 Keith has a normal BMI yet still developed type 2 diabetes. Twenty percent of adults with diabetes are not overweight or obese. Some researchers propose that increased weight gain is also responsible for the increased incidence of type 1 diabetes (see "The Accelerator Hypothesis" on the hypotheses page; Wilkin 2001; Wilkin 2008). On the other hand, taller height has long been recognized as associated with type 1 diabetes; in the 1920s, Dr. Elliot Joslin, a pioneer in diabetes treatment said, "overheight was more frequent a precursor of diabetes in children than was overweight in adults" (quoted in Gale 2005b).
A number of studies have found evidence that a higher body mass index (BMI), and sometimes increased height or weight gain, may affect the development of type 1 diabetes. For example:
It is important to note that even moderately increased growth rates, not necessarily to the level of obesity, appears to be associated with an increased risk of type 1 diabetes (Dahlquist 2006).
Some studies, however, have found that an increased BMI cannot explain the increased incidence of type 1 diabetes in their study areas (e.g., Svensson et al. 2007 and O'Connell et al. 2007).
In a prospective study from Australia that followed people over time, weight gain (but not taller height) early in life has been found to increase the risk of type 1 diabetes-related autoimmunity in children who have an increased genetic risk of type 1 diabetes (Couper et al. 2009). On the other hand, in a U.S. prospective study of genetically at-risk children, taller height was found to increase the risk of autoimmunity and type 1 diabetes. Weight gain, however, did not show an increased risk (Lamb et al. 2009). These authors suggest that the differences in their findings may be due to the different ages of the children, or because of differing genetic risk.
A large, multiethnic U.S. study looked at children who already had diabetes, in relation to BMI. It found that the large majority of children with type 2 diabetes (79%) were obese, and another 10% were overweight. In comparison, 13% of the children with type 1 diabetes were obese, and 22% overweight. Among U.S. youth without diabetes, 17% were obese, and 16% overweight. So, the obesity rate was lower among children with type 1 than the general population, although the opposite held for those overweight (Liu et al. 2010).
Interestingly, obesity is sometimes associated with vitamin D deficiency, probably because vitamin D can be deposited in fat stores which decreases availability to the rest of the body (Holick 2004). Vitamin D appears to be protective against the development of type 1 diabetes (see the vitamin D page).
In his Accelerator Hypothesis, Wilkin (2001) proposes that weight gain causes an increase in insulin resistance. Beta cells stressed by insulin resistance are more of a target to the immune system, and insulin resistance thus accelerates beta cell death and the appearance of type 1 diabetes. Weight gain and physical inactivity, Wilkin proposes, account for the rising incidence in both type 1 and type 2 diabetes in developed countries.
In the opinion of Gale (2007), the editor of the journal Diabetologia, "Children destined to develop type 1 diabetes grow faster and fatter in early life, but this could be a consequence rather than a cause of their predisposition to diabetes. Childhood obesity may have contributed to the linear rise of childhood type 1 diabetes over the past 50 years, but does not explain it." Looking at weight gain and diabetes without considering the role of environmental contaminants may not be sufficient. A provocative study found that people who were obese did not have an increased prevalence of diabetes if they also had very low concentrations of persistent organic pollutants (POPs). Only in people with certain POP levels was obesity associated with diabetes. On the other hand, the associations between POPs and diabetes were stronger in obese individuals than in people who were lean, implying that obesity may increase the toxicity of the POPs. This study found striking associations between POPs and diabetes, and is discussed further on the POP page. The dataset it used did not distinguish between type 1 and type 2 diabetes, although most participants probably had type 2 (Lee et al. 2006). There have not yet been any other studies large enough to further examine this finding, although it certainly merits further research.
Environmental contaminants and weight: ObesogensIn 2002, Baillie-Hamilton (2002) proposed the hypothesis that environmental contaminants could help to explain the modern obesity epidemic. She pointed out that numerous widely-used chemicals could actually produce weight gain in animals, including a number of POPs, pesticides, organophosphates, heavy metals, solvents, phthalates, and bisphenol A. Subsequent research has largely supported this hypothesis, and identified additional contaminants that can promote weight gain. When female mice are exposed to a low dose of the endocrine (hormone) disrupting drug diethylstilbestrol (DES) in the first five days of life, they gain more weight by six months of age than mice who are not exposed (Newbold et al. 2009). Can other endocrine (hormone) disrupting compounds have a similar effect in humans? The term "obesogen," coined by Drs. Grun and Blumberg, is now used to refer to chemicals than promote weight gain. The Collaborative on Health and the Environment provides a fact sheet on obesogens. Environmental Health Perspectives also has an informative article, Obesogens: An Environmental Link to Obesity (Holtcamp 2102).
