BackgroundCirculating nucleic acids (CNAs) offer unique opportunities for early diagnosis of clinical conditions. Here we show that microRNAs, a family of small non-coding regulatory RNAs involved in human development and pathology, are present in bodily fluids and represent new effective biomarkers.Methods and ResultsAfter developing protocols for extracting and quantifying microRNAs in serum and other body fluids, the serum microRNA profiles of several healthy individuals were determined and found to be similar, validating the robustness of our methods. To address the possibility that the abundance of specific microRNAs might change during physiological or pathological conditions, serum microRNA levels in pregnant and non pregnant women were compared. In sera from pregnant women, microRNAs associated with human placenta were significantly elevated and their levels correlated with pregnancy stage.Conclusions and SignificanceConsidering the central role of microRNAs in development and disease, our results highlight the medically relevant potential of determining microRNA levels in serum and other body fluids. Thus, microRNAs are a new class of CNAs that promise to serve as useful clinical biomarkers.

Gestational diabetes (GDM) is defined as carbohydrate intolerance that begins or is first recognized during pregnancy. Although it is a well-known cause of pregnancy complications, its epidemiology has not been studied systematically. Our aim was to review the recent data on the epidemiology of GDM, and to describe the close relationship of GDM to prediabetic states, in addition to the risk of future deterioration in insulin resistance and development of overt Type 2 diabetes. We found that differences in screening programmes and diagnostic criteria make it difficult to compare frequencies of GDM among various populations. Nevertheless, ethnicity has been proven to be an independent risk factor for GDM, which varies in prevalence in direct proportion to the prevalence of Type 2 diabetes in a given population or ethnic group. There are several identifiable predisposing factors for GDM, and in the absence of risk factors, the incidence of GDM is low. Therefore, some authors suggest that selective screening may be cost-effective. Importantly, women with an early diagnosis of GDM, in the first half of pregnancy, represent a high-risk subgroup, with an increased incidence of obstetric complications, recurrent GDM in subsequent pregnancies, and future development of Type 2 diabetes. Other factors that place women with GDM at increased risk of Type 2 diabetes are obesity and need for insulin for glycaemic control. Furthermore, hypertensive disorders in pregnancy and afterwards may be more prevalent in women with GDM. We conclude that the epidemiological data suggest an association between several high-risk prediabetic states, GDM, and Type 2 diabetes. Insulin resistance is suggested as a pathogenic linkage. It is possible that improving insulin sensitivity with diet, exercise and drugs such as metformin may reduce the risk of diabetes in individuals at high risk, such as women with polycystic ovary syndrome, impaired glucose tolerance, and a history of GDM. Large controlled studies are needed to clarify this issue and to develop appropriate diabetic prevention strategies that address the potentially modifiable risk factors.

Using an evidence-based approach, this Diabetes and Pregnancy Clinical Practice Guideline addresses important clinical issues in the contemporary management of women with type 1 or type 2 diabetes preconceptionally, during pregnancy, and in the postpartum setting and in the diagnosis and management of women with gestational diabetes during and after pregnancy.

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The HAPO Study Cooperative Research Group* OBJECTIVE-To examine associations of neonatal adiposity with maternal glucose levels and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, thereby assessing the Pederson hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adiposity. RESEARCH DESIGN AND METHODS-Eligible pregnantwomen underwent a standard 75-g oral glucose tolerance test between 24 and 32 weeks gestation (as close to 28 weeks as possible). Neonatal anthropometrics and cord serum C-peptide were measured. Associations of maternal glucose and cord serum C-peptide with neonatal adiposity (sum of skin folds Ͼ90th percentile or percent body fat Ͼ90th percentile) were assessed using multiple logistic regression analyses, with adjustment for potential confounders, including maternal age, parity, BMI, mean arterial pressure, height, gestational age at delivery, and the baby's sex.RESULTS-Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, cord serum C-peptide results were available for 19,885 babies and skin fold measurements for 19,389. For measures of neonatal adiposity, there were strong statistically significant gradients across increasing levels of maternal glucose and cord serum C-peptide, which persisted after adjustment for potential confounders. In fully adjusted continuous variable models, odds ratios ranged from 1.35 to 1.44 for the two measures of adiposity for fasting, 1-h, and 2-h plasma glucose higher by 1 SD.CONCLUSIONS-These findings confirm the link between maternal glucose and neonatal adiposity and suggest that the relationship is mediated by fetal insulin production and that the Pedersen hypothesis describes a basic biological relationship influencing fetal growth.

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