Triglyceride Induced Metabolic Inflammation: Potential Connection of Insulin Resistance and Recurrent Pregnancy Loss

Abstract

The underlying correlative mechanisms between Insulin resistance (IR) and recurrent pregnancy loss (RPL) in patients without polycystic ovarian syndrome (PCOS) remain inconclusive. To investigate the association between triglyceride (TG) levels, lymphocyte subsets, and IR in RPL patients without PCOS and obesity. Eighty-nine subjects with an unexplained RPL, independent of PCOS/obesity were enrolled in this study. A 75-g oral glucose tolerance test was performed on each subject with plasma tested for glucose and insulin. The fasting venous blood of all subjects was collected for routine clinical chemistry analysis. Lymphocyte subsets were analyzed by four-color flow cytometry. As a result, TG levels were significantly elevated in RPL patients with IR compared to those without IR. Pearson linear correlation model and receiver operating characteristic (ROC) curve analyses revealed a significant positive association between TG and HOMA-IR index value. In multiple logistic regression analysis, TG was significantly associated with the risk of hyperinsulinemia and increased CD3+CD4+/CD3+CD8+ ratio which was significantly negatively correlated with disposition index (DI30) and DI120, indicators for insulin sensitivity. In addition, DI30 and DI120 were significantly decreased in the higher CD3+CD4+/CD3+CD8+ group. Our findings showed that the elevated TG and altered immune responses in RPL patients with IR are independent of PCOS and obesity, and could be used as an indicator of IR in RPL patients. These results contribute to the understanding of the pathophysiology of IR in RPL for potential prevention and therapeutic targets.

High Insulin Resistance in Saudi Women with Unexplained Recurrent Pregnancy Loss: A Case–control Study

“…IR, defined as a decreased sensitivity or responsiveness to the metabolic action of insulin, is clinically assessed through tests such as FG/FI ratio and HOMA-IR. [ 7 ] However, there is no consensus on the cut-off value to define IR using HOMA-IR; some studies use a cut-off value of >2.5, while others of >2.69. [ 7 13 ] Another study defined IR if HOMA-IR was ≥3.15.…”

“…[ 7 ] However, there is no consensus on the cut-off value to define IR using HOMA-IR; some studies use a cut-off value of >2.5, while others of >2.69. [ 7 13 ] Another study defined IR if HOMA-IR was ≥3.15. [ 14 ]…”

“…Most women with PCOS are also hyper-insulinemic and insulin resistant, independent of obesity, compared with women without PCOS, with a prevalence ranging between 40% and 70%. [ 7 ] Several studies have demonstrated that insulin resistance (IR) is a potential cause of pregnancy loss. [ 8 ] Furthermore, a meta-analysis of 13 studies (five randomized) concluded that insulin-sensitizing agents such as metformin significantly reduced the possibility of miscarriage for women with PCOS.…”

The impact of early pregnancy metabolic disorders on pregnancy outcome and the specific mechanism

“…This would lead to lower probability of pregnancy and live birth and increased risk of miscarriage [ 82 ]. In addition, it has been proposed that patients with insulin resistance (IR) have significantly higher triglyceride (TG) levels (which brings about an increased ratio of CD3 + CD4 + ) and numbers of CD3 + CD8 + lymphocytes, reduced insulin sensitivity, and induction of metabolic inflammation, resulting in RSA [ 83 ].…”

Homeostasis Model Assessment for Insulin Resistance Mediates the Positive Association of Triglycerides with Diabetes

“…Mechanistically, Diagnostics 2024, 14, 733 2 of 15 triglyceride-rich very-low-density lipoprotein (VLDL) can form LDL through delipidation [17]. Epidemiological evidence suggests a link between high triglycerides and insulin resistance, as evidenced by positive associations with homeostatic model assessment (HOMA) for insulin resistance in diverse populations worldwide, including the US [8], South Korea [18], and China [19,20]. Likewise, inflammation might contribute to the triglyceride-diabetes nexus.…”