Association of Different Patterns of Insulin Resistance With Miscarriage in Population With Miscarriage History: a Multicenter Retrospective Cohort Study.

Abstract

Insulin Resistance (IR) has been increasingly linked to adverse reproductive outcomes, with emerging evidence suggesting a positive association between IR and miscarriage risk in women undergoing infertility treatment. However, the role of IR in miscarriage among the broader population remains poorly understood, leaving critical gaps in our knowledge of its impact on reproductive health. While prior studies have predominantly focused on fasting IR, the potential influence of postprandial IR-a dynamic metabolic state reflecting post-meal glucose handling-has been largely overlooked. This study aims to investigate the association between distinct patterns of IR, including fasting and postprandial states, and miscarriage risk in women with a history of miscarriage, offering novel insights into the metabolic underpinnings of reproductive loss. The retrospective cohort study included 1,042 women with a history of miscarriage, recruited from Sun Yat-sen Memorial Hospital and Shenzhen Baoan Women's and Children's Hospital. IR is divided into fasting IR and postprandial IR. Logistic regression models were used to investigate the association between different patterns of IR and miscarriage. In the multivariable logistic regression model, homeostasis model assessment of insulin resistance (HOMA-IR) was associated with a significant increased risk of miscarriage (OR [95% CI]: 1.97[1.33,2.94], P < 0.001). Stumvoll Insulin Sensitivity Index (ISI_Stumvoll) was associated with a decreased risk of miscarriage (OR [95% CI]: 0.66[0.45,0.98], P = 0.038). In the restricted cubic spline analysis, a positive monotonic relationship between HOMA-IR、ISI_Stumvoll and miscarriage was found (P_{non-linearity} = 0.130;P_{non-linearity} = 0.940). Compared with population defined as insulin-sensitive (IS) by both HOMA-IR and ISI_Stumvoll, those defined as IR by either HOMA-IR or ISI_Stumvoll exhibit a significantly higher risk of miscarriage. (OR [95% CI]: 1.88[1.43,2.49], P < 0.001). Fasting IR indicator HOMA-IR and postprandial IR indicator ISI_Stumvoll were associated with miscarriage in population with a history of pregnancy loss. The combination of both indicators was able to identify more individuals at higher risk of miscarriage.