Life-course exposure to perfluoroalkyl substances in relation to markers of glucose homeostasis in early adulthood

2021 ◽  
Author(s):  
Damaskini Valvi ◽  
Kurt Højlund ◽  
Brent A Coull ◽  
Flemming Nielsen ◽  
Pal Weihe ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Life Course ◽  
Beta Cell ◽  
Glucose Homeostasis ◽  
Beta Cell Function ◽  
Cell Function ◽  
Perfluoroalkyl Substances ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Altered Glucose

Abstract Objective To investigate the prospective associations of life-course perfluoroalkyl substances (PFASs) exposure with glucose homeostasis at adulthood. Methods We calculated insulin sensitivity and beta-cell function indices based on 2-h oral glucose tolerance tests at age 28 in 699 Faroese born in 1986-1987. Five major PFASs were measured in cord whole blood and in serum from ages 7, 14, 22 and 28 years. We evaluated the associations with glucose homeostasis measures by PFAS exposures at different ages, using multiple informant models fitting generalized estimating equations, and by life-course PFAS exposures using structural equation models. Results Associations were stronger for perfluorooctane sulfonate (PFOS) and suggested decreased insulin sensitivity and increased beta-cell function, e.g., β (95% CI) for log-insulinogenic index per PFOS doubling = 0.12 (0.02,0.22) for prenatal exposures; 0.04 (-0.10,0.19) at age-7; 0.07 (-0.07,0.21) at age-14; 0.05 (-0.04,0.15) at age-22; 0.04 (-0.03,0.11) at age-28. Associations were consistent across ages (P for age-interaction >0.10 for all PFASs) and sex (P for sex-interaction >0.10 for all PFASs, except perfluorodecanoic acid). The overall life-course PFOS exposure was also associated with altered glucose homeostasis (P=0.04). Associations for other life-course PFAS exposures were non-significant. Conclusions Life-course PFAS exposure is associated with decreased insulin sensitivity and increased pancreatic beta-cell function in young adults.

scholarly journals Advancing Dinner Timing Is an Effective Strategy in Improving Glucose Tolerance in Free-Living Adults: A Randomized Cross-Over Trial

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 585-585
Author(s):  
Hassan Dashti ◽  
Jesus Lopez ◽  
Céline Vetter ◽  
Millán Pérez-Ayala ◽  
Juan Carlos Baraza ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Disease Risk ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Effective Strategy ◽  
Free Living

Abstract Objectives Eating at times that conflict with our physiology and coincide with the biological evening has been associated with increased disease risk. In free-living adults from the ONTIME-MT study (#NCT03036592) study, we tested the hypothesis that advancing the timing of dinner relative to bedtime, simulated by advancing an evening oral glucose tolerance test (OGTT), will result in improved glucose control. Methods In a randomized, cross-over study design, following an 8h fast, each participant underwent two evening 2-hour 75-gram oral OGTT: early and late (4h vs. 1h prior to habitual bedtime), simulating early and late dinner timing. Habitual bedtime was determined using one-week of electronic sleep logs via smartphone application. The OGTT order was randomized and separated by 1-week washout period. Light intensity was kept bright (≥450 lux) and dim (0–25 lux) in the early and late conditions, respectively. Melatonin was assessed at the start and end of each OGTT by radioimmunoassay. Postprandial glucose and insulin were determined using incremental area under the curve (AUC). Insulin sensitivity and beta-cell function were evaluated using standard metrices: insulin sensitivity index (ISI), corrected insulin response (CIR), and disposition index (DI). Values were compared using paired t-tests and differences were considered significant at P < 0.05. Results A total of 750 participants (mean age = 37 ± 14; 70% female; mean BMI = 26.12 ± 5.66) underwent OGTTs in two evening timing conditions. As expected, melatonin levels were higher in the late vs. early condition (4.49 ± 4.15-fold lower in the early vs. late meal condition. In the early condition, there was an 8.68% lower AUC for glucose (P = .0001) and 4.4% higher insulin AUC (P = 0.059), relative to the late condition. In addition, the CIR was 16% (P = .0001) higher and the DI was higher by 20% (P = .014) in the early compared to the late condition. The ISI was similar in both conditions (P = 0.66). Conclusions In this large study, glucose tolerance was better during early vs. late evening OGTT. Better glucose tolerance was primarily attributed to improved insulin secretion and beta-cell function. These results indicate that for the general population, advancing dinner relative to bedtime may be a novel and an effective strategy to improve glucose tolerance. Funding Sources ONTIME-MT was funded by the NIH R01 grant R01DK105072.

scholarly journals HbA1c during early pregnancy reflects beta-cell dysfunction in women developing GDM

2020 ◽  
Vol 8 (2) ◽  
pp. e001751
Author(s):  
Latife Bozkurt ◽  
Christian S Göbl ◽  
Karoline Leitner ◽  
Giovanni Pacini ◽  
Alexandra Kautzky-Willer
Keyword(s):  
Beta Cell ◽  
Early Pregnancy ◽  
Beta Cell Function ◽  
Cell Function ◽  
Predictive Accuracy ◽  
High Specificity ◽  
Glucose Disposal ◽  
Large For Gestational Age ◽  
Oral Glucose ◽  
Altered Glucose

IntroductionIt is of current interest to assess eligibility of hemoglobin A1c (HbA1c) as a screening tool for earlier identification of women with risk for more severe hyperglycemia in pregnancy but data regarding accuracy are controversial. We aimed to evaluate if HbA1c mirrors pathophysiological precursors of glucose intolerance in early pregnancy that characterize women who develop gestational diabetes mellitus (GDM).Research design and methods220 pregnant women underwent an HbA1c measurement as well as an oral glucose tolerance test (OGTT) with multiple measurements of glucose, insulin and C-peptide for evaluation of insulin sensitivity and beta-cell function at 16th gestational week (IQR: 14–18). Clinical follow-ups were performed until end of pregnancy.ResultsIncreased maternal HbA1c ≥5.7% (39 mmol/mol) corresponding to pre-diabetes outside of pregnancy was associated with altered glucose dynamics during the OGTT. Pregnancies with early HbA1c ≥5.7% showed higher fasting (90.4±13.2 vs 79.7±7.2 mg/dL, p<0.001), mean (145.6±31.4 vs 116.2±21.4 mg/dL, p<0.001) as well as maximum glucose concentrations and tended to a delay in reaching the maximum glucose level compared with those with normal-range HbA1c (186.5±42.6 vs 147.8±30.1 mg/dL, p<0.001). Women with increased HbA1c showed impaired beta-cell function and differences in disposition index independent of body mass index status. We observed a high specificity for the HbA1c cut-off of 5.7% for GDM manifestation (0.96, 95% CI 0.91 to 0.98) or need of glucose-lowering medication (0.95, 95% CI 0.90 to 0.98) although overall predictive accuracy was moderate to fair. Further, elevated HbA1c was associated with higher risk for delivering large-for-gestational-age infants, also after adjustment for GDM status (OR 4.4, 95% CI 1.2 to 15.0, p=0.018).ConclusionsHbA1c measured before recommended routine screening period reflects early pathophysiological derangements in beta-cell function and glucose disposal that are characteristic of GDM development and may be useful in early risk stratification.

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