- The Gluten–Leaky Gut–Diabetes Connection
- A Gluten-Free Diet Protects Mice against Type 1 Diabetes
- Select Case Studies in Humans Suggest Benefits for Type 1 Diabetes
- Has Wheat Become More Problematic?
- Is There a Critical Window for Gluten Exposure?
- But Wait, Didn’t the AHA Say That Gluten Was Protective against Type 2 Diabetes?
- Summing It Up
The prevalence of diabetes has skyrocketed in recent decades. Consider the following:
- An estimated 9.4 percent of the U.S. population has diabetes, and 33.9 percent has prediabetes. Together, this adds up to 100 million affected Americans (1).
- Five million people in the United States are expected to have type 1 diabetes by 2050, including roughly 600,000 children and adolescents (2).
Diabetes has reached epidemic proportions and is a familiar topic on my blog. You may have seen my 2015 article on reversing type 2 diabetes and more recently, how a fasting mimicking diet might soon be a viable treatment option for type 1 diabetes.
But what if we could prevent diabetes in the first place? Wouldn’t that be the best solution? In this article, I’ll review how gluten consumption or avoidance might affect your risk for type 1 and type 2 diabetes. We’ll start with type 1 diabetes.
The Gluten–Leaky Gut–Diabetes Connection
In type 1 diabetes (T1D), the immune system attacks the beta cells of the pancreas. These beta cells are responsible for the secretion of the hormone insulin, and a loss of these cells results in unregulated blood sugar levels. Individuals with T1D must rely on insulin injections or an insulin pump to maintain blood glucose.
Pioneering researcher Dr. Alessio Fasano has spent a great deal of his career studying autoimmunity, and he believes that autoimmune diseases like T1D are preceded by a leaky gut (3). In 2006, research from his lab showed that gliadin, a protein component of gluten, can cause intestinal permeability by upregulating the molecule zonulin, even in healthy subjects (4). Diabetic-prone rats have 35 times higher zonulin levels compared to diabetic-resistant rats. They develop intestinal permeability, which is closely followed by production of autoantibodies against pancreatic beta cells and clinical signs of T1D. Similarly, zonulin upregulation seems to precede T1D diagnosis in humans (5).
Several epidemiological studies also point to a gluten–diabetes connection. Children with celiac disease have a 2.4 times greater chance of developing T1D (6). Additionally, celiac patients diagnosed later in life have a higher rate of autoimmune diseases (23.6 percent) than celiac patients who were diagnosed at a very young age (5.1 percent) (7). This suggests that longer exposures to gluten could increase the risk for developing autoimmune diseases like T1D.
What about those who are non-celiac? The evidence is limited. Studies in mice, however, may provide some clues.
More good news about a gluten-free diet: it may protect against diabetes
A Gluten-Free Diet Protects Mice against Type 1 Diabetes
Several studies using a non-obese diabetic (NOD) mouse model of diabetes suggest that consumption of a gluten-free diet might reduce the risk of diabetes. When maintained on standard mouse chow, NOD mice have higher levels of gut mucosal inflammation and a higher incidence of diabetes (8, 9). Switching NOD mice to a gluten-free diet significantly reduces hyperglycemia and the presence of autoantibodies.
A possible microbial explanation
Intriguingly, the gluten–diabetes connection may be mediated by changes in the gut microbiota. Mice on a standard gluten-containing chow have increased abundance of Barnesellia, Bifidobacterium, and Tannerella species, while mice on a gluten-free chow had greater microbial richness and an increased abundance of Akkermansia species (10). Akkermansia muciniphila is a beneficial bacterium that feeds off the mucus layer in the gut and stimulates endocannabinoid signaling, which reduces inflammation and improves gut integrity (11). Previous studies have shown that increased levels of Akkermansia muciniphila are associated with a reduced incidence of T1D (12).
The authors write:
Gluten could contribute to the pathogenesis of T1D in the NOD mouse by decreasing Akkermansia, a genus of [the gut] microbiota that protects against T1D. Alternatively, gluten-containing diets may promote ‘‘pathogenic or diabetogenic’’ bacteria. Further experiments are needed to prove these possibilities. (10)
Regulatory T cells
The gluten-free chow group also had a higher percentage of regulatory T cells (Tregs) in the mesenteric lymph nodes (MLN) compared to the standard gluten-containing chow (10). Regulatory T cells in the MLN drain into the gut and suppress inflammatory immune responses (13).
Select Case Studies in Humans Suggest Benefits for Type 1 Diabetes
Of course, it’s important to look beyond animal studies. One human case study from Denmark describes a six-year-old boy diagnosed with type 1 diabetes without celiac disease. His hemoglobin A1c (HbA1c), a common marker of long-term blood glucose control, was 7.8 percent at diagnosis. After adopting a gluten-free diet, HbA1c stabilized at 5.8 to 6.0 percent without the need for insulin therapy. Twenty months later, when the case study was published, he was still without daily insulin therapy and had a normal fasting blood glucose of 74 mg/dL (14). A small pilot study of children with newly diagnosed T1D found comparable results. After 12 months on a gluten-free diet, seven of 13 pediatric patients were still in partial remission, assessed by insulin-dose adjusted A1c (15).
Has Wheat Become More Problematic?
Farmers are constantly breeding for varieties that produce the most profit, with the least susceptibility to disease. The result is a crop that can be quite unlike its ancestral counterpart. A group of researchers in Israel tested the ability of modern wheat flour to cause diabetes and compared it to flours from several ancestral wheat landraces. They found that animals that received ancestral wheat had a lower incidence of T1D compared to animals fed the modern wheat variety (17).
