Overlooked: Type 1 Diabetes and the Environment

"Diabetes and obesity
are two of the most common and most costly health problems today.  12% of U.S. adults have diabetes, and if
current trends continue, more than 50% will have diabetes or pre-diabetes by
2020.  Annual U.S. spending on diabetes
is $194 billion (2010) and could reach $500 billion by 2020."

Source: The Collaborative on Health and the Environment Working Group
on Diabetes-Obesity Spectrum

As troubling as these statistics are, the number of children
diagnosed with diabetes continues to increase at a staggering rate and will add
exponentially to the toll on public health and health care expenditures.  The explosion in pediatric type 2 (formerly
known as “adult onset”) diabetes diagnoses has drawn much needed attention to
the impact of environmental factors (e.g., nutrition, exercise, poverty,
chemicals) on insulin resistance and metabolic syndrome.  Often overlooked, though, are the equally
devastating effects of these factors on the rise in type 1 (autoimmune)
diabetes, still the most prevalent form of diabetes in children.   Before
examining new research investigating the links between the environment and
autoimmune diabetes, let’s look at current epidemiology and how distinctions
between “type 1” and “type 2” diabetes are less clear-cut than previously
believed.

Epidemiology of Pediatric Diabetes

From the CDC: The SEARCH for
Diabetes in Youth is a multicenter study funded by CDC and NIH to examine
diabetes (type 1 and type 2) among children and adolescents in the United
States. SEARCH findings for the communities studied include the following:

• During
  2002–2005, 15,600 youth were newly diagnosed with type 1 diabetes annually, and
  3,600 youth were newly diagnosed with type 2 diabetes annually.
• Among
  youth aged <10 years, the rate of new cases was 19.7 per 100,000 each year
  for type 1 diabetes and 0.4 per 100,000 for type 2 diabetes. Among youth aged
  10 years or older, the rate of new cases was 18.6 per 100,000 each year for
  type 1 diabetes and 8.5 per 100,000 for type 2 diabetes.
• Non-Hispanic
  white youth had the highest rate of new cases of type 1 diabetes (24.8 per
  100,000 per year among those younger than 10 years and 22.6 per 100,000 per
  year among those aged 10–19 years).
• Type 2
  diabetes was extremely rare among youth aged <10 years. While still
  infrequent, rates were greater among youth aged 10–19 years than in younger
  children, with higher rates among U.S. minority populations than in
  non-Hispanic whites.
• Among
  non-Hispanic white youth aged 10–19 years, the rate of new cases was higher for
  type 1 than for type 2 diabetes. For Asian/Pacific Islander and American Indian
  youth aged 10–19 years, the opposite was true—the rate of new cases was greater
  for type 2 than for type 1 diabetes. Among non-Hispanic black and Hispanic
  youth aged 10–19 years, the rates of new cases of type 1 and type 2 diabetes
  were similar.

To summarize, the most recent data in the U.S. demonstrates
that new cases of pediatric type 1 diabetes are still much more common than of type
2, but in certain populations, new cases of type 2 are more prevalent.  Certainly social determinants are notable
contributing to major health disparities, but for youth <20 years old as a
whole, we are still seeing many more new cases of type 1 diabetes versus type
2.

Even so, differentiating between types 1 and 2 is not so
straightforward.  The Collaborative
on Health and the Environment (CHE) points out, “There is overlap among the various types of diabetes, and scientists
are beginning to look at diabetes as a spectrum of disease, with type 1
(autoimmune) on one end, and type 2 (metabolic) on the other. Indeed,
researchers have found that 15-35% of type 2 patients diagnosed before age 45
test positive for antibodies to GAD, one of the markers of type 1 diabetes.
Many children with diabetes, meanwhile, show signs of autoimmunity as well as
insulin resistance. It may be that a large number of people with diabetes have
both autoimmune and metabolic processes contributing to their disease.”

This change in thinking about
types of diabetes is supported by data from the CDC’s SEARCH study.  In an article published in 2011,
authors reviewed data on classification of diabetes type by autoimmunity and
insulin sensitivity (IS)/resistance (IR); a large overlap was noted. 

Most subjects fell into either the autoimmune plus IS (54.5%) or
nonautoimmune plus IR categories (15.9%) and had characteristics that align
with traditional descriptions of type 1 or type 2 diabetes. The group
classified as autoimmune plus IR (19.5%) had similar prevalence and titers of
diabetes autoantibodies and similar distribution of HLA risk genotypes to those
in the autoimmune plus IS group, suggesting that it includes individuals with
type 1 diabetes who are obese. The group classified as nonautoimmune plus IS
(10.1%) likely includes individuals with undetected autoimmunity but may also
include those with monogenic diabetes and thus requires further testing.

