Alterations in nitric oxide/cyclic-GMP pathway in nondiabetic siblings of patients with type 2 diabetes

In this study, we have compared resistance to insulin-mediated glucose disposal and plasma concentrations of nitric oxide (NO) and cyclic-GMP in healthy volunteers with (n = 35) or without (n = 27) at least one sibling and one parent with type 2 diabetes. The 62 volunteers were further divided into groups of those with normal glucose tolerance or impaired glucose tolerance. Insulin-mediated glucose disposal was quantified by determining the insulin sensitivity index (ISI) in response to a low-dose, constant infusion of insulin (25 mU/kg·h) and glucose (4 mg/kg·min) for 150 min. The mean (±sem) ISI [(mL kg−1 min−1/pmol/L) × 103] was significantly greater in those without a family history (30.3 ± 2.3) as compared with nondiabetic volunteers with a family history of type 2 diabetes, whether they had normal glucose tolerance (17.0 ± 7.2) or impaired glucose tolerance (9.5 ± 1.4). In addition, basal NO levels, evaluated by the measurement of its stable end products[ i.e. nitrite and nitrate levels (NO2−/NO3−)]...