenol A, dioxin, heavy metals, phthalates, and trichloroethylene). What rodents were used in these studies? Many of them used rodents that are genetically susceptible to the autoimmune disease systemic lupus erythematosus (SLE, also known as lupus). Whether these findings would have any relevance for type 1 diabetes is not known. Some researchers are also beginning to investigate the effects of chemicals on animals not prone to autoimmunity or autoimmune diseases.
 
Phthalates have been shown to induce autoimmunity in various strains of mice, including some that are not prone to autoimmunity. Different strains show differing effects, however, in that the susceptible strains show signs of disease (in this case, SLE), while the others do not (Lim and Ghosh 2005).
 
When mice not genetically prone to autoimmune disease were treated prenatally with dioxin (TCDD) during immune system development, they had immune dysregulation that included autoantibody production, and suggested an increased risk for later autoimmune disease. These findings suggest that developmental exposure to TCDD may increase the risk of autoimmune disease. These mice, however, are more sensitive than other strains of mice to the effects of dioxin (Mustafa et al. 2008).
 
While exposure to mercury can induce or exacerbate autoimmunity in genetically susceptible rodents (Hemdan et al. 2007), mercury has also been shown to induce autoimmunity even in mice that are not genetically susceptible to autoimmunity (Abedi-Valugerdi 2009). Exposure to mercury in combination with a bacterial infection aggravated autoimmune disease in genetically susceptible mice. And, mice that were not genetically susceptible to autoimmunity were made susceptible (Abedi-Valugerdi et al. 2005).
 
These examples show cases where chemicals could induce or affect autoimmunity even in animals not prone to autoimmunity. The health effects of the exposures varied by strain of animal. Perhaps the potential effects of environmental chemicals on the development of type 1 diabetes would likewise vary based on the genetic background of the individual.

Does Living With Animals Affect the Risk of Type 1 Diabetes?

The only study I have seen on this topic found that living with a dog (or more than one dog) during the first year of life was not associated with a higher or lower risk of developing type 1 diabetes in childhood (Wernroth et al. 2017). (Children with type 1 who actively care for a pet at home do have blood sugar control than those who don't, however (Maranda and Gupta 2016).

The Bottom Line

Animals with diabetes may provide important information that relates to diabetes in humans. However, the mechanisms and processes involved are not equivalent. NOD mice may or may not be appropriate for examining the effects of environmental chemicals or other environmental factors on the development of type 1 diabetes in humans. The ability of chemicals to influence the development of diabetes or autoimmunity in animals that are not bred to spontaneously develop these conditions might be more revealing. Animal research might be able to identify situations where timing is important (e.g., in the case of meat containing nitrites), or the mechanisms involved in disease development.

References

To see some studies of diabetes/obesity in dogs, cats, and other non-laboratory, non-human animals, see my PubMed collection Animals.