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Oxidized LDL, insulin sensitivity and beta-cell function in newborns

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BMJ PUBLISHING GROUP
DOI: 10.1136/bmjdrc-2020-001435

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  1. Ministry of Science and Technology of China National Key Research Program [2019YFA0802501]
  2. Canadian Institutes of Health Research (CIHR) [158616, 79896]
  3. National Natural Science Foundation of China [81903323]

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Elevated levels of OxLDL were found to be positively correlated with fetal insulin sensitivity and beta-cell function. The study suggests that OxLDL may impact glucose metabolic health in early life.
Introduction Oxidized low-density lipoprotein (OxLDL), a biomarker of oxidative stress, itself possesses proatherogenic and proinflammatory effects. Elevated circulating OxLDL levels have been consistently associated with insulin resistance and diabetes in adults. We sought to assess whether OxLDL may be associated with insulin sensitivity and beta-cell function in early life. Research design and methods In a birth cohort study, we assessed cord plasma OxLDL concentration and OxLDL to total LDL ratio in relation to glucose to insulin ratio (an indicator of fetal insulin sensitivity), proinsulin to insulin ratio (an indicator of fetal beta-cell function), and leptin and adiponectin concentrations in 248 singleton newborns. Results Cord plasma OxLDL concentration was positively correlated with glucose to insulin ratio (r=0.24, p<0.001) and proinsulin to insulin ratio (r=0.20, p<0.001) and was not correlated with leptin or adiponectin. Adjusting for maternal and neonatal characteristics, each log unit increase in cord plasma OxLDL concentration was associated with a 25.8% (95% CI 12.8% to 40.3%) increase in glucose to insulin ratio and a 19.0% (95% CI 6.8% to 32.9%) increase in proinsulin to insulin ratio, respectively. Similar associations were observed for cord plasma OxLDL to LDL ratio in relation to cord plasma glucose to insulin ratio and proinsulin to insulin ratio. Conclusions Higher OxLDL levels were associated with lower fetal beta-cell function (higher proinsulin to insulin ratio) but higher insulin sensitivity (higher glucose to insulin ratio). The study is the first to demonstrate that OxLDL may affect glucose metabolic health in early life in humans.

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