Greater reduction in the proinsulin-C-peptide ratio with a ketogenic vs control diet in patients with type 2 diabetes

Context The proinsulin to C-peptide (PICP) ratio reflects beta-cell stress and has been shown to decrease following diet-induced weight loss. Objective To compare the changes in PICP following a ketogenic (KD) or a low-fat diet (LFD) in individuals with type 2 diabetes (T2D). Methods The sample was 55 (±7) years of age, majority female (76%), and 54% African American. Participants (n = 51) were randomized to either a KD or a LFD for 12 weeks. PICP and the acute (ACP) and maximal (CPmax) C-peptide responses were determined using a hyperglycemic clamp. Multiple linear regression analyses were used to examine the effect of diet on changes in PICP. Spearman correlations were conducted to evaluate associations between changes in fasting and post-clamp PICP with changes in beta-cell function. Results Diet assignment was a significant predictor of change in fasting PICP (PICP0) (KD vs LFD β = −0.18 [−11.16, −0.05]) after adjusting for 12-week fasting glucose and baseline PICP0. Results were similar when 190-minute PICP (PICP190) was used as the outcome variable (KD vs LFD β = −0.23 [−6.99, −1.19]), after adjusting for 12-week fasting glucose and baseline PICP190. Spearman correlation analyses revealed that the change in ACP was inversely associated with changes in both PICP0 (ρ = −0.37, P = .009) and PICP190 (ρ = −0.38, P = .01) over the 12-week study. Conclusion A KD decreases the proportion of proinsulin secreted to a greater extent than a LFD in patients with early T2D, a change that was associated with an improvement in beta-cell function.