Metabolic profiling of pre-gestational and gestational diabetes mellitus identifies novel predictors of pre-term delivery.

Pregnant women with gestational diabetes mellitus (GDM) or type 2 diabetes mellitus (T2DM) are at increased risks of pre-term labor, hypertension and preeclampsia. In this study, metabolic profiling of blood samples collected from GDM, T2DM and control pregnant women was undertaken to identify potential diagnostic biomarkers in GDM/T2DM and compared to pregnancy outcome. Sixty-seven pregnant women (21 controls, 32 GDM, 14 T2DM) in their second trimester underwent targeted metabolomics of plasma samples using tandem mass spectrometry with the Biocrates MxP Quant 500 Kit. Linear regression models were used to identify the metabolic signature of GDM and T2DM, followed by generalized linear model (GLMNET) and Receiver Operating Characteristic (ROC) analysis to determine best predictors of GDM, T2DM and pre-term labor. The gestational age at delivery was 2 weeks earlier in T2DM compared to GDM and controls and correlated negatively with maternal HbA1C and systolic blood pressure and positively with serum albumin. Linear regression models revealed elevated glutamate and branched chain amino acids in GDM + T2DM group compared to controls. Regression models also revealed association of lower levels of triacylglycerols and diacylglycerols containing oleic and linoleic fatty acids with pre-term delivery. A generalized linear model ROC analyses revealed that that glutamate is the best predictors of GDM compared to controls (area under curve; AUC = 0.81). The model also revealed that phosphatidylcholine diacyl C40:2, arachidonic acid, glycochenodeoxycholic acid, and phosphatidylcholine acyl-alkyl C34:3 are the best predictors of GDM + T2DM compared to controls (AUC = 0.90). The model also revealed that the triacylglycerols C17:2/36:4 and C18:1/34:1 are the best predictors of pre-term delivery (≤ 37 weeks) (AUC = 0.84). This study highlights the metabolite alterations in women in their second trimester with diabetes mellitus and identifies predictive indicators of pre-term delivery. Future studies to confirm these associations in other cohorts and investigate their functional relevance and potential utilization for targeted therapies are warranted.This research was sponsored by QNRF, Grant no. NPRP10-1205-160010 (NAM)

Dynamic Changes in Circulating Endocrine FGF19 Subfamily and Fetuin-A in Response to Intralipid and Insulin Infusions in Healthy and PCOS Women

© Copyright © 2020 Ramanjaneya, Bensila, Bettahi, Jerobin, Samra, Aye, Alkasem, Siveen, Sathyapalan, Skarulis, Atkin and Abou-Samra. Background: The fibroblast growth factors (FGF) 19 subfamily, also referred to as endocrine FGFs, includes FGF19, FGF21, and FGF23 are metabolic hormones involved in the regulation of glucose and lipid metabolism. Fetuin-A is a hepatokine involved in the regulation of beta-cell function and insulin resistance. Endocrine FGFs and fetuin-A are dysregulated in metabolic disorders including obesity, type 2 diabetes, non-alcoholic fatty liver disease and polycystic ovary syndrome (PCOS). Our study was designed to examine the response of endocrine FGFs and fetuin-A to an acute intralipid, insulin infusion and exercise in PCOS and healthy women. Subjects and Measurements: Ten healthy and 11 PCOS subjects underwent 5-h saline infusions with a hyperinsulinemic-euglycemic clamp (HIEC) performed during the final 2 h. One week later, intralipid infusions were undertaken with a HIEC performed during the final 2 h. After an 8 week of exercise intervention the saline, intralipid, and HIEC were repeated. Plasma levels of endocrine FGFs and fetuin-A were measured. Results: Baseline fetuin-A was higher in PCOS women but FGF19, FGF21, and FGF23 did not differ and were unaffected by exercise. Insulin administration elevated FGF21 in control and PCOS, suppressed FGF19 in controls, and had no effects on FGF23 and fetuin-A. Intralipid infusion suppressed FGF19 and increased FGF21. Insulin with intralipid synergistically increased FGF21 and did not have effects on lipid-mediated suppression of FGF19 in both groups. Conclusion: Our study provides evidence for insulin and lipid regulation of endocrine FGFs in healthy and PCOS women, suggesting that FGF family members play a role in lipid and glucose metabolism. Clinical Trial Registration: www.isrctn.org, Identifier: ISRCTN42448814

Metabolic aspects of surgical subcutaneous fat removal: An umbrella review and implications for future research

