Area under the curve during <scp>OGTT</scp> in first‐degree relatives of diabetic patients as an efficient indicator of future risk of type 2 diabetes and prediabetes

Feizi, Awat; Meamar, Rokhsareh; Eslamian, Mohammad; Amini, Massoud; Nasri, Maryam; Iraj, Bijan

doi:10.1111/cen.13443

Cited by 15 publications

(11 citation statements)

References 36 publications

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“…Fasting glucose is an important clinical predictor of future pre-diabetes 15 . We, therefore performed ROC curve analyses to assess if microRNAs offered any predictive advantage over fasting glucose concentrations at 6- and 12-years, in stratifying NGT and pre-diabetes at 18 years of age.…”

Section: Resultsmentioning

confidence: 99%

Circulating microRNAs from early childhood and adolescence are associated with pre-diabetes at 18 years of age in women from the PMNS cohort

Joglekar

Kunte

Wong

et al. 2021

Preprint

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A high (20%) prevalence of glucose intolerance at 18-years was seen in women from the Pune Maternal Nutrition Study (PMNS) birth cohort. Here, we provide preliminary longitudinal analyses of circulating microRNAs in normal glucose tolerant (NGT@18y, N=10) and glucose intolerant (N=8) women (ADA criteria) at 6-, 12- and 17-years of their age using discovery analysis (OpenArray™ platform). Machine-learning workflows involving Lasso with bootstrapping/leave-one-out cross-validation (LOOCV) identified microRNAs associated with glucose intolerance at 18-years of age. Several microRNAs, including miR-212-3p, miR-30e-3p and miR-638, stratified glucose-intolerant women from NGT at childhood. Our results suggest that circulating microRNAs in childhood could predict pre-diabetes at 18-years of age. Validation of these findings in males and remaining participants from the PMNS birth cohort will provide a unique opportunity to study novel epigenetic mechanisms in the life-course progression of glucose intolerance and enhance current clinical risk prediction of pre-diabetes and progression to type 2 diabetes.

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Section: Resultsmentioning

confidence: 99%

Circulating microRNAs from early childhood and adolescence are associated with pre-diabetes at 18 years of age in women from the PMNS cohort

Joglekar

Kunte

Wong

et al. 2021

Preprint

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“…Maternal obesity and excessive weight gain can further aggravate insulin resistance during pregnancy, and are independent risk factors for GDM [ 37 ]. Time-glucose AUC in the OGTT reflects IR levels in GDM patients, and is associated with adverse perinatal outcomes in GDM patients and their offspring [ 38 , 39 ]. Therefore, circMAP3K4 may be significantly associated with GDM-related IR, as well as insulin-PI3K/Akt signaling pathway dysregulation in placental tissues.…”

Section: Discussionmentioning

confidence: 99%

circMAP3K4 regulates insulin resistance in trophoblast cells during gestational diabetes mellitus by modulating the miR-6795-5p/PTPN1 axis

