Can hypoglycemia be useful!?
Author: Sture Hobro
Hypoglycemia is thought to occur when blood glucose levels are under 70 mg/dL (3.9mmol/l) for diabetic patients and for healthy patient the level is set to 50 mg/dl (2.8 mmol/l). Typically, hypoglycemia occurs during diabetes treatment when insulin is injected, and glucose levels are low. Severe symptoms and even death can occur typically in diabetic patients.
However, in a groundbreaking experiment, Drenick let nine healthy male patients’ water fast for 50 days. As a result, glucose levels fell to around 3.9 mmol/l (70 mg/dl), which is borderline hypoglycemia, and ketone levels rose to an average of 14 mmol/l. As a final experiment, Drenick administered a dose of insulin to see the effect of insulin administration in starving humans. As a result, glucose levels in the blood fell to well below 1 mmol/l (18 mg/l), but more surprisingly (or not), without symptoms of hypoglycemia. At the same time, ketone levels were reduced from 14 to 11 mmol/l. The most important finding was that levels below 1 mmol/l and even as low as 0.5 mmol/l of glucose in the blood were without any symptoms of hypoglycemia when ketone levels were high.
We suggest a new better term, hypofuelemia (outside blood hypofuelemic) that will always be symptomatic. The important trigger of symptomatic hypofuelemia will be the availability of fuel, especially for the brain. The brain is behind the blood-brain barrier where only water-soluble fuels can pass freely. The fuels that easily pass the blood-brain barrier are fuels such as glucose and ketones, but not limited to that; medium-chain triglycerides can also pass through the blood-brain barrier, and several other fuels typically not available in large quantities such as lactate, acetate, citrate, and glutamine can also pass through the blood-brain barrier.
So, can hypoglycemia be useful? Well, when symptomatic and dangerous hypoglycemia sets in, is conditionalized and depends on the availability of other potential fuels. To draw a line and say that anything below 2.8 mmol/L of glucose in the blood is dangerous is wrong! Hypofuelemia may be a much better term to use and can be triggered by low glucose levels if other fuel sources are not present. If high levels of ketones are present, extremely low levels of glucose can obviously be well tolerated, as shown in Drenick’s pioneering work in 1972. Thus, forced hypoglycemia but not hypofuelemia may provide treatment benefits to cancer patients.
Figure A is a reproduction of the results from Drenick’s experiments in 1973 and shows how glucose levels fell below 1 mmol/l during nearly one hour when insulin was administered to fasting men. Figure B shows how we potentially can force hypoglycemia into cancer patients with CancerDialysis by also using small amount of insulin to block the gluconeogenesis and administer ketones in the dialysate (here 15 mmol/l).
