Should we continue or stop insulin sensitizing drugs during pregnancy?

Norman, Robert J.; Wang, Jim X.; Hague, William

doi:10.1097/00001703-200406000-00007

Cited by 62 publications

(45 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Pregnant women diagnosed with gestational diabetes are treated through diet (and exercise) or with insulin in order to avoid hyperglycemia and its adverse effects on fetal development. However, during recent years, other therapeutic approaches such as oral antidiabetic drugs like metformin or glyburide have also been used [2], since insulin therapy has several disadvantages in GDM, including the lack of a clear definition of the dose, the need for multiple daily injections, and the risk of hypoglycemia and excessive maternal weight gain [3]. In addition, insulin therapy is potentially associated with a risk of developing type 2 diabetes mellitus in the offspring later in life [4].…”

Section: Introductionmentioning

confidence: 99%

Role of Insulin in Placental Transport of Nutrients in Gestational Diabetes Mellitus

Ruiz-Palacios

Ruiz–Alcaraz²,

Sánchez-Campillo³

et al. 2017

Ann Nutr Metab

View full text Add to dashboard Cite

Background: Gestational diabetes mellitus (GDM) is associated with increased fetal adiposity, which may increase the risk of obesity in adulthood. The placenta has insulin receptors and maternal insulin can activate its signaling pathways, affecting the transport of nutrients to the fetus. However, the effects of diet or insulin treatment on the placental pathophysiology of GDM are unknown. Summary: There are very few studies on possible defects in the insulin signaling pathway in the GDM placenta. Such defects could influence the placental transport of nutrients to the fetus. In this review we discuss the state of insulin signaling pathways in placentas of women with GDM, as well as the role of exogenous insulin in placental nutrient transport to the fetus, and fetal adiposity. Key Messages: Maternal insulin in the third trimester is correlated with fetal abdominal circumference at that time, suggesting the important role of insulin in this process. Since treatment with insulin at the end of pregnancy may activate placental nutrient transport to the fetus and promote placental fatty acid transfer, it would be interesting to improve maternal hyperlipidemia control in GDM subjects treated with this hormone. More research in this area with high number of subjects is necessary.

show abstract

Section: Introductionmentioning

confidence: 99%

Role of Insulin in Placental Transport of Nutrients in Gestational Diabetes Mellitus

Ruiz-Palacios

Ruiz–Alcaraz²,

Sánchez-Campillo³

et al. 2017

Ann Nutr Metab

View full text Add to dashboard Cite

show abstract

“…In this regard, hyperinsulinemia from insulin resistance in PCOS women has been implicated in impaired glucoregulation (13) and reproductive dysfunction, including anovulation (14,15,16) and miscarriage (17,18). It is, therefore, not surprising that weight loss programs (19,20) and insulin sensitizers (21,22,23,24) have been successful therapeutic interventions for PCOS women, in terms ovulation induction, conception and improved glucoregulation.…”

Section: Introductionmentioning

confidence: 99%

Pioglitazone improves insulin action and normalizes menstrual cycles in a majority of prenatally androgenized female rhesus monkeys

Zhou

Bruns

Bird

et al. 2007

Reproductive Toxicology

View full text Add to dashboard Cite

PURPOSE OF THE STUDY-To determine whether pioglitazone will improve menstrual cyclicity in a fetal programming model for polycystic ovary syndrome.BASIC PROCEDURES-Eight prenatally androgenized (PA) and 5 control female rhesus monkeys of similar age, body weight and body mass index received an oral placebo daily for 6-7 months followed, after at least 90 days, by daily oral dosing with pioglitazone (3mg/kg) for an additional 6-7 months. Blood was sampled thrice weekly to monitor ovulatory function, and a variety of endocrine challenges were performed to quantify changes in ovarian, gonadotropin and glucoregulatory function. MOST IMPORTANT FINDINGS-Pioglitazone normalized menstrual cycles in 5 out of 8 (62%)PA females (pioglitazone responsive; Pio RESP ). Pioglitazone increased serum 17α-hydroxyprogesterone responses to an hCG injection in Pio RESP PA females, while diminishing serum progesterone, and increasing DHEA and estradiol responses to hCG in Pio RESP PA and all normal females.PRINCIPAL CONCLUSIONS-Insulin resistance plays a mechanistic role in maintaining anovulation in a majority of PA female monkeys.

show abstract

“…Insulin therapy is a protocol applied in pregnant women with GDM that are not responsive to diet and/or exercise to normalize their glycemia. However, this approach associates with a risk of the offspring to develop adulthood diseases such as diabetes mellitus type 2 [29,30] and of the mother to course with GDM in a future pregnancy [31]. Thus, we emphasize the need of a therapeutical approach considering the potential metabolic modulation of circulating adenosine level and/or adenosine receptors activation/inactivation complementing insulin therapy protocol in pregnant women with GDM to restore fetoplacental endothelial dysfunction for the benefit of the mother and the newborn [3].…”

Section: Adenosine Receptors Involvement On Insulin Effectmentioning

confidence: 99%

Insulin requires A1 adenosine receptors expression to reverse gestational diabetes-increased L-arginine transport in human umbilical vein endothelium

Guzmán-Gutiérrez

Armella

Toledo

et al. 2015

Purinergic Signalling

View full text Add to dashboard Cite

Gestational diabetes mellitus (GDM) associates with increased L-arginine transport and extracellular concentration of adenosine in human umbilical vein endothelial cells (HUVECs). In this study we aim to determine whether insulin reverses GDM-increased L-arginine transport requiring adenosine receptors expression in HUVECs. Primary cultured HUVECs from full-term normal (n = 38) and diet-treated GDM (n = 38) pregnancies were used. Insulin effect was assayed on human cationic amino acid transporter 1 (hCAT1) expression (protein, mRNA, SLC7A1 promoter activity) and activity (initial rates of L-arginine transport) in the absence or presence of adenosine receptors agonists or antagonists. A 1 adenosine receptors (A 1 AR) and A 2A AR expression (Western blot, quantitative PCR) was determined. Experiments were done in cells expressing or siRNA-suppressed expression of A 1 AR or A 2A AR. HUVECs from GDM exhibit higher maximal transport capacity (maximal velocity (V max )/ apparent Michaelis Menten constant (K m ), V max /K m ), which is blocked by insulin by reducing the V max to values in cells from normal pregnancies. Insulin also reversed the GDMassociated increase in hCAT-1 protein abundance and mRNA expression, and SLC7A1 promoter activity for the fragment −606 bp from the transcription start point. Insulin effects required A 1 AR, but not A 2A AR expression and activity in this cell type. In the absence of insulin, GDM-increased hCAT-1 expression and activity required A 2A AR expression and activity. HUVECs from GDM pregnancies exhibit a differential requirement of A 1 AR or A 2A AR depending on the level of insulin, a phenomenon that represent a condition where adenosine or analogues of this nucleoside could be acting as helpers of insulin biological effects in GDM.

show abstract

Should we continue or stop insulin sensitizing drugs during pregnancy?

Cited by 62 publications

References 36 publications

Role of Insulin in Placental Transport of Nutrients in Gestational Diabetes Mellitus

Role of Insulin in Placental Transport of Nutrients in Gestational Diabetes Mellitus

Pioglitazone improves insulin action and normalizes menstrual cycles in a majority of prenatally androgenized female rhesus monkeys

Insulin requires A1 adenosine receptors expression to reverse gestational diabetes-increased L-arginine transport in human umbilical vein endothelium

Contact Info

Product

Resources

About