Predictors of abnormal glucose tolerance in persons at risk of type 2 diabetes:: the RIAD study

Background and objective: Early detection of glucose intolerance is an important issue in diabetes care. In the metabolic syndrome it is associated with an increased incidence of cardiovascular events. So far it is not clear which anthropometric and metabolic/hormonal parameters are of importance in the conversion of normal to impaired glucose tolerance. Patients and Methods: The participants of the RIAD (Risk factors in IGT for Atherosclerosis and Diabetes) study had to meet the following criteria: related to type 2 diabetic patients, obesity and/or dyslipidaemia. A total of 358 subjects (age: 40-70 years) with normal glucose tolerance (NGT) in an oral glucose tolerance test (OGTT, 75 g glucose), were examined after a follow-up of 2.90 +/- 0.47 years. 284 of them remained with normal glucose tolerance, while 64 developed an impaired glucose tolerance (IGT) and ten type 2 diabetes (T2DM). The data of the initial screening examination were analysed in three groups (NGT-NGT; NGT-IGT; NGT-T2DM). Plasma glucose (PG), insulin, C-peptide and proinsulin were measured in the fasting state, as well as every 30 minutes during an OGTT, and also basal plasminogen activator inhibitor (PAI) and inflammatory parameters. Results: Subjects who converted to IGT or diabetes show, already in the stage of normal glucose tolerance, clear tendency for the development of the metabolic syndrome. They were more obese and had higher fasting and 2hPG values. The early phase insulin secretion, c0alculated as a ratio of DeltaInsulin 30'/DeltaPG 30', was lower in the IGT and the diabetes groups (n.s.). Both groups showed a significantly increased insulin resistance. Both converter groups revealed significantly higher PAI (Plasminogen-Activator-Inhibitor) levels and a striking but not significant increase in inflammatory parameters. Conclusions: Subjects who develop IGT and type 2 diabetes, will already in the stage of NGT show an impairment of insulin secretion and higher insulin resistance. Both processes seem to develop parallel to each other and determine the progress of the glucose intolerance. Fasting and 2h post-challenge glucose were the most important predictors of subsequent glucose intolerance.