Aims/hypotheses: Chronic hyperglycaemia in-

Design Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and its prevalence is constantly rising worldwide. Diagnosis is commonly in the late second or early third trimester of pregnancy, though the development of GDM starts early; hence, first-trimester diagnosis is feasible. Objective Our objective was to identify microRNAs that best distinguish GDM samples from those of healthy pregnant women and to evaluate the predictive value of microRNAs for GDM detection in the first trimester. Methods We investigated the abundance of circulating microRNAs in the plasma of pregnant women in their first trimester. Two populations were included in the study to enable population-specific as well as cross-population inspection of expression profiles. Each microRNA was tested for differential expression in GDM vs control samples, and their efficiency for GDM detection was evaluated using machine-learning models. Results Two upregulated microRNAs (miR-223 and miR-23a) were identified in GDM vs the control set, and validated on a new cohort of women. Using both microRNAs in a logistic-regression model, we achieved an AUC value of 0.91. We further demonstrated the overall predictive value of microRNAs using several types of multivariable machine-learning models that included the entire set of expressed microRNAs. All models achieved high accuracy when applied on the dataset (mean AUC = 0.77). The significance of the classification results was established via permutation tests. Conclusions Our findings suggest that circulating microRNAs are potential biomarkers for GDM in the first trimester. This warrants further examination and lays the foundation for producing a novel early non-invasive diagnostic tool for GDM.

Data availabilitySummary statistics generated by COVID-19 Host Genetics Initiative are available online (https://www.covid19hg.org/results/r6/). The analyses described here use the freeze 6 data. The COVID-19 Host Genetics Initiative continues to regularly release new data freezes. Summary statistics for samples from individuals of non-European ancestry are not currently available owing to the small individual sample sizes of these groups, but the results for 23 loci lead variants are reported in Supplementary Table 3. Individual-level data can be requested directly from the authors of the contributing studies, listed in Supplementary Table 1.

No abstract

Highlights Laboratory diagnostic parameters in symptomatic Covid19 disease patients. Monocyte distribution width and monocyte modification in infection disease and sepsis. SARS COV2 infection, prognosis in severe respiratory failure with multiple organ failure, clinical and laboratory finding.

Leptin concentrations are not significantly modified in obese Type 2 diabetic patients. GLP-1(7-36)amide baseline concentrations are reduced in Type 2 diabetes; moreover, diabetic subjects show an impaired response of GLP-1 to oral glucose in euglycaemic, isoinsulinaemic conditions. This impairment, which is not the result of differences in glycaemia or insulinaemia during assessment, could contribute to the pathogenesis of hyperglycaemia in Type 2 diabetes mellitus.

The use of fasting plasma glucose (FPG) only has been proposed for the screening and diagnosis of diabetes, but its sensitivity has been reported to be unsatisfactory. The use of HbA1C, alone or combined with FPG, has been suggested for the screening of diabetes and impaired glucose tolerance (IGT). In a sample of 1215 adult subjects without previously known diabetes, we assessed the sensitivity and specificity of FPG and HbA1C in diagnosing diabetes and IGT, determined by oral glucose tolerance test (OGTT). All lean diabetic patients, and 85% of overweight and obese diabetic individuals, had FPG > or =7 mmol/l. FPG >6.1 mmol/l had a sensitivity of 98.8% and a specificity of 32.9%; HbA1C had a lower specificity and sensitivity for the screening of diabetes. A screening strategy for diabetes based on FPG, with OGTT in all overweight subjects with FPG >6.1 mmol/l, is suggested. Neither FPG nor HbA1C is effective in the screening of IGT; although combined FPG and HbA1C could be useful for case finding, screening for IGT with OGTT is advisable in all subjects at high risk.

Objective: Insulin sensitivity and secretion during early and late pregnancy were assessed in women with normal glucose tolerance and gestational diabetes mellitus (GDM). Research Design and Methods:The oral glucose tolerance test (OGTT) was performed in 903 women at 16 -20th gestational week, of whom 37 had GDM (GDM1 group), and 859 repeated the OGTT at wk 26 -30. At the second test, 55 had GDM (GDM2 group); the others remained normotolerant (ND group). Insulin sensitivity from OGTT (as quantitative insulin sensitivity check index and OGTT insulin sensitivity) and ␤-cell function (as the ratio of the areas under the insulin and glucose concentration curves, adjusted for insulin sensitivity) were assessed in both tests. Results:In early pregnancy the quantitative insulin sensitivity check index was not different in the three groups, whereas OGTT insulin sensitivity was lowest in GDM2, intermediate in GDM1, and highest in ND. In late pregnancy both indices were reduced in GDM compared with ND and lower than in early pregnancy. In early pregnancy GDM1, but not GDM2, had lower ␤-cell function than ND. During the late visit, GDM2 also showed impaired ␤-cell function compared with ND; furthermore, the adaptation to the increase to insulin resistance from early to late pregnancy was defective in GDM2. Conclusions:In early pregnancy insulin sensitivity, as assessed from the OGTT but not from fasting measurements, is impaired in women who developed GDM. ␤-Cell function impairment is evident only when GDM is manifest and is characterized by inappropriate adaptation to the pregnancy induced increase in insulin resistance. (J Clin Endocrinol Metab 93: 876 -880, 2008) N ormal pregnancy can be considered a state of insulin resistance because insulin sensitivity decreases in pregnancy, reaching its nadir in the third trimester and rapidly returning to prepregnancy levels after delivery (1-4). Although the specific mechanisms behind the progressive insulin resistance during pregnancy have not been completely clarified, an important contribution seems to come from the endocrine modifications characteristic of pregnancy, including the increase in estrogens, progesterone, human placental lactogen, cortisol, and TNF-␣ (5, 6). Both insulin resistance (7) and a defective insulin secretion and action (8, 9) also characterize gestational diabetes mellitus (GDM).The euglycemic glucose clamp, the "gold standard" for assessing insulin sensitivity, has been used in pregnancy, but the test is complex, so most of the studies were performed on a small number of patients (1-3). Studies on insulin secretion, which usually simply evaluated the area under the concentration curve (1, 2), only rarely also using the glucose clamp (9), have involved a small number of patients, who were obese in most cases (1, 9). Evaluation of insulin sensitivity and secretion in large numbers Abbreviations: AUC, Area under the curve; AUC glu , area under the glucose concentration curve; AUC ins , area under the insulin concentration curve; AUCR, area under the curv...