diabetes and the gut

Why we need to talk about it?

It is estimated that the number of people with diabetes is set to rise from 366 million worldwide as of 2011 to 522 million in 2030. Population growth, ageing, and urbanisation leading to a sedentary lifestyle is predicted to cause a 50.7% increase in diabetes[1, 2]. Diabetes is a serious condition if not managed, in 2012, it caused 1.5 million deaths [3]. The cost to the NHS of dealing with diabetes estimated to account for 10% of the NHS budget for England and Wales, with estimates totaling £40 billion by 2035 [4].

There are several different types of diabetes, the two key, and very different, types being:

Type 1 diabetes

An autoimmune condition where the body attacks cells in the pancreas that make insulin, insulin’s primary role is to manage blood sugar (glucose) levels. In type 1 diabetes, the level of glucose in your blood becomes too high as your body cannot produce enough insulin or the cells are unable to produce any insulin. Type 1 diabetics require injections of specific measures of insulin on a daily basis to manage blood glucose levels. Type 1 diabetes is not linked to age, diet or being overweight and is typically diagnosed in early infancy/childhood.

Type 2 diabetes

It accounts for 90-95% of all diabetes diagnoses [5]. A metabolic disorder causing the glucose in your blood to become too high due to your body becoming ineffective at using the insulin it has produced and/or your body is unable to produce enough insulin. T2D requires the management of blood sugar levels through diet and lifestyle or medication, such as metformin [6]. T2D is more frequently diagnosed in men at a younger age than women [7]. However, the biggest risk factor for the development of T2D is being overweight or obese [7]. Other risk factors include genetics, ethnicity [8], family history of T2D [9], lack of physical activity [10],  smoking [11], and ageing [5] – these all play an important role in how your gut microbiome functions.

 

So what has diabetes got to do with the gut?

We know that the microbes in your gut play an important role in metabolism and even the risk of developing obesity and cardiovascular disease. What is less known, but emerging, is the role of these microbes and association with diabetes.

Some highlights about what we know about the gut microbiome and T2D:

• From both animal and human studies, obesity and T2D are associated with dysbiosis (aka out of whack microbes – see here) [12].
• Scientists have even identified specific bacteria that may increase the risk of T2D due to how they affect your metabolism [12]. Pretty clever stuff, eh?
• Butyrate is produced by certain beneficial bacteria, it is a short-chain fatty acid that provides fuel for the cells in your gut. Interestingly, levels of butyrate-producing bacteria were lower in those with T2D. The role of short-chain fatty acids produced by your microbes is becoming clearer and they are thought to support immune health and metabolism (how we break down and use nutrients and energy) [12].
• Can probiotics help? One study looked at the effect of providing Akkermansia miciniphila (a type of bacteria) to diabetic mice – it exhibited antidiabetic effects! Of course, this was a study in mice so we still have a long way to go but it’s a start [13].
• Medication used to manage T2D, such as metformin might also interfere with your gut microbiome [14].

The prevalence of T1D has increased since World War II [15], which cannot be explained by purely genetic factors, so what is going on in our environment? Research in this field is more in its infancy than T2D, but here are some highlights:

• Key developments in the gut microbiome mostly occur during early childhood, it is during this time that the immune system also matures and T1D antibodies can develop [16] – you can read more about this here. Could the development of the gut microbiome, immune system and the presence of T1D antibodies be linked? This is an early school of thought but researchers are looking into it. There are plenty of studies in mice but mice and humans are very different beings!
• Probiotics may reduce the risk of autoimmunity but this has only been found in those carrying a high genetic risk of being predisposed to T2D [17].
• T2D compared to those without have a different gut microbiome. T1D typically have a more pro-inflammatory environment and increased levels of specific bacterial species, such as Bacteroidetes and reduced levels of Firmicutes [15].
• It’s not just bacteria that we need to think about when looking at the gut microbiome but also intestinal fungi. Higher levels of some species of fungi have been observed in those with T1D and on the flip side, poor blood sugar control may increase susceptibility to fungi overgrowth [18].

