[REDLAN]

The situation is somewhat complicated and improperly understood.

the current hypothesis (i.e. it is still unproven) is that the damage is caused through glycation of proteins.

Until about 20 years ago nobody realised that glucose stuck to proteins at all, nor how important this process is in regulating the activity of enzymes. Plants use the same trick,this is what stevia is - the plant sticks glucose to an important regulatory molecule so it can deactivate it and store it for use later.

It appears that glucose sticks quite readily to proteins all on their own. The problem for your body is that this can change the shape of the protein and stop it working. Irregular shaped proteins can also clump together causing further problems. To prevent this happening the body has an array of anti-AGE's as they are known which prevent/reverse glucose sticking to proteins. Some of the B vitamins are thought to be very active in this regard.

In diabetes glucose levels rise high enough to exceed the capacity of your anti-AGE's to protect your body. The excess of damaged proteins then damage/disrupt other essential cellular processes - in particular they are thought to be the primary cause of microvascular damage - which leads to retinopathy, and nephropathy.

on retinopathy the DCCT found that retinopathy is very very sensitive to blood glucose levels, which strengthens the glycation hypothesis. Further supporting evidence comes from rodent studies, which show that dosing diabetic rats with very high levels of anti-AGE's can stop retinopathy occuring.

There are problems with the hypothesis however, and it is that there is a high degree of variabilty of complication rates of individuals with the same Hba1c. In particular neuropathy does not appear to be very closely related to hba1c levels.

Also for people with type 2, retinopathy rates are much less sensitive to hba1c levels than they are for type 1 suggesting that there are other mechanisms.

On ketones causing damage....

ketones if they reach a high enough level will cause damage to body tissues. the mechanism is different - it occurs through reduction in pH of body tissues (particularly blood and interstitial fluids). This is what happens in DKA.

Whether low levels of ketones cause damage over the long term is not known. There is a threshold effect in that normally the blood is buffered to remain within a very narrow pH. Exceeding or approaching close to threshold at which the body is able to maintain a normal pH could cause damage. Trouble is nobody knows what this threshold is.

There are no long term studies evaluating the safety or otherwise of ketogenic diets. Ketogenic diets are used in children to control epilepsy, where they appear to be a successful treatment. In the long term studies that I have seen of this group, almost nobody remains on a ketogenic diet for very long. Drop out rates are extremely high - 80%+ so it's impossible to say whether ketones are harmful or not.

Potentially long term elevation of ketone levels could be harmful.