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Purpose: Hyperglycemia and glycemic variability (GV) are associated with oxidative stress in patients with diabetes mellitus (DM). Oxysterol species, produced by the non-enzymatic oxidation of cholesterol, are potential biomarkers of oxidative stress. This study examined the relationship between auto-oxidized oxysterols and GV in patients with type 1 DM., Methods: Thirty patients with type 1 DM using a continuous subcutaneous insulin infusion pump therapy and a healthy control group (n = 30) were included in this prospective study. A Continuous Glucose Monitoring System device was applied for 72 h. Blood samples were taken for oxysterols produced by non-enzymatic oxidation [7-ketocholesterol (7-KC) and cholestane-3β, 5α, 6β-triol (Chol-Triol)] levels at 72 h. Short-term glycemic variability parameters, mean amplitude of glycemic excursions (MAGE), the standard deviation of glucose measurements (Glucose-SD), and mean of daily differences (MODD) were calculated with continuous glucose monitoring data. HbA1c was used to evaluate glycemic control and HbA1c-SD (the SD of HbA1c over the past year) for long-term glycemic variability., Results: 7-KC and Chol-triol levels were significantly higher in the study group than in the control group. Strong positive correlations were found between 7-KC with MAGE(24-48 h) and Glucose-SD(24-48 h). 7-KC was positively correlated with MAGE(0-72 h) and Glucose-SD(0-72 h). No significant correlation was found between HbA1c and HbA1c -SD with oxysterol levels. The regression models showed that SD(24-48 h) and MAGE(24-48 h) predicted 7-KC levels while HbA1c did not., Conclusions: Glycemic variability leads to higher levels of auto-oxidized oxysterol species in patients with type 1 DM independent of long-term glycemic control., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Silicosis is one of the prolonged and irreversible occupational diseases. Crystalline silica dust, which has been linked with silicosis, occurs in different industrial areas such as constructions, ceramic, quarry, and pottery. There are significant numbers of newly diagnosed cases every year in Turkey. Patients with silicosis suffer from inflammatory respiratory disorders and silicosis-related complications such as rheumatoid arthritis, systemic sclerosis, and vasculitis. Oxysterols are defined as 27-carbon intermediates or end products of cholesterol. They are also implicated in the etiology of disease states such as atherosclerosis, neurodegenerative, and inflammatory diseases. The aim of the study is to evaluate cholesterol oxidation products in the patients with silicosis and determination of sphingosine-1-phosphate (S1P) levels which is a sphingolipid metabolite. In addition to these parameters, it is aimed to determine the possible lipid peroxidation by different parameters. For this purpose, blood samples and urine were collected from 47 patients and 30 healthy individual with their consents. In order to evaluate oxysterols, 7-ketocholesterol and cholestan 3β,5α,6β-triol levels were measured by LC-MS/MS method. The measured levels of 7-KC were 0.101 ± 0.005 µmol/l in patient and 0.050 ± 0.003 µmol/l in control plasma samples. Triol levels were measured as 0.038 ± 0.005 µmol/l in patient group and 0.033 ± 0.004 µmol/l in control group (p < 0.001). In addition, lipid peroxidation products were measured by human-8-isoprostane, human-4-hydroxynonenal (4-HNE), and human malondialdehyde (MDA) ELISA kits. The measured levels of HNE in the patient and control groups were 735.14 ± 288.80 pg/ml and 595.72 ± 108.62 pg/ml in plasma and 606.02 + 118.23 pg/ml and 531.84 + 107.18 pg/ml in urine, respectively (p < 0.05). F2-iP results of patients and controls were 450.0 + 101.40 pg/dl and 386.9 + 112.7 pg/ml for urine and 432.7 ± 188,8 pg/dl and 321.9 ± 69.4 pg/dl for plasma, respectively (p < 0.05). MDA levels of plasma were measured as 44.1 ± 14.6 nmol/ml in the patient and 31.9 ± 10.5 nmol/ml in the control (p < 0.05). Levels of MDA for urine samples were 30.15 + 5.06 nmol/ml and 25.15 + 6.07 nmol/ml in patients and controls, respectively (p < 0.05). S1P levels were decreased in patients compared to control group (49.05 ± 10.87 and 67.57 ± 16.25, p < 0.001). The results not only indicate a correlation between cholesterol oxidation, lipid peroxidation, and silicosis, but also provide better understanding of the role of the lipids in the mechanism of this inflammatory disease.

Purpose: To assess the plasma oxysterol species 7-ketocholesterol (7-Kchol) and cholestane-3β,5α,6β-triol (chol-triol) as biomarkers of oxidative stress in type 1 and type 2 diabetes mellitus (DM)., Methods: In total, 26 type 1 and 80 type 2 diabetes patients, along with 205 age- and gender-matched healthy controls, were included in this study. Oxysterols were quantified by liquid chromatography coupled with tandem mass spectrometry and N,N-dimethylglycine derivatization. Correlations between oxysterols and clinical/biochemical characteristics of the diabetes patients, and factors affecting 7-Kchol and chol-triol, were also determined., Results: Plasma 7-Kchol and chol-triol levels were significantly higher in type 1 and type 2 diabetes patients compared to healthy controls (P < 0.001). Significant positive correlations were observed between oxysterol levels and levels of glycated hemoglobin (HbA1c), glucose, serum total cholesterol, low-density lipoprotein, very-low-density lipoprotein, and triglycerides, as well as the number of coronary risk factors. Statins, oral hypoglycemic agents, and antihypertensive agents reduced the levels of oxysterols in type 2 diabetes patients. Statin use, HbA1c levels, and the number of coronary risk factors accounted for 98.8% of the changes in 7-Kchol levels, and total cholesterol, smoking status, and the number of coronary risk factors accounted for 77.3% of the changes in chol-triol levels in type 2 diabetes patients., Conclusions: Plasma oxysterol levels in DM, and particularly type 2 DM, may yield complementary information regarding oxidative stress for the clinical follow-up of diabetes patients, especially those with coronary risk factors.