Duration and severity of hypoglycemia needed to induce neuropathy.

The duration and severity of hypoglycemia needed to induce neuropathy is not known. To test these variables, the percentage of teased fibers of peroneal and tibial nerves showing graded pathologic abnormalities was estimated in groups of rats that had been made hypoglycemic for various times and severities one week earlier. The techniques used maintained core temperature, pO2, pCO2, and hematocrit within physiologic limits. A control group was anesthetized and mechanically ventilated but insulin was not given. A second control group underwent no experimental manipulation. Life could not be sustained with hypoglycemia below 1 mmol/l. In 23 rats that were hypoglycemic (1.4 +/- 0.2 mmol/l, mean +/- S.E.M.) for various times less than 11 h, the frequency of axonal degeneration of teased myelinated fibers (0%-1%) was not different than in controls. In 9 young rats that were hypoglycemic (1.4 +/- 0.0 mmol/l) for various times of 12 or more hours, the frequency of fiber degeneration was significantly higher than in controls (P less than 0.01) and increased to as high as 26%. By contrast, in 5 older rats that were hypoglycemic (1.5 +/- 0.1 mmol/l) for various times of 12 or more hours, the frequency of degeneration was not different from that of controls. Both duration and severity of hypoglycemia are risk factors for fiber degeneration. The peripheral nerves are more vulnerable to prolonged severe hypoglycemia in younger rats than in older rats.