Although obesity is a preventable disease, maintaining a normal body weight can be very challenging and difficult, which has led to a significant increase in the demand for surgical subcutaneous fat removal (SSFR) to improve physical appearance. The need for SSFR is further exacerbated because of the global rise in the number of bariatric surgeries, which is currently the single most durable intervention for mitigating obesity. Fat tissue is now recognized as a vital endocrine organ that produces several bioactive proteins. Thus, SSFR-mediated weight (fat) loss can potentially have significant metabolic effects; however, currently, there is no consensus on this issue. This review focuses on the metabolic sequelae after SSFR interventions for dealing with cosmetic body appearance. Data was extracted from existing systematic reviews and the diversity of possible metabolic changes after SSFR are reported along with gaps in the knowledge and future directions for research and practice. We conclude that there is a potential for metabolic sequelae after SSFR interventions and their clinical implications for the safety of the procedures as well as for our understanding of subcutaneous adipose tissue biology and insulin resistance are discussed

The impact of prior obesity surgery on glucose metabolism after body contouring surgery: A pilot study

Body contouring surgery enhances physical appearance by means of surgical subcutaneous fat removal (SSFR). However, it remains unclear how SSFR may affect glucose metabolism and its broader effects on the endocrine system, especially in individuals who have undergone obesity (bariatric) surgery. This study aimed to evaluate the impact of SSFR on glucose excursion and insulin resistance in such patients, by examining them over three visits (within 1 week before surgery, 1 week after surgery, and 6 weeks after surgery). The independent impact of SSFR and history of obesity surgery on glucose homeostasis was evaluated in 29 participants, of whom ten patients (34%) had a history of obesity surgery. Indices of glucose metabolism were evaluated using cluster robust-error logistic regression. Results indicated that SSFR led to a gross improvement in insulin resistance at 6 weeks after the surgery in all patient’s irrespective of BMI, type 2 diabetes mellitus (T2D) status, or history of obesity surgery (OR 0.22; p = 0.042). However, no effect was observed on glucose excursion except for a transient increase at visit 2 (1 week after surgery) in those without prior obesity surgery. Interestingly, participants with a history of obesity surgery had approximately half the odds being in the upper tertile for HOMA-IR (OR 0.44; p = 0.142) and ten-folds lower odds of having severely abnormal glucose excursion (OR 0.09; p = 0.031), irrespective of their BMI, T2D status, or time post SSFR. In conclusion, this study showed that body contouring surgery through SSFR resulted in (at least) short-term improvement in insulin resistance (independent of the participant’s BMI, T2D status, or history of obesity surgery) without affecting glucose excursion under the GTT. On the contrary, obesity surgery may have a long-term effect on glucose excursion, possibly due to sustained improvement of pancreatic ß-cell function

COVID-19 Disease Severity in Persons Infected with Omicron BA.1 and BA.2 Sublineages and Association with Vaccination Status

[No abstract available

Transforming growth factor-[beta]1 regulates steady-state PTH/PTHrP receptor mRNA levels and PTHrP binding in ROS 17/2.8 osteosarcoma cells

The effect of transforming growth factor [beta]1 (TGF-[beta]1) on the expression of mRNA for the parathyroid hormone receptor and binding of iodinated parathyroid hormone-related protein in ROS 17/2.8 osteosarcoma cells was evaluated. TGF-[beta]1 stimulated a 2-7-fold increase in steady state mRNA levels for the parathyroid hormone receptor at a maximal dose of 5 ng/ml, with increased levels of expression at 6 h of TGF-[beta]1-incubation, and peak levels at 8-24 h. Receptor binding studies revealed a significant increase in PTHrP-specific binding with TGF-[beta]1 doses as low as 0.5 ng/ml and a 55% increase in numbers of receptors with no alteration in binding affinity with 5.0 ng/ml TGF-[beta]1. Time course studies indicated that receptor binding was increased at 24 h with peak levels reached at 48 h of treatment. PTH-stimulated cAMP levels were significantly increased in ROS 17/2.8 cells treated with TGF-[beta]1 (0.5 ng/ml) for 48 h. These data indicate that TGF-[beta]1 upregulates steady-state mRNA, ligand binding and PTH/PTHrP receptor signaling in rat osteosarcoma cells. The effects of TGF-[beta]1 on bone may be attributed in part to regulation of the PTH/PTHrP receptor at the molecular level.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31617/1/0000549.pd

An integrated multi-omic approach demonstrates distinct molecular signatures between human obesity with and without metabolic complications: a case–control study