This is not the first study to identify differences between modern and ancient wheats. A group of researchers in the Netherlands found that the presence of glia-ɑ9, a major immune recognition sequence of alpha-gliadins, is higher in modern wheat compared to ancient varieties. They suggest that selective wheat breeding may have inadvertently contributed to the increased prevalence of celiac disease (18).
Is There a Critical Window for Gluten Exposure?
For many years, scientists have been aware of critical periods during development in which infants are more readily influenced by certain inputs. Babies constantly put things in their mouths, effectively training their immune systems and acquiring oral tolerance to potential allergens. It certainly seems plausible that there could be an optimal time for the immune system to be exposed to certain foods, such as gluten.
I’ve talked about critical windows for gluten exposure in relation to celiac disease previously on my podcast. Epidemiological studies have suggested that there might also be a critical period for gluten exposure relative to T1D. In one study, researchers followed a cohort of children at risk for T1D from birth for an average of 4.7 years. They found that children exposed to cereal grains (including wheat, oats, barley, rye, and rice) before three months or after seven months tended to have greater pancreatic autoimmunity compared to children introduced to cereal grains between four and six months (19).
However, a randomized controlled trial published in 2011 did not support these epidemiological findings. The BABYDIET study included 150 infants with a family history of T1D and an at-risk HLA genotype. They were randomly assigned to receive their first gluten exposure at six months or 12 months of age. After three years, the two groups had no significant differences in markers of islet autoimmunity or T1D diagnoses (20).
But Wait, Didn’t the AHA Say That Gluten Was Protective against Type 2 Diabetes?
Thanks to an American Heart Association (AHA) news report, you may have seen some headlines a few months ago that concluded that gluten was protective against type 2 diabetes (T2D). In an abstract presented at an AHA meeting, they reported that people who ate the most gluten tended to have the lowest incidence of type 2 diabetes.
In my recent article on the coconut oil debacle, I discussed my concerns about industry influence in the AHA, so I won’t rehash that here. Instead, let’s look at the limitations of the evidence they cite. The study results were presented at an AHA meeting and, to my knowledge, have not yet been published in a journal, so we’ll have to go off what was included in the press release and abstract:
- The study was observational. This is not a randomized clinical trial. They simply looked at how much gluten people tended to eat and made associations with the incidence of diabetes. We could easily see how the healthy user bias might play in here. If whole grains are promoted as healthy, people who are eating the government recommended six-plus servings of grains (including gluten) may also be adhering to other healthy practices, such as exercising, eating fruits and vegetables, and avoiding smoking and excessive alcohol consumption, and thus have less risk of developing T2D.
- They relied on self-reported gluten intake. Food frequency questionnaires ask subjects to recall their consumption over a defined period in the past and are notoriously imprecise.
- There were no “gluten-abstainers.” They only looked at people eating varying doses of gluten, ranging from four to 12 grams per day. None of their participants was on a gluten-free diet.
- No dietary data. What are people who eat a low-gluten diet eating instead? Are people who are eating less gluten eating more soy, corn, and rice?
- Low strength of association. The study found only a 13 percent difference in T2D incidence between low-gluten eaters and high-gluten eaters. Given the number of subjects, this is a fairly minor association. In fact, if you look at the language in the study abstract, they make light of the fact that higher gluten consumption was associated with less incidence of T2D.
- Third variables: The one thing wheat does have going for it is that it’s a potent prebiotic, and sadly, one of the primary sources of fiber in the Standard American Diet. If you remove wheat from your diet and don’t replace it with other prebiotic fibers, your risk of diabetes could increase. This doesn’t necessarily mean that you wouldn’t be better off eating a gluten-free diet rich in other prebiotic fibers. In the abstract, the authors note: “The associations were slightly attenuated after further adjusting for cereal fiber […] but not other carbohydrate components.” I look forward to seeing the full methods published to see if fiber was one of the components included in the adjusted analysis.
The bottom line: without a robust clinical trial that addresses these limitations, the AHA should refrain from making sweeping claims that could misguide the public.
Meanwhile, animal studies are allowing us to randomize treatments and understand the mechanisms at play in T2D, which is extremely difficult to do in human nutrition studies. For example, one study found that a gluten-free diet promotes glucose tolerance in a mouse model of T2D (21). Furthermore, epidemiological studies in humans have found no association between celiac disease and T2D. If avoiding gluten was problematic, we would expect celiac patients on long-term gluten-free diets to be developing T2D.
It’s also prudent to note that a randomized crossover study found that three months of a Paleolithic (gluten-free) diet was sufficient to improve glycemic control and HbA1c in T2D patients (22). This was a pilot study, so it only had 13 patients, but I certainly look forward to seeing more research of this kind.
Summing It Up
That was a lot of research! In case you got bogged down in the details, here are the major points:
Type 1 Diabetes:
- Animal studies suggest that gluten-free diets may be protective, possibly by altering the microbiome.
- Human case studies suggest that children diagnosed with T1D could benefit from a gluten-free diet.
- Modern wheat varieties are potentially more diabetogenic than ancient wheats.
- Randomized controlled trials don’t support a critical window for gluten exposure in infants to reduce the risk of developing T1D.
Type 2 Diabetes:
- An AHA report suggesting that gluten consumption is protective against T2D received a great deal of media hype, but the evidence is observational and not clear-cut.
- Animal studies suggest that gluten-free diets may improve insulin sensitivity.
- A Paleo-type diet has been shown to improve glycemic control in a small cohort of T2D patients.
Overall, my reading of the evidence and my clinical experience both favor avoiding gluten for preventing, and even potentially reversing, diabetes.