Insulin secretion and anti-GAD65 antibodies in subjects with impaired glucose tolerance.
The study was designed to evaluate the pattern of insulin secretion and the presence of anti-GAD65 antibodies as beta-cell autoimmune marker in subjects with impaired glucose tolerance (IGT) and their impact on the further development of glucose intolerance. 29 subjects with IGT, of mean BMI 24.7 +/- 2.4 kg/m(2) and mean age 37.7 +/- 7.0 years were enrolled in the study. They were followed-up once yearly for three years. A group of 59 age- and weight-matched subjects with normal glucose tolerance (NGT) served as a control group. 42 newly-diagnosed diabetic patients, of mean BMI 24.4 +/- 2.7 kg/m(2) and mean age 37.2 +/- 6.9 years were also studied. According to their response during IVGTT the subjects with IGT were divided into two groups. The first group (n = 11)(IGT-I) showed reduced FPIS (34.0 +/- 8.9 mU/l vs 114.4 +/- 41.2, p < 0.001), SPIS being within normal values, and reduced AUC for total insulin secretion (1554.1 +/- 496.3 vs 2323.6 +/- 804.5 mU/l x 60 min, p < 0.001); the difference with type 1 diabetic patients being significant (p < 0.001), the pattern of insulin secretion being quite similar to that of type 2 diabetic patients. The other group (n = 18) (IGT-II) demonstrated normal insulin secretion (FPIS, SPIS, AUC for insulin secretion), not differing from that of the controls with NGT. Anti-GAD65 were present in 3.3% of subjects with NGT, in 73.7% of patients with type 1 diabetes and in none of type 2 diabetic patients. 18% from the group with IGT-I were anti-GAD65 positive, and 22% - from IGT-II. 5 of the subjects with IGT-I developed diabetes during the follow-up period - 2 at the 1st year, 1 at the 2nd year and 2 - at the third year. One of these patients was anti-GAD65 positive (having the highest anti-GAD65 level amongst the others with IGT - 15.2 U/ml), showing pattern of insulin secretion similar to that of type 1 diabetic patients. 3 of the subjects with IGT-II reverted to NGT within the first year and 2 - at the second year, none of them being anti-GAD65 positive. The anti-GAD65 positive patients from this group remained with IGT, and none progressed to diabetes mellitus. We consider that IVGTT allows precise assessment of the phases of insulin secretion and in combination with the study of anti-GAD65 antibodies helps to identify the subjects with IGT at risk of developing diabetes mellitus. As far as the decrease in the FPIS is considered it could be proposed that such subjects are assigned to certain protective measures - diet, physical activity and some drugs affecting postprandial glucose levels.