Because of conflicting reports on plasma levels of total immunoreactive glucagon (IRG) in obesity, we investigated, by gel filtration, the individual IRG fractions in grossly obese patients (N = 16; BMI 40 ± 2) as compared with normal weight subjects (N = 18). Mean total IRG was 142 ± 12 pg/ml in normal subjects and 190 ± 15 pg/ml (P < 0.02) in obese subjects. IRG3500 was 16 ± 2 pg/ml in normal subjects and 34 ± 5 pg/ml (P < 0.005) in the obese subjects. Obese patients with normal glucose tolerance demonstrated 30 ± 5 pg/ml IRG3500 (N = 11; P < 0.01) as compared with those who were obese with impaired glucose tolerance (42 ± 12 pg/ml, N = 5; P < 0.0025), although the total IRG of the latter group (173 ± 31 pg/ml) was not different from that of normal subjects. IRG9000 was of comparable magnitude in the entire groups of obese and normal subjects. A wide variability of big plasma glucagon levels was found in all three groups, mean levels not being significantly different. These data suggest that plasma IRG3500 levels are elevated in grossly obese patients, particularly in those patients with impaired glucose tolerance, a finding that may be masked by mere measurements of total plasma IRG.

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