(A) Corrected early insulin response to glucose (CIR) during OGTT (Botnia PPP cohort; N=3,300), (B) Disposition index (DI) represents early insulin response to glucose corrected for insulin sensitivity by the Matsuda index (CIR × ISI, Botnia PPP cohort; N=3,300). (C) Insulin secretion measured as first phase insulin response during an IVGTT (Botnia cohort; N=505). (D) Intact proinsulin-to-insulin ratio in the fasting state (Helsinki Birth Cohort, N=1,600). (F) Change in fasting plasma glucose concentrations during 24-year follow-up in non-diabetic subjects (Malmoe study, N=13,674) (E) Change in insulin secretion (disposition index) over time in non-diabetic subjects (Botnia prospective cohort, N=2,444). Bars represent mean ± SEM. Blue lines represent non-risk and red lines risk genotype carriers of rs10830963 in MTNR1B.