Maternal Serum Heme-Oxygenase-1 (HO-1) Concentrations in Early Pregnancy and Subsequent Risk of Gestational Diabetes Mellitus

Background: Heme oxygenase-1 (HO-1) concentrations have been recently reported to be elevated in impaired glucose tolerance and type 2 diabetes mellitus (T2DM). However, no study has examined the association between HO-1 concentrations and gestational diabetes mellitus (GDM). Methods: In a case-control study, nested within a prospective cohort of pregnant women (186 GDM cases and 191 women who remained eu-glycemic through pregnancy), we assessed the association of maternal serum HO-1 concentrations, measured in samples collected at 16 weeks gestation, on average, with subsequent risk of GDM. Maternal serum HO-1 concentrations were determined using ELISA. We fitted multivariate logistic regression models to derive estimates of odds ratios (ORs) and 95% confidence intervals (CIs). Results: Median serum HO-1 concentrations in early pregnancy were lower in women who subsequently developed GDM compared with those who did not (1.60 vs. 1.80 ng/mL, p-value = 0.002). After adjusting for maternal age, race, family history of T2DM and pre-pregnancy body mass index, women with HO-1≥3.05 ng/mL (highest decile) experienced a 74% reduction of GDM risk (95% CI; 0.09–0.77) compared with women whose concentrations were<1.23 ng/mL (lowest quartile). Conclusion: Serum HO-1 concentrations were inversely associated with subsequent GDM risk. These findings underscore the role of oxidative stress in the pathogenesis of GDM. Additional studies are warranted to confirm the clinical utility of serum HO-1 in diagnosis of GDM, particularly in the early pregnancy

Placental mitochondrial DNA content and placental abruption: a pilot study

Background: Mitochondrial biogenesis and adequate energy production are important for embryogenesis and placentation. Previous studies documented alterations in maternal blood mitochondrial DNA (mtDNA) copy number—a marker of mitochondrial dysfunction—in pregnancies complicated by placental abruption. To further understand the role of mitochondrial dysfunction in the pathogenesis of placental abruption, we conducted a pilot study using placental specimen collected from 103 placental abruption cases and 102 non-abruption controls. Real-time quantitative polymerase chain reaction (PCR) was used to assess the relative copy number of mtDNA in DNA extracted from placental samples collected immediately after delivery. Logistic regression procedures were used to estimate adjusted odds ratios (OR) and 95 % confidence intervals (CI). Results: Higher odds of placental abruption was observed with increasing mtDNA copy number (p value for trend = 0.05). The odds of placental abruption was elevated among women who delivered placentas with higher mtDNA copy number (≥120.5, the median) as compared with those with lower values (<120.5) (adjusted OR = 2.38; 95 % CI 1.11–5.08). Conclusion: We found preliminary evidence for associations of target tissue-specific mitochondrial dysfunction with an adverse perinatal outcome, placental abruption. Larger studies and replication of findings in other populations will further our understanding of relationships between cellular and genomic biomarkers of normal and abnormal placental function and vascular placental disorders

Circulating early- and mid-pregnancy microRNAs and risk of gestational diabetes.

AIMS: Epigenetic regulators, including microRNAs (miRNAs), are implicated in type 2 diabetes, but evidence linking circulating miRNAs in pregnancy and risk of gestational diabetes (GDM) is sparse. Potential modifiers, including pre-pregnancy overweight/obesity and offspring sex, are unexamined. We hypothesized that circulating levels of early-mid-pregnancy (range 7-23weeks of gestation) candidate miRNAs are related to subsequent development of GDM. We also hypothesized that miRNA-GDM associations might vary by pre-pregnancy body-mass index (ppBMI) or offspring sex. METHODS: In a case-control analysis (36GDM cases/80 controls) from the Omega study, a prospective cohort study of pregnancy complications, we measured early-mid-pregnancy plasma levels of 10miRNAs chosen for potential roles in pregnancy course and complications (miR-126-3p, -155-5p, -21-3p, -146b-5p, -210-3p, -222-3p, -223-3p, -517-5p, -518a-3p, and 29a-3p) using qRT-PCR. Logistic regression models adjusted for gestational age at blood draw (GA) were fit to compare circulating miRNAs between cases and controls. We repeated analyses among overweight/obese (ppBMI≥25kg/m RESULTS: Mean age was 34.3years (cases) and 32.9years (controls). GA-adjusted miR-155-5p (β=0.260/p=0.028) and -21-3p (β=0.316/p=0.005) levels were positively associated with GDM. MiR-146b-5p (β=0.266/p=0.068) and miR-517-5p (β=0.196/p=0.074) were borderline. Associations of miR-21-3p and miR-210-3p with GDM were observed among overweight/obese but not lean women. Associations of six miRNAs (miR-155-5p, -21-3p, -146b-5p, -223-3p, -517-5p, and -29a-3p) with GDM were present only among women carrying male fetuses (all p\u3c0.05). CONCLUSIONS: Circulating early-mid-pregnancy miRNAs are associated with GDM, particularly among women who are overweight/obese pre-pregnancy or pregnant with male offspring. This area has potential to clarify mechanisms underlying GDM pathogenesis and identify at-risk mothers earlier in pregnancy

