Aims/hypothesis. Study the influence of age, zygosity and birth weight on insulin action and insulin secretion in twins.

Methods. In vivo insulin action and insulin secretion were measured using the euglycaemic, hyperinsulinaemic clamp technique and intravenous glucose tolerance test, respectively. We examined 104 monozygotic (MZ) twins and 88 dizygotic (DZ) twins in two age groups (25–34 and 57–66 years).

Results. There were no differences in birth weight, body mass index, waist to hip ratio or lean body mass between monozygotic and dizygotic twins. Younger monozygotic twins had a slightly higher insulin-stimulated glucose uptake (M) than younger dizygotic twins. In contrast, elderly monozygotic twins had a lower insulin-stimulated glucose uptake value compared with elderly dizygotic twins. Elderly monozygotic twins had a reduced insulin secretion relative to insulin resistance compared to dizygotic twins during oral glucose tolerance test (OGTT). Birth weight per se was not associated with insulin secretion or action in the twins. However, correcting for the genetic influence on birth weight using intrapair differences among monozygotic twin pairs, low birth weight was associated with insulin resistance and low insulin secretion after both oral and intravenous glucose administration in elderly MZ twins.

Conclusion/interpretation. Zygosity status has a major age (or time) dependent impact on in vivo insulin secretion and insulin action in twins independent of birth weight and adult antropometry. An additional non-genetic impact of low birth weight on insulin secretion and insulin action was found in elderly monozygotic twins. Ageing could play an important role by unmasking the influence of an adverse intrauterine environment on insulin resistance and low insulin secretion in twins.