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dissolutewastrel OP t1_j5vzuu4 wrote

#Abstract

> Diabetes represents a spectrum of disease in which metabolic dysfunction damages multiple organ systems including liver, kidneys and peripheral nerves1,2. Although the onset and progression of these co-morbidities are linked with insulin resistance, hyperglycaemia and dyslipidaemia3,4,5,6,7, aberrant non-essential amino acid (NEAA) metabolism also contributes to the pathogenesis of diabetes8,9,10. Serine and glycine are closely related NEAAs whose levels are consistently reduced in patients with metabolic syndrome10,11,12,13,14, but the mechanistic drivers and downstream consequences of this metabotype remain unclear. Low systemic serine and glycine are also emerging as a hallmark of macular and peripheral nerve disorders, correlating with impaired visual acuity and peripheral neuropathy15,16. Here we demonstrate that aberrant serine homeostasis drives serine and glycine deficiencies in diabetic mice, which can be diagnosed with a serine tolerance test that quantifies serine uptake and disposal. Mimicking these metabolic alterations in young mice by dietary serine or glycine restriction together with high fat intake markedly accelerates the onset of small fibre neuropathy while reducing adiposity. Normalization of serine by dietary supplementation and mitigation of dyslipidaemia with myriocin both alleviate neuropathy in diabetic mice, linking serine-associated peripheral neuropathy to sphingolipid metabolism. These findings identify systemic serine deficiency and dyslipidaemia as novel risk factors for peripheral neuropathy that may be exploited therapeutically.

> Handzlik, M.K., Gengatharan, J.M., Frizzi, K.E. et al. Insulin-regulated serine and lipid metabolism drive peripheral neuropathy. Nature (2023).

> https://doi.org/10.1038/s41586-022-05637-6

> Received > 20 December 2021

> Accepted > 07 December 2022

> Published > 25 January 2023

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HiroshiHatake t1_j5wiyap wrote

Family with type two diabetes here. If I'm reading correctly, supplementation of serine and glycine can help avoid neuropathy - so how do we supplement?

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cshaiku t1_j5wn7rn wrote

> supplementation of serine and glycine can help avoid neuropathy

I ran the study through chatGPT and this is its answer:

> The study suggests that supplementation of serine and glycine can help to avoid diabetic peripheral neuropathy. The study also suggests that a STT, similar to an oral glucose tolerance test, could identify patients who are particularly susceptible to sensory neuropathy and that normalizing circulating serine levels via dietary supplementation could delay the onset and progression of sensory neuropathy in diabetic mice. However, it is important to note that this is a study conducted in mice and more research is needed to confirm these findings in humans. Additionally, the study raises several key questions that still need to be addressed.

To tackle that last point about several key questions, I asked chatGPT to elaborate further:

> provide 5 examples of the key questions raised

> Why does serine and glycine deprivation suppress hepatic fatty acid synthesis and gene expression in the liver?

> What are the exact mechanisms by which diverse sphingolipid species contribute to neuropathy?

> How can the neurotoxic dyslipidaemia be managed?

> What are the diverse genetic changes that influence circulating serine and glycine?

> How does diabetes-induced rewired hepatic metabolism influence deficiencies in serine and glycine?

I am not a scientist, doctor, or whatnot, but I think it is fascinating if using chatGPT to analyse this kind of information may prove helpful in some way. Diabetes is incredibly debilitating and I hope we can solve it in our lifetimes, so anything one can do to foster further research, discussion, and all that is welcome, imho.

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KetosisMD t1_j5wutqe wrote

Type 2 Diabetes (over 95% of diabetes) is easily reversible with a proper low carb diet.

https://www.dietdoctor.com/diabetes

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cshaiku t1_j5x21pn wrote

Much easier said than done, for millions of people.

Granted, I have made tremendous progress since being diagnosed in 2010. I've lost over 80 lbs, recovered from being fatigued all of the time, gained metabolism and newfound energy to want to do things, etc. But it has not been easy.

There can be other complications to people's health that will greatly impact a low-carb diet, no matter how amazing that may be. I still appreciate you sharing that for others to know, in any case.

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