The clinical status of CF patients who will need insulin therapy deteriorates before the start of insulin. In patients with CF-related diabetes, with or without fasting hyperglycaemia, insulin therapy improves anabolism and provides good glycaemic control with few severe hypoglycaemic episodes.

Background During pregnancy, maternal metabolism undergoes substantial changes to support the developing fetus. Such changes are finely regulated by different mechanisms carried out by effectors such as microRNAs (miRNAs). These small non-coding RNAs regulate numerous biological functions, mostly through post-transcriptional repression of gene expression. miRNAs are also secreted in circulation by numerous organs, such as the placenta. However, the complete plasmatic microtranscriptome of pregnant women has still not been fully described, although some miRNA clusters from the chromosome 14 (C14MC) and the chromosome 19 (C19MC and miR-371-3 cluster) have been proposed as being specific to pregnancy. Our aims were thus to describe the plasma microtranscriptome during the first trimester of pregnancy, by assessing the differences with non-pregnant women, and how it varies between the 4th and the 16th week of pregnancy. Methods Plasmatic miRNAs from 436 pregnant (gestational week 4 to 16) and 15 non-pregnant women were quantified using Illumina HiSeq next-generation sequencing platform. Differentially abundant miRNAs were identified using DESeq2 package (FDR q-value ≤ 0.05) and their targeted biological pathways were assessed with DIANA-miRpath. Results A total of 2101 miRNAs were detected, of which 191 were differentially abundant (fold change < 0.05 or > 2, FDR q-value ≤ 0.05) between pregnant and non-pregnant women. Of these, 100 miRNAs were less and 91 miRNAs were more abundant in pregnant women. Additionally, the abundance of 57 miRNAs varied according to gestational age at first trimester, of which 47 were positively and 10 were negatively associated with advancing gestational age. miRNAs from the C19MC were positively associated with both pregnancy and gestational age variation during the first trimester. Biological pathway analysis revealed that these 191 (pregnancy-specific) and 57 (gestational age markers) miRNAs targeted genes involved in fatty acid metabolism, ECM-receptor interaction and TGF-beta signaling pathways. Conclusion We have identified circulating miRNAs specific to pregnancy and/or that varied with gestational age in first trimester. These miRNAs target biological pathways involved in lipid metabolism as well as placenta and embryo development, suggesting a contribution to the maternal metabolic adaptation to pregnancy and fetal growth.

IntroductionGestational diabetes mellitus (GDM) is a consequence of an imbalance between insulin sensitivity (IS) and secretion during pregnancy. MicroRNAs (miRNAs) are small and secreted RNA molecules stable in blood and known to regulate physiological processes including glucose homeostasis. The aim of this study was to identify plasmatic miRNAs detectable in early pregnancy predicting IS at 24th-29th week of pregnancy.Research design and methodsWe quantified circulating miRNAs in 421 women in plasma collected at 9.6±2.2 weeks of pregnancy using next-generation sequencing.Resultswe detected 2170 miRNAs: 39 (35 positively and 4 negatively) were associated with IS as estimated by the Matsuda Index at 26.4±1.0 weeks of pregnancy. Lasso regression identified 18 miRNAs independently predicting Matsuda Index-estimated IS. Together with gestational age, maternal age and body mass index at first trimester, they explain 36% of IS variance in late second trimester of pregnancy. These miRNAs regulate fatty acid biosynthesis and metabolism among other pathways.ConclusionsIn summary, we have identified first trimester plasmatic miRNAs predictive of Matsuda Index-estimated IS in late second trimester of pregnancy. These miRNAs could also contribute to initiate and support IS adaptation to pregnancy potentially through lipid metabolism regulation.

The contribution of adiposopathy to glucose-insulin homeostasis remains unclear. This longitudinal study examined the potential relationship between the adiponectin/leptin ratio (A/L, a marker of adiposopathy) and insulin resistance (IR: homeostasis model assessment (HOMA)), insulin sensitivity (IS: Matsuda), and insulin response to an oral glucose tolerance test before and after a 16-week walking program, in 29 physically inactive pre- and postmenopausal women with obesity (BMI, 29-35 kg/m; age, 47-54 years). Anthropometry, body composition, VOmax, and fasting lipid-lipoprotein and inflammatory profiles were assessed. A/L was unchanged after training (p = 0.15), despite decreased leptin levels (p < 0.05). While the Matsuda index tended to increase (p = 0.07), HOMA decreased (p < 0.05) and fasting insulin was reduced (p < 0.01) but insulin area under the curve (AUC) remained unchanged (p = 0.18) after training. Body fatness and VOmax were improved (p < 0.05) while triacylglycerols increased and HDL-CHOL levels decreased after training (p < 0.05). At baseline, A/L was positively associated with VOmax, HDL-CHOL levels, and Matsuda (0.37 < ρ < 0.56; p < 0.05) but negatively with body fatness, HOMA, insulin AUC, IL-6, and hs-CRP levels (- 0.41 < ρ < - 0.66; p < 0.05). After training, associations with fitness, HOMA, and inflammation were lost. Multiple regression analysis revealed A/L as an independent predictor of IR and IS, before training (partial R = 0.10 and 0.22), although A/L did not predict the insulin AUC pre- or post-intervention. A significant correlation was found between training-induced changes to A/L and IS (r = 0.38; p < 0.05) but not with IR or insulin AUC. Although changes in the A/L ratio could not explain improvements to glucose-insulin homeostasis indices following training, a relationship with insulin sensitivity was revealed in healthy women with obesity.

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