Abnormalities in erythrocyte insulin binding in offspring of conjugal non insulin dependent diabetic parents

Abstract

Insulin binding to erythrocyte insulin receptors was studied in 23 offspring (13 men and 10 women) born of conjugal diabetic parents having type 2 diabetes. Nine of the offspring were obese and 14 were non-obese, but all had normal glucose tolerance. Twenty-three age-, sex- and weight-matched non-diabetic subjects without a family history of diabetes were studied as controls. In the non-obese offspring mean basal plasma immunoreactive insulin (IRI) was elevated (P < 0.01), but the mean stimulated IRI showed no change in comparison to that of controls. In the obese offspring mean basal plasma IRI was similar, but the mean stimulated IRI was lower than that of obese controls (P < 0.01). Mean specific insulin binding was decreased in both obese (P < 0.01) and non-obese (P < 0.01) offspring when compared with the respective controls. Scatchard analysis of the binding data and the higher insulin concentrations required to achieve 50% inhibition of tracer binding indicated decreased receptor affinity in both obese and non-obese offspring. Analysis by average affinity profiles also indicated decreased receptor affinity, as shown by a lower average affinity constant K_c for the empty sites, in the offspring in comparison to that of controls (P < 0.001). Abnormalities in insulin binding to its receptor along with decreased affinity in the face of normal glucose tolerance may be an early biochemical marker of potential diabetes in this group at high risk of developing diabetes.