Why is Diabetes Increasing?
Hypotheses to Explain Why Diabetes and Obesity are Increasing
Numerous hypotheses attempt to explain why the incidence and prevalence of diabetes and obesity are increasing. The true reasons probably involve numerous factors and vary by individual.
Type 2 Diabetes and Obesity
The prevailing view to explain the increasing incidence of obesity and type 2 diabetes are lifestyle factors, especially increased caloric intake and lack of exercise. While these factors are indeed associated with type 2, so are other environmental factors.
Kolb and Mandrup-Poulsen (2010) propose that the major risk factors for type 2 diabetes (overnutrition, low dietary fiber, sedentary lifestyle, sleep deprivation and depression) have been found to induce low-grade inflammation, which could eventually lead to type 2 diabetes development.
Endocrine Disrupting Chemicals
Baillie-Hamilton (2002) first proposed that exposure to environmental chemicals may contribute to the global obesity epidemic. Grun and Blumberg (2006) coined the term "obesogen," referring to chemicals that can disrupt fat cell generation and energy balance.
Alonso-Magdalena et al. (2011) review the evidence that exposure to endocrine disrupting chemicals can contribute to the development of type 2 diabetes. They argue that enough evidence already exists to consider these compounds as risk factors for type 2 diabetes development and other diseases related to insulin resistance (which may include gestational diabetes as well). Type 2 diabetes involves is caused by increased insulin resistance, as well as disruption of the insulin-producing beta cells and loss of beta cell mass. Interestingly, in a U.S. study, 32% of obese adults were metabolically healthy, and 24% of normal-weight adults were metabolically abnormal (insulin resistance was one of the measurements of metabolic health in this study). Insulin resistance may in fact be a better indicator of type 2 diabetes risk than obesity. Existing evidence shows that endocrine disrupting chemicals can lead to increased insulin resistance, as well as disrupt beta cell function.
Casals-Casas and Desvergne (2011) propose the term "metabolic disruption" to refer to the subset of endocrine disrupting compounds that can affect metabolism. These chemicals have been associated with the development of obesity, increased insulin resistance, type 2 diabetes, and metabolic syndrome. The "Parma Consensus Statement on Metabolic Disruptors" agrees that we should broaden the term "obesogen" to include other metabolic effects (Heindel et al. 2015).
Type 1 Diabetes
A number of researchers have proposed hypotheses to explain the rising incidence of type 1 diabetes in children, or to explain how type 1 diabetes develops. For example:
The Spring Harvest Hypothesis
Gale (2005) argues that a more rapid progression of type 1 diabetes, rather than more frequent initiation of disease, is behind the rise of type 1 diabetes in children. Increasing incidence in children is due to the disease appearing at a younger and younger age. The major role of the environment, then, is to change the rate of disease progression. Some of these environmental factors might include a decreasing age of puberty, a failure of regulatory T cells (see the autoimmunity page for more on these cells), changes that make beta cells more vulnerable (e.g., excess growth or weight gain. Other factors, such as viruses or diet may indeed be involved in disease initiation, but may not be responsible for the rising rates of disease.
The Trigger-Booster Hypothesis
Knip et al. (2005) propose an explanation for the process that leads to the development of type 1 diabetes. First, genetic susceptibility is required. Then, something with seasonal variation triggers the autoimmune process (see the incidence page for more on seasonality), and they propose enteroviruses as the most likely trigger. Diabetes would only develop if this is followed by exposure to an antigen, such as the bovine insulin in cow's milk. Other modifying factors may also influence the disease process, such as early diet, vitamin D deficiency, or excess growth or weight gain. It is interesting that although infections with enteroviruses have become less frequent in developed countries over the past few decades, while type 1 incidence in children has been increasing. These authors resolve this paradox by proposing that the decreasing prevalence of enteroviruses increases the susceptibility of children to the diabetes-related effects of these viruses, causing more invasive viral infections. Other environmental factors that also may in part be responsible for the increasing incidence of type 1 diabetes in children include the increased processing of milk products, higher growth rates in height and weight, and a decreased microbial load in early life.
