ABNORMAL CIRCULATING PANCREATIC-ENZYME ACTIVITIES IN MORE THAN 25 PERCENT OF RECENT-ONSET INSULIN-DEPENDENT DIABETIC-PATIENTS - ASSOCIATIONOF HYPERLIPASEMIA WITH HIGH-TITER ISLET-CELL ANTIBODIES

Pancreatic amylase and lipase activities were measured in sera of 307 Caucasian insulin-dependent diabetes mellitus patients (IDDM) at clini cal onset, 303 nondiabetic siblings of registered patients, and 207 co ntrol subjects under age 40 years. In all subject groups lipasemia and pancreatic (but not salivary) amylasemia increased with age and were significantly correlated. Using age-dependent reference ranges, reduce d pancreatic enzyme levels were measured in 18% of patients, 6% of sib lings, and only 2% of control subjects (p < 0.001). Increased lipase l evels were noted in 10% of patients and in only 3% of siblings and 2% of control subjects (p < 0.001). Using both univariate and multivariat e statistical analysis, elevated lipase activities at clinical onset w ere associated with higher titers of autoantibodies against islet cell cytoplasmic antigens and glucagon, but not against insulin or the 65- kDa isoform of glutamic acid decarboxylase (GAD65-Ab), or with markers of genetic predisposition or metabolic dysregulation. These findings indicate the presence of modest, but statistically significant, variat ions in circulating pancreatic enzyme levels in 28% of IDDM patients a t clinical onset (p < 0.001 vs. 5% in control subjects). Increased lip ase levels may express a form or a stage of the disease with exocrine cell damage; their association with higher titers of islet cell and gl ucagon autoantibodies is not yet explained. Lower lipase and isoamylas e levels are thought to result from the reduced acinar cell function i n the vicinity of insulin-depleted islets. It must be tested whether p ancreatic enzyme activities in serum can also be altered during the pr eclinical stage and can thus be considered as an additional marker for the disease process in the pancreas.