Question: Why should postprandial blood glucose be kept under 140 milligrams per deciliter?
Short Answer: When blood glucose rises above 140 mg/dL, this is the approximate point at which it spills into the polyol pathway at a greater-than-normal rate, which represents a suboptimal state of metabolism that is likely to hurt antioxidant status and compromise detoxification pathways as well as the recycling of vitamin K and folate. It must be kept in mind that a healthy person will adapt to glycemic loads they consume regularly. Thus, a one-time spike above 140 mg/dL should never be used to conclude anything whatsoever. Only repeated spikes above this level with repeated consumption of the same glycemic load over several days to several weeks should be used as a cause for concern.
is it also bc glucose is converted to fructose in the pathway?
Question: Why should postprandial blood glucose be kept
under 140 milligrams per deciliter?
Short Answer: When blood glucose rises
above 140 mg/dL, this is the approximate point at which it spills into the
polyol pathway at a greater-than-normal rate, which represents a suboptimal
state of metabolism that is likely to hurt antioxidant status and compromise
detoxification pathways as well as the recycling of vitamin K and folate. It
must be kept in mind that a healthy person will adapt to glycemic loads they
consume regularly. Thus, a one-time spike above 140 mg/dL should never be used
to conclude anything whatsoever. Only repeated spikes above this level with
repeated consumption of the same glycemic load over several days to several
weeks should be used as a cause for concern.`
Yes, the polyol pathway only gets activated above a certain level of glucose. I don’t remember the exact level but it was quite high so 140 is probably close.
I’m not sure the reason for why it’s bad is because the polyol pathway leads to conversion of glucose to fructose. It might be the sorbitol accumulation that is more problematic.
In the polyol pathway glucose is converted to sorbitol with the enzyme aldose reductase. Sorbitol is then further converted to fructose. Aldose reductase inhibitors have been found to be beneficial in diabetics by preventing the conversion of glucose to sorbitol. See this study as an example: Epalrestat: an aldose reductase inhibitor for the treatment of diabetic neuropathy - PubMed
This is why I think in general, for someone that has good insulin sensitivity and whose blood glucose rarely spikes high, the area under the curve of the blood glucose is most important for longevity. On the other hand, if someone is insulin resistant or diabetic and is experiencing very high spikes, then preventing the spikes may start becoming more important than simply reducing the area under the curve.
It appears that in most tissues, most of the sorbitol is converted to fructose, because the conversion of glucose to sorbitol is generally rate-limiting. However, some tissues have less (or none at all) of the enzyme that converts sorbitol to fructose leading to sorbitol accumulation in these tissues when the polyol pathway is activated. See the below taken from here: Biochemistry, Polyol Or Sorbitol Pathways - StatPearls - NCBI Bookshelf
Fundamentals
Normally, glucose is processed by the glycolysis pathway and is utilized for ATP production and energy. When glucose levels become exorbitantly elevated, other pathways are upregulated to handle the glucose effectively. These pathways include the glycation pathway, the hexosamine pathway, the protein kinase C pathway, the alpha-ketoaldehyde pathway, and the sorbitol pathway.[2][3][4][5][6] Research has indicated that all these pathways share a common characteristic of producing reactive oxygen species. [7]
The first step in the sorbitol pathway is the conversion of glucose to sorbitol via the enzyme aldolase reductase. This step utilizes a hydrogen group donated by NADPH. This is also the rate-limiting reaction of this entire pathway. The second step in this pathway is the conversion of sorbitol into fructose via the enzyme sorbitol dehydrogenase. This step donates a hydrogen group to NAD+, creating a byproduct of NADH.[8] This step is reversible. The sorbitol pathway plays a role in metabolizing glucose and is involved in maintaining the redox balance by utilizing substrates such as NADPH and NAD+ to drive the reactions."
Issues of Concern
A point of concern regarding the sorbitol pathway is that not all tissues have the enzyme sorbitol dehydrogenase, and these include the retina, kidneys, and Schwann cells. As a result, in diabetic patients or those with extremely high glucose levels, sorbitol accumulates to toxic levels and leads to complications within these organs. This pathway provides some explanations of the formation of complications in diabetic patients. Without early intervention and adequate glycemic control, the complications formed from the polyol pathway can become permanent and significantly decrease quality of life.
Cellular Level
Tissues with sorbitol dehydrogenase include the ovaries, seminal vesicles, liver, and the lens, albeit at a low level of activity. Tissues without sorbitol dehydrogenase include kidneys, the retina, and Schwann cells. It is in these tissues where complications can arise due to the deficient enzyme.