High Glucose Promotes Inflammation and Weakens Placental Defenses against E. coli and S. agalactiae Infection: Protective Role of Insulin and Metformin.

Placentas from gestational diabetes mellitus (GDM) patients undergo significant metabolic and immunologic adaptations due to hyperglycemia, which results in an exacerbated synthesis of proinflammatory cytokines and an increased risk for infections. Insulin or metformin are clinically indicated for the treatment of GDM; however, there is limited information about the immunomodulatory activity of these drugs in the human placenta, especially in the context of maternal infections. Our objective was to study the role of insulin and metformin in the placental inflammatory response and innate defense against common etiopathological agents of pregnancy bacterial infections, such as E. coli and S. agalactiae, in a hyperglycemic environment. Term placental explants were cultivated with glucose (10 and 50 mM), insulin (50-500 nM) or metformin (125-500 µM) for 48 h, and then they were challenged with live bacteria (1 × 105 CFU/mL). We evaluated the inflammatory cytokine secretion, beta defensins production, bacterial count and bacterial tissue invasiveness after 4-8 h of infection. Our results showed that a GDM-associated hyperglycemic environment induced an inflammatory response and a decreased beta defensins synthesis unable to restrain bacterial infection. Notably, both insulin and metformin exerted anti-inflammatory effects under hyperglycemic infectious and non-infectious scenarios. Moreover, both drugs fortified placental barrier defenses, resulting in reduced E. coli counts, as well as decreased S. agalactiae and E. coli invasiveness of placental villous trees. Remarkably, the double challenge of high glucose and infection provoked a pathogen-specific attenuated placental inflammatory response in the hyperglycemic condition, mainly denoted by reduced TNF-α and IL-6 secretion after S. agalactiae infection and by IL-1ß after E. coli infection. Altogether, these results suggest that metabolically uncontrolled GDM mothers develop diverse immune placental alterations, which may help to explain their increased vulnerability to bacterial pathogens.

[Atypical preeclampsia: case report]. / Preeclampsia atípica. Reporte de un caso.

BACKGROUND: Preeclampsia that occurs at < 20 weeks of gestation is rare and has been usually reported with molar or hydropic degeneration of the placenta and antiphospholipid syndrome. CASE REPORT: To describe the clinical presentation of atypical preeclampsia of a patient of 37 years old at her first gestation who developed this entity at 18.5 weeks of gestation. She had history of pre-existing hypertension and infertility. This pregnancy was obtained through in vitro fertility. She reported a severe headache and was admitted to our hospital secondary to elevated blood pressure of 160/110 mm Hg. The laboratory evaluation revealed platelet count 51,000, alanine aminotransferase of 331 UI/L, aspartate aminotransferase of 285 UI/L, lactate dehydrogenase 421 UI/L and urinalysis with +2 proteinuria, soluble fms-like tyrosine kinase-1/placental growth factor ratio 895.5. The diagnosis of chronic hypertension and superimposed preeclampsia and incomplete HELLP syndrome was supported. After termination of pregnancy, the patient improved rapidly. She was discharged home on postoperative day 7 with a blood pressure of 120/70 mm Hg with normal laboratory. CONCLUSIONS: Clinicians should consider the diagnosis of preeclampsia and HELLP syndrome before 20 weeks of gestation in women presenting with clinical or laboratory abnormalities consistent with this disease.