Abstract

Although women have higher high-density lipoprotein cholesterol (HDL-C) than have men, their HDL particles are also prone to become small, dense, and dysfunctional in case of type 2 diabetes mellitus (T2DM). To assess the vascular risk related to HDLs of different sizes/densities without direct measurement, we adjusted HDL-C to its main apolipoprotein (apoA-I) as [HDL-C/apoA-I]. This ratio estimates HDL sizes and provides indices as to their number, cholesterol load, and density. We stratified 280 Caucasian T2DM women according to [HDL-C/apoA-I] quartiles (Q) to determine how they are segregated according to cardiometabolic risk, β-cell function, glycaemic control, and vascular complications. Five parameters were derived from combined determination of HDL-C and apoA-I: HDL size, HDL number, cholesterol load per particle (pP), apoA-I pP, and HDL density. An adverse cardiometabolic profile characterized QI and QII patients whose HDLs were denser and depleted in apoA-I, whereas QIII patients had HDLs with characteristics closer to those of controls. QIV patients had HDLs of supernormal size/composition and a more favourable phenotype in terms of fat distribution; insulin sensitivity (64% vs 41%), metabolic syndrome, and β-cell function (32% vs 23%); exogenous insulin (44 vs 89U·d-1 ); and glycaemic control (glycated haemoglobin, 56 vs 61mmol·mol-1 ), associated with lower prevalence of microvascular/macrovascular complications: all-cause microangiopathy 47% vs 61%; retinopathy 22% vs 34%; all-cause macroangiopathy 19% vs 31%; and coronary artery disease 6% vs 24% (P<.05). [HDL-C/apoA-I] can stratify T2DM women according to metabolic phenotype, macrovascular and coronary damage, β-cell function, microangiopathic risk, and retinopathy. This ratio is a versatile and readily available marker of cardiometabolic status and vascular complications in T2DM women.

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