Fructose Normalizes Defective Hypoglycemia Response in Type 1

Fructose infusion can help restore the impaired counterregulatory response to hypoglycemia seen in many type 1 diabetes patients. The findings could have "major implications" for the care of patients undergoing intensive insulin treatment, who are at greatest risk of developing defective responses to hypoglycemia.

The problem may arise from defects in systems for sensing glucose deficiency and for initiating the release of glucagon and epinephrine, which trigger endogenous glucose production, Dr. Ilan Gabriely and Dr. Harry Shamoon of the Albert Einstein College of Medicine in the Bronx point out.

Fructose is known to have a catalytic effect on glucokinase, which plays a key role in regulating insulin secretion. The researchers hypothesized that fructose would strengthen the counterregulatory response to hypoglycemia due to this catalytic effect, and showed that it indeed did so in a previous study with non-diabetic patients.

In the current study, Drs. Gabriely and Shamoon conducted stepped hypoglycemic clamp studies with and without fructose infusion in eight patients with intensively controlled diabetes. Patients were kept at 5.0, 4.4, 3.9 and 3.3 mmol/L of glucose, at 50 minutes for each step.
Fructose coinfusion raised the glucose threshold that triggered epinephrine secretion from 3.3 mmol/L to 3.9 mmol/L, and fructose coinfusion amplified epinephrine secretion by 56%. Production of endogenous glucose in response to hypoglycemia was 90% higher with fructose infusion.

"We may speculate that fructose-induced activation of glucokinase either bypasses or corrects the defective metabolic signaling by hypoglycemia in individuals with HAAF (hypoglycemia-associated autonomic failure), yielding clues to its pathogenesis and/or treatment," the researchers conclude.
Diabetes 2005;54:609-616.

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