Optimal benefit reflects clinical benefit as a theoretical scale of 0%–100%. C-peptide values were derived from clinical data, which generally include oral glucose tolerance tests for those in prediabetes/stage 2 diabetes and mixed-meal tolerance tests for those after diagnosis (stage 3). The levels may be summarized as more than 0.80 nmol/L in prediabetes/stage 2 diabetes, 0.20–0.80 nmol/L in new-onset diabetes, 0.04–0.20 nmol/L 1–5 years after diagnosis, and less than 0.04 nmol/L in long-standing diabetes. The loss of C-peptide over a wide range associates with changes in hypoglycemia frequency, but the relationship with HbA1c levels flattens at high and low C-peptide levels. (i) In some individuals during prediabetes/stage 2 diabetes, adequate C-peptide response and skilled insulin adjustments buffer HbA1c levels to hyperglycemia. Insulin release and lower C-peptide levels do not markedly affect hyperglycemia. (ii) In the first five years following T1D diagnosis, declining C-peptide values coincide with declining HbA1c levels, particularly among individuals with less effective self-management, adolescents, and young adults. (iii) Gubitosi-Klug et al. (4) demonstrated that after long-standing T1D, even small amounts of C-peptide provide protection against hypoglycemia.