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In recent years, there has been a dramatic increase in the number of pregnancies complicated by gestational diabetes mellitus (GDM). GDM occurs when maternal insulin resistance develops and/or progresses during gestation, and it is not compensated by a rise in maternal insulin secretion. If not properly managed, this condition can cause serious short-term and long-term problems for both mother and child. Lifestyle changes are the first line of treatment for GDM, but if ineffective, insulin injections are the recommended pharmacological treatment choice. Some guidance authorities and scientific societies have proposed the use of metformin as an alternative pharmacological option for treating GDM, but there is not yet a unanimous consensus on this. Although the use of metformin appears to be safe for the mother, concerns remain about its long-term metabolic effects on the child that is exposed in utero to the drug, given that metformin, contrary to insulin, crosses the placenta. This review article describes the existing lines of evidence about the use of metformin in pregnancies complicated by GDM, in order to clarify its potential benefits and limits, and to help clinicians make decisions about who could benefit most from this drug treatment. [ABSTRACT FROM AUTHOR]

Introduction—The purpose of this study was to determine the relative impact of modifiable and non-modifiable risk factors in the development of gestational diabetes mellitus (GDM), with a particular focus on maternal preconception body mass index (BMI) and age, two important determinants of insulin resistance. Understanding the factors that contribute most to the current escalation of GDM rates in pregnant women could help to inform prevention and intervention strategies, particularly in areas where this female endocrine disorder has an elevated prevalence. Methods—A retrospective, contemporary, large population of singleton pregnant women from southern Italy who underwent 75 g OGTT for GDM screening was enrolled at the Endocrinology Unit, "Pugliese Ciaccio" Hospital, Catanzaro. Relevant clinical data were collected, and the characteristics of women diagnosed with GDM or with normal glucose tolerance were compared. The effect estimates of maternal preconception BMI and age as risk factors for GDM development were calculated through correlation and logistic regression analysis by adjusting for potential confounders. Results—Out of the 3856 women enrolled, 885 (23.0%) were diagnosed with GDM as per IADPSG criteria. Advanced maternal age (≥35 years), gravidity, reproductive history of spontaneous abortion(s), previous GDM, and thyroid and thrombophilic diseases, all emerged as non-modifiable risk factors of GDM, whereas preconception overweight or obesity was the sole potentially modifiable risk factor among those investigated. Maternal preconception BMI, but not age, had a moderate positive association with fasting glucose levels at the time of 75 g OGTT (Pearson coefficient: 0.245, p < 0.001). Abnormalities in fasting glucose drove the majority (60%) of the GDM diagnoses in this study. Maternal preconception obesity almost tripled the risk of developing GDM, but even being overweight resulted in a more pronounced increased risk of developing GDM than advanced maternal age (adjusted OR for preconception overweight: 1.63, 95% CI 1.320–2.019; adjusted OR for advanced maternal age: 1.45, 95% CI 1.184–1.776). Conclusions—Excess body weight prior to conception leads to more detrimental metabolic effects than advanced maternal age in pregnant women with GDM. Thus, in areas in which GDM is particularly common, such as southern Italy, measures aiming to counteracting maternal preconception overweight and obesity may be efficient in reducing GDM prevalence. [ABSTRACT FROM AUTHOR]

