Insulin Antagonism Is Not a Primary Abnormality of Amyotrophic Lateral Sclerois but Is Related to Disease Severity*

Sensitivity to insulin was studied in 13 patients with amyotrophic lateral sclerosis (ALS) and 10 age- and weight-matched normal subjects by performing euglycemic clamp studies at low (1.5 mU/kg X min) and high (10 mU/kg X min) insulin infusion rates. Mean glucose disposal rates were similar in the ALS patients and normal subjects at both the low [4.8 +/- 0.6 (+/- SEM) vs. 5.2 +/- 0.6 mg/kg X min] and high (9.2 +/- 1.3 vs. 9.8 +/- 0.5 mg/kg X min) insulin infusion rates, respectively. Binding of [125I] iodoinsulin to monocytes was also similar in seven patients with ALS (3.8 +/- 1.0%/10(7) cells) and 10 normal subjects (3.9 +/- 0.9). However, glucose disposal rates correlated inversely with disease severity in the ALS patients, at both the low (r = -0.76; P less than 0.01) and high (r = -0.83; P less than 0.001) insulin infusion rates. We conclude that insulin antagonism is not a primary abnormality of ALS, but may be related to the inactivity associated with disease progression.