Fasting Diet Combined With Beta Cell Regeneration Might Reverse Type 1 Diabetes

Periodic fasting has long been demonstrated to have beneficial effects on autoimmune disorders, cancer prevention and treatments, cardiovascular disease, and a myriad of other ailments. This most recent paper by Cheng et al. might add the treatment of Type 1 diabetes to that list [1]. If successful in humans, it has the potential to reverse some or most of the loss of insulin-producing cells within the pancreas. Just as remarkable, the treatment itself is relatively straightforward, consisting of a regimented protocol of periodic fasting-like conditions.

Generally speaking, Type 1 diabetes results from an autoimmune mediated depletion of insulin-secreting pancreatic beta islet cells. In contrast, Type 2 results from lower cellular sensitivity to insulin. Type 2 is primarily caused by environmental factors such as poor diet.

The current medical approach to treating Type 1 diabetes is the periodic administration of insulin, usually through self-administered injections. Most new therapies focused on curing Type 1 diabetes are looking to repopulating beta islet cells through the use of reprogrammed induced pluripotent stem (iPS) cells.

However, these approaches are not as simple as the method demonstrated by Cheng et al in this recent study. The treatment consists of a “fasting mimicking diet” (FMD), which for mice corresponds to 3-4 day cycles of a high-fat and low-calorie diet, maintained for at least a month, followed by refeeding. This was performed on transgenic diabetic mice and also normal mice that had their beta cells depleted through the administration of high doses of a toxic drug.

Results were also repeated using human diabetic primary beta cells in culture. In this case, the treatment consisted of the addition of human serum from individuals undergoing FMD. The results were impressive, with all sets of experimental models exhibiting almost normal responses to glucose and insulin tolerance tests. Perhaps even more unexpectedly, the regrowth of pancreatic islets, following FMD and re-feeding, led to higher ratio of cells differentiating into beta cells, as opposed to other types.

Furthermore, normal diet combined with the addition of the drugs rapamycin and H89, which inhibit mTor and PKA respectively, led to similar results, suggesting that these signalling pathways are required for beta islet cell differentiation.

Conclusion

Can it be so simple that Type 1 diabetes in humans can be reversed by adhering to a similar diet, perhaps in combination with rapamycin and a PKA inhibitor?

Our optimism should be tempered with the fact that earlier studies have also had high hopes. The discovery of a new hormone in 2015, dubbed betatrophin, also appeared to promote beta-islet cell expansion. Unfortunately, this work was later found to be statistically invalid and thus retracted[2]. Clearly, reproducibility is key for all trials.

Right now the study authors have stated that a pilot clinical trial has demonstrated the feasibility of this approach, and more expanded and randomized trials are set to begin. We look forward to the results!

Literature

[1] Chia-Wei Cheng, Valentina Villani, Roberta Buono, Min Wei, Sanjeeve Kumar, Omer H. Yilmaz, Pinchas Cohen, Julie B. Sneddon, Laura Perin, Valter D. Longo. “Fasting-mimicking diet promotes Ngn3-driven β-cell regeneration to reverse diabetes”Cell. 2017 Feb 23; 168(5): 775–788.e12. doi: 10.1016/j.cell.2017.01.040

[2] Yi, Peng, Ji-Sun Park, and Douglas A. Melton. “Retraction Notice to: Betatrophin: A Hormone That Controls Pancreatic Β Cell Proliferation.” Cell 168.1-2 (2017): 326. PMC. Web. 30 Mar. 2017.