Links Between Insulin Resistance and Diabetes/Obesity
Insulin resistance is a major contributor to type 2 diabetes. It can be caused by obesity, as well as by other factors such as hormones, which play a role in the insulin resistance encountered during pregnancy, leading to gestational diabetes.
Some environmental chemicals have been shown to cause insulin resistance in animal studies, and exposures are associated with insulin resistance in humans as well. It is likely that this is one mechanism by which chemicals contribute to the development of type 2 diabetes.
Increased insulin resistance can possibly accelerate the progression of type 1 diabetes in people who already have compromised beta cell function. Based on various hypotheses, anything that can increase insulin resistance may also increase the risk of developing type 1 diabetes. Exposure to chemicals that cause insulin resistance, then, could potentially accelerate the development of diabetes. An accelerated disease process is thought to be one reason for the increasing incidence of type 1 diabetes in younger children. Some chemicals, then, may potentially contribute to increasing incidence of type 1 diabetes in children via inducing insulin resistance. Further studies could determine whether these exposures do indeed increase insulin resistance in people and accelerate the appearance of type 1 diabetes. However, insulin resistance is much more likely to be a driving mechanism in type 2 diabetes than in type 1.
About Insulin Resistance
Insulin resistance is a measurement of the body's cells and tissues to use insulin. If a person is insulin resistant, that is, has a higher level of insulin resistance, then their body does not respond as well to insulin as someone who is insulin sensitive.
In insulin resistance, insulin molecules are not able to enter cells. Glucose molecules then remain inside cells, unprocessed, while glucose molecules also remain in blood, leading to high blood sugar. Beta cells in the pancreas, which produce insulin, respond to high blood sugar, and produce even more insulin, leading to high insulin levels as well as sugar levels in the blood. Insulin resistance is a hallmark of type 2 diabetes. Metabolic syndrome is also known as "insulin resistance syndrome."
Thin people and small children are more sensitive to insulin, and a little might go a long way. For example, when first diagnosed with diabetes, my son only needed about a half a unit of insulin when he ate a meal. He was sensitive to insulin, and had low insulin resistance. Someone who is insulin resistant might require 20 units or more of insulin per meal.
Insulin Resistance and Type 2 Diabetes
Insulin resistance is a major driver of type 2 diabetes. It is one reason that people with pre-diabetes have high levels of insulin in their bodies; their beta cells are churning out insulin to keep up with the increased demand. Eventually the beta cells can't keep up anymore, leading to type 2 diabetes.
Pregnancy can cause insulin resistance, as can puberty, probably due to hormones. Obesity also induces insulin resistance. My insulin dose doubled during pregnancy.
Does Insulin Resistance Contribute to Type 1 Diabetes?
While insulin resistance is not usually thought to play a role in type 1 diabetes, a number of studies suggest that increased insulin resistance may play some role in the development of type 1 diabetes (although not an overwhelming role; autoimmunity is the main mechanism promoting type 1). For example:
In a group of close relatives of people with type 1 diabetes who also tested positive for autoantibodies, The European Nicotinamide Diabetes Intervention Trial (ENDIT), found that insulin resistance accelerates progression to type 1 diabetes in those who do not produce much insulin, but does not affect progression in people who still produce relatively higher amounts of insulin (Bingley et al. 2008).
Another study of antibody-positive relatives, this time in North America, found clear evidence of an association between insulin resistance and progression to type 1 diabetes (Xu et al. 2007).
A Finnish study of siblings of children with type 1 diabetes found that increased insulin resistance was associated with the development of type 1 diabetes in those who were antibody-positive (Mrena et al. 2006).
An Australian study found that antibody-positive relatives who progress more quickly to type 1 diabetes have greater insulin resistance for their level of insulin secretion (Fourlanos et al. 2004).
In Finnish children who were at genetic risk and already antibody positive, insulin resistance was slightly higher in those who went on to develop type 1 diabetes, although its role was minor compared to other factors (such as autoantibody levels, younger age, and reduced insulin secretion) (Siljander et al. 2013).
The TrialNet study (of family members of people with type 1 diabetes) found no increased risk of multiple type 1-related autoantibodies or type 1 diabetes with higher BMI or insulin resistance, in people who tested positive for one type 1-related autoantibody. However, among everyone (including those who were negative for autoantibodies), there was a slight increased risk of type 1 diabetes in those with a higher BMI, as well as a higher risk of type 1 in obese adolescents, and in adults with higher insulin resistance (Meah et al. 2016).
A study from Sweden found that while autoantibody levels were important predictors of the risk of developing type 1 diabetes, those who did develop type 1 also had trouble maintaining glucose levels even with higher beta cell function. This finding implies that "insulin resistance might be an important accelerator of disease" (Åkerman et al. 2017).