Call on Type 1 Diabetes and the Environment
Listen to Dr. Mark Atkinson, Dr. Jill Norris, and Dr. Kristina Thayer discuss the role of the environment in type 1 diabetes on this call, Type 1 Diabetes and the Environment, sponsored by the Collaborative on Health and the Environment (2014).
The Hygiene Hypothesis
Kolb and Elliot (1994) proposed that improved hygiene is the cause of the increasing incidence of type 1 diabetes. Bach (2002) argues that the main factor in the increased prevalence of autoimmune diseases in industrialized countries is the reduction in the incidence of infectious diseases in those countries. It may be that parasites and beneficial gut microorganisms stimulate the immune system (Gale 2002), and that exposure to these microorganisms early in life may protect against type 1 diabetes (Björkstén 2009). Björkstén (2009) suggests that the term "hygiene hypothesis" is misleading, and a better name might be the "microbial deprivation hypothesis." Hmm, kind of a mouthful... not quite catchy enough I think.
Another suggestion, the "Biodiversity Hypothesis," proposes that "an environment with diverse macrobiota and microbiota modifies and enriches the human microbiota, which in turn is crucial in the development and maintenance of appropriate immune function." Our built environment, processed food, and other lifestyle factors may not provide the microbial stimulation necessary for the proper development of our immune function. Many chronic inflammatory disorders (including allergic, autoimmune, and metabolic disorders) are linked to alteration in the human microbiota (von Hertzen et al. 2015).
Others suggest that while the "hygiene hypothesis" should be thrown out, the newer names that have been suggested aren't exactly compelling... (Scudellari 2017).
The Accelerator Hypothesis
Wilkin (2001) proposes that weight gain is driving the rising incidence of both type 1 and type 2 diabetes. Weight gain causes increased insulin resistance, and the resulting high glucose levels accelerates destruction of the beta cells. Beta cells stressed by insulin resistance are more of a target to the immune system, and insulin resistance thus accelerates beta cell death and type 1 diabetes. He proposes that type 1 and type 2 diabetes are essentially the same disease, distinguished only by the addition of an autoimmune response in type 1. This hypothesis, needless to say, has generated a lot of controversy [e.g., see Gale (2007), Fourlanos et al. (2008) and updates by Wilkin (2007), (2008), and (2012)].
The Overload Hypothesis
Dahlquist (2006) proposes that a number of environmental factors may accelerate the autoimmune process in type 1 diabetes by overloading beta cells, leading to their destruction. These factors include insulin resistance due to excess fat accumulation, an increased need for insulin due to high growth rates, physical stress (including infection), or psychological stress. She argues that the increasing incidence of type 1 diabetes and the shift to a younger age of diagnosis, is likely due to the societal increase in these factors that overload the beta cells, and not factors associated with triggering autoimmunity (like early infant diet or viruses). These accelerating factors include a large number of risk factors which all act together and lead to beta cell overload.
The Beta Cell Stress Hypothesis
Ludvigsson (2006) believes that the search for one cause of type 1 diabetes may be futile; different mechanisms may play a role in different countries, for example, and several mechanisms may all contribute to the progression of disease. Ludvigsson's hypothesis essentially combines all of the environmental factors described here, proposing that they interact in complex ways. For example, some factors (e.g., vitamin D deficiency, better hygiene) may contribute to an imbalance in the immune system, facilitating an autoimmune reaction provoked by viruses, toxic chemicals, or dietary proteins such as wheat or dairy. Increased demand for insulin (due to factors such as rapid growth), or increased insulin resistance (due to stress, infections, puberty, etc.) may lead to beta cell stress and beta cell dysfunction. Eventually, diabetes develops. It is possible that increased beta cell stress could stimulate or even initiate autoimmunity.
