Risk Assessment of Diabetes Mellitus during and after Pregnancy in Women with Prolactinomas.

CONTEXT: Prolactin (PRL) is a crucial mediator of gluco-insulinemic metabolism. OBJECTIVE: Dissecting glucose metabolism during and after pregnancy in patients with prolactinomas. METHODS: 52 patients treated with cabergoline (CAB) were evaluated before conception, during pregnancy and up to 10 years after delivery. During pregnancy, CAB was discontinued, while it was restarted in 57.7 % of patients after delivery, due to recurrent hyperprolactinemia (RH). Hormonal (serum PRL) and metabolic (HbA1c, fasting glucose/FG, glucose tolerance) parameters were assessed. RESULTS: During pregnancy, PRL gradually increased, while FG remained stable. An inverse correlation between PRL and FG was found in the first (p=0.032) and third (p=0.048) trimester. PRL percent increase across pregnancy was inversely correlated with third trimester FG. Serum PRL before conception emerged as predictive biomarker of third trimester FG (τ=2.603; p=0.048). Elderly patients with lower HbA1c at first trimester and lower FG at 3 years postpartum, delivered infants with reduced birth weight. Breastfeeding up to 6 months correlated with lower FG at 4 and 10 years postpartum. A positive correlation between BMI and FG at 10 years after delivery (p=0.03) was observed, particularly in overweight/obese patients requiring higher CAB doses. Patients with RH who had to restart CAB showed shorter breastfeeding duration and higher FG at 2 years postpartum. CONCLUSIONS: Low PRL levels before pregnancy may be detrimental to FG during pregnancy. CAB duration and dose may influence long-term glucose tolerance, besides family history and BMI. Pre-conceptional metabolic management should be recommended to reduce the risk of gestational and type 2 diabetes mellitus.

Prolactin effects on the pathogenesis of diabetes mellitus.

BACKGROUND: Prolactin (PRL) is a pituitary hormone promoting lactation in response to the suckling reflex. Beyond its well-known effects, novel tissue-specific and metabolic functions of PRL are emerging. AIMS: To dissect PRL as a critical mediator of whole-body gluco-insulinemic sensitivity. METHODS: PubMed-based search with the following terms 'prolactin', 'glucose metabolism', 'type 2 diabetes mellitus', 'type 1 diabetes mellitus', 'gestational diabetes mellitus' was performed. DISCUSSION: The identification of the PRL-glucose metabolism network poses the basis for unprecedented avenues of research in the pathogenesis of diabetes mellitus type 1 or 2, as well as of gestational diabetes. In this regard, it is of timely relevance to define properly the homeostatic PRL serum levels since glucose metabolism could be influenced by the circulating amount of the hormone. RESULTS: This review underscores the basic mechanisms of regulation of pancreatic ß-cell functions by PRL and provides a revision of articles which have investigated the connection between PRL unbalancing and diabetes mellitus. Future studies are needed to elucidate the burden and the role of PRL in the regulation of glucose metabolism and determine the specific PRL threshold that may impact the management of diabetes. CONCLUSION: A careful evaluation and context-driven interpretation of PRL levels (e.g., pregnancy, PRL-secreting pituitary adenomas, drug-related hyper- and hypoprolactinemia) could be critical for the correct screening and management of glucometabolic disorders, such as type 1 or 2 as well as gestational diabetes mellitus.

Acute ischemic stroke thrombi have an outer shell that impairs fibrinolysis.

OBJECTIVES: Thrombi responsible for large vessel occlusion (LVO) in the setting of acute ischemic stroke (AIS) are characterized by a low recanalization rate after IV thrombolysis. To test whether AIS thrombi have inherent common features that limit their susceptibility to thrombolysis, we analyzed the composition and ultrastructural organization of AIS thrombi causing LVO. METHODS: A total of 199 endovascular thrombectomy-retrieved thrombi were analyzed by immunohistology and scanning electron microscopy (SEM) and subjected to ex vivo thrombolysis assay. The relationship between thrombus organization and thrombolysis resistance was further investigated in vitro using thrombus produced by recalcification of citrated whole blood. RESULTS: SEM and immunohistology analyses revealed that, although AIS thrombus composition and organization was highly heterogeneous, AIS thrombi shared a common remarkable structural feature in the form of an outer shell made of densely compacted thrombus components including fibrin, von Willebrand factor, and aggregated platelets. In vitro thrombosis experiments using human blood indicated that platelets were essential to the formation of the thrombus outer shell. Finally, in both AIS and in vitro thrombi, the thrombus outer shell showed a decreased susceptibility to tissue plasminogen activator-mediated thrombolysis as compared to the thrombus inner core. INTERPRETATION: Irrespective of their etiology and despite their heterogeneity, intracranial thrombi causing LVO have a core shell structure that influences their susceptibility to thrombolysis.