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Department of Internal Medicine 3, Pathological Biochemistry, Carl Gustav Carus Medical School, University of Technology Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany¹ Department of Radiopharmaceutical Biology, Institute of Radiopharmacy, Research Center Dresden-Rossendorf, D-01314 Dresden, Germany

(Correspondence should be addressed to S Kopprasch; Email: steffi.kopprasch{at}uniklinikum-dresden.de)

^* (S Kopprasch, J Pietzsch, and I Ansurudeen contributed equally to this work)

Modification of low-density lipoprotein (LDL) and abnormal aldosterone and cortisol metabolism have been implicated in the pathogenesis of type 2 diabetes (DM2) and diabetic vascular disease. Since LDL serves as a major cholesterol source for adrenal steroidogenesis, we investigated whether LDL modification in prediabetic and diabetic subjects influences adrenocortical aldosterone and cortisol release. LDL was isolated from 30 subjects with normal glucose tolerance (NGT-LDL), 30 subjects with impaired glucose tolerance (IGT-LDL), and 26 patients with DM2 (DM2-LDL). Oxidation and glycoxidation characteristics of LDL apolipoprotein B100 of each individual was assessed by gas chromatography–mass spectrometry analysis. Human adrenocortical cells (NCI-H295R) were incubated for 24 h with 100 µg/ml LDL and after removal of supernatants stimulated for a further 24 h with angiotensin II (AngII). In supernatants, aldosterone and cortisol secretion was measured. IGT-LDL and DM2-LDL were substantially more modified than NGT-LDL. Each of the five measured oxidation/glycoxidation markers was significantly positively associated with glycemic control, measured as HbA_1c. LDL from all subjects stimulated both the basal and AngII-induced aldosterone and cortisol release from adrenocortical cells. However, hormone secretion was significantly inversely related to the degree of LDL oxidation/glycoxidation. We conclude that LDL modifications in IGT and DM2 subjects may have significant clinical benefits by counteracting prediabetic and diabetic overactivity of the renin–angiotensin–aldosterone system and enhanced cortisol generation.