Figure 1.

A: Key differences and similarities in chronic glycemia and insulin distribution affecting insulin sensitivity between participant groups. Pe. hyperinsulinemia, peripheral hyperinsulinemia. B: Scatterplot depicting correlation between mean basal insulin concentration (x-axis), glycosylated hemoglobin (HbA_1c, darker shade of blue represents higher HbA_1c), and mean rate of glucose disposal (Rd) during hyperinsulinemic, euglycemic clamp. Insulin was infused at 40 mU/m²/min when Rd was measured. The figure shows that participants with type 1 diabetes (T1DM) (squares) had higher basal insulinemia (further to the right on the x-axis), higher chronic glycemia (darker shade of blue), and lower Rd (further down on the y-axis). GCK-MODY participants (triangles) had glycemia similar to that of T1DM participants (similar shade of blue) but lower insulinemia (further to the left on the x-axis) and higher Rd (further up on the y-axis). Despite having differing glycemia (differing shades of blue), GCK-MODY and control (circles) participants generally had lower and similar insulinemia and higher Rd than T1DM participants. Coefficient of determination (R²) between basal insulin concentration and Rd was 0.36. R² between HbA_1c and Rd was 0.09. R² for the multivariable linear regression model including both basal insulin concentration and HbA_1c as dependent variables and Rd as an independent variable was 0.36. Thus, these linear regression analyses show that insulinemia alone explained 36% of the variance in Rd, a factor that was virtually unchanged with the addition of chronic glycemia in multivariable linear regression analysis. Collectively, these data suggest hyperinsulinemia stemming from peripheral insulin delivery plays a far greater role than hyperglycemia in causing peripheral insulin resistance in type 1 diabetes. FFM, fat-free mass.