This randomised controlled study in obese men demonstrates that treatment with t10c12CLA, which induces insulin resistance, also increases plasma proinsulin concentrations, independently of changes in insulin concentrations. Treatment with t10c12CLA caused a marked increase in proinsulin (~20%). This isomer-specific, fatty-acid-induced hyperproinsulinaemia was closely related to insulin resistance, and also independent of changes in plasma concentrations of specific insulin, C-peptide, glucose, adiponectin and obesity. Thus, proinsulin seems to be independently related to changes in insulin sensitivity, when measured prospectively in a controlled fashion. This association has previously only been described in observational cross-sectional studies [3, 4].
Interestingly, the association between insulin and insulin resistance did not remain significant after adjusting for proinsulin concentrations.
It is possible that hyperproinsulinaemia occurred due to a compensatory increase in beta cell function to match insulin resistance . The increased C-peptide concentrations following treatment with t10c12CLA may support such an idea, but it is unclear why insulin was not also significantly increased. As we did not measure insulin secretion directly, we cannot draw firm conclusions regarding the effects of the treatment on insulin secretion. The proinsulin : insulin ratio, a reflection of beta cell function , also increased after t10c12CLA, but was not related to insulin resistance.
Interestingly, adiponectin was not related to insulin sensitivity, but to proinsulin (inverse correlation). However, this latter relationship should be interpreted cautiously as adiponectin did not change significantly after t10c12CLA.
Different CVs among insulin-like peptides may affect results in statistical analyses in favour of proinsulin over insulin. The current CV, in fact, was similar among the peptides. However, it cannot be ruled out that the stronger correlation to insulin resistance in multivariate analyses could be explained by the fact that proinsulin has a longer half-life than insulin.
This is the first study to provide human data on the effects of CLA on proinsulin, adiponectin and C-peptide concentrations. As hyperproinsulinaemia predicts Type 2 diabetes [1, 9] and cardiovascular death , our results are clinically relevant, especially as t10c12CLA is a constituent of commercial weight-loss supplements. Supporting previous data [6, 10], our results suggest that CLA supplementation might increase cardiovascular risk.
In summary, t10c12CLA elevates markers of insulin secretion in obese men, but the hyperproinsulinaemia induced seems to mainly reflect impaired insulin sensitivity.