Derangements of pyruvate dehydrogenase in circulating lymphocytes of NIDDMpatients and their healthy offspring

Pyruvate dehydrogenase (PDH) is poorly active in circulating lymphocytes of NIDDM patients; in vitro, it is unresponsive to insulin at 5 mu U/ml and a ctivated at 50 mu U/ml, instead of activated and inhibited as in healthy co ntrols. This study examines whether healthy offspring of NIDDM patients wit h a family history for this disease have these alterations. Twenty seven he althy offspring (23+/-10 yr, median 18 yr) and their parents (13 diabetic w ith a family history for NIDDM and 11 healthy without this history) were en rolled. Twenty healthy individuals without the history and matched for age and gender with the offspring served as controls. Minimum levels for enzyme activity before and after cell stimulation with insulin at 5 mu U/ml were computed for a 95% Cl with no more than 5% of the controls excluded. Increa sed or unvaried enzyme activity in response to insulin at 50 mu U/ml was de fined as abnormal. All NIDDM parents and 11/27 offspring had below normal e nzyme activity and defective and reversed enzyme response to insulin at 5 a nd 50 mu U/ml; three offspring had altered enzyme response to insulin at bo th concentrations, four to insulin at 5 mu U/ml, three to insulin at 50 mu U/ml and six, together with the healthy parents, had no alterations. We con clude that in healthy individuals a family history for NIDDM is frequently signaled, irrespective of age, by molecular derangements, with an apparent genetic background, in their circulating lymphocytes. (C) 1999, Editrice Ku rtis.