Objective: To establish whether the relation between size at birth and non-insulin dependent diabetes is mediated through impaired β cell function or insulin resistance.

Design: Cohort study.

Setting: Uppsala, Sweden.

Subjects: 1333 men whose birth records were traced from a cohort of 2322 men born during 1920-4 and resident in Uppsala in 1970.

Main outcome measures: Intravenous glucose tolerance test at age 50 years and non-insulin dependent diabetes at age 60 years.

Results: There was a weak inverse correlation (r=-0.07, P=0.03) between ponderal index at birth and 60 minute insulin concentrations in the intravenous glucose tolerance test at age 50 years. This association was stronger (r=-0.19, P=0.001) in the highest third of the distribution of body mass index than in the other two thirds (P=0.01 for the interaction between ponderal index and body mass index). Prevalence of diabetes at age 60 years was 8% in men whose birth weight was less than 3250 g compared with 5% in men with birth weight 3250 g or more (P=0.08; 95% confidence interval for difference −0.3% to 6.8%). There was a stronger association between diabetes and ponderal index: prevalence of diabetes was 12% in the lowest fifth of ponderal index compared with 4% in the other four fifths (P=0.001; 3.0% to 12.6%).

Conclusion: These results confirm that reduced fetal growth is associated with increased risk of diabetes and suggest a specific association with thinness at birth. This relation seems to be mediated through insulin resistance rather than through impaired β cell function and to depend on an interaction with obesity in adult life.