Objectives: To examine the hypothesis that obesity complicated by the metabolic syndrome, compared to uncomplicated obesity, has distinct molecular signatures and metabolic pathways. Methods: We analyzed a cohort of 39 participants with obesity that included 21 with metabolic syndrome, age-matched to 18 without metabolic complications. We measured in whole blood samples 754 human microRNAs (miRNAs), 704 metabolites using unbiased mass spectrometry metabolomics, and 25,682 transcripts, which include both protein coding genes (PCGs) as well as non-coding transcripts. We then identified differentially expressed miRNAs, PCGs, and metabolites and integrated them using databases such as mirDIP (mapping between miRNA-PCG network), Human Metabolome Database (mapping between metabolite-PCG network) and tools like MetaboAnalyst (mapping between metabolite-metabolic pathway network) to determine dysregulated metabolic pathways in obesity with metabolic complications. Results: We identified 8 significantly enriched metabolic pathways comprising 8 metabolites, 25 protein coding genes and 9 microRNAs which are each differentially expressed between the subjects with obesity and those with obesity and metabolic syndrome. By performing unsupervised hierarchical clustering on the enrichment matrix of the 8 metabolic pathways, we could approximately segregate the uncomplicated obesity strata from that of obesity with metabolic syndrome. Conclusions: The data suggest that at least 8 metabolic pathways, along with their various dysregulated elements, identified via our integrative bioinformatics pipeline, can potentially differentiate those with obesity from those with obesity and metabolic complications

Characteristic MicroRNAs Linked to Dysregulated Metabolic Pathways in Qatari Adult Subjects With Obesity and Metabolic Syndrome

BackgroundObesity-associated dysglycemia is associated with metabolic disorders. MicroRNAs (miRNAs) are known regulators of metabolic homeostasis. We aimed to assess the relationship of circulating miRNAs with clinical features in obese Qatari individuals.MethodsWe analyzed a dataset of 39 age-matched patients that includes 18 subjects with obesity only (OBO) and 21 subjects with obesity and metabolic syndrome (OBM). We measured 754 well-characterized human microRNAs (miRNAs) and identified differentially expressed miRNAs along with their significant associations with clinical markers in these patients.ResultsA total of 64 miRNAs were differentially expressed between metabolically healthy obese (OBO) versus metabolically unhealthy obese (OBM) patients. Thirteen out of 64 miRNAs significantly correlated with at least one clinical trait of the metabolic syndrome. Six out of the thirteen demonstrated significant association with HbA1c levels; miR-331-3p, miR-452-3p, and miR-485-5p were over-expressed, whereas miR-153-3p, miR-182-5p, and miR-433-3p were under-expressed in the OBM patients with elevated HbA1c levels. We also identified, miR-106b-3p, miR-652-3p, and miR-93-5p that showed a significant association with creatinine; miR-130b-5p, miR-363-3p, and miR-636 were significantly associated with cholesterol, whereas miR-130a-3p was significantly associated with LDL. Additionally, miR-652-3p’s differential expression correlated significantly with HDL and creatinine.ConclusionsMicroRNAs associated with metabolic syndrome in obese subjects may have a pathophysiologic role and can serve as markers for obese individuals predisposed to various metabolic diseases like diabetes

apoA2 correlates to gestational age with decreased apolipoproteins A2, C1, C3 and E in gestational diabetes.

Pregnant women with gestational diabetes mellitus (GDM) are at risk of adverse outcomes, including gestational hypertension, pre-eclampsia, and preterm delivery. This study was undertaken to determine if apolipoprotein (apo) levels differed between pregnant women with and without GDM and if they were associated with adverse pregnancy outcome. Pregnant women (46 women with GDM and 26 women without diabetes (ND)) in their second trimester were enrolled in the study. Plasma apos were measured and correlated to demographic, biochemical, and pregnancy outcome data. apoA2, apoC1, apoC3 and apoE were lower in women with GDM compared with control women (p=0.0019, p=0.0031, p=0.0002 and p=0.015, respectively). apoA1, apoB, apoD, apoH, and apoJ levels did not differ between control women and women with GDM. Pearson bivariate analysis revealed significant correlations between gestational age at delivery and apoA2 for women with GDM and control women, and between apoA2 and apoC3 concentrations and C reactive protein (CRP) as a measure of inflammation for the whole group. Apoproteins apoA2, apoC1, apoC3 and apoE are decreased in women with GDM and may have a role in inflammation, as apoA2 and C3 correlated with CRP. The fact that apoA2 correlated with gestational age at delivery in both control women and women with GDM raises the hypothesis that apoA2 may be used as a biomarker of premature delivery, and this warrants further investigation

Corrigendum: Association of Complement-Related Proteins in Subjects With and Without Second Trimester Gestational Diabetes (Front. Endocrinol., (2021), 12, (641361), 10.3389/fendo.2021.641361)

In the original article, there was an error. One of the funders wasmissed out in the Acknowledgements. A correction has been made to the Acknowledgements section. “The authors would like to thank Qatar Metabolic Institute, Medical Research Center, Translational Research Institute, Hamad Medical Corporation, Doha, Qatar for supporting the study. And Medical Research Center, Hamad Medical Corporation for the article processing fees support”. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated