Ashley V Hill1,2, Ramkumar Menon3, Maria Perez-Patron1, Genny Carrillo4, Xiaohui Xu1, Brandie D Taylor1,5. 1. Department of Epidemiology and Biostatistics, Texas A&M University, College Station, TX, USA. 2. Division of Adolescent and Young Adult Medicine, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 3. Division of Maternal-Fetal Medicine and Perinatal Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA. 4. Department of Environmental and Occupational Health, Texas A&M University, College Station, TX, USA. 5. Department of Epidemiology and Biostatistics, College of Public Health, Temple University, Philadelphia, PA, USA.
Abstract
PROBLEM: High-mobility group box 1 (HMGB1), a danger-associated molecular pattern marker, may indicate sterile inflammation through innate immune pathways. HMGB1 is implicated in hyperglycemia and excess glucose in trophoblast. Metabolic dysfunction and dyslipidemia are associated with gestational diabetes mellitus (GDM), but few studies examined associations between HMGB1 and GDM. We determined HMGB1 levels, and the ratio of HMGB1 to innate immune markers, in women with GDM at parturition. METHOD OF STUDY: This case-control study of 50 GDM pregnancies and 100 healthy controls utilized data and plasma samples from PeriBank. HMGB1, pentraxin-3, and interleukin (IL)-6 were measured by ELISA. Logistic regression calculated odds ratios (OR) and 95% confidence intervals (CI) adjusting for age, pre-pregnancy body mass index, and type of labor. RESULTS: There were no significant associations between HMGB1 and GDM. The ratio of HMGB1 to pentraxin-3 and IL-6 did not alter the odds of GDM. There was a significant statistical interaction between HMGB1 and maternal age (P = .02). When associations were examined by age groups, HMGB1 was associated with reduced odds of HMGB1 among women ≤25 (AOR = 0.007 CI 95% <0.001-0.3). Odds ratios increased as age increased (AOR range 1.2-3.8) but results were not statistically significant. CONCLUSION: High-mobility group box 1 was not associated with GDM. However, we found evidence that maternal age was a potential effect modifier of the relationship between HMGB1 and GDM. As there is growing evidence that HMGB1 may play important roles in reproduction, future studies should explore maternal factors that may alter HMGB1 levels.
PROBLEM: High-mobility group box 1 (HMGB1), a danger-associated molecular pattern marker, may indicate sterile inflammation through innate immune pathways. HMGB1 is implicated in hyperglycemia and excess glucose in trophoblast. Metabolic dysfunction and dyslipidemia are associated with gestational diabetes mellitus (GDM), but few studies examined associations between HMGB1 and GDM. We determined HMGB1 levels, and the ratio of HMGB1 to innate immune markers, in women with GDM at parturition. METHOD OF STUDY: This case-control study of 50 GDM pregnancies and 100 healthy controls utilized data and plasma samples from PeriBank. HMGB1, pentraxin-3, and interleukin (IL)-6 were measured by ELISA. Logistic regression calculated odds ratios (OR) and 95% confidence intervals (CI) adjusting for age, pre-pregnancy body mass index, and type of labor. RESULTS: There were no significant associations between HMGB1 and GDM. The ratio of HMGB1 to pentraxin-3 and IL-6 did not alter the odds of GDM. There was a significant statistical interaction between HMGB1 and maternal age (P = .02). When associations were examined by age groups, HMGB1 was associated with reduced odds of HMGB1 among women ≤25 (AOR = 0.007 CI 95% <0.001-0.3). Odds ratios increased as age increased (AOR range 1.2-3.8) but results were not statistically significant. CONCLUSION:High-mobility group box 1 was not associated with GDM. However, we found evidence that maternal age was a potential effect modifier of the relationship between HMGB1 and GDM. As there is growing evidence that HMGB1 may play important roles in reproduction, future studies should explore maternal factors that may alter HMGB1 levels.
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