Association between insulin resistance and c-reactive protein among Peruvian adults

<p>Abstract</p> <p>Objective</p> <p>Insulin resistance (IR), a reduced physiological response of peripheral tissues to the action of insulin, is one of the major causes of type 2 diabetes. We sought to evaluate the relationship between serum C-reactive protein (CRP), a marker of systemic inflammation, and prevalence of IR among Peruvian adults.</p> <p>Methods</p> <p>This population based study of 1,525 individuals (569 men and 956 women; mean age 39 years old) was conducted among residents in Lima and Callao, Peru. Fasting plasma glucose, insulin, and CRP concentrations were measured using standard approaches. Insulin resistance was assessed using the homeostasis model (HOMA-IR). Categories of CRP were defined by the following tertiles: <0.81 mg/l, 0.81-2.53 mg/l, and >2.53 mg/l. Logistic regression procedures were employed to estimate odds ratios (OR) and 95% confidence intervals (CI).</p> <p>Results</p> <p>Elevated CRP were significantly associated with increased mean fasting insulin and mean HOMA-IR concentrations (p < 0.001). Women with CRP concentration >2.53 mg/l (upper tertile) had a 2.18-fold increased risk of IR (OR = 2.18 95% CI 1.51-3.16) as compared with those in the lowest tertile (<0.81 mg/l). Among men, those in the upper tertile had a 2.54-fold increased risk of IR (OR = 2.54 95% CI 1.54-4.20) as compared with those in the lowest tertile.</p> <p>Conclusion</p> <p>Our observations among Peruvians suggest that chronic systemic inflammation, as evidenced by elevated CRP, may be of etiologic importance in insulin resistance and diabetes.</p

Gene Organization and Transcriptional Analysis of the tprJ, tprI, tprG, and tprF Loci in Treponema pallidum Strains Nichols and Sea 81-4

The tpr gene family of Treponema pallidum subsp. pallidum, the causative agent of syphilis, has recently become the focus of intensive investigation. TprF and TprI sequences are highly conserved among different isolates and are the targets of strong humoral and cellular immune responses of the host, and immunization with a recombinant peptide from the amino terminus of these antigens has been shown to alter significantly lesion development following homologous challenge. This indicates that these antigens are expressed during infection and strongly suggests a key functionality. tprF and tprI are located immediately downstream of the tprG and tprJ genes, respectively, separated by very short intergenic spacers (55 nucleotides for G-F and 56 nucleotides for J-I). Preliminary analysis using gene-specific primers failed to amplify tprJ in the Sea 81-4 isolate. In this study, sequence and transcriptional analysis of these loci showed a similar gene organization in the Nichols and Sea 81-4 strains, a complex pattern of transcription, and the presence of G homopolymeric repeats of variable lengths upstream of the tprF, tprI, tprG, and tprJ transcriptional start sites. However, distinctive features were also identified in the Sea 81-4 isolate, including a tprG-like open reading frame in the tprJ locus, a frameshift and a premature termination in the tprG coding sequence, a longer tprG-tprF intergenic spacer, and absence of cotranscription of the tprG-tprF genes

The dotplot of serum HO-1 concentrations according to GDM case-control status with median (+++), the lowest, or the highest quartile bar lines (---) indicated.

<p>The dotplot of serum HO-1 concentrations according to GDM case-control status with median (+++), the lowest, or the highest quartile bar lines (---) indicated.</p

Relation between maternal serum HO-1 concentrations and the adjusted relative odds of gestational diabetes mellitus (GDM) (solid line), with 95% CI (dotted lines).

<p>The vertical bars along the serum HO-1 concentrations axis indicate distribution of study subjects. The estimates were adjusted by maternal age, race/ethnicity, family history of diabetes and pre-pregnancy body mass index. (Excluded 3 subjects with serum HO-1 measurements>4 ng/mL, all are non-GDM.).</p

Characteristics of study participants according to gestational diabetes (GDM) case-control status.

1<p>Mean ± SD (standard deviation).</p

Antibody Responses Elicited against the Treponema pallidum Repeat Proteins Differ during Infection with Different Isolates of Treponema pallidum subsp. pallidum

Variation in the expression of the different Tpr proteins in the syphilis spirochete, Treponema pallidum subsp. pallidum, may have important implications in its ability to evade host immune detection and cause persistent infection. In the present study we examined the pattern of antibody responsiveness to different Tpr members during infection with three isolates of T. pallidum. There was variability in the specificities and temporal patterns of reactivity of the antibodies elicited against the individual Tpr proteins, suggesting that isolates may express different repertoires of Tpr proteins during infection