Diabetes is a complex condition involving multiple body systems, including the gut and the gut barrier function. Helping diabetic patients with a personalised nutrition plan shouldn’t focus exclusively on foods’ glycaemic index, but also on gut health and specifically on the gut barrier’s health. Recent studies have found a strong correlation between diabetes (both type1 and type2) and raised zonulin levels. Keep on reading below to understand what this means, its implications and how it can be addressed.
What is zonulin?
Zonulin proteins are involved in modulating gut permeability, and accordingly to studies zonulin can be considered a biomarker for gut barrier dysfunction. The gut barrier’s role is to let nutrients in/out in order to be absorbed and to prevent pathogens/toxins/allergens to enter the circulation via the gut. Junctions in the gut wall adapt to the situation – letting “good” stuff in or tightening to keep “bad” stuff out. What happens when those junctions are dysregulated and just let everything in? We will experience different symptoms ranging from general inflammation, skin rashes, IBS symptoms, food intolerances etc… This scenario is also known as “leaky gut” or intestinal permeability.
Relationship with diabetes
A 2014 study found a correlation between elevated zonulin and insulin resistance, dyslipidemia and inflammation. This study evaluated a total of 388 patients to find that all patients with type 2 diabetes (143) had higher serum zonulin levels than impaired or normal glucose tolerant subjects. Another study associated poor glycemic control with a worse intestinal barrier function. A recent study showed that whilst dietary intervention (Okinawan style diet) can modulate blood glucose levels, lower BMI and plasma lipids, zonulin levels remain high. Higher zonulin levels are also associated with obesity, where a higher intestinal absorption is usually seen.
Diabetes and leaky gut
A cause of the increased intestinal permeability in diabetes can be caused by an increased general inflammation typical of this condition and obesity, which is often present in diabetic patients. Research is now trying to understand if increased zonulin (because of obesity, altered gut microbiota, celiac disease, or other gut inflammatory conditions) can play a part in the development of type2 diabetes in predisposed subjects.
Strategies
Addressing gut health and gut barrier integrity in diabetics is of vital importance in achieving patient’s health goals. Supplementation with glutamine and targeted probiotics can be a strategy, along with identifying the root causes of increased intestinal permeability via a personalised one-to-one assessment.
References
Fasano, A. (2012) “Intestinal permeability and its regulation by zonulin: Diagnostic and therapeutic implications,” Clinical Gastroenterology and Hepatology, 10(10), pp. 1096–1100.
Fasano, A. (2012) “Zonulin, regulation of tight junctions, and autoimmune diseases,” Annals of the New York Academy of Sciences, 1258(1), pp. 25–33.
Fasano, A. (2020) “All disease begins in the (leaky) gut: Role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases,” F1000Research, 9, p. 69.
Jayashree, B. et al. (2013) “Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes,” Molecular and Cellular Biochemistry, 388(1-2), pp. 203–210.
Moreno-Navarrete, J.M. et al. (2012) “Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance,” PLoS ONE, 7(5).
Ohlsson, B. (2019) “An okinawan based Nordic diet improves glucose and lipid metabolism in health and type 2 diabetes, in alignment with changes in the endocrine profile, whereas zonulin levels are elevated (review),” Experimental and Therapeutic Medicine [Preprint].
Yuan, J.-H. et al. (2021) “Impaired intestinal barrier function in type 2 diabetic patients measured by serum LPS, zonulin, and IFABP,” Journal of Diabetes and its Complications, 35(2), p. 107766.
Zhang, D. et al. (2014) “Circulating zonulin levels in newly diagnosed Chinese type 2 diabetes patients,” Diabetes Research and Clinical Practice, 106(2), pp. 312–318.
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