Mechanistic Insights Into the Heterogeneity of Glucose Response Classes in Youths With Obesity: A Latent Class Trajectory Approach

OBJECTIVEIn a large, multiethnic cohort of youths with obesity, we analyzed pathophysiological and genetic mechanisms underlying variations in plasma glucose responses to a 180 min oral glucose tolerance test (OGTT).RESEARCH DESIGN AND METHODSLatent class trajectory analysis was used to identify various glucose response profiles to a nine-point OGTT in 2,378 participants in the Yale Pathogenesis of Youth-Onset T2D study, of whom 1,190 had available TCF7L2 genotyping and 358 had multiple OGTTs over a 5 year follow-up. Insulin sensitivity, clearance, and β-cell function were estimated by glucose, insulin, and C-peptide modeling.RESULTSFour latent classes (1 to 4) were identified based on increasing areas under the curve for glucose. Participants in class 3 and 4 had the worst metabolic and genetic risk profiles, featuring impaired insulin sensitivity, clearance, and β-cell function. Model-predicted probability to be classified as class 1 and 4 increased across ages, while insulin sensitivity and clearance showed transient reductions and β-cell function progressively declined. Insulin sensitivity was the strongest determinant of class assignment at enrollment and of the longitudinal change from class 1 and 2 to higher classes. Transitions between classes 3 and 4 were explained only by changes in β-cell glucose sensitivity.CONCLUSIONSWe identified four glucose response classes in youths with obesity with different genetic risk profiles and progressive impairment in insulin kinetics and action. Insulin sensitivity was the main determinant in the transition between lower and higher glucose classes across ages. In contrast, transitions between the two worst glucose classes were driven only by β-cell glucose sensitivity.     

Clinical, sonographic, and epidemiologic features of second- and early third-trimester spontaneous antepartum uterine rupture: a cohort study

OBJECTIVE: To present prenatal findings and maternal and neonatal outcomes following second- and early third-trimester spontaneous antepartum uterine rupture events in our institute. METHOD: Charts of patients with full-thickness second- or early third-trimester symptomatic uterine ruptures locally treated between 1984 and 2007 were evaluated. RESULTS: There were seven events involving six women, all requiring emergency laparotomy, and cesarean section (CS). During the study period in our institute, there were 120 636 singleton deliveries (> or =22 weeks' gestation), including 5 of our cases, while in 2 cases, the rupture occurred earlier (<22 weeks' gestation). The rupture occurred after > or = 1 previous CSs in five cases. Six events were associated with abnormal placentation: placenta previa (n = 3), placenta percreta (n = 1), or both (n = 2). Other associated events included short, interpregnancy (IP) interval (n = 3) and past uterine rupture (n = 2). Pregnant women at gestational age > or = 22 weeks, who had the combination of placenta previa, and previous CS (n = 3), had a higher chance for spontaneous symptomatic antepartum uterine rupture when compared to women with placenta previa without a previous CS (OR 29.3, 95% CI 1.5-569.3, p = 0.007). There were no maternal deaths. Three of the five viable neonates survived. CONCLUSIONS: Spontaneous symptomatic second- or early third-trimester uterine rupture in nonlaboring women is a very rare, obstetric emergency, which is hard to diagnose. Maternal and neonatal outcomes can be optimized by awareness of risk factors, recognition of clinical signs and symptoms, and availability of ultrasound to assist in establishing diagnosis, and enabling prompt surgical intervention.     

Soluble receptor for advanced glycation end products (sRAGE) and endogenous secretory RAGE (esRAGE) in amniotic fluid: modulation by infection and inflammation

Abstract Objective: The receptor for advanced glycation end products (RAGE) has been proposed to participate in the innate and adaptive immune responses. RAGE can induce production of pro-inflammatory cytokines and chemokines, as well as neutrophil chemotaxis in a manner that may be suppressed or stimulated by soluble, truncated forms of RAGE including the soluble form of RAGE (sRAGE) and endogenous secretory RAGE (esRAGE). The objective of this study was to determine whether intra-amniotic infection/inflammation (IAI) is associated with changes in the amniotic fluid concentration of sRAGE and esRAGE. Study design: Amniotic fluid (AF) was retrieved from patients in the following groups: 1) mid-trimester (14-18 weeks of gestation; n=68); 2) term not in labor (n=24); 3) term in labor (n=51); 4) preterm labor and intact membranes (n=124); and 5) preterm PROM (n=80). Intra-amniotic infection and inflammation were defined as the presence of a positive amniotic fluid culture for microorganisms and an AF interleukin-6 concentration >/=2.6 ng/mL, respectively. The AF concentration of sRAGE and esRAGE were determined using specific and sensitive ELISAs which measured total immunoreactive sRAGE and esRAGE, respectively. Patients were matched for gestational age at amniocentesis to compare the AF concentration of sRAGE and esRAGE in patients with and without IAI. Non-parametric statistics were used for analysis and a P<0.05 was considered significant. Results: 1) Patients at term not in labor had higher median AF concentrations of sRAGE and esRAGE than those in the mid-trimester (P<0.001 for both comparisons) and those at term in labor (P=0.03 and P=0.04, respectively); 2) patients with preterm labor and intact membranes with intra-amniotic infection/inflammation (IAI) had higher median AF concentrations of sRAGE and esRAGE than those without IAI (P=0.02 and P=0.005, respectively); 3) similarly, patients with preterm PROM with IAI had higher median AF concentrations of sRAGE and esRAGE than those without IAI (P=0.03 and P=0.02, respectively). Conclusion: Intra-amniotic infection/inflammation is associated with increased amniotic fluid concentrations of sRAGE and esRAGE. Changes in the amniotic fluid concentration of sRAGE and esRAGE may represent part of the immune response to intra-amniotic infection/inflammation.     

Child protection involvement and victims of intimate partner violence: is there a bias?

Several studies have explored the disproportionate number of children of color involved in child protective services, raising concerns that racial bias in the system results in more women of color being referred to child protection. The authors conducted a case series to analyze whether a woman's race and ethnicity influenced referrals to child protective services in a domestic violence context. Data were obtained through interview records of 263 women (38% women of color) at a Minneapolis-based advocacy and therapy organization. The findings suggest that women who face multiple forms of oppressions may have greater risk of being involved with child protection services.