How Costly is Diabetes?

Diabetes is an increasingly prevalent metabolic condition, with more than 1 in 10 people in the United States (US) has diabetes, and around 1.4 million Americans are diagnosed every year [1]. This condition has also cost hundreds of billions of dollars in terms of healthcare expenditure [1], and has multiple complications including kidney, heart, stroke, and loss of vision [2]. There are mainly 2 types of diabetes (excluding gestational diabetes, which refers to diabetes that occurs during a woman’s pregnancy) [2]:

• Type 1 diabetes mellitus (T1DM): an autoimmune disease whereby the body produces antibodies to attack the cells that produce insulin. This causes the body to be unable to produce any insulin and hence must rely on daily insulin injections. T1DM is usually diagnosed in younger age patients.
• Type 2 diabetes mellitus (T2DM): your body is unable to use insulin efficiently, leading to high levels of blood sugars as they do not react to the insulin. T2DM is usually diagnosed in adulthood.

In recent years, studies have shown the composition of the microorganisms in your gut, also termed as the gut microbiota (or gut microbiome), is implicated with blood sugar control and even diabetes (both Type 1 and Type 2). How are they associated with each other, and does one affect the other? Read on to find out more about the connections between them.

What is the gut microbiota?

Before we investigate the associations between gut microbiota and blood sugar or diabetes, we first need to understand: what exactly is the gut microbiota? The health of the human digestive system is greatly affected by the composition of the microorganisms that resides within our gut. These may include bacteria, virus and even fungi species. The number of bacterial cells here is estimated to be more than 10 times the number of human cells [3]. Composition and amount of gut microbiota are affected by many factors: environmental, lifestyle, dietary habits, antibiotics consumption, and many more [4].

The gut microbiota is also involved in the fermentation of prebiotics, to form metabolites such as short-chain fatty acids (SCFAs) and butyrate which confers certain health benefits to us. Prebiotics are defined by the International Scientific Association for Probiotics and Prebiotics (ISAPP) as ‘a substrate that is selectively utilized by host microorganisms conferring a health benefit’ [5].

How is the gut microbiota involved in diabetes?

Dysbiosis refers to a change of the composition of gut microbiota due to factors like diet, toxins, drugs, and pathogens [6], and this has been linked with many diseases, such as obesity, diabetes, and certain inflammatory conditions such as inflammatory bowel disease (IBD).

Type 1 diabetes mellitus

The incidence of T1DM is thought to be related to the interactions between both the immune system (innate immunity) and the gut microbiota [7].

In mice studies, the changes in the gut microbiota composition were also associated with development of type 1 diabetes with its effects on the immune system [8]. The Environmental Determinants of Diabetes in the Young (TEDDY) study carried out in humans aimed to identify the microbial composition that are predictive of T1DM and has shown protective effects of SCFAs in early-onset T1DM [9].

Type 2 diabetes mellitus

Research has shown that the composition of the gut microbiota differs in patients with type 2 diabetes and non-diabetic adults [10]. Patients with T2DM have a significantly higher proportion of Bacteroides and Proteobacteria than non-diabetic adults, and a significantly lower proportion of Firmicutes species [10]. This ratio was associated with an increased blood sugar levels after glucose load [10].

The metabolites of the fermentation of prebiotics and dietary fiber by the gut microbiota plays a central role in several homeostasis and cell signaling pathways [11]. These species are often found in lower abundance in patients with T2DM [11]. Metabolites such as SCFAs (butyrate and acetate etc.) strongly influence sugar metabolism and homeostasis, including the uptake of glucose by cells and preventing the breakdown of complex components to glucose molecules, all of which helps in reducing blood sugar levels [11].

Another possible explanation of how the gut microbiota affects T2DM could be via inflammation. T2DM as a metabolic condition is also associated with chronic, low levels of inflammation [12]. Different species of gut microorganisms have different effects on inflammation: some having pro-inflammatory effects (such as Fusobacterium), while others have anti-inflammatory properties (such as Akkermansia muciniphila). These anti-inflammatory properties of the good gut microbiota can potentially aid in improving insulin sensitivity, playing a crucial role in T2DM [12].

What can we do to improve the health of our gut microbiota?

One of the crucial regulators of the gut microbiota is your diet, with changes shown as rapidly as within 24 hours [7]. Consuming more prebiotics has also been linked with a lower incidence of T2DM [13]. A diet rich in prebiotics has been demonstrated to improve the gut microbiota composition (e.g., butyrate-producing bacterial species), leading to greater HbA1c reduction [14]. Prebiotics enhance the proliferation of good gut bacteria, which in turn will crowd out the bad bacteria. Other than promoting gut microbiota stability, the intake of prebiotics also promotes the fermentation by the gut microbiota (as they are also prebiotics in nature), leading to increased concentration of beneficial SCFAs [7].

Conclusion

The gut microbiota is not only associated with the health of your gut. It also plays a role in the development of many other diseases and body systems, which includes blood sugar levels and diabetes mellitus. Prebiotics’ actions on promoting a healthy gut microbiota also has indirect effects in controlling blood sugar levels, and subsequently diabetes mellitus.

References

1. American Diabetes Association (ADA). Statistics About Diabetes. 2022 April. Available on: https://www.diabetes.org/about-us/statistics/about-diabetes
2. Centers for Disease Control and Prevention (CDC). Diabetes: What is Diabetes? 2021 Dec. Available on: https://www.cdc.gov/diabetes/basics/diabetes.html
3. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474(11):1823-1836. Available on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433529/
4. Rutsch A, Kantsjö JB., Ronchi F. The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology. Immunol. 2020;11. Available on: https://www.frontiersin.org/articles/10.3389/fimmu.2020.604179/full
5. Gibson G., Hutkins R., Sanders M. et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14,491–502. Available on: https://www.nature.com/articles/nrgastro.2017.75
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8. Wen L, Ley RE, Volchkov PY, et al. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature. 2008;455(7216):1109-1113. Available on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574766/
9. Vatanen T, Franzosa EA, Schwager R, et al. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature. 2018;562(7728):589-594. Available on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296767/
10. Larsen N, Vogensen FK, van den Berg FW, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One. 2010;5(2):e9085. Available on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816710/
11. Cunningham, A.L., Stephens, J.W., Harris, D.A. Gut microbiota influence in type 2 diabetes mellitus (T2DM). Gut Pathog. 2021;13,50. Available on: https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-021-00446-0
12. Gurung M, Li Z, You H, et al. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine. 2020 Jan;51:102590. Available on: https://www.thelancet.com/journals/ebiom/article/PIIS235239641930800-X/fulltext
13. McRae MP. Dietary Fiber Intake and Type 2 Diabetes Mellitus: An Umbrella Review of Meta-analyses. J Chiropr Med. 2018;17(1):44-53. Available on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883628/
14. Zhao L, Zhang F, Ding X, et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science. 2018 Mar 9;359(6380):1151-1156. Available on: https://pubmed.ncbi.nlm.nih.gov/29590046/