A study has shown experimentally that exposure to a mixture of persistent organic pollutants (POPs), taken from farmed Atlantic salmon, can lead to obesity (and insulin resistance) in rats. Of these POPs, the organochlorine pesticides and DDT inhibited insulin action in the fat cells themselves, and affected gene expression. Some types of PCBs also reduced insulin action in the fat cells, but not as strongly (Ruzzin et al. 2010). Exposure to the POP tributyltin has also been found to increase weight gain in animals (Grün et al. 2006). Rubin et al. (2001) found that mother rats exposed to low doses of bisphenol A had heavier offspring, even after the exposure ended. The weight gain persisted longer in females, and, interestingly, was higher at lower doses. Exposure to bisphenol A in utero and in early life can not only affect the body weight of animals, but affect fat cells as well (Rubin and Soto 2009). In humans, Verhulst et al. (2009) found that prenatal exposure to the POPs DDE and PCBs is associated with increased BMI during the first three years of life. Smink et al. (2008) found that in utero exposure to higher levels of the POP hexachlorobenzene (HCB) was associated with a higher BMI at age 6 (but not taller height). A study by Karmaus et al. (2009) found that in utero exposure to DDE, but not to PCBs, is associated with increased weight and BMI in adult women. Mendez et al. (2010) found that in utero exposure to the POP DDE was associated with more rapid growth in the first 6 months of life, and higher BMI at 14 months of age, in children of normal weight mothers. Valvi et al. (2011) found that in utero levels of PCBs and DDT were associated with weight changes at age 6.5, in children with moderate exposure levels. In older adults, POPs have been associated with abdominal obesity in Sweden (Lee et al. 2012). A further study found that girls exposed to higher levels of PFOA in the womb, were more likely to be overweight or obese at age 20 (PFOA is a chemical used in the manufacturing of teflon) (Halldorsson et al. 2012).
Levels of several phthalate metabolites have been associated with abdominal obesity and insulin resistance in U.S. men (Stahlhut et al. 2007). In another U.S. study of people aged 6-80, various phthalate metabolites were associated with body mass index (BMI) and waist circumference, although results varied by age and gender (Hatch et al. 2008). For more studies on this topic, see the pages on specific environmental contaminants. Curiously, some overweight elderly people seem to have a lower risk of death than those who are thin. Some researchers propose that the extra fat tissue provides a relatively safe place to store toxic chemicals (many persistent chemicals bind to fat molecules), as compared to storing the chemicals in more critical organs. They have found that in people with low levels of POPs, excess fat did contribute to increased mortality, as we'd expect. In people with higher levels, however, excess fat was protective. Weight loss in the elderly may be dangerous for those with higher POP levels (Hong et al. 2011).
A number of review articles summarize recent findings on endocrine disrupting compounds and obesity, including:
The May 25, 2009 issue of the journal Molecular and Cellular Endocrinology published a special issue on the role of environmental endocrine disrupting contaminants in the development of obesity and diabetes. A number of articles may be of interest here:
Environmental contaminants and heightThe effects that environmental contaminants can have on other growth rates, such as height, are less consistent. In humans, prenatal exposure to DDE has been associated with increased height and weight in boys at puberty (Gladen et al. 2000). The effects of contaminants appear to depend on gender, as well as the type of contaminant. PCBs, for example, have usually been associated with lower growth rates in animals and humans, but sometimes various PCB types have been associated with increased height in boys (Lamb et al. 2006) or girls (Hertz-Picciotto et al. 2005).
The bottom lineEnvironmental contaminant exposures may contribute to increased weight gain, especially if exposure occurs during development. Increased weight gain is associated with type 2 diabetes. But, weight gain may also be able to accelerate the appearance of type 1 diabetes and may contribute to the increasing incidence of type 1 diabetes, as well as type 2. The possibility that weight gain can increase the risk of type 2 diabetes only in people exposed to certain levels of contaminants deserves further study. |