Familial longevity is marked by enhanced insulin sensitivity

Insulin resistance is a risk factor for various age‐related diseases. In the Leiden Longevity study, we recruited long‐lived siblings and their offspring. Previously, we showed that, compared to controls, the offspring of long‐lived siblings had a better glucose tolerance. Here, we compared groups of offspring from long‐lived siblings and controls for the relation between insulin and glucose in nonfasted serum (n = 1848 subjects) and for quantitation of insulin action using a two‐step hyperinsulinemic‐euglycemic clamp (n = 24 subjects). Groups of offspring and controls were similar with regard to sex distribution, age, and body mass index. We observed a positive bi‐phasic linear relationship between ln (insulin) levels and nonfasted glucose with a steeper slope from 10.7 mU L−1 insulin onwards in controls compared to offspring (P = 0.02). During the clamp study, higher glucose infusion rate was required to maintain euglycemia during high‐dose insulin infusion (P = 0.036) in offspring, reflecting higher whole‐body insulin sensitivity. After adjustment for sex, age, and fat mass, the insulin‐mediated glucose disposal rate (GDR) was higher in offspring than controls (42.5 ± 2.7 vs. 33.2 ± 2.7 μmol kg−1 min−1, mean ± SE, P = 0.025). The insulin‐mediated suppression of endogenous glucose production and lipolysis did not differ between groups (all P > 0.05). Furthermore, GDR was significantly correlated with the mean age of death of the parents. In conclusion, offspring from long‐lived siblings are marked by enhanced peripheral glucose disposal. Future research will focus on identifying the underlying biomolecular mechanisms, with the aim to promote health in old age.