So it’s no longer simply type 1 OR
type 2 – many diabetics in fact have evidence of autoimmunity AND insulin
resistance.  In fact, many of the same
environmental factors suspected to influence epigenetic expression of insulin
resistance and metabolic syndrome (including obesity) also are likely to
contribute the rising numbers of patients with autoimmune conditions like
diabetes.   

Environmental Factors

After several years of intense
focus on the environment and type 2 diabetes, researchers are now intently
looking at rising rates of type 1 diabetes and the role of potential
environmental factors.  Two recently
published studies from Australia are of great interest.  “Cyclical Variation in the Incidence of Childhood Type 1 Diabetes in
Western Australia (1985-2010)” reports
that “the incidence of type 1 diabetes in children aged 0–14 years increased by
an average of 2.3% a year between 1985 and 2010, and a significant 5-year
cyclical pattern in the incidence rate trend was observed” and concludes, “The
cyclical pattern in incidence observed in Western Australia supports the role
of environmental factors in childhood type 1 diabetes. These factors may either
be environmental risk or protective factors that modify the likelihood of developing
type 1 diabetes de novo or of progressing to clinical type 1 diabetes in those
with established autoimmune prediabetes.” 
This last sentence highlights the fact that environmental factors may
push those at risk, already with immune dysregulation, past some tipping point
to develop what we clinically diagnose as diabetes.  I’ve written previously about the “iceberg” model of
disease progression for other conditions, specifically for autism and atopic
disorders (e.g., asthma, allergies). 
This functional medicine model works well to explain root cause factors
likely responsible for the increases in prevalence noted over the past 20 years
for many chronic childhood health conditions. 

One of the implicated factors,
vitamin D deficiency, is the subject of a second important diabetes paper to
emerge recently from Australia.  “Serum vitamin D levels are lower in Australian children and
adolescents with type 1 diabetes than in children without diabetes” found
that “children with T1DM have lower 25OHD than controls, even in an environment
of abundant sunlight.  Whether low
vitamin D is a risk factor or consequence of T1DM is unknown.”  25OHD is the most commonly evaluated lab
marker for vitamin D status, and low levels have also been associated
with a need for more insulin in children with existing type 1 diabetes.  One notable publication reviewed the impact
of maternal vitamin D
status and the risk of type 1 diabetes developing later in offspring.   The Norwegian authors discovered that “the
odds of type 1 diabetes was more than twofold higher for the offspring of women
with the lowest levels of 25-OH D compared with the offspring of those with levels
above the upper quartile” and commented, “Given future replication in
independent cohorts, our findings provide support for the initiation of a
randomized intervention trial to prevent type 1 diabetes in children by
enhancing maternal 25-OH D status during pregnancy.”  A nutritional trial of vitamin D to prevent
diabetes?  That is exactly the type of
preventive approach that could change the lives of millions of children – for relatively
low cost with potentially huge health care cost savings down the line. 

What other environmental factors
are under investigation?  CHE hosts a wealth
of resources on their Diabetes/Obesity Working Group site, and Working
Group Coordinator Sarah Howard has created another website with specific
information about type 1 diabetes and environmental contaminants including persistent
organic pollutants, air pollutants, bisphenol A and phthalates, flame
retardants, trichloroethylene, heavy metals, pesticides and radiation.  Also under the microscope, as in many other
autoimmune disorders, is the role of gut microbiota in the development of type
1 diabetes.  According to Dr. Vaarala
from the National Public Health Institute in Helsinki, Finland, “The gut immune
system has a key role in controlling insulin-specific immunity induced by
dietary insulin. Indeed, indications for aberrant function of the gut immune
system have been reported in type 1 diabetes, such as intestinal immune activation
and increased intestinal permeability. Research on the gut immune system in
human type 1 diabetes is needed to reveal the role of oral immunity in this
disease.”  Research is needed to evaluate
whether specific pre- and probiotic strains could modify these gut immune
interactions to prevent diabetes in susceptible children.  Finnish studies have
shown that administering probiotics to pregnant and breastfeeding mothers can
lower the rate of atopy in offspring – perhaps the same will be true for
diabetes.

(Originally written for the Deirdre Imus Environmental Health Center, September 2012)