We developed a novel method for evaluating insulin sensitivity (IS) in peripheral tissues using blood specimen, platelet, as one of the target organ of insulin, in order to simplify and shorten the measurement of IS in outpatients with diabetes and/or obesity.
We defined the lowest concentration (LC) of ADP to induce platelet second aggregation (PSA), as we found out that the insulin actions on LC of ADP-induced PSA was larger than that on other concentration of ADP-induced PSA.Then we measured LC of ADP-induced platelet aggregation (PA), after 3 min preincubation with various concentrations of human recombinant insulin. Serious changes of significant plalatetet aggregation rate (PAR) was evoked from a low insulin concentration (0.063 or 0.125 nmol/l) in normal subjects, on the contrary, a significant changes of PAR could be evoked from a relatively high insulin concentration (more than 0.5 nmol/l) in insulin resistant subjects. So we settled, the minimal insulin concentration (MIC) by
which significant change of PAR could be induced comparing to the basal PAR without preincubation of insulin, as an insulin sensitivity on platelet. And the changes of PA at every insulin concentration in normal subjects was significantly larger than those in insulin resistant subjects, we calculated the total changes in PAR (% of total changes in PAR). After then, we computed the insulin sensitivity index (ISI) of platelet. ISI values in 50 normal subjects, 60 diabetics and 40 obese subjects were distributed logarithmically, then we calculated log (ISI) value (MISI) for clinical evaluation value. In the clinical study, we measured insulin sensitivity on platelet, hyperinsulinemic euglycemic clamp and other metabolic markers in ten normal subjects, 12 diabetics and 10 obese subjects. Correlation coefficient between glucose infusion rate (GIR) and MISI was 0.79 (p<0.001), that between GIR and homeostatic model assessment (HOMA) was 0.54 (p<0.01) and that between GIR and body mass index (BMI) was 0.66 (p<0.01), respectively. These data would demonstrate that insulin sensitivity on platelet in vitro would reflect an insulin sensitivity on peripheral tissues in vivo.
These data suggested that an simple method for the measurement of insulin sensitivity on human platelet would be a useful device to evaluate easily and quickly insulin resistance of outpatients with diabetes and obesity. Less