Background. Screening strategies for gestational diabetes mellitus (GDM) earlier than 24-28 weeks of gestation should be considered to prevent adverse pregnancy outcomes. Nonetheless, there is uncertainty about which women would benefit most from early screening and which screening strategies should be offered to women with GDM. The Italian National Healthcare Service (NHS) recommendations on selective screening for GDM at 16-18 weeks of gestation are effective in preventing fetal macrosomia in high-risk (HR) women, but the appropriateness of timing and effectiveness of these recommendations in medium- (MR) and low-risk (LR) women are still controversial. Patients and Methods. We retrospectively enrolled 769 consecutive singleton pregnant women who underwent both anomaly scan at 19-21 weeks of gestation and screening for GDM at 16-18 and/or 24-28 weeks of gestation, in agreement with the NHS recommendations and risk stratification criteria. Comparison of maternal characteristics, fetal biometric parameters at anomaly scan (head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC), femur length (FL), estimated fetal weight (EFW)), and neonatal birth weight (BW) percentile among risk groups was examined. Results. 219 (28.5%) women were diagnosed with GDM, while 550 (71.5%) were normal glucose-tolerant women. Out of 164 HR women, only 62 (37.8%) underwent the recommended early screening for GDM at 16-18 weeks of gestation. AC and EFW percentiles, as well as neonates' BW percentiles, were significantly higher in HR women diagnosed with GDM at 24-28 weeks of gestation with respect to normal glucose-tolerant women, as well as MR and LR women who tested positive for GDM. Comparative analysis between MR and LR women with GDM and women with normal glucose tolerance revealed significant differences in both AC and EFW percentiles (P < 0.05), while there was no significant difference in neonatal BW percentiles. Conclusion. In MR and LR women with GDM, a mild acceleration of fetal growth can be detected at the time of anomaly scan. However, in these at-risk categories, the NHS recommendations for screening and treatment of GDM at 24-28 weeks of gestation are still effective in normalizing BW and preventing fetal macrosomia, thus supporting a risk factor-based selective screening program for GDM. [ABSTRACT FROM AUTHOR]

Keywords: glucose homeostasis; gene transcription; insulin resistance; insulin signaling; microRNAs It is interesting to note that mice with a partial functional loss of Prep1 have smaller pancreatic islets and reduced insulin secretion on one hand, while, on the other, they show higher insulin sensitivity in peripheral tissues, and exhibit protection from both streptozotocin-induced diabetes and diet-induced steatohepatitis. The authors also describe the association between miRNAs and metabolism, by evaluating the effects of these small mRNA molecules on insulin signaling, on glucose uptake and on the mitochondrial oxidative metabolism. Glucose homeostasis, gene transcription, insulin resistance, insulin signaling, microRNAs. [Extracted from the article]

Aims: The Italian National Institute of Health has recently introduced a selective screening based on the risk profile of pregnant women, which while recommending against screening of women at low risk (LR) for GDM, it recommends an early test for women at high risk (HR) for GDM. Herein, we assessed the accuracy and cost-effectiveness of this screening and developed a new index that improves these requirements.Methods: We retrospectively enrolled 3974 pregnant women. GDM was diagnosed with a 2h 75-g OGTT at 16-18 weeks (early test) or 24-28 weeks of gestation, according to the IADPSG guidelines.Results: 55.6% of HR women had GDM, although only 38.4% underwent early screening. Among 2654 women at medium risk, 20.9% had GDM; paradoxically, among 770 LR women, that would not have been screened, 26.6% received a GDM diagnosis. Based on these unsatisfactory results, we elaborated the Capula's index, that reduced both screening tests (p<0.001) and potentially undetected GDM cases (p<0.001), and corrected the paradoxical prevalence estimates of GDM obtained with the current Italian guidelines. Also, Capula's index improved correlation of GDM risk profile with obstetric and neonatal adverse events.Conclusions: Capula's index improves accuracy of selective screening for GDM. [ABSTRACT FROM AUTHOR]

Recent Italian guidelines exclude women <35 years old, without risk factors for gestational diabetes mellitus (GDM), from screening for GDM. To determine the effectiveness of these measures with respect to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria, we evaluated 2,448 pregnant women retrospectively enrolled in Calabria, southern Italy. GDM was diagnosed following the IADPSG 2010 criteria. Among 538 women <35 years old, without risk factors, who would have not been tested according to the Italian guidelines, we diagnosed GDM in 171 (31.8%) pregnants (7.0% of total pregnants). Diagnosis was made at baseline (55.6%), 1 hour (39.8%), or 2 hours (4.7%) during OGTT. Despite of appropriate treatment, GDM represented a risk factor for cesarean section, polyhydramnios, increased birth weight, admission to neonatal intensive care units, and large for gestational age. These outcomes were similar to those observed in GDM women at high risk for GDM. In conclusion, Italian recommendations failed to identify 7.0% of women with GDM, when compared to IADPSG criteria. The risk for adverse hyperglycaemic-related outcomes is similar in low-risk and high-risk pregnants with GDM. To limit costs of GDM screening, our data suggest to restrict OGTT to two steps (baseline and 1 hour). [ABSTRACT FROM AUTHOR]