This is just a snapshot of the research touching on the idea that the gut microbiome may play an important role in both the development of T1D and T2D.

 

What does this all mean?

What is difficult about linking the gut microbiome (as a cause) and diabetes is that all other factors have to be controlled, which is very difficult to do when there are so many different factors that interplay in the development of these two very different conditions. From what we do know, the gut microbiome may play a really important role in understanding an individual’s risk of developing certain conditions and its management through novel therapeutic strategies, like supporting specific bacteria. We are a long way off knowing what this looks like but it’s the start of a fascinating area of research.

 

References

1. Whiting, D.R. et al. (2011). IDF Diabetes Atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Research and Clinical Practice, 94 (3), 311–
2. Zghebi, S.S. et al. (2017). Examining trends in type 2 diabetes incidence, prevalence and mortality in the UK between 2004 and 2014. Diabetes, obesity & metabolism, 19 (11), 1537– Available from http://www.ncbi.nlm.nih.gov/pubmed/28387052 [Accessed 13 October 2019].
3. GLOBAL REPORT ON DIABETES WHO Library Cataloguing-in-Publication Data Global report on diabetes(2016). Available from http://www.who.int/about/licensing/copyright_form/index.html [Accessed 14 October 2019].
4. Kanavos, P., Van Den Aardweg, S. and Schurer, W. (2012). Diabetes expenditure, burden of disease and management in 5 EU countries.
5. Wu, Y. et al. (2014). Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention[]. International journal of medical sciences. 1185–
6. Tripathi, B.K. and Srivastava, A.K. (2006). Diabetes mellitus: complications and therapeutics. Medical science monitor : international medical journal of experimental and clinical research, 12 (7), RA130-47. Available from http://www.ncbi.nlm.nih.gov/pubmed/16810145 [Accessed 14 October 2019].
7. Kautzky-Willer, A., Harreiter, J. and Pacini, G. (2016). Sex and gender differences in risk, pathophysiology and complications of type 2 diabetes mellitus[]. Endocrine Reviews. Endocrine Society 278–
8. Rhee, E.J. (2015). Diabetes in Asians. Endocrinology and Metabolism. Korean Endocrine Society 263–
9. Scott, R.A. et al. (2013). The link between family history and risk of type 2 diabetes is not explained by anthropometric, lifestyle or genetic risk factors: The EPIC-InterAct study. Diabetologia, 56 (1), 60–
10. Joseph, J.J. et al. (2016). Physical activity, sedentary behaviors and the incidence of type 2 diabetes mellitus: The multi-ethnic study of atherosclerosis (MESA). BMJ Open Diabetes Research and Care, 4 (1), . BMJ Publishing Group.
11. Maddatu, J., Anderson-Baucum, E. and Evans-Molina, C. (2017). Smoking and the risk of type 2 diabetes[]. Translational Research. Mosby Inc. 101–
12. TilgH, Moschen AR (2014), Microbiota and diabetes: an evolving relationship, Gut 2014;63:1513-1521
13. Everard A, Belzer C, Geurts L, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci USA 2013;110:9066–
14. Shin NR, Lee JC, Lee HY, et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 2014;63:727–35
15. Heli Siljander, Jarno Honkanen, Mikael Knip (2019) Microbiome and type 1 diabetes: EBioMedicine, https://doi.org/10.1016/j.ebiom.2019.06.031.
16. Belkaid, T.W. Hand Role of the microbiota in immunity and inflammation, Cell, 157 (1) (2014), pp. 121-141
17. Uusitalo, X. Liu, J. Yang, C.A. Aronsson, S. Hummel, M. Butterworth, et al. Association of early exposure of probiotics and islet autoimmunity in the TEDDY study, JAMA Pediatr, 170 (1) (2016), pp. 20-28
18. Nowakowska, A. Kurnatowska, B. Stray-Pedersen, J. WilczyńskiSpecies distribution and influence of glycemic control on fungal infections in pregnant women with diabetes, J Infect, 48 (4) (2004), pp. 339-346