Postmortem diagnosis of diabetic metabolic derangement: elevated alpha 1-antitrypsin and haptoglobin glycosylation levels as an index of antemortem hyperglycemia.

Fatal diabetic metabolic derangement is difficult to diagnose postmortem because of the paucity of characteristic morphologic findings. Hyperglycemia is an indicator of diabetic derangement. Conventional biochemical parameters for postmortem diagnosis of antemortem hyperglycemic states are not sufficiently resistant to antemortem and postmortem non-diabetic influences or are suited only for long and medium-term assessment of diabetes control. In the search for other, more reliable, indices of immediately antemortem blood glucose levels, we investigated the value of glycosylation levels of serum proteins with very brief biologic half-lives: a) In vitro studies were performed on the glycosylation course of the short-lived serum proteins alpha 1-antitrypsin (alpha 1-AT) and haptoglobin (HP). b) Glycosylation levels were measured after purification of alpha 1-AT and HP from sera of living and deceased non-diabetics and diabetics. c) The resistance of alpha 1-AT and HP glycosylation levels to autolysis was investigated. Our studies revealed the following: 1) alpha 1-AT and HP glycosylate considerably more rapidly than either albumin or hemoglobin. This rapid glycosylation, combined with the rapid turnover of both proteins; facilitates detection of short-term changes in glycemia. 2) alpha 1-AT and HP glycosylation levels are autolysis-stable and can be assessed even after advanced hemolysis. 3) alpha 1-AT and HP glycosylation levels appear to allow reliable ante- and postmortem discrimination between normoglycemic and hyperglycemic metabolic states. As a tool in the postmortem diagnosis of antemortem hyperglycemic states, alpha 1-AT and HP glycosylation levels combine the advantages of a short-term parameter with resistance to non-diabetic influences.