Postpartum screening is critical for early identification of type 2 diabetes in women previously diagnosed with gestational diabetes mellitus (GDM). Nevertheless, its rate remains disappointingly low. Thus, we plan to examine the rate of postpartum glucose tolerance test (ppOGTT) for Italian women with GDM, before and after counseling, and identify demographic, clinical, and/or biochemical predictors of adherence. With these aims, we retrospectively enrolled 1159 women with GDM, in Calabria, Southern Italy, between 2004 and 2011. During the last year, verbal and written counseling on the importance of follow up was introduced. Data were analyzed by multiple regression analysis. A significant increase of the return rate was observed following introduction of the counseling [adjusted odds ratio (AOR) 5.17 (95% CI, 3.83-6.97), P < 0.001]. Interestingly, previous diagnosis of polycystic ovary syndrome (PCOS) emerged as the major predictor of postpartum follow up [AOR 5.27 (95% CI, 3.51-8.70), P < 0.001], even after stratification for the absence of counseling. Previous diagnosis of GDM, higher educational status, and insulin treatment were also relevant predictors. Overall, our data indicate that counseling intervention is effective, even if many women fail to return, whereas PCOS represents a new strong predictor of adherence to postpartum testing. [ABSTRACT FROM AUTHOR]

Maternal gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy, which can adversely affect the short- and long-term health of mothers and newborns. In recent years, several studies have revealed the early impact of maternal hyperglycemia on fetal growth trajectory and birth weight abnormalities in GDM-exposed pregnancies. However, an intense debate continues regarding the mode and optimal timing of diagnosis and treatment of this condition. The purpose of this review is to provide a brief overview of the understanding of GDM and its implications for fetal growth, addressing the modulatory role of medical nutrition therapy and available pharmacological antidiabetic agents (i.e. insulin, metformin, and glyburide), and to identify gaps in current knowledge toward which future research should be directed. [ABSTRACT FROM AUTHOR]

Aims To determine the prevalence of both prediabetes and type 2 diabetes mellitus (T2DM) by postpartum oral glucose tolerance test (ppOGTT) in Italian women diagnosed with gestational diabetes mellitus (GDM), and identify antepartum predictors of glucose intolerance. Methods Retrospective study of 454 Caucasian women that underwent a 75 g OGTT between 6 and 12 weeks postpartum in Calabria (Southern Italy) between 2004 and 2012. Prediabetes and T2DM were diagnosed according to the American Diabetes Association (ADA) criteria. Data were examined by univariate analysis and multiple regression analysis. Results 290 women (63.9%) were normal, 146 (32.1%) had prediabetes (85 impaired fasting glycemia; 61 impaired glucose tolerance), and 18 (4.0%) had T2DM. Of the continuous variables, pre-pregnancy body mass index (BMI), age at pregnancy, fasting plasma glucose (FPG) at gravid OGTT, and week at diagnosis of GDM were associated with prediabetes and T2DM, whereas the parity was associated with T2DM only. For categorical traits, pre-pregnancy BMI ≥25 and previous diagnosis of polycystic ovary syndrome (PCOS) emerged as the strongest predictors of prediabetes whereas the strongest predictors of T2DM were FPG ≥100 mg/dl (5.6 mmol/l) at GDM diagnosis and pre-pregnancy BMI ≥25. Moreover, FPG at GDM screening was a good predictor of T2DM after receiver-operating-characteristic analysis. Conclusions Our findings confirm the high prevalence of glucose intolerance in the early postpartum period in women with previous GDM. PCOS emerges as a new strong antepartum predictor of prediabetes. [ABSTRACT FROM AUTHOR]