Bai

et al. 2022

J Transl Med

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Background Insulin resistance (IR) during gestational diabetes mellitus (GDM) has been linked to dysregulated insulin-PI3K/Akt pathway. A defective insulin-PI3K/Akt pathway and dysregulated circular RNA (circRNA) levels have been observed in the placentas of patients with GDM; however, the mechanisms underlying this association remain unclear. Methods circRNAs potentially associated with GDM were selected through bioinformatics analysis and initially identified by quantitative real-time PCR (qPCR) in 9 GDM patients and 9 healthy controls, of which circMAP3K4 was further validated in additional 84 samples by qPCR. circMAP3K4 identity and localization were verified. Pearson correlation analysis was applied to evaluate the correlation between circMAP3K4 expression in the placental tissues of GDM patients and IR-related indicators. An IR model of trophoblasts was constructed using glucosamine. Interactions between miR-6795-5p and circMAP3K4 or PTPN1 were confirmed using a dual-luciferase reporter assay. The circMAP3K4/miR-6795-5p/PTPN1 axis and key markers in the insulin-PI3K/Akt pathway in placentas and trophoblasts were evaluated through qRT-PCR, immunofluorescence, and western blotting. The role of circMAP3K4 in glucose metabolism and cell growth in trophoblasts was determined using the glucose uptake and CCK8 assay, respectively. Results circMAP3K4 was highly expressed in the placentas of patients with GDM and the IR trophoblast model; this was associated with a dysregulated insulin-PI3K/Akt pathway. circMAP3K4 in the placentas of GDM patients was positively correlated with weight gain during pregnancy and time-glucose area under the curve of OGTT. circMAP3K4 and PTPN1 could both bind to miR-6795-5p. miR-6795-5p and PTPN1 were downregulated and upregulated, respectively, in the placentas of GDM patients and the IR trophoblast model. circMAP3K4 silencing or miR-6795-5p overexpression partially reversed the decrease in glucose uptake, inhibition in cell growth, and downregulated IRS1 and Akt phosphorylation in IR-trophoblasts; this restoration was reversed upon co-transfection with an miR-6795-5p inhibitor or PTPN1. Conclusion circMAP3K4 could suppress the insulin-PI3K/Akt signaling pathway via miR-6795-5p/PTPN1 axis, probably contributing to GDM-related IR.

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“…The oral glucose tolerance test with the area under a curve (OGTT-AUC) was derived from the OGTT curve, using the trapezoidal method between 0-120 minutes according to our previous study (22). The lipid index is a combined measure, which constructed lipid pro les including TG, cholesterol, HDL, and LDL by using exploratory analysis factor (EFA).…”

Section: Discussionmentioning

confidence: 99%

New risk models for predicting diabetes and prediabetes in the first-degree relatives of patients with type 2 diabetes and a comparison with the FINDRIC

Shahraki

Feizi

Aminorroaya

et al. 2021

Preprint

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Background We aimed to develop a risk model, monitoring the FDRs of patients with type 2 diabetes, who have normal glucose tolerance, to predict the onset of developing diabetes and prediabetes. In this study, 1765 FDRs of patients with type 2 diabetes mellitus, who had normal glucose tolerance, were subjected to statistical analysis. Diabetes risk factors including anthropometric indices, physical activity, fast plasma glucose, plasma glucose concentrations two-hour after oral glucose administration, glycosylated hemoglobin, blood pressure, and lipid profile at the baseline were considered as independent variables. Kaplan-Meier, log Rank test, univariate, and multivariable proportional hazard Cox regression were conducted. The optimal cut point for risk score was created according to receiver operating characteristic curve (ROC) analysis. Results The best diabetes predictability was achieved by a model in which waist to hip ratio (WHR), HbA1c, OGTT and the lipid profile were included. The best prediabetes risk model included HbA1c, systolic blood pressure, the lipid profile, and the oral glucose tolerance test (OGTT). These multivariable risk models were compared with FPG, HbA1c, and OGTT. The predictive efficiencies of models were higher than FPG and HbA1c; however the best predictive model of the current study showed comparable predictive efficiency to OGTT-AUC. Additionally, both diabetes models showed better performance than FINDRISC. Conclusion We recommend regular tests for FDRs of patients with type 2 diabetes to predict the risk of diabetes and prediabetes by using the OGTT-AUC. As a health check assessment tool, our diabetes models showed a more precise predictor compared to FINDRISC in our population.

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Area under the curve during OGTT in first‐degree relatives of diabetic patients as an efficient indicator of future risk of type 2 diabetes and prediabetes

Abstract: The data suggest that the glycaemic response to an OGTT may predict the risk of development of diabetes in first-degree relatives of DM patients.

Cited by 15 publications

References 36 publications

Circulating microRNAs from early childhood and adolescence are associated with pre-diabetes at 18 years of age in women from the PMNS cohort

Circulating microRNAs from early childhood and adolescence are associated with pre-diabetes at 18 years of age in women from the PMNS cohort

circMAP3K4 regulates insulin resistance in trophoblast cells during gestational diabetes mellitus by modulating the miR-6795-5p/PTPN1 axis

New risk models for predicting diabetes and prediabetes in the first-degree relatives of patients with type 2 diabetes and a comparison with the FINDRIC

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