In German adults with newly diagnosed type 1 diabetes, insulin antibody levels were associated with insulin resistance (Burkart et al. 2018).
In Sweden and Norway, data from two large population-based studies showed that overweight/obesity was associated with increased risk of latent autoimmune diabetes in adults (LADA), particularly when in combination with a family history. These findings support the hypothesis that factors linked to insulin resistance, such as excessive weight, could promote onset of autoimmune diabetes (Hjort et al. 2018).
It is known that many individuals with type 1 diabetes are also insulin resistant. It is becoming more and more difficult to distinguish between type 1 and type 2 diabetes in overweight youth. Some authors suggest that there is an interplay between insulin resistance and autoimmunity in type 1 diabetes. Insulin resistance may also play a role in the development of complications in diabetes (Nokoff et al. 2012). A meta-analysis of 38 studies on adults with type 1 diabetes found that insulin resistance is a prominent feature of type 1 diabetes (Donga et al. 2015), but its role in type 1 development and progression is still not clear (Kaul et al. 2015).
Insulin resistance is also associated with complications of type 1 diabetes: patients with complications were more insulin resistant than those without (Pop et al. 2016; Šimonienė et al. 2019). For example, people with type 1 diabetes who were more insulin resistance had a higher risk of kidney disease (Vladu et al. 2017).
The "Beta Cell Stress" hypothesis (see the why is diabetes increasing? page) suggests that any phenomenon that induces insulin resistance, and thereby puts extra pressure on the beta cells, should be regarded as a risk factor for type 1 diabetes. When the demand for insulin is great, beta cells may have to work harder to produce adequate insulin. If the immune system is prone to react, increased insulin production could stimulate the autoimmune process (Ludvigsson 2006; Sepa and Ludvigsson 2006). Non-immune processes like insulin resistance can likely amplify autoimmunity and contribute to type 1 diabetes (Redondo et al. 2019). Increasing insulin resistance is likely to be one accelerator of type 1 diabetes, speeding up the process in people who already have compromised beta cells, but probably does not initiate the disease (Gale 2007).
What Causes Insulin Resistance?
A number of factors may be able to increase insulin resistance, including pregnancy (perhaps playing a role in gestational diabetes), vitamin D deficiency, infections, weight gain, stress, and puberty. The hormone level changes during pregnancy and puberty are thought to lead to increased insulin resistance.
Other factors can decrease insulin resistance, such as maintaining an appropriate body weight, and exercise. One intervention study had overweight/obese Latino teenagers exercise strenuously for 12 weeks, and measured their responses. They found changes in the activity of genes (gene expression, explained on the epigenetics page). These genes were associated with a variety of processes, including how insulin works, and surprisingly, type 1 diabetes. Those who responded most to the intervention had the most number of genes affected (Miranda et al. 2014).
A review of human and animal evidence linking chemicals to insulin resistance show links between insulin resistance and numerous chemicals; most of the recent experimental studies show convincing results. The most convincing evidence so far is with phthalates and air pollutants, where data from human studies has been confirmed in animal studies. The next strongest evidence is for persistent organic pollutants and BPA. The authors of this review also outline future research steps and ways to more easily screen chemicals for their ability to cause insulin resistance (Hectors et al. 2013). To read an article about this review, see Toxicity testing from the bottom up: proposed protocol for screening pollutants linked to insulin resistance, published in Environmental Health Perspectives (Potera 2013). Additional reviews also link endocrine disrupting chemicals to insulin resistance (e.g., Vanni et al. 2020).
A review of environmental chemicals and insulin resistance in children finds that despite scare evidence, epidemiological studies show a statistical link between exposure to pesticides, PCBs, BPA, phthalates, aromatic polycyclic hydrocarbides (air pollutants), and dioxins, and insulin resistance (Rotondo and Chiarelli, 2020).
Another review discuss the role of endocrine disrupting chemicals in the development of insulin resistance and other related conditions, such as obesity, type 2 diabetes, metabolic syndrome, and points out that these chemicals may also be involved in the development of non-alcoholic fatty liver disease (NAFLD) (Polyzos et al. 2012).
Some authors have proposed that environmental chemicals, including bisphenol A, persistent organic pollutants, heavy metals, and more, affect the functioning of the mitochondria, and thereby induce insulin resistance (Lim et al. 2010).
BPA Exposure During Development Leads to Glucose Intolerance and Insulin Resistance in Adulthood in Mice
These graphs show how exposure to BPA during development affects health outcomes in male mice in adulthood. On the left, insulin resistance is higher in mice exposed to the lower dose of BPA. On the right, glucose intolerance was higher in mice exposed to both doses of BPA.
Source: Alonso-Magdalena et al. 2010, EHP.
To see these and additional articles relating to insulin resistance in all types of diabetes, as well as the numerous environmental factors that can affect insulin sensitivity/resistance, see my PubMed collection, Insulin resistance.