A recent issue of the EJCI includes a paper entitled Decreased ability of high density lipoproteins to transfer cholesterol esters in non-insulin-dependent diabetes mellitus by Ahnadi et al.
The idea that some patients with abnormal plasma lipoproteins, including those with non-insulin-dependent diabetes mellitus (NIDDM), have an impaired transfer of cholesterylesters (CE) from HDL to apo Bcontaining lipoproteins was reported first by Fielding et al. However, other investigators subsequently showed increased transfer rates in dyslipidaemic plasma. In addition, it was found that net mass CE transfer is accelerated in plasma from insulin-dependent diabetes mellitus (IDDM) patients. The plasma activity level of cholesteryl ester transfer protein (CETP) is also increased in complicated IDDM.
The work by Ahnadi et al. intends to contribute to the solution of the above-mentioned apparent discrepancy by using an in vitro CE transfer assay, specifically designed to measure the effects of HDL structure on CE transfer. The authors conclude that patients with NIDDM have an impaired transfer of CE, which is caused partly by a decreased ability of HDL to act as a CE donor.
Although the data are obtained using adequate methodology, it is my opinion that this conclusion cannot be drawn from the present experiments, because the data obtained in vitro cannot be extrapolated to the in vivo situation. In a way the authors seem to agree with this opinion, as suggested by the last line of their discussion. The reason for the observed low in vitro rates of CE transfer, using HDL from NIDDM patients, may very well be that the CE transfer rates are actually elevated in these patients, resulting in low HDL2 and total HDL-cholesterol, with obvious effects on overall HDL structure. Thus, an accelerated in vivo transfer could drain the HDL from part of its CE, making the isolated HDL an inferior CE donor in vitro. This possible mechanism has not been recognized by the authors, but may very well explain their results.
It appears that plasma CETP activity levels and the constellation of acceptor lipoproteins are important factors determining the net mass transfer of CE. Active transfer of HDL-CE into the VLDL-LDL pathway may occur in diabetes mellitus, contributing to the tendency for low HDL-cholesterol. Elevated plasma free fatty acids could further accelerate this process. On the contrary, net mass transfer of CE from LDL to HDL may occur in healthy normolipidemic individuals, resulting in high HDL-cholesterol.

doi.org/10.1111/j.1365-2362.1993.tb00742.x, hdl.handle.net/1765/93649
European Journal of Clinical Investigation

van Tol, A. (1993). CETP-catalysed transfer of cholesterylesters from HDL to apo B-containing lipoproteins in plasma from diabetic patients. European Journal of Clinical Investigation, 23(12), 856–856. doi:10.1111/j.1365-2362.1993.tb00742.x