The Balance Shift Hypothesis
Since there is too much evidence from animal, human and epidemiological studies to completely rule out any of the hypotheses that explain the increasing incidence in type 1 diabetes, a multi-factoral process may explain it. There are similarities among the immunological mechanisms underlying each hypothesis (e.g., viruses, vitamin D deficiency, cow's milk, hygiene, etc.). In healthy individuals, it is likely that protective and diabetogenic factors are in balance, and a change in one factor might be compensated for by changes in other factors. In diabetic patients, however, this compensatory mechanism does not occur, leading to type 1 diabetes. It is likely that a multi-factorial process that leads to a disequilibrium between protective and diabetogenic factors is the cause of the increasing incidence. We should focusing on multiple mechanisms for its resolution (Egro 2013).
The Environmental Chemical Hypothesis
Dr. Duk-Hee Lee and I have written a hypothesis proposing that exposure to environmental chemicals can influence the development of type 1 diabetes development. We focused on endocrine disrupting compounds and their ability to influence the immune system, as well as other factors associated with type 1 diabetes (Howard and Lee 2012). We built on the work of other authors. Holladay (1999) proposed that prenatal exposure to compounds toxic to the developing immune system, including many environmental chemicals, may play a role in postnatal autoimmune disease, although he did not address type 1 diabetes in particular. Longnecker and Daniels (2001) proposed that environmental chemicals may be associated with type 1 (and type 2) diabetes. Their review of epidemiological literature (not animal studies) found limited evidence however, and for type 1 focused on nitrate/nitrite and PCBs. Carpenter (2008) more recently proposed that persistent organic pollutants may be risk factors for developing both types of diabetes, and reviewed evidence from both human and animal studies, suggesting further study. This webpage focuses primarily on this hypothesis, since the role of chemicals in the development of diabetes has been neglected (Jones et al. 2008).
More recently, Drs. Bodin, Stene, and Nygaard, of the Norwegian Institute of Public Health, reviewed the evidence in a paper entitled, Can exposure to environmental chemicals increase the risk of diabetes type 1 development? They found that, "Although information on environmental chemicals as possible triggers for T1DM is sparse, we conclude that it is plausible that environmental chemicals can contribute to T1DM development via impaired pancreatic beta-cell and immune-cell functions and immunomodulation. Several environmental factors and chemicals could act together to trigger T1DM development in genetically susceptible individuals, possibly via hormonal or epigenetic alterations." The full text of this paper is available free online (Bodin et al. 2015). I also propose that developmental exposure to chemicals could increase the risk of type 1 diabetes later in life (Howard 2018), and have written an updated review of the evidence (Howard 2019). Some other reviews of type 1 diabetes and endocrine disrupting chemicals also propose the same idea (e.g., Predieri et al. 2020).
Dr. Duk-Hee Lee and I propose that environmental chemical exposures may be linked to type 1 diabetes development.
While the hypotheses listed above are more "mainstream," the journal Medical Hypotheses has published a number of other hypotheses concerning type 1 diabetes (or related conditions as noted) that may have validity, or at least are interesting to consider. Or at least funny. For example, some authors propose that the following environmental factors may influence the development of type 1 diabetes:
Zinc-containing silica nanoparticles (Junnila 2015)
Food proteins, processed food, exotic fruits (Landin-Olsson et al. 2013)
Lack of vitamin B6 derivative (Rubí 2012)
Injury to autonomic nerves supplying the pancreas through persistent physical efforts during defecation in infancy (Quinn 2010) (no, that is not a typo)
Electrification (diabetes and other diseases) (Milham 2010)
A series of 10 hypotheses, involving wheat gluten, vitamin D, and hygiene (Barbeau et al. 2007)
Flavonoids as potential therapeutic agents for type 1 diabetes (Ardestani and Yazdanparast 2007)
The Unitarian Hypothesis: cell membrane damage (all types of diabetes) (Morrison et al. 2006)
Food processing and additives (both types of diabetes) (Elliott 2006)
The mycobacterium paratuberculosis (Dow 2006)
An evolutionary adaptation to cold climates (Moalem et al. 2005)
Disruptions in early bonding and attachment (Mead 2004)
The presence of Claviceps purpurea in grasslands (Bannister and Stockdale 2003)
Well, at least there's some creativity here.