In middle-aged siblings of patients with type 2 diabetes mellitus normal glucose tolerance is associated with insulin resistance and with increased insulin secretion. The SPIDER study.

OBJECTIVES: To evaluate the frequency of impaired glucose tolerance (IGT) and of Type 2 diabetes mellitus (Type 2 DM) in siblings of patients with Type 2 DM, and to assess insulin release and insulin sensitivity in siblings with normal glucose tolerance (NGT), compared with NGT spouses of probands without family history of Type 2 DM. DESIGN AND METHODS: We evaluated 87 families including 103 Type 2 DM patients (87 probands), and we carried out an oral glucose tolerance test (OGTT) in 130 siblings and in 60 spouses. Among NGT subjects, 12 siblings and 16 spouses underwent a low-dose insulin-glucose infusion test (LDIGIT) to evaluate C-peptide release and insulin sensitivity. RESULTS: After the OGTT, 24 siblings were classified as having Type 2 DM, 31 as IGT, and only 14 spouses as IGT (P=0.0012 vs siblings). NGT siblings (n=75) showed higher insulin levels at 120 min than NGT spouses (n=46) at OGTT, in spite of identical blood glucose levels; at LDIGIT, NGT siblings secreted more C-peptide and showed a lower insulin sensitivity than NGT spouses. CONCLUSIONS: These data indicate that middle-aged siblings of probands with Type 2 DM have a high frequency of IGT and Type 2 DM, and that NGT siblings have increased insulin resistance and increased insulin secretion when compared with adequate controls.

Fluorimetric methods for the measurement of intermediate metabolites (lactate, pyruvate, alanine, beta-hydroxybutyrate, glycerol) using a COBAS FARA centrifugal analyser.

Intermediate products of the metabolism of glucose, fat and amino-acid are important in the evaluation of such metabolic disorders as diabetes mellitus, liver disease and metabolic acidosis. In the present study, methods for the measurement of intermediate metabolites (lactate, pyruvate, alanine, beta-hydroxybutyrate and glycerol) have been adapted to a fast centrifugal analyzer: the COBAS FARA. Correlation coeffcients rangedfrom 0.90 to 0.99, compared to established manual spectrophotometric methods. Within-run coeffcients of variation (CVs) ranged between 2.9 and 8.8% at low levels, between 1.5 and 5.7% at medium levels and between 1.2 and 5.6% at high levels. Between-run CVs were between 4.0 and 15.0% at low levels, between 1.7 and 7.0% at medium levels and between 1.3 and 2.7% at high levels. These fluorimetric assays for the determination of intermediate metabolites on COBAS FARA (Roche) have a good sensitivity and precision, are less costly than manual methods and can be used on a routine basis.